Authors & Works cited in this section (citations below): Up
Ameta, Sandeep et al. “Multispecies autocatalytic RNA reaction networks in coacervates
Arendt, Detlev. 2020. “Elementary nervous systems.”
Badiou, Alain with Nicolas Truong. 2009. In Praise of Love.
Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology.
Baluska, Frantisek & Levin. On Having No Head: Cognition throughout Biological
Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.
Barbieri, Marcello. “A general model on the origin of biological codes.”
Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain.
Barrett, Nathaniel. On the nature and origins of cognition as a form of motivated activity
Baum, David et al. 2023. “The ecology-evolution continuum and the origin of life.
Bechtel & Bich. 2024. “Organisms Need Mechanisms; Mechanisms Need Organisms
Bechtel, William & Bich. Grounding cognition: heterarchical control mechanisms in
Bertalanffy, Ludwig. Problems of Life: An Evaluation of Modern Biological Thought.
Bich, Leonardo et al. “Glycemia Regulation: From Feedback Loops to Organizational Clos…
Bich, Leonardo. “Integrating Multicellular Systems: Physiological Control and Degrees
Bich, Leonardo & Skillings. There Are No Intermediate Stages: Org View on Development
Blokhuis, Alex et al. 2020. “Universal motifs and the diversity of autocatalytic systems
Bly, Robert & M. Woodman. The Maiden King: The Reunion of Masculine and Feminine.
Borsley, Leigh & Roberts. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry
Brown, Gordon et al. Permacrisis: A Plan to Fix a Fractured World.
Buchler, Nicolas et al. 2003. “On schemes of combinatorial transcription logic
Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition.
Caneva, Kenneth L. 1993. Robert Mayer and the Conservation of Energy.
Capra, Emily & Laub. “The Evolution of Two-Component Signal Transduction Systems
Christensen, Wayne. 2007. “The Evolutionary Origins of Volition
Davies, Paul. 2019. The Demon in the Machine.
Deacon, Terrence & Garcia-Valdecasas. “A thermodynamic basis for teleological causality.
Deacon, Terrence W. 2021. “How Molecules Became Signs.
DiFrisco, James & M. Mossio. “Diachronic identity in complex life cycles.
Eronen, Markus I. & Daniel Stephen Brooks. “Levels of Organization in Biology.
Farnsworth, Keith. “How an information perspective helps overcome the challenge of biology
Farnsworth, Keith D. “How biological codes break causal chains to enable autonomy
Fields, Chris & Michael Levin. 2020. “How Do Living Systems Create Meaning.
Fine, Jacob & Pearlman. “On the origin of life: an RNA-focused synthesis and narrative
Floridi, Luciano. 2010. Information: A Very Short Introduction.
Frank, Thomas. 2021. The People, No: A Brief History of Populism.
Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.”
Gershenson, Carlos et al. 2020. “Self-Organization and Artificial Life.
Godfrey-Smith, Peter & Kim Sterelny. 2016. “Biological Information.”
Green, Sara. 2022. “Philosophy of Systems and Synthetic Biology.
Guttinger, Stephan. 2021. “Process and Practice: Understanding the Nature of Molecules.”
Hoffmann, Peter. Life’s Ratchet: How Molecular Machines Extract Order from Chaos.
Hooker, Cliff. 2024. “On the Organizational Roots of Bio-cognition.”
Hordijk, Wim. 2019. “A History of Autocatalytic Sets.”
Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agenc
Jain, Sanjay & Krishna. A model for the emergence of cooperation, interdependence, and
Japyassu, Hilton & Kevin Laland. 2017. “Extended spider cognition.”
Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence.
Kaiser, M.I. & Trappes. “Broadening the problem agenda of biological individuality
Kandel, Eric R. et al. (eds.) Principles of Neural Science, 6th Edition.
Katsumi, Y. et al. “Allostasis as a core feature of hierarchical gradients in the human brain
Kauffman, Stuart. A World Beyond Physics: The Emergence and Evolution of Life.
Kay, Leigh & Zerbetto. “Synthetic Molecular Motors and Mechanical Machines
Keenan, Jesse et al. The role of science in resilience planning for military-civilian domains in
Kim et al & S.I.Walker. Informational architecture across non-living and living collectives
Konnyu, Szathmáry et al. 2024. “Kinetics and coexistence of autocatalytic reaction cycles
Krishnamurthy, R. “Life’s Biological Chemistry: A Destiny or Destination Starting from
Labatut, Benjamin. 2023. The Maniac.
Lange, Marc. “Because Without Cause: Scientific Explanations by Constraint.”
Lim, Wendell et al. Cell Signaling: Principles and Mechanisms.
Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical… Second Edition.
Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.”
Masland, Richard. We Know It When We See It: What the Neurobiology of Vision Tells
Mediano, Pedro et al. “Greater than the parts: a review of the information decomposition
Merindol, R. & Walther. “Materials Learning from Life: Concepts for Active, Adaptive
Montevil, Mael & Soto. “Modeling Organogenesis from Biological First Principles
Montevil, Mael & Mossio. 2015. “Biological organisation as closure of constraints
Moore, Thomas. Soul Mates: Honoring the Mysteries of Love and Relationship.
Moreno, A. & Mossio. Biological Autonomy: A Philosophical and Theoretical Enquiry.
Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.
Nagel, Sidney et al. 2023. “Memory formation.
Nunes-Neto, Nei, Moreno & El-Hani. “Function in ecology: an organizational approach
Ouazan-Reboul, Vincent et al. Self-organization of primitive metabolic cycles due to non-
Papale, Francois et al. 2024. “The evosystem: A centerpiece for evolutionary studies.”
Pattee, Howard. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem
Pattee, Howard. “Epistemic, Evolutionary, and Physical Conditions for Biological Information
Pattee, Howard. 2015. “The Physics of Symbols Evolved Before Consciousness.”
Pattee, H. “Universal principles of measurement and language functions in evolving
Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut
Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.
Peng, Zhen et al. “The hierarchical organization of autocatalytic reaction networks and its
Peng, Zhen et al. “An ecological framework for the analysis of prebiotic chemical reaction
Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery.
Popper, Karl R. 1990. A World of Propensities.
Pross, Addy & Pascal. “On the Emergence of Autonomous Chemical Systems through
Pross, Addy. 2012. What is Life?: How Chemistry Becomes Biology.
Ramakrishnan, Naren & Bhalla. “Memory Switches in Chemical Reaction Space
Ross, Lauren. “The explanatory nature of constraints: Law-based, mathematical, and
Rosslenbroich, Bernd. 2023. Properties of Life: Toward a Theory of Organism Biology.
Ruiz-Mirazo & Moreno. 2024. “On the Evolutionary Development of Biological Org
Saborido, Cristian & Heras-Escribano. “Affordances and organizational functions.”
Salthe, Stanley N. 2018. “Perspectives on Natural Philosophy.
Schuster, Peter. 2019. “What is special about autocatalysis?
Shapiro, Robert. 2007. “A Simpler Origin for Life.”
Shirt-Ediss, Ben et al. “Modelling the prebiotic origins of regulation and agency in evolving
Skene, Keith “Systems theory, thermodynamics and life: Integrated thinking across ecology,
Soto, Ana M. & Sonnenschein. “Information, programme, signal: dead metaphors that negate
Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions
Stein, Murray & Corbett 2017 Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales.
Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design.
Swenson, Rod. Selection is Entailed by Self-Organization and Natural Selection Is a
Tagami, Shunsuke & Li. “The origin of life: RNA and protein co-evolution on the ancient Earth
Toepfer, Georg. “‘Organization’: Its Conceptual History and Its Relationship to
Torres-Oviedo et al. “Muscle Synergy Organization Is Robust Across a Variety of Postural
Trefil, James et al. “The Origin of Life: A case is made for the descent of electrons
Valsiner, J. “Breaking the Arrows of Causality: The Idea of Catalysis in its Making”
Van de Vijver, G. & Haeck. “Judging Organization: A Plea for Transcendental Logic
Virenque, Louis & M. Mossio. “What is Agency? A View from Autonomy Theory.
Vitas, Marko & Andrej Dobovisek. 2019. “Towards a General Definition of Life.”
Wagner, Nathaniel & Ashkenasy. Systems Chemistry: Logic Gates, Arithmetic Units, and
Williams, R.J.P. & da Silva. 2006. The Chemistry of Evolution: The Development of our
Winning, Jason & Bechtel. “Rethinking Causality in Biological and Neural Mechanisms:
Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women.
Woodman, Marion. Leaving My Father’s House: A Journey to Conscious Femininity.
Yurchenko, Sergey. “Is information the other face of causation in biological systems?
Citations collected in 2024 (works listed above):
“Reverse and forward engineering approaches may challenge the philosophical perspective on how-possibly-models, which are often taken to be stepping-stones for how-actually explanations. In systems and synthetic biology, however, how-possibly models can be explanatory in their own right – in explaining how possibly biological functions can be realized in natural or artificial systems.” Green, Sara. 2022. “Philosophy of Systems and Synthetic Biology.” Stanford Encyclopedia of Philosophy. p. 19.
“However, systems biology may give a novel interpretation of Aristotle’s dictum that the whole is more than the sum of the parts by specifying what more means in the context of contemporary biology….
“An interesting reframing of Aristotle’s dictum in this discussion is that living systems at the same time are more and less than the sum of the parts.” Green, Sara. 2022. “Philosophy of Systems and Synthetic Biology.” Stanford Encyclopedia of Philosophy. pp. 31, 32.
“Interpreting top-down effects as constraining relations may exemplify what philosophers of science have called ‘medium downward causation’, which interprets downward causation as boundary conditions.” Green, Sara. 2022. “Philosophy of Systems and Synthetic Biology.” Stanford Encyclopedia of Philosophy. p. 33.
“… stigmergy (persistent information left in a shared environment)…” Gershenson, Carlos, Vito Trianni, Justin Werfel & Hiroki Sayama. 2020. “Self-Organization and Artificial Life.” Artificial Life. 26:391-408. doi: 10.1162/artl_a_00324. p. 395.
“Life on earth is based on ordered sequences of proteins and nucleic acids, and on their mutual ordered interactions. And the solution to the quest for the origin of life is the answer to the question, of how this order came about.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. xii.
“Also note a general, important point about all this fine-tuning (both astrophysical and chemical) that fine-tuning can only concern the necessary conditions for life, and by no way is compelling regarding the sufficient conditions.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 25.
“In the first category [of new, important discoveries for prebiotic chemistry] I would name the science of autocatalytic sets, which has been developed by people at various levels of abstraction. Rosen, Varela, Kauffman, and Ganti belong to these visionaries. Interestingly, they published their first ideas roughly at the same time. It has taken quite a while for people to take notice, since they have been beguiled by molecular biology and the Miller experiments. Also, the work by Manfred Eigen (again in the same period), especially quasispecies theory and the molecular cooperation problem (but not his favored solution to it) also stands out. Experimentally I value the studies on spontaneous template replication (von Kiedrowski) and some of the work on reproducing vesicles (Luisi). Sometimes important experiments have been driven by theory (Waechterhaeuser). This could be said for the RNA world and ribozymes, also (Joyce, Szostak) For a later stage of evolution, the work by Yarus on the possible ingredients of the emergence of the genetic code is exciting. And we shall see how far Sutherland will get with the small molecules….
“Ganti’s conceptualization (chemical super system composed of three different autocatalytic systems, i.e., chemoton = metabolism with template replication with boundary) is not only elegant, but also erects the right goalpost. It is a cornerstone of the emerging field of systems chemistry.” Eors Szathmary in conversation with: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. pp. 45-7.
“Units of evolution and units of life have a large, but not complete overlap in my view. A mule is not a unit of evolution but it is alive. A virus is evolvable but not alive.” Eors Szathmary in conversation with: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 46.
“Thus, in enzymatic reactions, the concentration of the substrate must reach the KM value; in a bimolecular reaction, concentrations must be such to overwhelm dissociation forces, and so on. This may sound very trivial, but it is something that is occasionally, if not often, forgotten by theoreticians who use to work without mentioning concentration.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 65.
“Obviously, with one single molecule no real chemistry can be achieved. Here comes the threshold of concentration. In normal wet chemistry, in order to self-replicate, the replicator A must bind to another molecule A. The need to form the A-A complex (A2) from two A molecules is a severe constraint. First, in order to make an appreciable concentration of this complex, there must be a significant amount of A, so as to overcome the effect of diffusion; and the real difficulty arises when spontaneous decay is introduced. If the concentration of A is low enough, the population will decline no matter how large the growth rate is….
“Thus, it will not be enough to find a way to make ordered sequences of DNA, RNA, and proteins, but we will have to find a way to concentrate them in a small compartment having dimensions of a few microns.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. pp. 66, 67.
“Take a small protein with 50 residues in an ordered sequence: if its biogenesis would be possible with both L and D forms of the constituting amino acids, this very protein sequence would exist in 2 stereoisomers (c. a 10 followed by 15 zeroes). By applying the trick of using only L form, nature reduces this number to just one. Indeed, this is one of the greatest ordering factors in the structures of biological life.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 69.
“Actually, I see the trend as moving in the opposite direction, with a RNA-first origins now seeming more likely than it did 20 years ago. At that time the two biggest obstacles appeared to be prebiotic ‘clutter’ and enantiomeric cross-inhibition. The former is not yet overcome, but the creative new approach of Powner and Sutherland to the prebiotic synthesis of RNA has shown a potential path forward. Also, there are now several examples of chemical processes that break chiral symmetry, most notably the work of Blackmond and colleagues. The chemists have not been sleeping!” Gerald Joyce in conversation with: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 81.
“But let us conclude this brief section with two important statements coming from all these studies:
“1. Starting from the 10 prebiotic amino acids, short prebiotic peptides can be obtained.
“2. Proteins with a much simpler structure, even based only on the primordial amino acids, are very likely to have been present in prebiotic time.
“A more general kind of conclusion is that, in order to have proteins in prebiotic times, one does not have to wait for ribozymes and their eternal evolution as demanded by the prebiotic RNA-world.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 106.
“Three criteria of autopoiesis:
“1. Self-boundary: Does the system have a boundary of its own making?
“2. Self-maintenance: Is the system capable of maintaining its own identity via dynamic processes, i.e. those components that are being used up are made anew by the system itself?
“3. Self-generation: Does this happen throughout a network of reactions that are generated by the system itself?
“Thus, a virus is not an autopoietic system, as it does not produce the protein coat of its boundary or its nucleic acids.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 129.
“We have spoken in the previous section about the self-maintenance of the cell, or in general about the autopoietic unity. What is it precisely that is maintained? The answer is: the overall cell organization. Here is where the notion of organization acquires its full value. The organization is the invariant of the dynamics of the biological systems: it is the unitarian complex of relations that form the identity of the living….
“The notion of invariance of the relations is what makes autopoiesis a scientifically rigorous description of biological systems, able to distinguish the invariant aspects of the living dynamics (the organizational relations) from the variable ones and to link them to each other. The structure, the concrete unity of the components, is the variable element; it varies from cell to cell, and it also varies during development, but these changes do not affect the invariance of the biological organization.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 133.
“The notion [autopoiesis] introduced by Maturana and Varela proposes to think of biological systems as autonomous agents whose cognitive activity consists not in extrinsic processes of computational problem-solving, but in maintaining themselves – i.e., maintaining the continuity of their processes of self-production – by continuously re-establishing a relationship of dynamical coupling with their environmental niche.” Luisa Damiano in conversation with: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 136.
“The lack of emphasis on DNA, self-reproduction, and evolution in the theory of autopoiesis was certainly a reason for its lukewarm reception in the community of molecular biology – a difficulty that might have been avoided had its authors been less rigid about the matter.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 145.
“Conversely, we call illusion a sensory experience that we live as valid, and that we invalidate as we compare it with another experience of which we chose not to doubt. As I accepted that, I realized that what we distinguish when we talk of knowing was an operational coherence between interacting systems, which was the result of a history of structural coupling.” Humberto Maturana in conversation with: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 160.
“As I say to my students: living cells are molecular autopoietic systems; they are thermodynamically open systems; this means that they interact with the medium; they do so thanks to their specific metabolism; metabolism permits then the recognition of the environment, and therefore is the basic element of cognition (it is not cognition, but its ‘pragmatic arm’). And in this way, I link autopoiesis, cognition, metabolism, and homeostasis in the greater design of biology.” Humberto Maturana in conversation with: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 162.
“It seems clear that in the biological cell, the link between the internal and the outside world is metabolism itself…. The living system and the environment change together in a congruent way, and induce changes and adaptation in each other.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 167.
“Cognition then, operates at various levels, and as the sophistication of the organisms grow in evolution, so does its ‘sensorium’ (sensorial tools) for the environment, and do does the extent of co-emergence between organisms and environment…. In all these cases, the organisms contribute to the ‘creation’ of their environments. For example, the onset of photosynthetic organisms may have indeed created a novel oxygen-rich environment. Similarly, the spider web, the woody constructions of the beaver, and the cities constructed by mankind modify the structure of their environments. In all these cases, the environment is created by the organism, and this creation permits the being of the living organism.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 169.
“And… what about evolution? Although evolution is not emphasized in the basic definition of autopoiesis, for the same reason DNA mechanism is not, it is indeed an important part of the thinking of Maturana and Varela….
“Evolution, almost paradoxically, is seen as a consequence of self-maintenance: the unit tends to maintain its own identity and has no urge to change. When there is the need for adaptation, the cell adjusts with minimal changes, so as to disturb its own identity as little as possible. Adaptation is a consequence of the interaction with the environment, and it happens with the same rules as cognition, namely responding from within.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 180.
“Of course, self-assembly of this kind [micelles] occurs in water, and not, say, in ethanol. Any self-organization process must be defined in a given set of initial conditions. Initial conditions, as always in thermodynamics, determine the outcome of the process, and in particular whether the process is also under thermodynamic control or not.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 194.
“When surfactant molecules solubilize in water, generally the process is slow at the very beginning, and gets faster with time: the more surface bilayer is formed, the more the process speeds up, because there is more and more active surface where the next steps of aggregation can take place. The same behavior is observed in crystallization; in both cases we are looking at a particular kind of an autocatalytic process: the product of the reaction (organized surface bilayer or crystals) speeds up further self-organization.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 199.
“Polymerization appears to be a simple method to increase molecular order: starting from a gaseous or liquid monomer mixture, long covalent macromolecules with a vast series of emergent properties can be obtained. At first sight, there is a strong similarity between polymerization and two other processes mentioned earlier, crystallization and surfactant aggregate formation. In all these cases, in fact, starting from a disordered mixture, the low-molecular-weight components are stringed together in a compact ensemble – a crystal, a micelle, and a polymer chain…. … there is, however, an interesting difference between a polymerization process and a self-assembly process of surfactant aggregates: whereas the surfactant self-assembly is attended by an overall increase of entropy (because of water being made ‘free’), polymerization is generally attended by a decrease of entropy – as free monomers are being attached to each other and immobilized in a covalent string.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 199.
“Is polymerization a self-organization process? Namely, is the polymer the result of the internal rules of the system? The answer is not as clear as in the case of the formation of a micelle or of a crystal. I believe that a positive answer can be given in the case of spontaneous polymerization, as in the formation of nylon starting from a mixture of dicarboxylic acid chloride and alkyl diamines…. However, in the case of step-wise polymerization – for example, in the Merrifield synthesis – this is not the case, and I would not include this polymerization process in the category of self-organization.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 199.
“A very particular and important [of self-organization under kinetic control] case is given by those reactions under kinetic control that lead to stereoregular biopolymers. Polysaccharides, polypeptides, and nucleic acids are all stereoregular macromolecules. Clearly the linear, stereoregular chains are not the most stable products thermodynamically; an equilibrium random mixture of all possible enchainments would be entropically more favored, as it would correspond to billions of possibilities. Thus, the constitutional order and the stereoregularity of biopolymers results from a clear case of kinetic control.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 201.
“… we can go back to the question of whether stereoregularity is a self-organization process. Again, the answer is positive, if the catalyst is considered as one of the determinants of the ‘internal rules’ of the system. For example, if the growing polymer is considered as a complex with the catalyst, then it can be defined as a self-organizing system.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 201.
“… the design of both the anthill and the beehive is not imposed externally. Instead, it is the result of the internal work of the ant and the honey bee social systems. It is self-organization, if we consider the individuals themselves and their genome as part of the internal rules of their systems….
“Moreover, this complex self-organization pattern has no localized center that determines the organization: the ordered complexity is an emergent, collective property, and one might even draw an analogy between the swarm intelligence and the formation of a micelle: the parts come together and form an ordered ensemble. In one case the self-assembly is determined by simple thermodynamic driving forces (hydrophobic interactions, etc.); in the other, complex genomic and social factors are at work.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 210.
“In this chapter, we have dealt mostly with the following aspects of self-organization:
“1. Self-organization equilibrium (static) systems under thermodynamic control (originated from spontaneous processes with a negative free-energy change), such as supramolecular complexes, crystallization, surfactant aggregation, certain nano-structures, protein folding, protein assembly, and DNA duplex.
“2. Self-organization systems arriving at equilibrium, but being under kinetic control (biological systems with genomic, enzymatic, and/or evolutionary control, such as protein biosynthesis, virus assembly, formation of beehive and anthill, and swarm intelligence.
“3. Out-of-equilibrium systems (non-linear, dynamic processes), such as the Zabotinski-Belousov reaction, and other oscillating reactions; bifurcation, and order out of chaos; convection phenomena, tornadoes, vortexes – and the self-organized criticality, as well as fractals.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. pp. 227-9.
“Hans Primas uses this argument [that a context dependent theory can offer insights on independent reality even if not definitive] to introduce the notion of contextual ontology, which refers to emergent properties arising from hidden features of the independent reality. This permits a clear view of the relation between contextual and fundamental theories, and also a generalization that is relevant for philosophy of science at large:
“‘Only if we maintain multiple sets of contextual ontologies, we can tolerate the coexistence of complementary view in our experience of reality. While an independent reality itself is directly inaccessible, the numerous inequivalent contextual descriptions allow us to get deeper insight into the structure of independent reality.’” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 230; reference/subquote: Primas, Hans. 1998. “Emergence in exact natural sciences.” Acta Politechnica Scand. 91:86-7.
“Going from mammal myoglobin to hemoglobin, a higher level of hierarchic structure is found, as mammal hemoglobin is formed by four chains, each of them very similar to that of myoglobin. In this case, a new quality arises from this assembly, the cooperativity: whereas the binding of oxygen to myoglobin (single chain) gives a normal hyperbolic saturation curve, in the case of mammal hemoglobin, the binding isotherm is sigmoid [much faster and larger uptake of oxygen]. The difference is the very basis of respiration in mammals and is due to the cooperativity of the four chains in hemoglobin, which can be viewed as an emergent property arising from the interaction of the four chains.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 232.
“There is nothing wrong, in principle, with reductionism if it stops at the level of structure: we can all agree that water consists of hydrogen and oxygen; and that living cells are constituted by molecules, which in turn are constituted by atoms. The problem with reductionism is not at this level, but with the claim that the properties of water can be reduced to the properties of hydrogen and oxygen.
“In other words, the previous assertion by Ayala [‘that organisms are ultimately made up of the same atoms that make up inorganic matter, and of nothing else.’] that all living systems consist of the same atoms that make up the inorganic matter, is something with which we can agree. However, what is missing in this view is the appreciation of the emergent properties – from atoms to molecules, from molecules to genes and enzymes, from these to cells, and from cells to organs; whereby each time, at each level of complexity, there is the onset of novel properties that are not present at the lower level – and, importantly, that cannot be explained on the basis of the constituents.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 233; subquote: Ayala, F.J. 1983. “Beyond Darwinism? The challenge of macroevolution to the synthetic theory of evolution.” Cited in Primas, Hans. 1998. “Emergence in exact natural sciences.” Acta Politechnica Scand. 91:86-7.
“The ontological view that emergent properties of molecules cannot be explained as a matter of principle on the basis of the components is opposed by several scientists, who argue that this is tantamount to assuming that a mysterious force of some undefined nature is at work.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 234.
“At any rate, is the main consideration about emergence valid, namely that the novel properties are not deducible from – and are not reducible to – those of the components? It should be clear that this does not imply mysterious forces, but simply reflects the limits of our capability.
“Thus, going back to our cell: at each level of increasing complexity in going from atoms/molecules to biological complexes, to organelles and to the entire organism, there arise novel properties that cannot be described in terms of the lower constituents, and therefore the properties of a cell, or any other living organism, cannot be interpreted on the basis of atoms and molecules. This is so, regardless of whether it is a matter of principle or a practical difficulty. Emergence really makes the difference between the reductionist interpretation and a more holistic view of reality.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 235.
“‘Once instability is included, the meaning of the laws of nature… change radically, for they now express possibilities of probabilities.’” Prigogine, I. Quoted in: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 237; subquote: Prigogine, I. 1997. The End of Certainty–Time, Chaos and the New Laws of Nature. Free Press.
“… autocatalytic self-replication processes are not mysterious, strange chemical pathways, but on the contrary, they enjoy a certain degree of generality in the world of chemistry.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 253.
“No longer than 20 years ago, self-replication was one of those mysterious processes considered the monopoly of living matter. The fact that we are now able to achieve it in the laboratory means that we understand self-replication and self-reproduction in terms of simple rules of chemistry….
“We have also learned that self-replication is not a prerogative only of nucleic acids, but it can be shared by different kinds of chemical families; see the formose reaction, the self-replicating peptides, and the self-reproducing micelles and vesicles. The list should include the cellular automata and the other devices of artificial life.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 261.
“‘I have been trying to imagine a framework for the origin of life, guided by a personal philosophy which considers the primal characteristics of life to be homeostasis rather than replication, diversity rather than uniformity, the flexibility of the genome rather than the tyranny of the gene, the error tolerance of the whole rather than the precision of the parts …. I hold the creativity of quasi-random complicated structures to be a more important driving force of evolution than the Darwinian competition of replicating monads.’” Dyson quoted in: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 261; quote: Dyson, F.J. 1985. Origins of Life. Cambridge UP.
“By these methods [of small unilamellar vesicle preparation], eventually followed by extrusion, vesicles of different average size, say 50 nm and 200 nm, can be prepared, and if the two preparations are mixed with each other, a bimodal distribution is observed. In other words, the two species, contrary to the case of micelles, do not fuse and equilibrate with each other. This is because vesicles and liposomes are generally not equilibrium systems; they are kinetically trapped systems – the activation energy to change size is too high. This also means that in all these cases the liposomal system does not reach (does not have?) a state of absolute minimal energy.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 284.
“… liposomes do not fuse with each other and therefore do not exchange material, contrary to micelles. Also vesicles are generally characterized by a very poor permeability; compounds swimming in the outside bulk water are not easily promoted inside….
“The restricted permeability of liposomes may allow for a significant concentration gradient across the bilayer….” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 286.
“The surprising result … is that the size distribution of the newly formed vesicles is extremely close to that of the initially present preformed ones. This has been confirmed using different sizes of the starting monodisperse solutions of vesicles.
“It is as if there was a kind of stamp, that makes the new vesicles have the same size as those that are already present in the solution (the term ‘template effect’ – rather than matrix effect – might also have been appropriate, except that this term is generally used in connection with macromolecular primary sequences with an informational content).” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 306.
“Although, for some, SB [synthetic biology] is not really a novel branch of science, but actually a new dress for bioengineering within the broader field of biotechnology. It is indeed an offspring of the union between bioengineering and molecular biology, and in this vast field, it claimed from the very beginning a very ambitious program: that of creating new forms of life, alternative to the extant ones, which would permit us to tackle the energy problems of our world successfully, and produce new drugs cheaply. This ambitious statement becomes less high-sounding if one considers that, in reality, the new forms of life are restricted to bacterial life; and that SB aims at synthesizing simpler biological structures, not necessarily living, but still alternative to those found in nature.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 335.
“For the construction of these large systems, you need parts. In fact, in the field of SB the notion of ‘bio brick’ has become very important: those are components, which are often commercially available. You can find nowadays several companies selling customized DNA coding sequences, customized genomes and plasmids, all kinds of qPCR, reverse transcription kids, Y-chromosome detection kits, and so on.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 347.
“The smallest sizes of a genome, as already mentioned, are those of Mycoplasma genitalium (580 kb) and Buchnera spp (450 kb), with a value that agrees well with the calculations of Shimkets, according to which the minimum genome size for a complete living organism should be approximately 600 kb. It is argued that these two organisms have undergone massive gene losses and that their limited encoding capacities are due to their adaptation to the highly permissive intracellular environments provided by the hosts. They are, however, parasites and the next step of complexity concerns microbes with thousands of expressed proteins….
“The values of DNA content of free-living prokaryotes can vary over a tenfold range, from 1,450 kb for Halomonas halmophila to the 9,700 kb genome of Azospirillium lipoferum sp59b….
“Mushegian and Koonin calculated an inventory of 256 genes that reepresents the amount of DNA required to sustain a modern type of minimal cell under permissible conditions….
“Andres Moya and his group in Valencia arrived at the smaller number of 206 genes based on their work with Buchnera sp. and other organisms.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. pp. 377-8; references: Shimkets, L.J. 1998. “Structure and sizes of genomes of the archaea and bacteria.” In: F.J. De Bruijn, J.R. Lupksin & G.M. Weinstock (eds). Bacterial Genomes: Physical Structure and Analysis. Kluwer. pp. 5-11; Mushegian, A. & E.V. Koonin. 1996. “A minimal gene set for cellular life derived by comparison of complete bacterial genomes.” PNAS USA. 93:10268-10273; Gil, R., F.J. Silva, J. Pereto & A. Moya. 2004. “Determination of the core of a minimal bacteria gene set.” Microb. Molec.. Biol. Rev. 68:518-537.
“Sustained life is a property of an ecological system rather than a single organism or species. Traditional biology has tended to concentrate attention on individual organisms rather than on the biological continuum. The origin of life is thus looked for as a unique event in which an organism arises from the surrounding milieu. A more ecologically balanced point of view would examine the proto-ecological cycles and subsequent chemical systems that must have developed and flourished while objects resembling organisms appeared.” Morowitz, Harold J. quoted in: Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 383. From: Beginnings of Cellular Life. 1992. Yale UP. p. 54. [Note: my citation of some of the above passage made in Quotes2021 varies a bit in the sequence from this.]
“In addition to proteins and ribosomes, other macromolecular complexes have been incorporated in liposomes with the phenomenon of spontaneous overcrowding….
“It is commonly accepted that liposomes arise from the closure of planar bilayer sheets. One first assumption is now that the rate of closure is slowed down by the presence of bound macromolecules. In other words, sheets with one or two bound proteins already would take longer to close, and this would give more time for the binding of more incoming protein molecules. Such a kinetic effect would not be enough for the observed intense overcrowding in some liposomes. A second assumption is necessary, based on the cooperativity (which is an autocatalyltic effect) of intermolecular protein interactions. In particular, in those few liposomes that stochastically have incorporated a larger initial number of macromolecules, there will be a cooperative, non-linear addition of further macromolecules, driven by an increase of entropy (as for hydrophobic forces in water). In other words, the macromolecules attract each other and the more they do so, the higher is their initial number inside a closing compartment….
“There is a nice, simple experiment which can be carried out in the laboratory to confirm the above: you take a cellular extract, with the plasmid of GFP, and dilute 1:100 with water. No protein synthesis takes place because of the excessive dilution. Then you add a small aliquot of phospholipids in methanol, to form spontaneous liposomes in situ. And then you will observe the green color appear in some of the liposomes [from the manufacture of fluorescent proteins from the GFP and its increased concentration]. This is indeed an easy experiment to perform, and quite instructive.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. pp. 393-6.
“We have mentioned above that the idea to relate the spontaneous overcrowding to the origin of a pristine metabolism leads almost automatically to the idea of the very origin of life….
“Then, the phenomenon of spontaneous overcrowding will take place. There will be then a combinatorial, stochastic, distribution of solutes inside these crowded protocells, which tendentiously will be all different from each other in terms of composition and concentration….
“This scenario is what we can call the protocellular multiverse, borrowing metaphorically from the language of the cosmologists when they talk about a large number of universes, each with its own characteristics.” Luisi, Pier Luigi. 2016. The Emergence of Life: From Chemical Origins to Synthetic Biology; Second Edition. Cambridge UP. p. 396.
“By the term ‘organization’ I mean a certain mode of interaction among the parts of a system, distinctively realized by biological systems, when compared to other kinds of natural systems, or to artifacts. Broadly speaking, organization refers to a regime in which a set of entities happen to be related to each other so as to constitute a system that displays both functional differentiation and integration.” Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.” From: Organization in Biology. Mossio, Matteo (ed). pp.1-22. Springer. p. 2.
“It is now quite common to make a distinction… between two attitudes within systems biology: a ‘pragmatic’ one and a ‘theoretic’ one….
“Instead of producing models that include more and more experimental data, theoretical systems biology looks for what Green and Wolkenhauer call ‘organizing principles’, which are used to select relevant data. One may say that while pragmatic systems biology aims at getting knowledge by adding more details, theoretical systems biology pursues the same objective by abstracting from details. The principles on which theoretical systems biology focuses are mathematical descriptions of recurrent constraints, relations, and patterns that are similar (‘isomorphic’) in different systems, not necessarily or exclusively biological….
“When compared to the pragmatic approach, theoretical systems biology makes a further step in challenging the reductionist persepective. Systemic principles are understood as general hypotheses, which means that they are supposed to explain the data (top-down) and not be explained by them (bottom-up).” Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.” From: Organization in Biology. Mossio, Matteo (ed). pp.1-22. Springer. pp. 6-7.
“Of course, organization cannot be the explanans of this very initial phase [for origin of life], in which organized systems emerge from the integration of different kinds of preexisting processes and components. Once these systems have appeared, however, the process toward primitive living cells implies a set of intermediate forms of organization, each playing a role in the emergence of the next, more complex one. During that long process, thus, each form of organization plays both the role of explanans of the next one and of explanandum of the previous one.” Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.” From: Organization in Biology. Mossio, Matteo (ed). pp.1-22. Springer. pp. 8-9.
“A milestone in this tradition [study of biological organization] is the account put forward by Jean Piaget, whose core idea was to integrate into a single coherent picture thermodynamic openness and organizational closure. On the one hand, as emphasized by Bertalanffy, organisms are thermodynamically open systems, traversed by a continuous flow of matter and energy. On the other hand, they realize ‘closure,’ i.e., the mutual dependence between a set of constituents which maintain each other through their interactions and which could not exist in isolation.
“In Piaget’s view, closure captures a fundamental aspect of the very idea of ‘organization,’ through the association between division of labor and mutual dependence that it implies. In other words, biological organisms are organized precisely because they realize closure. The centrality of closure and its connection to organization, as well as its distinction from (and, complementarity to) thermodynamic openness have become givens in most subsequent accounts of biological organization.” Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.” From: Organization in Biology. Mossio, Matteo (ed). pp.1-22. Springer. p. 13; reference: Piaget, Jean. 1967. Biologie et connaissance. Edition de la Pleiade.
“A concerted attempt to answer this question [nature of relationship between organizational closure and thermodynamic openness] was made by Robert Rosen. In Life Itself, Rosen reinterprets the Aristotelian categories of causality and claims that the distinction between closure and openness should be grounded on a distinction between efficient cause and material cause. By relying on this distinction, Rosen’s central thesis is that: ‘a material system is an organism if, and only if, it is closed to efficient causation’. In turn, a natural system is closed to efficient causation if, and only if, all components having the status of efficient causes within the system are materially produced by the system itself. What matters here is that closure is located at the level of efficient causes: what constitutes the organization is the set of efficient causes subject to closure, and its maintenance (and stability) is the maintenance of the closed network of efficient causes.” Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.” From: Organization in Biology. Mossio, Matteo (ed). pp.1-22. Springer. p. 14.
“In particular, Stuart Kauffman argues that biological organization implies a circular relationship between work and constraints, in the form of what he labels a ‘work-constraint (W-C) cycle.’ When a (W-C) cycle is realized, constraints that apply to the system are produced and maintained by the system itself. Hence, the system needs to use the work generated by the constraints in order to generate those very constraints, by establishing a mutual relationship – a cycle – between constraints and work.” Mossio, Matteo. 2024. “Introduction: Organization as a Scientific Blind Spot.” From: Organization in Biology. Mossio, Matteo (ed). pp.1-22. Springer. p. 14; reference: Kauffman, Stuart. 2000. Investigations. Oxford UP.
“The causal structure of evolution is profoundly impenetrable. In fact, I believe that the whole undertaking is completely hopeless, unless it is informed by an adequate ontology and epistemology, specifically developed for the task. Luckily, such a foundation is available in the form of William Wimsatt’s perspectival realism….
“At the heart of Wimsatt’s ontology lies the recognition that the causal structure of the world resembles a rich and dynamic tropical-rainforest ecosystem rather than the eliminativist desert suggested by traditional ontological reductionism. In this lush ontological forest, there are areas that exhibit cleanly separated levels of organization, defined as ‘local maxima of regularity and predictability in the phase space of alternative modes of the organization of matter’. Examples are the subatomic, atomic, and molecular levels studied by physics and chemistry. In other areas of reality, however, this compositional hierarchy breaks down into more localized and less resolved causal structures, captured by perspective–defined as ‘intriguingly quasi-subjective cuts on the phenomena characteristic of a system’‘ Ultimately, even perspectives break down, resulting in causal thickets, which are hard to disentangle since they lack any discernible regularity or layering. The causal structure underlying the process of organismic evolution is a perfect example of such an impassable thicket.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. pp. 160-1; reference: Wimsatt, William. 2007. Re-engineering Philosophy for Limited Beings. Harvard UP.
“… James Griesemer suggests a radical change of philosophical focus for evolutionary theory, from selecting the best among competing approaches and generalizing it toward a comparative analysis of the strengths, weaknesses, and complementarities of different local perspectives. These perspectives are not right or wrong, better or worse, per se, but succeed or fail to achieve their specific purpose. Griesemer distinguishes three kinds of evolutionary perspectives: structural, functional, and processual. To this, I will add a fourth perspective here which emphasizes the agency of evolving organisms. A truly comprehensive science of evolution will have to include all four. Together, they yield more inclusive explanations of relevant evolutionary phenomena than each one of them on their own. In addition, a comparative approach allows us to reveal and assess the abstractions, idealizations, and simplifications, that each approach is bound to make. Finally, the robustness of specific claims ‘can only be assessed if a scientific community pursues phenomena from a variety of perspectives… It is not enough merely to compete.’ Is it really that surprising that a field centered on biological diversity would profit from a more diversified epistemic approach?” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 162; reference: Griesemer, James. 2006. “Genetics from an evolutionary process perspective.” In: E.M. Neumann & C. Rehmann-Sutter (Eds). Genes in Development. pp. 199-237. Duke UP; subquote: p. 363.
“If each constitutive constraint in a living system is both dependent on and generative for at least one other constraint, then there is closure of constraints, which represents a specific kind of organizational closure. It means that the constrained overall dynamics of the system determine the conditions for the continued existence of the constraints. In this way, the processes and constraints of a living system logically and materially entail each other. One is required for the existence of the other.
“This raises the question of how living processes and constraints co-emerge through their dialectic dynamic interactions. Kauffman argues that living organization must be powered by work-constraint cycles. Incorporating this into the account of Montevil and Mossio, we can say that the constrained release of energy by the organized system provides the physical work required to maintain its existing constraints and to constantly generate new ones. In this way, work-constraint cycles can explain various kinds of self-organization far from equilibrium, but are not yet specific enough or sufficient to account for the emergence, persistence, and propagation of organizational closure in living systems. For this, we need the additional concept of organizational continuity. It means that closure at any particular time dynamically presupposes closure of constraints that have operated earlier….
“On this view, the organism can be seen as a continuously changing but persistently closed organization of constraints that ‘lifts itself’ out of the thermodynamic background of all possible physicochemical processes. It does this through work-constraint cycles that recursively actualize a closure of constraints.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. pp. 163-4; references: Kauffman, Stuart. 2000. Investigations. Oxford UP; Montevil, M. & M. Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191.
“Specifically, to be a proper unit of evolution [in an approach that attempts to avoid the circular definition of Dawkins’ replicator model which takes replication itself for granted], an entity must adhere to the following three principles: (1) the principle of multiplication, entity A must give rise to more entities of type A; (2) the principle of heredity, entity A must produce entities of type A (not B); and (3) the principle of variability, the copying process is not perfect such that, every so often, entity A will give rise to an entity A’ (which, in fact, may be identical to entity B)…. What is new in this approach centered on the unit of evolution is an explicit focus on the notion of biological ‘multiplication.’” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 169.
“Alternatively, it has been proposed that autocatalytic processes could lead to stable self-maintenance without complex genomes or hierarchical organization. Based on this general idea, Eigen and Schuster developed their own minimal autocatalytic model, the hypercycle, as a proof of concept. Unfortunately, hypercycles were shown to be extremely vulnerable to ‘selfish’ replicators within them. In the meantime, Stuart Kauffman was proposing more general and robust models for autocatalytic sets. Kauffman’s models consist of networks of chemical reactions that are capable of self-maintenance thorough catalytic closure: every reaction within the set is catalyzed by at least one product of the network itself. Even though this avoids error catastrophes, it is difficult for autocatalytic sets to generate the kind of variability that evolution requires. In stark contrast to the fragility of template-based replication, these sets are too rigid, since any reaction that does not contribute to the self-maintenance of the network is quickly outcompeted. Because of this, the system strongly converges to one particular optimal and invariant set of autocatalytic reactions (an attractor in the sense of being a strongly self-maintaining organization), which leaves very little heritable variability for selection to act upon.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 170; references: Eigen, M. & P. Schuster. 1979. The Hypercycle – A Principle of Natural Self-organization. Springer; Kauffman, Stuart – works between 1971 and 1993 (The Origins of Order).
“In contrast [to pure copying when there is no material continuity between original and copy], biological multiplication always involves some material and temporal overlap between parents and offspring and between reproducer and reproduced. Organisms arise from material components of other organisms, and they do this in a gradual manner.
“This implies some kind of development, which for the purpose of my evolutionary argument can be defined in a broad and minimal sense as ‘acquiring the capacity to reproduce’…. To avoid confusion, I will use the term ontogenesis to describe the totality of regulatory processes–metabolic, physiological, developmental, and behavioral–that are involved in acquiring the capacity to reproduce.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 171.
“Ontogenesis and reproduction do not only influence each other, but cannot exist independently–they must co-emerge for organisms to be evolvable. They dynamically presuppose each other. The resulting system is a true unit of evolution called a reproducer.
“Reproducers are more complex than replicators, since they include ontogenesis and material overlap between generations. Ontogenesis and reproduction together form the life cycle of the reproducer. This life cycle must be completed for biological multiplication to continue from generation to generation. Variability cannot disrupt life cycle completion without disrupting evolution. In other words, freshly multiplied entities a must be organized in a way that enables them to mature into entities A, which have the capacity to reproduce. Otherwise, they are not evolvable. This constitutes a principle of ontogenesis (or development), which we must add to the principles of multiplication, heredity, and variability to define a proper unit of evolution.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. pp. 171-2.
“… it is quite probable that, even if they could evolve, purely self-organizing reproducers would easily be outcompeted by those possessing some kind of inherent hereditary processes, which lead to a much more efficient and stable propagation of organization across generations. Thus, heritable variability must be reliably regenerated and re-established through ontogenesis during each generation. For reproducers to meet the minimal conditions for evolution by natural selection, they require not only ontogenesis and material overlap between parents and offspring but also some kind of inter-generational continuity of organization that allows for heritable variability to be regenerated.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 172.
“Without the cell to interpret and replicate it, however, there is no sense in which the genome carries a code. Therefore, replication must be seen as a highly specialized and context-dependent ontogenetic process, embedded in a hierarchy of reproductive organizations.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 173.
“The reproducer account blurs the distinction between structural, functional, and processual perspectives. It shifts our focus from replicators to the more general category of reproducers as the fundamental (processual) units of evolution. Considered from a functional point of view, the central question about biological multiplication shifts from a simple template-based copying process (replication) to the propagation of complex biological organization across generations (reproduction)….
“There are several such accounts in the literature. The ones I will focus on here extend the notions of organizational closure and organizational continuity across generations, beyond the temporal boundaries of the individual organism. One option, from a functional point of view is to treat entire reproductive lineages as organized systems. However, such higher-order organization remains difficult to delineate precisely. Instead, we can take a more focused approach and consider the reproducer-reproduced dyad as a continuously organized system. The important point here is to distinguish the boundaries of self-maintaining organization from the boundaries of the individual.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 174.
“… organizational continuity is a special case of causal continuity. Now that we have extended it to organizational closure across generations, it enables a new principle of heredity as continuous self-maintenance of cross-generational functional organization.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 175.
“Behind this revision of the minimal conditions for evolution by natural selection lies an even more significant implication for evolutionary theory. It is rooted in the simple fact that organizational closure must be retained throughout ontogenesis and reproduction for a life cycle to be completed. And the life cycle must be completed for evolution to occur. In other words, without organizational continuity and the functional conservation it enables, there is no reproducer, and thus no proper unit of evolution. Without organizational continuity, there are no evolvable systems.
“If we accept this general conclusion, we must face another profound consequence: any proper unit of evolution, any evolvable system, must involve some kind of agency. It must be an autonomous agent with some degree of self-determination, since self-determination and autonomy are fundamental properties of organized systems.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. pp. 175-6.
“… it is important to reiterate what agency is, and what it is not. Most importantly, agency is the capacity of an organism to originate causal effects from within its own boundaries, particularly those that define its interactions with its external environment.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 176.
“What happens to evolutionary theory if we do take agency at face value? Walsh provides a very thorough philosophical analysis of this question and concludes that a number of implications follow from agential emergentism. First, evolution must be treated as a fundamentally ecological or relational phenomenon arising from the purposive engagement of the organism with its experienced environment. Second, it is not possible to causally separate the processes of inheritance, reproduction, and development: ‘fragmented’ evolutionary theory is an idealization. Third, there is no privileged control by replicator genes: genetic causation always has to be interpreted in its organismic context.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 177.
“His [Aristotle’s] four causes–material, formal, efficient, and final–are not really causes in the modern sense, but rather aitia, denoting something (or someone) responsible for a given phenomenon. For simplicity, I will use the less technical (but also less precise) notion of (be)causes here. (Be)causes correspond to different categories of determinants that complement each other to yield a full understanding of a phenomenon. This does not imply that Aristotle had a non-factive notion of causation, even though our modern scientific notion of ‘cause’ is much more restricted: it roughly corresponds to efficient (be)causes only.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 178.
“The organizational account of organismic agency relies on material, efficient, and formal (be)causes–mechanistic and relational explanations–which complement each other. Organizational closure, achieved through the closure of constraints, is the defining relational property of living systems. It is a formal (be)cause. However, it is not simply imposed on the material flows constituting the organism. Instead, it is continually regenerated, constantly (re)emerging over time through the dialectic dynamic interactions of material processes and the constraints they generate. These processes represent the material and efficient (be)causes of the organism….
“The agential perspective adds a fourth kind of explanation to evolutionary theory–naturalistic teleological explanation–thus completing the Aristotelian repertoire of (be)causes.” Jaeger, Johannes. 2024. “The Fourth Perspective: evolution and Organismal Agency.” From: Organization in Biology. Mossio, Matteo (ed). pp.159-186.. Springer. p. 179.
“Explanations of what is possible and impossible for a system are sometimes said to be provided by constraints in what are called ‘constraint-based explanations’ or ‘explanation by constraint’. These constraints are (i) claimed to have a mathematical, formal, or physical character and they are (ii) said to provide non-causal explanations. Two types of constraints that are discussed in this work are design constraints and topological constraints. Design constraints limit the process of designing, creating, or developing a final product, such as the evolutionary development of species in biology and the manufacture of products in engineering. These constraints clarify what systems it is possible (and impossible) to construct in a given context. On the other hand, topological constraints are mathematical features of a pre-existing system that limit the behavior the system is able to produce. These are said to capture various ‘constraints on mechanisms’ in the biological sciences and they figure in the well-known Koenigsberg bridge example. Both design constraints and topological constraints are said to provide non-causal explanations, as they derive their explanatory power from formal or mathematical relations.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. p. 2
“… constraint-based explanations have at least four characteristic features that distinguish them from ‘standard’ scientific explanations. In constraint-based explanations, the constraints that are cited in the explanation are factors that: (1) limit the values of the explanatory target of interest, (2) are often conceived of as separate from or external to the process they limit, (3) are considered relatively fixed compared to other explanatory factors, and (4) structure or guide the explanandum outcome, as opposed to triggering it.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. p. 4.
“If the constraint limits the system to exhibit a single outcome or a very small number of outcomes, the final outcome is said to be ‘fully determined’ by the constraint.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. p. 5.
“Particular constraints limit the upper and lower bounds of blood vessel size given the goals of these structures, which include the delivery of nutrients and removal of wastes from different sites of the body. The supply and removal of these materials takes place via diffusion, in which materials travel across walls of these vessels. Given this goal, two main constraints that dictate blood vessel size are Poiseuelle’s law and the laws of diffusion. Poiseuelle’s law states that as blood vessel radius decreases, resistance to flow increases by a power of four. In this manner, small changes in radius drastically increase blood flow resistance, as ‘a blood vessel that is half as wide as another has a resistance to flow 16 times greater’. This drastic increase in resistance will limit how small the vessels can be, as high enough levels of resistance will become impossible for the pumping heart to overcome and stagnant blood can clot. This law might seem to indicate that relatively large vessels will be ideal for transporting blood and, thus, selected for in organisms. However, the size of vessels are also limited in the upward direction, by the laws of diffusion. If vessel size is too large, blood flow will be too fast to allow for the diffusion of nutrients and wastes in and out of the circulating blood. A small enough vessel ensures that the vasculature can serve this purpose. Thus, Poiseuelle’s law places a lower limit on blood vessel size, while the laws of diffusion place a higher limit. In other words, ‘the constraints of diffusion mandate that vessels be small, while the laws of hydraulics mandate that vessels be large’….
“The laws in this example are best understood as empirical law constraints as opposed to mathematical or causal constraints…. These empirical laws capture relationships that must be discovered in the natural world, while mathematical properties do not have this feature (as they can be known a priori or identified without empirical study)…. ..empirical law constraints are discovered through empirical study of the natural world and they fail to meet our standard conception of a manipulable’ explanans….
“An interventionist conception of causal explanation involves an explanans that can be manipulated or changed through intervention, but this strains our conception of the explanatory role of these laws…. Thus, these empirical laws are a sort of non-causal, non-mathematical explanatory constraint.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. pp. 6, 7, 8; subquotes: Gilbert, S.F. 2010. Developmental Biology: 9th Ed. Sinauer Associates, Inc. p. 457.
“Now scientists do cite ‘constraints’ in these optimality cases [such as the evolution of bee honeycombs into hexagonal shapes], but they are used to specify available phenotypes to optimize on, so that optimal states can ultimately be explained and distinguished from sub-optimal ones. If these cases focused on explaining possible versus impossible phenotypes, they would fit a constraint-based explanation framework, but this is not their focus. Instead of explaining this impossible-possible distinction, they use specification of possible phenotypes to divide them into optimal and suboptimal states, which is the primary explanatory target. As these optimality explanations do not specify explananda outcomes that are strictly off-limits–but merely more or less optimal given various criteria–they fail to qualify as constraint-based explanations.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. pp. 10-11.
“First, some of these constraints are ‘structural’ in the sense that they are a ‘physical’ causes, which limits outcomes by physically blocking or reducing options. We see this with the marble [rolling on a surface with basins and ridges], river [flowing between banks], and blood vessel cases, in which physical barriers guide the flow or moment of a causal process. Notice how different this is from law-based and mathematical constraints, which both limit the outcome, but are not as tangible as physical barriers…. Second, structure can also refer to a perceived fixed nature of the cause, in the sense that it does not change much (or at all) relative to other explanatory factors. Just as there is a fixed character to a building’s frame and an organism’s skeletal system, these causal constraints have a fixed, stable nature.
“In the two cases above [marble on contoured surface or metabolic pathway (or factory assembly line)], the constraints reduce available values of the effect of interest, in particular, they limit the location of movement and type of product formed. Similar to law-based and mathematical constraints, these factors dictate which outcomes are off-limits and which are actual possibilities. However, unlike law-based and mathematical constraints, the constraints in these examples are causal in nature. These constraints meet both criteria for causal explanation, which law-based and mathematical constraints could not fulfill. These causal constraints involve a (a) manipulable explanans and a (b) dependency relation that contains empirical information.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. p. 15.
“While these constraints are causal [contoured surface for a marble or river banks], they are importantly different from standard causal factors that figure in scientific explanation. This difference is well-captured by the fact that these causal constraints meet the four constraint criteria …, while standard causal factors do not meet these criteria. A first obvious difference here is the role that causal constraints play in limiting the explanatory target or reducing the potential values it can take on. Standard causal factors dictate (or control) which of a set of possible outcomes some system will take on, while constraints determine which set of outcomes are possible or available, versus impossible. If a light switch is wired to a light bulb and not a fan or a toaster, the result of flipping the switch is limited to turning the bulb on/off, as opposed to producing outcomes in the other systems. The circuit captures a causal constraint in that it limits the flow of electricity to a particular downstream system and explains what downstream outcomes are possible or not…. In this case, the electrical circuitry is a structuring cause as it structures the final outcome and dictates what form the final outcome will take, but it does not have the capacity to ‘trigger’ this outcome, or control when it takes place, which is a feature of the switch.” Ross, Lauren N. 2023. “The explanatory nature of constraints: Law-based, mathematical, and causal.” Synthese. 202:56. doi: 10.1007/s11229-023-04281-5. pp. 15-16.
“… we will put forward the thesis that complex chemical systems (self-producing and self-reproducing protocells) progressively transform into hypercomplex biological organisms (living cells) thanks to a combination of factors that operate not only at different spatial/temporal scales and with different weights but also following intrinsically different dynamic principles. Some of these principles have to do with the composition, architecture, and necessarily interactive self-maintaining dynamics of the individuals involved, whereas some others have to do with their reproduction, inheritance, diversification, and open, collective dynamics. Accordingly, organizational aspects will be primarily associated to the development – and adequate coupling – of basic control mechanisms at the molecular and physiological description levels, while evolutionary and ecological aspects will rather cover the ‘propagation’ and ‘sedimentation’ processes working at the level of the population, or the whole ecosystem/biosphere. We will argue that even if they seem quite orthogonal to each other, these two phenomenological domains must actually get tied up during the process of origins of life, establishing a mutual – though causally asymmetric – connection that is further reinforced once biological evolution takes off.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 191.
“On the one hand, one can identify the network approach, in which the dynamics of a population of reacting molecules in homogenous – typically aqueous solution – conditions is explored, assuming a more or less concentrated ‘organic chemistry soup’ where the potential couplings/interactions among those molecular components can be captured through mathematical mappings or graphs. On the other hand, we find the protocell approach, in which both physical and chemical transformations take place in heterogeneous conditions – typically a mixture of aqueous and organic domains, like a lipid vesicle suspension – where the couplings/interactions among the system components must be analyzed making use of additional tools, since they are also influenced by spatial constraints on their free movement/diffusion.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 192.
“Indeed, the assumption that protocellularity is central in the early stages of biogenesis brings forward a concept of prebiotic individual that goes definitely beyond the molecular level: rather than populations of molecules as such, what one should consider is populations of molecular organizations constructed within compartments. Or, more accurately expressed, one should consider molecular organizations that also build their own boundaries and constantly traffic with matter and energy through them to achieve a precarious self-maintenance, with potential to propagate through reproduction and evolve as a protocell population. Taking seriously into account a global constraint, like a vesicle membrane, that derives from and exerts spatial control on a set of encapsulated chemical species/transformations (introducing new rules for dynamic behavior that need not be strictly stoichiometric – e.g., osmotic and volume effects, generation/management of electrochemical gradients) has far-reaching implications, both in a proto-metabolic and in proto-evolutionary sense.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 195.
“The central issue here, in a situation in which nature must have faced a huge bottleneck (perhaps the biggest bottleneck it has ever faced), would be to develop material constraints that would enable these systems to solve two fundamental problems at once: (i) increase the robustness of the precarious individuals/agents and (ii) preserve the level of complexity they reach, in a way that is both operational for each individual, during its existence as a protocell (its ‘proto-ontogeny’), and for the collection of individuals it may bring about (its ‘proto-phylogeny’ or ‘proto-lineage’).” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 201.
“Metabolic organization (the core of the individual dimension) is run and maintained in each (proto-)organism through a set of ‘rate-dependent’ causal connections: namely, causal connections that crucially depend on specific conditions of distance, velocity, and energy requirements…. The idea of organizational integration expresses the fact that the different parts and processes of a system are highly interdependent: there is a need to coordinate the distances, times, rates, and energies involved in all of them….
“Thus, the pressure for integration is inherent in any system whose identity is based on a far-from-equilibrium, cyclic set of synthetic processes (always coupled to matter and energy sources from the environment), namely, on a logic of self-construction that depends on the specific energy requests and the actual rates of their (always precarious) constitutive/interactive dynamics. That is why such systems cannot increase in complexity unless they enlarge the web of endogenous (higher-order) constraints and their assorted integration – including mechanisms to control the relationship with the environment (which will lead to the development of minimal forms of agency). In sharp contrast with this, the maintenance of an evolutionary process, per se, is much less demanding. Or, rather, it is demanding but in a completely different way: what matters there is the reliability in the transmission of constraints across generations, within the dynamics of populations of reproducing systems, all of which is averaged out in a very long and complex sedimentation process. In this context, part of the causal connections operate as if they were ‘rate-independent’, even if they must be continuously supported by the set of (rate-dependent) cyclic causal connections that constitute, maintain, and reproduce each protocell in far-from-equilibrium conditions.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. pp. 202-3.
“… the reproduction of a protocellular and minimal metabolic organization involves managing quite a number of processes, like the duplication of certain structures of the system, coordinated with surface increase (and other modifications) in the compartment, as well as with an adequate temporal and spatial allocation of the components during growth (so as to ensure that, when fission actually occurs, the new entity is able to repeat a similar self-productive cycle). In other words, reproduction requires a fair degree of control of the proto-metabolic processes, since growth and fission are the specific expression of the self-production regime of these protocells.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 204.
“… the possibility that some protocells managed to achieve relatively reliable reproduction cycles would depend critically on the synthesis of a number of material constraints controlling the processes of growth and fission. Certainly, there would be an organizational and material continuity between the initial, ‘mother protocell’ and its subsequent offspring and, in this sense, the functional role of the constraints more specifically involved in the reproductive processes would not be distinguishable, in principle, from the nonreproductive functions. However, more and more reliable self-reproductive systems require additional control mechanisms: in particular, hereditary mechanisms that should be focused in managing the variability generated in these protocells, preserving the level of complexity reached and making ‘statistical numbers,’ so to speak, ‘no-longer-statistical.’ But this, in turn, requires, as we will expand in the next section, a dynamic decoupling with regard to the current organization and the specific times, rates, and energies required by each individual metabolism.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 205.
“In Bich et al. we argued, precisely, that (biological) regulation involves second-order control hierarchies that necessarily work ‘offline’ in a relevant sense, or to a relevant extent. In other words, achieving effective control when the complexity of a system is very high requires a subsystem that is endogenously synthesized but operationally decoupled from the dynamics of the controlled processes, so that it can be modified without disrupting those underlying synthetic processes.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 207; reference: Bich, L., M. Mossio, K. Ruiz-Mirazo & A. Moreno. 2016. “Biological regulation: Controlling the system from within.” Biology and Philosophy. 31:237-265.
“… we concluded the previous section highlighting that self-reproducing protocell systems demand, right from the beginning, a rather elaborate set of basic functions (those first-order, material constraints acting as ‘process controllers’: catalysts, compartments, etc.) just to realize themselves and that the prebiotic evolutionary dynamics they bring about would contribute to expand their potentially available space for functionalities (including trans-generational constraints – such as hereditary mechanisms of various kinds). We consider that this hypothetical but plausible protocellular scenario is, indeed, complex enough to defend the need for second-order control mechanisms that help those systems navigate an internal dynamic space with multiple stationary states.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. pp. 207-8.
“In other words, regulatory meta-controls [e.g. processes of constraints to enable reproduction’s modifications] somehow reflect, also due to the intrinsic dynamical decoupling they involve, the interweaving between the physiological and the evolutionary dimensions of biological phenomena. This interweaving is asymmetric … because the physiological sphere always has causal priority (real self-constructing individuals are the material agents performing all relevant interactions, after all) even if the evolutionary sedimentation process, working at larger and longer scales, has a deep impact on the physiological mechanisms and organization of the resulting individuals.” Ruiz-Mirazo, Kepa & Alvaro Moreno. 2024. “On the Evolutionary Development of Biological Organization from Complex Prebiotic Chemistry.” From: Organization in Biology. Mossio, Matteo (ed). pp. 187-218. Springer. p. 209.
“Internalist models are at odds with a view of information as information emerges only within a system that includes the interaction between the components that constitute the system (among which some external devices could be included).” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. p. 377.
“The relational or systemic view of information is embraced by the extended cognition approaches in its embodied, extended, and particularly in its enactivist versions. Extended cognition is more akin to the niche construction perspective, because it implies reciprocal causation between the organism and the artefact, or modified environment.” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. p. 377.
“According to the MM [mutual manipulability criterion], if experimental changes in the external entity (the perceptual field or web) leads to changes in the cognitive system (for example, changes in the attention system) and, reciprocally, changes in the cognitive state of the system, entail changes in the external entity [the spiders are able to tighten certain web threads to focus more attention on these areas under certain conditions or prey probabilities], then this entity can be regarded as a part of the cognitive system, and accordingly one can say that cognition extends to include the external entity.” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. p. 379.
“With respect to the coupling-constitution fallacy [‘the argument that the coupling of an element to a system does not imply that this element is constitutively relevant to the system’], we agree that coupling does not inherently entail constitution. For instance, although cognitive activity is coupled to regionally enhanced blood flow in the active brain area, blood flow is not considered to constitute the cognitive process. However, such examples fail the MM criteria [see quote above]: they are coupled to cognition through a one-way, but not through a reciprocal causal path (in this instance, experimentally induced increases in blood flow in a brain area is not expected to lead to increased neural activity in that area). Thus, the reciprocal causality eliminates the possibility of erroneously taking background conditions for components of the cognitive system.” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. p. 380.
“Web-building spiders can actively focus attention on a particular web portion. They do that by pulling more strongly the web threads on the more profitable areas of the trap, a behaviour that has been shown to lead to enhanced capture success in these web regions.
“Enhanced attention to specific web areas can be induced by manipulating thread tension. It is possible to increase the tension of particular web sections experimentally, for example, inducing spiders to build their webs over movable supports; one can change the distances between the supports after the web has been built, thus altering artificially the tension of the horizontal, or alternatively of the vertical threads of the web. In experiments in which researchers artificially tensed the radial threads that led to one web area, the spider increased attention to that area, responding more quickly to stimuli coming from that particular region of the web.
“Naturally, it is also possible to alter the state of the foraging system in spiders, by simply letting the spiders get hungrier. Hungry spiders will increase web thread tension, so as to respond promptly even to usually less noticeable, and less profitable prey, such as small fruit flies.
“Spiders can also learn to focus attention on particular areas of the web. Where researchers have experimentally presented prey items exclusively on the horizontal threads of the web, the spiders have learned to pull these threads more strongly, and thus to respond more quickly to prey offered in the horizontal dimension….
Thus, to the extent that the above results are experimentally correct, there is reciprocal causation between the web and the foraging system, satisfying the MM criterion. Those cognitive processes associated with spider foraging, particularly the attention system, would appear to extend to the web, mediated by behavioural manipulations of the tension of the radial threads.” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. pp. 380-1.
“Descriptive and experimental work has been performed to understand web-building rules. This research suggests that spiders use many distinct external cues while building the web, such as prey-induced vibratory stimuli and prey nutrients, wind intensity, gravity, and humidity. Spiders also use internal cues to guide web building, such as the amount of silk supply, spider size, weight, and leg length.
“A spider also relies on cues that she herself has produced, through building earlier stages of the web, using the configuration of previous laid threads to organise the next steps of web building. These cues include the spider position in the web (near or far from, and above or below, the hub), or cues from sticky lines already present in the web that are sensed anew on each radius…. Moreover, while walking on previously laid lines, spiders do not solely respond automatically to present stimuli, but also rely on memory and attention. Spiders also do not invariably respond instantaneously to the immediate thread configuration because in many contexts spiders walk long journeys (relative to their body sizes) from one point of the web to another, and must keep track of the distances travelled in order to fix the new line at a precise point: they need to memorise the distances travelled at each step, while building the trap.” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. p. 382.
“Manipulations of regions of the CNS involved in web building have also been performed. Spiders with laser induced lesions in the C3 region of the supraoesophageal ganglion build smaller and rounded webs, with reduced regularity in the positioning of repetitive components. Interventions in the CNS with neurotoxins also resulted in significant changes in web properties. Chlorpromazine, diazepam and psilocybin prevent onset of web building and sodium pentobarbital causes end of radius construction before completion. D-amphetamine causes irregular radius and spiral spacing, while LSD-25 results in unusually regular webs. Amphetamine, scopolamine and caffeine cause various alternations in web geometry. Substances present in potential prey, such as harvetman, cause the construction of more irregular webs, and some parasites even manipulate the web-building behaviour of their host spiders, injecting substances that cause them to build altered web structures to be exploited by the parasites themselves.” Japyassu, Hilton F. & Kevin N. Laland. 2017. “Extended spider cognition.” Animal Cognition. 20:375-395. doi: 10.1007/s10071-017-1069-7. pp. 383-4.
“We think that the inadequacy of feedback loops [‘to explain how hormones regulate certain bodily functions such as glucose metabolism’] takes four forms. First, they tend to favor the idea of a neat localization of functional components. While it usually works for manmade machines because their parts have been designed separately and assembled, a neat localization applies much less clearly for organisms, in which a given function can be jointly performed by several components and a given component or structure can perform different functions. In addition, some functions can be distributed over the entire system and thus are non-localizable. Second, feedback loops tend to represent the system as a flat chain of interacting components. … the system is described as a set of functional components realizing a chain of steps, with no hierarchies or distinction of levels. Although they perform different functions, each component interacts in the same way with the following one in the chain, by either activating or inhibiting its activity (be it through a signal or not), following the kind of perturbation affecting the system. In this respect, there seems to be – to use a philosophical expression – only one kind of ‘causal relation’ at work in a feedback loop, which makes us claim that the resulting representation flattens the characteristic complexity of the system. Third, feedback loops do not foster the search of additional components and variables that might play a role in the homeostatic behavior. Of course, feedback diagrams can be enriched by new empirical knowledge; yet, they focus exclusively on the relation between several variables so as to understand the stability of the variable of interest (glucose). Accordingly, they ignore – and do not encourage exploring – the relationship between these variables and other physiological components which converge in diverse ways to control the concentration of glucose. Fourth, a description in terms of feedback assumes the existence of a value (or, more precisely, an interval of values) to be kept stable – a set point – without providing an explanation of how it is established or how it can be modified.” Bich, Leonardo, Matteo Mossio & Ana M. Soto. 2020. “Glycemia Regulation: From Feedback Loops to Organizational Closure.” Frontiers ni Physiology. 11(69):1-13. doi: 10.3389/fphys.2020.00069. p. 4.
“On the other hand, living systems possess a specialized class of organized constraints (which means that they are also maintained by the organism), that we label regulatory, that act as higher-order controllers upon first-order constraints.” Bich, Leonardo, Matteo Mossio & Ana M. Soto. 2020. “Glycemia Regulation: From Feedback Loops to Organizational Closure.” Frontiers ni Physiology. 11(69):1-13. doi: 10.3389/fphys.2020.00069. p. 5.
“Regulation provides the organism with the possibility of acting upon its own dynamics. Conceptually, a regulatory subsystem includes a set of dynamic constraints operating in a way that is distinct from first-order constraints, and collectively satisfying two main requirements:
“(1) The presence of constraints that act as second-order controllers, which means they modulate the activity of other constraints in the system, instead of directly channeling metabolic processes [Note: An example of a second-order constraint is a kinase enzyme catalyzing the phosphorylation of another enzyme in the system, leading to the activation or inhibition of the latter, while being localy unaffected by such interaction (for example, the kinase is not consumed in the reaction.];
“(2) The presence of constraints that being specifically sensitive to variations in internal or external conditions, begin to perform a qualitatively different function and, thereby, bring about the activity of the regulatory subsystem.” Bich, Leonardo, Matteo Mossio & Ana M. Soto. 2020. “Glycemia Regulation: From Feedback Loops to Organizational Closure.” Frontiers ni Physiology. 11(69):1-13. doi: 10.3389/fphys.2020.00069. p. 6.
“However, while the standard organizational formulations assume a definitional distinction between ‘boundary conditions’ and ‘internal constraints’, we argue that the notion of affordance and the situated approach presented in this paper is a promising starting point to understand why some elements of the environment become part of the closure of constraints, moving from being ‘external elements’ to part of the ‘organizational closure’.” Saborido, Cristian & Manuel Heras-Escribano. 2023. “Affordances and organizational functions.” Biology & Philosophy. 38:6. doi: 10.1007/s10539-023-09891-4. pp. 5-6.
“More specifically, the mutually beneficial combination of ecological psychology and the organizational account of functions can be summarized in three main points: (1) it develops the idea of organizational function towards an openness to the environment, which overcomes the traditional criticism to the excessive emphasis on organismal agency; (2) it substantiates the idea that the main unit of analysis is the organism-environment system, because ‘system’ means the functional organization that emerges from the history of mutual interactions between organism and environment; (3) the very idea of organization includes an etiological component, as there is cross-generational inheritance, both genetic and non-genetic, which allows the offspring to be adapted to the environment thanks to this situated organizational account. The organizational contribution of the environment facilitates adaptation of the offspring thanks to non-genetic ecological inheritances: some authors claimed that non-genetic ecological inheritances extend to affordances, as they play a contribution in the adaptation of the organism because they show the offspring in which sense they have to be related to the environment.” Saborido, Cristian & Manuel Heras-Escribano. 2023. “Affordances and organizational functions.” Biology & Philosophy. 38:6. doi: 10.1007/s10539-023-09891-4. p. 6.
“In fact, the very notion of interrelationship with the environment through affordances is functional from an organizational point of view: the capacity of organisms to perceive possibilities for action in their environment is a contribution to the closure of constraints in their organization. Thanks to the detection of affordances, elements of the environment become intrinsic parts of biological organizations.” Saborido, Cristian & Manuel Heras-Escribano. 2023. “Affordances and organizational functions.” Biology & Philosophy. 38:6. doi: 10.1007/s10539-023-09891-4. p. 7.
“One of the great contributions of ecological psychology is to understand that the object of analysis of cognitive science cannot be only the nervous system, or the organism, or its environment, but the integration of all of them, or what is called the organism-environment system….
“The organizational account of functions is highly suitable to be related to affordances because it illuminates what ecological psychologists refer to when they use the expression ‘organism-environment system’…. We propose that the organizational approach to functions can explain in which sense the organism and the environment form a unit or system.” Saborido, Cristian & Manuel Heras-Escribano. 2023. “Affordances and organizational functions.” Biology & Philosophy. 38:6. doi: 10.1007/s10539-023-09891-4. p. 11.
“Different theorists characterize how these processes [causal loops in an organism’s processes] are closed in different terms. For Maturana and Varela, it is closure of construction (autopoiesis), for Rosen, closure of efficient causation, and for Moreno and Mossio, closure of constraints.” Bechtel, William & Leonardo Bich. 2024. “Organisms Need Mechanisms; Mechanisms Need Organisms.” In: New Mechanism, History, Philosophy and Theory of the Life Sciences. Cordovil, J.L. et al (eds.) pp. 85-107. doi: 10.1007/978-3-031-46917-6_5. p. 87.
“Many organisms rely on detecting chemicals in their environment and moving as a result. The chemicals alter constraints in the sensors and the altered constraints in the sensors result in changes in the production mechanism, altering what it does.
“Allowing measurements to affect the constraints in control mechanisms seems to be in tension with the account of closure of constraints…. Especially when control mechanisms make measurements of conditions external to the organism, this seems to undermine closure–a given constraint is causally modified by things other than the constraints constituting the organism.
“The resolution to this challenge is to recognize that measurement is a different type of interaction from those involved in the production and maintenance of a constraint within a regime of closure.” Bechtel, William & Leonardo Bich. 2024. “Organisms Need Mechanisms; Mechanisms Need Organisms.” In: New Mechanism, History, Philosophy and Theory of the Life Sciences. Cordovil, J.L. et al (eds.) pp. 85-107. doi: 10.1007/978-3-031-46917-6_5. p. 95.
“Our thought leaders relate to populism not so much as scholars but as privileged class putting down a challenge to itself.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 8.
“How does it help reformers, I wonder, to deliberately devalue the coinage of the American reform tradition?
“It is my argument that reversing the meaning of ‘populist’ tells us something important about the people who reversed it: denunciations of populism like the ones we hear so frequently nowadays arise from a long tradition of pessimism about popular sovereignty and democratic participation….
“The name I give to that pessimistic tradition is ‘anti-populism,’ and as we investigate its history, we will find it using the same rhetoric over and over again–in 1896, in 1936, and today. Whether it is defending the gold standard or our system of health-care-for-a-few, anti-populism mobilizes the same sentiments and draws the same stereotypes; it sometimes even speaks to us from the same prestigious institutions. Its most toxic ingredient–a highbrow contempt for ordinary Americans–is as poisonous today as it was in the Victorian era or in the Great Depression.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 16.
“On the subject of elite failure, there is no international program of inquiry as there is with populism. There are no calls for papers, no generous foundation grant program, no Stanford global elitisms project, no incentives at all to discover why experts keep blundering. Indeed, anti-populists find it harder to criticize their colleagues for fouling things up than they do to deride the voting public of America for being angry over those foul-ups.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 17.
“It was [Pat] Buchanan who coined Nixon’s famous phrase ‘silent majority,’ and who urged him to cast himself as the embodiment of a middle-American uprising against elites; it was Buchanan who roared, in a speech at the 1992 Republican convention, that the libs had launched a ‘cultural war’ against ordinary Americans….
“What distinguished Pat Buchanan from his fellow Republicans was the startling innovation he brought to their primary contests: ripping corporate America and his own party for betraying working-class people with international trade agreements. Among conservatives this sneak attack was considered shocking, since it came from a man who virtually worshipped Ronald Reagan, destroyer of working-class organizations and the ultimate author of those trade agreements….
“But by the time of his own presidential run in 2016, Trump had pretty much taken over Buchanan’s old program, from the ecumenical bigotry right down to his 1992 campaign slogan, ‘America First.’ Trump had always been critical of America’s trade practices, and now he seemed to understand that the real audience for such a critique was not his fellow business leaders but American workers, abandoned by the increasingly upper-class Democratic Party.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. pp. 214-7.
“But in their revulsion against Trump’s ugly rhetoric, the Democrats committed an elementary mistake, dismissing the anti-elitist impulse itself because the man who was thought to embody it was so manifestly a blowhard.
“What they failed to understand is what centrist Democrats have persistently failed to understand since the 1970s: technocratic competence isn’t enough, especially when that competence somehow never means improving the lives of working people. Just because the imbecile Trump denounced elites doesn’t mean those elites are a legitimate ruling class. Just because the hypocrite Trump pretended to care about deindustrialization doesn’t mean deindustrialization is of no concern.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 222.
“But beginning in the 1970s, liberalism began to change. Over the course of countless intra-party debates, the Democrats came to think of themselves not as the voice of working-class people at all but as a sort of coming together of the learned and the virtuous….
“Democrats had put the New Deal behind them and remade themselves as leaders for an age of innovation and flexibility, affluence and sophistication, investment bankers and tech billionaires. When their turn in power came in 2008, new-style Democratic leaders declined to break up Wall Street banks. They delivered a version of national health insurance that, amazingly, did not inconvenience Big Pharma or private insurance companies. Silicon Valley executives, radiating futurific exuberance, swarmed through the Barack Obama White House and its would-be successor organization, the Hillary Clinton presidential campaign, helping usher the nation into a new golden age of cyber-transformation.
“Right until the end, this post-ideological, Learning Class fantasy ambled high-mindedly along.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. pp. 223, 226.
“If you wish to democratize the country’s economic structure, he argued [Lawrence Goodwyn, historian of mass movements], you must practice ‘ideological patience,’ a suspension of moral judgment of ordinary Americans. Only then can you start to build a movement that is hopeful and powerful and that changes society forever.
“If you’re not interested in democratizing the country’s economic structure, however, individual righteousness might be just the thing for you. This model deals with ordinary citizens by judging and purging: by canceling and scolding. It’s not about building: it’s about purity, about stainless moral virtue. Its favorite math is subtraction; its most cherished rhetorical form is denunciation; its goal is to bring the corps of the righteous into a tight orbit around the most righteous one of all.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 228.
“The prophets of reproach who make up the modern Left aren’t particularly interested in that, however. And once you start looking for this erasure–for this peculiar lacuna in the worldview of a certain type of liberal–you notice it everywhere. Social class is the glaring, zillion-watt absence, for example, in those anti-Trump yard signs that have become so popular in nice suburban neighborhoods and that strain for inclusiveness–
“In this house, we believe
Black lives matter
Women’s rights are human rights
No human is illegal
Science is real
Love is love
And kindness is everything.
“– but that say nothing about the right to organize or to earn a living wage.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. pp. 231-2.
“After turning their backs on working-class issues, traditionally one of the core concerns of left parties, Democrats stood by while right-wing demagoguery took root and thrived. Then, after the people absorbed a fifty-year blizzard of fake populist propaganda [1970s to Trump], Democrats turned against the idea of ‘the people’ altogether.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 241.
“The liberal establishment I am describing in this chapter is anti-populist not merely because it dislikes Donald Trump–who is in no way a genuine populist–but because it is populism’s opposite in nearly every particular. Its political ambition for the people is not to bring them together in a reform movement but to scold them, to shame them, and to teach them to defer to their superiors. It doesn’t seek to punish Wall Street or Silicon Valley; indeed, the same bunch that now rebukes and cancels and blacklists could not find a way to punish elite bankers after the global financial crisis back in 2009. This liberalism desires to merge with these institutions of private privilege, to enlist their power for what it imagines to be ‘good.’ The wealthy liberal neighborhoods of America have become utopias of scolding because scolding is how this kind of concentrated power relates to ordinary citizens. This isn’t ‘working-class authoritarianism’; it’s the opposite. Those people on top, this kind of liberalism says: They have more than you because they deserve to have more than you. Those fine people dominate you because they are better than you.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 242.
“The legatees of Thomas Jefferson, lukewarm in all things, no longer really believe their own founding philosophy; the hard-eyed heirs of the robber barons, meanwhile, have swiped the democratic vocabulary of their enemies; and between these two parties the greatest democracy in the world has become a paradise for the privileged.” Frank, Thomas. 2021. The People, No: A Brief History of Populism. NY: Picador. p. 245.
“… stigmergy (persistent information left in a shared environment)….” Gershenson, Carlos. 2020. “Self-Organization and Artificial Life.” Artificial Life. 26:391-408. doi: 10.1162/artl_a_00324. p. 395.
“All patterns of matter and energy in space and time are axiomatically equivalent to embodied information. The word ‘information’ alone is better reserved for relational information, which is information presented by system A about system B, rather than just that embodied in A. Embodied information is that which specifies the form of the object which embodies it, simply by virtue of the embodiment: it equates to the information that would be necessary and sufficient to recreate the pattern that is the form of the object.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 1.
“Closure to efficient causation (hereafter clef) describes a closed loop in causal relations, where e.g. A is the efficient cause of B and B is the efficient cause of A.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 2.
“The commitment to structure over material comes from the fact that patterns are the source of variety and dynamic behaviours in the natural world, with matter and energy performing the role of a substrate through which patterns act in space and time. The substrate is necessary for the natural world as is the space and time in which it can be arranged. But without particular arrangement, natural reality would be no more than uniformly random–the expected eventual ‘heat death’ outcome for the universe. It is therefore pattern, i.e., non-uniformity of arrangement, that brings about anything interesting in the universe and the pattern is what we interpret as embodied information.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 2.
“Information – as pattern in a natural dynamic system – can therefore be identified with the ‘stillness’ of the pattern relative to that expected from random displacement….
“This implies that a pattern is effectively ‘frozen’ in the midst of thermal (entropic) movement: it holds information at time t about its configuration at time t-T. This information transmission through time is fundamental to defining an object since the object only exists because it is a persistent pattern and that is only because information about its configuration at the time of observation (t) informs the observer of its configuration at an earlier time (t-T). Embodied information of this kind serves to give existence (diachronic identity) to an object for which all the material parts are continually replaced, e.g., a vortex in a fluid.
“Patterns can only be persistent if they are reinforced: physical forces must influence the trajectories of the moving particles so that the ‘freezing’ inequality dm(T) < DnT [differential of particle location over time over all particles of the pattern is less than the mean displacement rate or diffusion rate of the n particles of the system] remains true. Physical forces emanate from the particles themselves. The direction and strength of these forces at the locations of the particles is determined by the positions of the particles relative to one another. Reinforcement thus results from the pattern in the vector sum of forcefields being positively correlated with that of the pattern in particle locations….
“One obvious cause of persistent pattern, and probably the first acting in the history of the universe, is gravity. It is self-reinforcing because it concentrates matter in space, creating a pattern that further concentrates the gravitational forces…. What the placement of force-generating bodies does is determine a particular shape of the forcefield for a particular configuration, thereby specifying the coordinates of the force-generating particles, in space and time, effectively constraining the forcefield. Any pattern of particle locations is, in turn, influenced by the forces that it constrains. The emergent feedback between displacement and force leads to an attractor (e.g., a black hole, or the equilibrium of a mass-spring system).” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. pp. 2-3.
“Imposing the particular over the general is both a potential source of information (by creating a pattern) and also a consequence of pattern (information) constraining the system. Some have wondered how ‘intangible information’ can influence physical reality, but if ‘patterns of force fields affecting particles’ is all we observe and if ‘pattern in matter and energy distribution is embodied information’, then it is not a mystery. Persistence of a pattern, as opposed to a transient state in random reconfiguration, is achieved only when the pattern exerts a positive feedback to make itself more likely than any other possible configuration.
“The persistent configuration that results from reinforcement is the foundation for information, but not sufficient to call it information in a useful sense. A pattern which just persists in isolation is static (frozen) and the most we can say about its causal power is that it causes its own persistence. More interesting, by far, is the effect of one pattern on another, either interacting with it, or creating it de novo. The only way one pattern can create another is by ‘selecting’ it from among random configurations through correlation. This is the way crystal structures grow.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 3.
“When more than one pattern forms it is possible for members of the set of patterns to interact. The physical effect of a pattern in a force field is to constrain the form of any force-carrying configuration that it encounters…. The result is that the force-interacting patterns will tend to match with one another–a (muted or partial) reflection of each will form in the other and they will therefore share mutual information [example is two molecules bonding and changing their configurations]….
“Forces induce changes in the patterns that embed shared information, which is then relational information because it now involves ‘information about a thing’, not just information embodied in the pattern of a thing.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 3.
“Let us then define efficient causation as the action of one spatial pattern of forces on another, either to change it (transferring information among the patterns), or to reinforce it (maintaining stasis)….” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 4.
“Formal cause is classically the ‘template’ or design (i.e., information) responsible for a particular outcome of efficient cause. It comes in two distinct kinds. The first may be called the general conditions, roughly encompassing ‘the laws of physics’…. The second kind of formal cause may be termed particular conditions and concerns the consequences of the particular location of particles in space and time and their particular kind (from among all the possible fundamental particles). General formal conditions are strictly single valued (no degrees of freedom) but particular formal conditions are uniformly probable, subject only to the general conditions (e.g., particles are not allowed to occupy the same space-time coordinates). The appearance of a hierarchy among formal conditions is a consequence of their different degrees of freedom. General conditions constrain particular conditions and both constrain the action of forces to yield efficient cause from the combination of force and formal cause.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 4.
“Material cause (that which results from the nature of the substance) can now be seen as a consequence of force field patterns at the atomic scale. It gives water its fluid, solvent, electrostatic and other special properties that are necessary for biochemistry. It also gives steel its strength and hardness (and the temperature dependence of these). Material is governed by formal cause which is the particular spatial arrangement of atoms making particular the pattern of the force field that holds the atoms in place. Traditional material cause, deriving from the composition of substances either acting or being acted upon by efficient cause can be replaced by a ‘micro-formal’ cause, since it is formal cause at the atomic scale. In every case, the interatomic forces are determined by the atomic species (each with its own electrostatic force field) together with their configuration: force constrained by particular form. This effectively unites material and formal cause, both of which generate efficient cause via forcefields.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 5.
“The positioning of the constituent parts of a system is embodied information which can now be termed form. When particles are positioned in a form that is not random, then the form has a coherent spatial structure, i.e., its parts share mutual information and this shared information is the basis for effective information.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 5.
“Coherent action enables work to be done and is equivalent to the process we call Aristotle’s efficient cause: the action that brings about a transformation (or resists it). Hence efficient cause can be interpreted as the constraint of physical forces by form: force acting under formative constraint gives efficient cause.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 5.
“The basic element of efficient cause for biology is the physical configuration of atoms within biologically relevant molecules which, as forms, both constrain and are constrained by intermolecular forces to act in coherent ways. The effects of these coherent interactions include binding and electrostatic repelling such as in hydrophobic interactions along with their consequences such as conformational changes: indeed the whole repertoire of biochemical interactions that together produce, e.g., protein folding.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 5.
“Taking a biological example, suppose the large scale pattern were a functional molecular machine such as the ATP-synthase complex, composed of amino acid sequences (the small-scale patterns). Could we – even in principle – deduce from the amino acids, its ability to add a phosphate to ADP, making ATP? Standing in the way of that are (a) the particular sequences of amino acids in the polypeptides, (b) the way they are folded into functional proteins, (c) the way these are assembled into the machine and (d) the way the machine operates dynamically (like a little dynamo). At least folding and the dynamo behaviour are new concepts that are necessarily associated with higher levels of organisation than the amino acids and (because of the thermodynmic equivalence of amino acid sequences) unlike jigsaw pieces, the order in which they are joined is not strictly determined by their individual properties (therefore not predictable from knowledge of them as individuals components). This example, typical of biological systems, shows the appearance of properties that can only be attributed to a larger scale pattern because they are not already fully specified in the smaller scale constituent patterns….
“Returning to the case of ATP synthase, the highest-level pattern translates the flow of protons across a membrane into rotation of a large molecular complex and it is this rotation, not the pattern, that is the emergent phenomenon.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. pp. 7, 8.
“Hence, if a property of a biological system does not depend solely on the properties of its molecular parts, then it is an emergent property and we would have to conclude that the biological system was irreducible in respect to that property. This seeming violation of the reductionist paradigm can arise because properties at one level are the consequence of properties of its lower level components together with the arrangement of those components (the higher level embodied information). Properties and arrangements, being ontologically different entities, cannot be reduced together to a single description at the lowest level.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 8.
“By regarding efficient cause as the informed constraint of forces, clearly delineating the separate constituents – information and force – we can have a simple mechanism-based understanding of downward causation. It can be illustrated in a very simple and graphic way by soap bubbles on the surface of water: alone they are hemispherical (energy minimising), but when formed together as a group, they adhere and distort into an approximately hexagonal shape, characteristic of space and energy minimising packing. The shape of level L structures is determined by the configuration (embodied information) of level L + 1. This is a case of downward causation involving change in the constituent parts of the whole…. In other words: downward causation is efficient cause that is informed by information embodied at the higher level of pattern.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 8.
“It [homeostasis] also implies a means of detecting the changing environment, without being determined by it in a linear chain of efficient causation (as would be the case for a non-clef system). This requires isolation from exogenous causation, but not from the information embodied by exogenous forces.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 10.
“The reductionist approach has been so successful that it has misguided us towards believing that the small scale is the only real one and that all processes are in fact processes at that scale. Understanding that everything, except elementary subatomic particles, exists because of information embodied in the particular arrangement of those particles, enables us to see it the other way round…. Rather than the smallest level being the fundamental basis of reality, it seems the largest level, the one where the forcefield is a unitary whole with a particular (and typically changing) pattern, is the source of the reality that we experience.” Farnsworth, Keith D. 2022. “How an information perspective helps overcome the challenge of biology to physics.” BioSystems. 217:104683. doi: 10.1016/j.biosystems.2022.104683. p. 12.
“… we can think of constraint closure like this: it is a set of both constraints on the release of energy in non-equilibrium processes, and those processes, such that the system constructs its own constraints. This is an amazing idea. Cells do this, automobiles do not.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. x.
“The universe, whatever might happen, can have made only a tiny fraction–1 over 10 to the 39th–of the possible proteins each consisting of 200 amino acids.
“History enters when the space of the possible is vastly larger than what can become actual…. Thus, the becoming of the universe above the level of atoms is a historical process.
“The physicist’s phrase for this historicity is ‘nonergodic.’ ‘Ergodic’ means, roughly, that the system visits all its possible states over some ‘reasonable’ time period.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. pp. 3, 4.
“If we ask whether the universe has created all stable atoms, the answer is yes. So the universe is roughly ergodic with respect to atoms, but it is not ergodic with respect to complex molecules.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 4.
“The universe can explore and surge upward in complexity indefinitely in this sense, there is an indefinite ‘sink’ upward in complexity. The universe can explore indefinitely vast realms.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 4.
“The closure of mutual catalysis is not seen in any of the parts alone. Rather, the closure is a collective property.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 9.
“We [free living systems] do not live alone. We make our living world together. No individual is alive alone. We all are joined together in the evolving, emerging, unfolding of the biosphere as a whole. We are the conditions of one another’s existence.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 10.
“More generally, to be a function something must abet the survival of a Kantian whole–like us or a fruit fly or any living thing.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 14.
“‘Work is the constrained release of energy into a few degrees of freedom.’” Atkins, Peter. Quoted in: Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 19; subquote: Atkins, Peter W. 1984. The Second Law. NY: W.H. Freeman and Co.
“During the expansion of the gas, as work is done [piston in a cylinder], entropy increases but in a very specific way. The increase in entropy would be greater were the cylinder not there at all and the gas expanded in all spatial directions, that is, into all degrees of freedom, the full space of possibilities, everywhere. But the boundary conditions constrain the release of energy into only a few degrees of freedom, and only then is work done. As a result, the increase in entropy is less than were the constraints not there…. Due to constraints, entropy still increases, but more slowly…. Well, it took work to construct the cylinder that then serves as a constraint on the release of energy. It took work to construct the piston. It took work to assemble the piston inside the cylinder and arrange for the gas to be at the head of the cylinder. Physicists ignore this when they merely impose boundary conditions with no consideration of from whence they came.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 21.
“So surely, no constraints, no work. And often, no work, no constraints.
“Call this the Constraint Work cycle….
“Our machines do not do this. An automobile constrains the motion of many parts but does not construct new constraints. Life does.
“As we soon will see, this propagating work and constraint construction can loop back to close on itself! Thus, a set of constraints on a set of non-equilibrium processes can achieve a work task closure that constructs the very same set of constraints. The constraints do work tasks that construct the same constraints, or boundary conditions.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 22.
“All three tasks are performed in a cycle [three constraints that are needed to reciprocally form each other]. This is a work task closure.
“The cycle of work here need not be a thermodynamic work cycle. This is because all three work tasks might be exergonic. But a work cycle linking both exergonic and endergonic work tasks might be involved, in which case a thermodynamic work cycle could be accomplished.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 29.
“The three closures–constraint, work task, and catalytic–are ‘holistic’ properties, not to be found in any one of the parts alone.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 30.
“Second, if we call catalyzing a reaction in the set a catalytic task, the system achieves catalytic task closure. All the reactions that need to be catalyzed are catalyzed.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 44.
“Life is a fundamentally new linking of non-equilibrium processes and boundary condition constraints on the release of energy into a few degrees of freedom that thus is thermodynamic work. But stunningly, the work done can construct constraints on the release of energy in further non-equilibrium processes….
“Such a system is a ‘machine’ but not of matter alone, energy alone, free energy alone, entropy alone, or boundary conditions alone. It is a new union of these.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. pp. 52, 53.
“This [experimental results to see the probability that random proteins could catalyze a reaction to test the feasibility of merging an autocatalytic set with a small metabolism to yield a speedup of a significant part of the metabolic network] could yield a first step in which a collectively autocatalytic set catalyzes a small metabolism that resides in the same vicinity, ‘side by side’ if you will. If the products of the metabolism can feed the autocatalytic set, the two can co-evolve: a self-reproducing system and its supporting catalyzed connected metabolism.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 67.
“Random polypeptides often fold and can with a probability of about one in a hundred thousand to one in a million bind a molecular epitope, or bump, and catalyze a given reaction.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 69.
“For example, consider a bacterium swimming up a glucose gradient. The sugar matters to the bacterium. Mattering is now part of the universe. Agency introduces meaning into the world! Agency is fundamental to life.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 91.
“All of the niche creation of which we speak [as constraints produced in the environment available for other organisms and species to combine with their own constraint regimes] in this open-ended evolution is enablement, not cause.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. p. 117.
“The filling of these niches [as evolution expands with new species] by ever new, unprestatable organisms, creates yet further new contexts and opportunities. The total system ‘explodes’ in a self-amplifying way into the very adjacent possible it itself creates….
The same claims are true for the global economy, which has exploded in diversity from perhaps 1,000 goods and services–stone tools, for example, some 50,000 years ago–to billions today. Like species in a biosphere, goods and services afford niches for ever new goods and services, enabled to come into existence by what exists now.” Kauffman, Stuart A. 2019. A World Beyond Physics: The Emergence and Evolution of Life. Oxford UP. pp. 124-5.
“But it is not always obvious whether a biological system at a given time is the beginning of a new life or just a later developmental stage of the parent. This is especially the case in life cycles involving metamorphosis, metagenesis (alternation of generations), vegetative reproduction, fusion, fission, and symbiosis, as we will see.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 177.
“Organisational continuity is sufficient for diachronic identity only when there are no changes in the number of organised systems that are organisationally continuous with one another.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 178.
“Let us propose, then, that a necessary condition for diachronic identity of organisms is that they continually exhibit closure of constraints. Any temporal interval where this property of organisational continuity is not present then marks a temporal boundary of an organism’s life….” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 181.
“If a system continually realises closure of constraints, then at any given moment the organisation of its parts is causally dependent on the effects of functional constraints that have operated at a previous moment. The organism at t2 does not need to have the same set of constraints with the same inter-relationships as the organism at t1, but some of the constraints at t2 must be causally dependent on those at t1. The particular set of constraints and their inter-relations–which we refer to as a regime of closure–can change over time as long as later regimes causally depend on earlier regimes. Hence, what must remain the same over time is closure construed as a general theoretical principle and not as a specific regime of closure.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 183.
“The idea of conceptualising diachronic identity in terms of causal continuity, as opposed to material or functional conservation or resemblance, is not new. It was expressed in its modern form in Kurt Lewin’s notion of genidentity, which has been promoted by some philosophers of biology as a criterion of diachronic identity for biological individuals.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 184.
“In contrast, the conservation of a principle of closure over the course of ontogenesis does not entail that each stage displays the same characteristic functioning or activity. The principle of closure is something more abstract; this is why we treat it as a necessary condition and not as providing ‘thick’ sufficient conditions for individuation. Sometimes a principle of closure will correspond to a unitary regime of closure that picks out temporal boundaries without difficulty This is relatively more likely to be the case in organisms that do not undergo massive functional changes during ontogenesis, e.g., non-eukaryotes and some eukaryotes, and in direct developers. But in our proposal the concept of a regime of closure is not attributed an individuating role as a condition of persistence.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. pp. 185-6.
“Ontologically, the key dynamic category that binds together stages into the same life cycle is not activities, but developments. Activities are homeomerous or ‘like-parted,’ in that what is happening in any sub-interval of the duration of an activity is itself the same kind of activity. Every sub-interval of the burning of a candle is also a burning. Developments are heteromerous or ‘non-like-parted’ in the sense that what is present in any sub-interval of the development is not the same kind of development. The larval stage of holometabolous development is not itself a metamorphosis. This implies that the sortals capable of determining boundaries for developments will be complex specifying a normal or typical series of stages as well as a relation that makes them stages of the same process.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 186.
“The idea of organisational continuity is therefore more germane to a process model than a substance model of organism identity.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 186.
“To a first approximation, one might hold that organisational continuity provides both necessary and sufficient criteria for diachronic identity. The idea would be that any temporal interval where continuity is broken marks a temporal boundary of an organism’s life, either due to death or birth, which appears to be straightforward from an organisational perspective. An organism dies when it loses the property of closure of constraints, as this is responsible for its capacity to maintain itself far from equilibrium, and is born when a closed regime appears. Any corpse or parts that remain after death, as well as any preceding material constituents will be spatiotemporally continuous but not organisationally continuous with the organism.
“To see why this solution generally does not work, recall that organisational continuity between two successive stages is present as long as both stages instantiate the principle of closure of constraints, the stages are spatiotemporally continuous with one another, and the later stage is causally dependent on constraints acting in the previous stage. The problem is that these conditions are satisfied not only between stages of metamorphosis, but also when the earlier stage is a parent and the later stage is an offspring. Parents and offspring are organised systems, they are spatiotemporally continuous with one another, and the offspring is dependent on constraints exerted by the parent, at least in the sense that the very generation of the former depends on constraints exerted by the latter. Hence, parents and offspring are organisationally continuous with one another. If organisational continuity were not only necessary but also always sufficient for diachronic identity, then parents and offspring would count as continuations of the same organism.
“This has the unwelcome consequence that whenever a parent continues to exist after reproducing, we would have a spatially scattered system comprising both parents and offspring as parts….
“To address this problem, we can modify our criterion by proposing that organisational continuity is sufficient for diachronic identity unless there is a change in the local number of organised systems that are organisationally continuous with one another, either via an event of multiplication (fission) or reduction (fusion). When a spatial separation of this sort appears or disappears, we have a temporal boundary and a change of identity.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. pp. 187, 188.
“In general, spatial separation occurs when the involved systems do not realise a global closure with mutual dependence. In borderline cases where it is unclear whether there is one organised system or two, the critical consideration is whether the putatively distinct systems are functionally interdependent in virtue of constraint relationships.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 188.
“… we propose that parent and offspring can be discriminated by the presence of transitory asymmetrical dependence relationships. In reproduction, the materials that will constitute the offspring begin as parts of the parent(s)…. Eventually what begins as a part of the parent breaks the symmetry of dependence: it depends on the parent but the parent does not depend on it. When there is a transitory relation of asymmetric causal dependence during the process of multiplication of organised systems, the dependent system can be identified as the offspring, whereas the non-dependent organised system is the parent. If an asymmetry is not present but there is still multiplication of organised systems–e.g., in binary fission–then neither of the resultant systems is a continuation of the parent and both are offspring (new individuals).” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 189.
“An individual x and an individual y merge to form an individual z…. In fusion, one of two outcomes can occur:
“1. x is the same individual as z and y becomes a part of z during fusion, or y is the same individual as z and x becomes a part of z during fusion; or
“2. neither x nor y is the same individual as z, and x and y cease to exist upon fusion.
“The first case corresponds to parental persistence after fission, and the second corresponds to parental cessation upon fission.
“An outcome of spatial merging that is not fusion would be:
“3. neither x nor y is the same individual as z, and x and y persist through merging.
“Because this does not involve a disruption of the identities of the fusing entities, we will call this ‘integration’ or x and y.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 191.
“… we have seen how diachronic identity for organisms can be plausibly grounded in a special kind of causal continuity. In order to capture sameness over time despite radical developmental changes such as metamorphoses, continuity should not be based on conservation of matter, function, form, or activity, but rather on a causal dependence relation called ‘organisational continuity.’ For two stages of a developmental process to be organisationally continuous with one another, they must be spatiotemporally continuous, must realise closure of constraints (by whatever particular regime of closure), and the later stage must be dependent on constraints exerted in the earlier state.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. p. 194.
“Organisational continuity is consistent with dramatic developmental change, but it does not differentiate development and reproduction. This is because parent and offspring are organisationally continuous with one another just as the successive stages of parental development are. To distinguish parent and offspring, then, it is necessary to adopt working notions of fission and fusion. We argued that the reproduction of organised systems entails their spatial multiplication, and that the presence of a temporary asymmetrical dependence relationship between systems largely determines whether one of them is a continuation of the life of the parent. With fusion, similarly, the outcome is determined by the presence of asymmetrical dependence as well as by whether the fusing systems retain their separate closures.” DiFrisco, James & Matteo Mossio. 2020. “Diachronic identity in complex life cycles.” DiFrisco, James & Matteo Mossio (eds). pp. 177-199. Diachronic Identity in Comple Life Cycles: An Organisational Perspective. Routledge. pp. 194-5.
“‘I thought I was the best, or at least one of the best. But then artificial intelligence put the final nail in my coffin. It is simply unbeatable. In that situation, it doesn’t matter how much you try. I don’t see the point. I started playing when I was five. Back then, it was all about courtesy and manners. It was more like learning an art form than a game. As I grew up, Go started to be seen as a mind game, but what I learned was an art. Go is a work of art made by two people. Now it’s totally different. After the advent of AI, the concept of Go itself has changed. It is a devastating force. AlphaGo did not beat me, it crushed me. After that, I continued playing but I had already decided to retire. With the debut of AI, I’ve realized that I cannot be at the top, even if I make a spectacular comeback and return to being the number one player through frantic efforts. Even if I become the best that the world has ever known, there is an entity that cannot be defeated.” Labatut, Benjamin. 2023. The Maniac. A novel of which the quote is supposedly taken from Lee Sedol, a top Korean Go champion. NY: Penguin Press. pp. 349-350.
“A second well-established fact of life is that the sequential string processing of individual genes ends abruptly at the completion of the primary sequence of a protein molecule. These linguistically terminal strings have the necessary physical constraints to dynamically transform themselves into 3-dimensional structures, by folding, resulting in characteristic biological actions such as self-assembly, allosteric response, pattern-recognition, and selective catalysis. After the terminal string is synthesizd, none of the subsequent transformations, recognitions, or actions involves anything that is explained by sequential computation. An enzyme molecule might be usefully compared to a very simple homunculus or to a complex Maxwell demon, but not to a string-processing automaton.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 330.
“We can not ignore the fact that a physical description of DNA as a double helix with complementary base pairing is a strong contribution to the explanation of its symbolic function. What does this physical description show? It shows that we can ignore an enormous amount of the physical detail and still understand the symbolic behavior. More precisely, our physical description tells us what structures or patterns the cell must recognize and what structures are irrelevant for the symbolic reference in the cell. This specific recognition of the symbolically relevant molecular patterns within this mass of other physical detail I would call the cell’s primeval perception process.
“Another fundamental fact of life is that all primeval perception or pattern recognition and selective action is mediated by enzymes or enzyme-like molecules. This is the case for the cell’s sensing of the external environment, for sensing between the cells, and for intracellular recognition of patterns. At this molecular level the recognition-action process is generally pictured as a conditional physical template matching of the enzyme with a target structure, such that if the fit is good enough, a change of shape is induced in the enzyme causing specific, but in a sense gratuitous, physical actions to occur in the target structure, usually involving a specific chemical reaction. This mechanical strategy also appears at many higher levels of aggregation (e.g., ribosomes, microtubules, membranes, and so on). I do not see in any of these molecular or aggregate conditional pattern-recognizers and action-executors any dependence on string processing during their actual functioning. At the same time, I do not see any example of a functioning structure that was not syntactically constrained by strings during the initial synthesis of the parts.
“Looking more closely at how this comes about in the cell we see that this type of symbol-matter-function dependence is an exceptional kind of interdependence that I call semantic closure. We can say that the molecular strings of the genes only become symbolic representations if the physical symbol tokens are, at some stage of string processing, directly recognized by translation molecules (tRNA’s and synthetases) which thereupon execute specific but arbitrary actions (protein synthesis). The semantic closure arises from the necessity that the translation molecules are themselves referents of the gene strings.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. pp. [scanned copy; page count is probably off] 330-331.
“Semantic closure is, therefore, one condition for evolution by natural selection. In effect, this semantic loop is what defines the ‘self’ in self-replication.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 332.
“Computationalists assume that semantic closure could be attained by simply adding the appropriate robotics (i.e., sensors and effectors), at the very beginning and the very end of computation.
“The message of cell psychology is that cells don’t work that way. Information processing models are as unlike the symbol-matter architecture of the cell as you can get. In cells there is no semantic isolation. Every enzyme recognition and catalysis is a direct semantic act. The cell is a semantically closed network of information processing nodes and direct recognition and action nodes.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 332.
“Measurement is a very restricted form of perception. To measure something means that you are not measuring everything. More formally, a measurement is a mapping from a physical system to a symbol: but the essence of this mapping is the high selectivity or simplification of the system to only the attribute we have chosen to observe. The problem is this: Can we understand the measurement by decomposing the process in detail? To understand in detail would put back into the measuring device all the complexity of interaction that the function of measurement requires that the device ignore. In other words, a detailed physical description of a measurement process will look just like any physical interaction of two systems…..
“Most of the ‘processing time’ of the physicist goes into the design and construction of the measuring devices, just as cells spend most of their time in the design and construction of enzymes.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 333.
“The particular situation is specified by initial conditions, obtained by measurements, and other auxiliary conditions called boundary conditions or constraints. A constraint is the name for a set of complicated boundary conditions.
“Constraints are a basic problem because they can always be decomposed in principle to obey only laws and more initial conditions. Constraints are just a simpler alternative description of the local situation. For example, a measuring device is one type of constraint. We could, in principle, decompose the device into laws and more initial conditions, that then we would have to make more measurements of all the new initial conditions, thereby losing the function, as we said before.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 334.
“Rules are not discussed in general by physics because rules can only be executed by exceptional boundary conditions or constraints like measurements, that when described in physical detail, only become complicated with no improvement in clarity as a rule. Rule-executing constraints are a special case of machine constraint. As Polanyi has clearly pointed out, a machine constraint has a biological origin that cannot in any causal or explanatory sense be attributed to physical laws. Rule-executing constraints may be called natural, like enzymes, or artificial, like transistors, but in both cases they are biologically synthesized. Syntactic rule execution may be interpreted as a special case of measurement where the initial conditions have symbolic content.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 334; reference: Polanyi, M. 1968. “Life’s irreducible structure.” Science. 160:1308-1311.
“For example, we could say that for the cell the gene string represents the primary sequence of a protein because we know that the syntactical rules needed for interpreting this string (i.e., synthesizing the protein) are a part of the cell’s semantically closed self-replication loop. We could not say that in this loop the gene represents 3.6 billion years of history because the process of interpreting the strings to give this meaning is not specified within this narrow semantic closure. Such a representation can presumably be interpreted within the semantic closure of an evolutionary selection loop, as well as within the closure of an evolutionary biologist’s brain, but here we cannot supply the details. The point is that what a given syntactic structure represents depends on the particular semantic closure loop within which it is interpreted. A given syntactic string can, therefore, represent as many properties as there are semantic loops in which it acts as a constraint. The multiplicity of function in evolution as well as the multiplicity of meaning in natural language support such a multiple-closure concept of representation and meaning.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 335.
“Now back to cell psychology. Are gene strings symbols? Do the molecules have meaning? To answer this question I am proposing a necessary condition on the use of concepts like symbol, referent, and meaning. Strings have no meaning unless these strings and the dynamics they constrain comprise an empirically traceable process of closure, a syntactic-semantic loop that is self-defining and self-constructing. The cell is the first natural level of semantic closure, and I would say that the cell’s genes have a primeval symbolic function and meaning for the cell. The same genes may evolve additional meanings for the multicellular organism, and for any higher levels where semantic closure exists.” Pattee, Howard H. 1982. “Cell Psychology: An Evolutionary Approach to the Symbol-Matter Problem.” Cognition and Brain Theory. 5(4):325-341. p [scanned copy; page count is probably off]. 336.
“In Life Itself, Rosen’s account of closure is based on a reinterpretation of the Aristotelian categories of causality and, in particular, on the distinction between efficient cause and material cause. Let us consider an abstract mapping f between the sets A and B, so that f: A–>B. If we interpret the mapping in causal terms, and look for the causes of B, Rosen claims that A is the material cause of B, while f is the efficient cause. By relying on this distinction, Rosen’s central thesis is that ‘a material system is an organism [a living system] if, and only if, it is closed to efficient causation’. In turn, a natural system is closed to efficient causation if, and only if, all components having the status of efficient causes within the system are materially produced by the system itself.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 180.
“… Kauffman argues that a circular relationship between work and constraints must be established in a system in order to achieve self-determination, in the form of a ‘work-constraint (W-C) cycle’. When a (W-C) cycle is realised, constraints which apply to the system are not independently given (as in the Carnot engine) but rather are produced and maintained by the system itself. Hence, the system needs to use the work generated by the constraints in order to generate those very constraints, by establishing a mutual relationship, i.e. a cycle, between constraints and work.
“In a fundamental sense, the account of closure that we provide in this paper lies at the intersection between Rosen’s and Kauffman’s proposals. In particular, our central thesis is that organisational closure should be understood as closure of constraints, a regime of causation which is at the same time distinct from – and related to – the underlying causal regime of thermodynamic openness.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 180.
“What do we mean by constraints? In contrast to fundamental physical equations and their underlying symmetries, constraints are contingent causes, exerted by specific structures or dynamics, which reduce the degrees of freedom of the system on which they act….
“In describing physical and chemical systems, constraints are usually introduced as external determinations (boundary conditions, parameters, restrictions on the configuration space, etc.), which contribute to determining the behaviour and dynamics of a system, although their existence does not depend on the dynamics on which they act.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 181.
“Like all open systems, be they physical or chemical, biological systems are traversed by a flow of energy and matter, which takes the form of processes and reactions occurring in open thermodynamic conditions. In this respect, organisms do not differ, qualitatively, from other natural thermodynamically open systems. At the same time, however, one of the specificities of biological systems is the fact that the thermodynamic flow is constrained and canalised by a set of constitutive constraints in such a way as to establish a specific form of mutual dependence between those very constraints. Accordingly, the organisation of the constraints can be said to achieve self-determination as self-constraint, since the conditions of existence of the constitutive constraints are, because of closure, mutually determined within the organisation itself.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 181.
“In a general sense, processes refer to the whole set of changes (typically physical processes, chemical reactions, etc.) that occur in biological systems and involve the alteration, consumption, production and/or constitution of relevant entities. Constraints, on the other hand, refer to entities which, while acting upon these processes, can be said from the appropriate viewpoint to remain unaffected by them. A given theoretical entity, as we will see, cannot be qualified as a constraint per se, but only in relation to a specific process and the relevant time scale at which this process occurs. This context- and scale-dependence is, in our view, a general feature of constraints.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 182.
“Definition 1 (Constraint). Given a process A ->B (A becomes B), C is a constraint on A ->B, at a specific time scale τ, if and only if the following two conditions are fulfilled:
“I. The situations A -> B and AC -> BC (i.e. A -> B under the influence of C) are not, as far as B is concerned, symmetric at a time scale τ.
“Note CA->B “those aspects of C which play a role in the above asymmetry between A -> B and AC -> BC at time scale τ.
“II. A temporal symmetry is associated with all aspects of CA->B with respect to the process AC -> BC, at time scale τ.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 182.
“We believe that the distinction between limiting and generative constraints corresponds to a difference in the time scale at which their causal effects are described. We maintain that the constrained dynamics or outcomes could in most biological cases occur in an unconstrained way at the relevant (very long, or infinite) time scale; yet, at biological (shorter) time scales, constraints are indeed required in order to actually achieve these specific dynamics and outcomes because they contribute to producing otherwise improbable (or virtually impossible) effects. In particular, each constitutive constraint within a biological organism enables the maintenance of other constraints as well as, because of closure, the whole system. As a result, although constraints are mostly limiting at longer time scales, they can be pertinently conceived as generative at shorter time scales: in this sense, this characterisation is perfectly consistent with our account that claims that biological organisation could not exist without the causal action of constraints.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. pp. 183-4.
“The central outcome of the theoretical distinction between constraints and processes is a distinction between two regimes of causation. For a given effect of a process or reaction, one can theoretically distinguish, at the relevant time scale, between two causes: the inputs or reactants (in Rosen’s terms, the ‘material’ causes) that are altered and consumed through the process, and the constraints (the ‘efficient’ causes, at τ), which are conserved through that very process. Insofar as they are irreducible to the thermodynamic flow, and then to the material inputs or reactants, constraints constitute a distinct regime of causation.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 184.
“… constraints are defined as entities which, at specific time scales, are conserved (symmetric) with respect to the process, and are therefore not the locus of a transfer. However, constraints are typically subject to degradation at longer time scales, and must be replaced or repaired. When the replacement or repair of a constraint depends (also) on the action of another constraint, a relationship of dependence is established between the two.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 184.
“Definition 2 (Dependence between constraints). Following the above line of reasoning, we define a relationship of dependence between constraints as a situation in which, given two time scales τ1 and τ2 considered jointly, we have
“1. C1 is a constraint at scale τ1.
“2. There is an object C2 which at scale τ2 is a constraint on a process producing aspects of C1 which are relevant for its role as a constraint at scale τ1 (i.e. they would not appear without this process).
“In this situation, we say that C1 is dependent on C2, and that C2 is generative for C1.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 184.
“… dependence between constraints [i.e., catalysts in series] can occur in two different ways, depending on the relations between the time scales involved: slow dependence with τ2 > τ1 or fast dependence with τ1 > τ2 ….
“In the first case [slow dependence where C2 catalyzes the formation of C1 on a slow time scale that then catalyzes a second reaction at a faster timescale] τ2 > τ1, the generative constraint C2, acts as a constraint at a longer time scale than the dependent constraint, which means that it is associated with a slower process. In the second case, τ1 > τ2, the [initial one in series] generative constraint, C2, is associated with a faster process than the process constrained by C1.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 185.
“Definition 3 (Direct dependence between constraints), C1 depends directly on C2 if and only if
“1. C1 depends on C2.
“2. There is at least one relevant aspect of C1 that depends on C2 and which fulfils the following condition: none of the different processes that occur at τ2 and contribute to the maintenance of this aspect follows the one constrained by C2, A2 -> C1 under the influence of C2, in physical time [i.e. C1 is alone responsible for C2] .” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 185.
“Definition 4 (Closure) A set of constraints C realises overall closure if, for each constraint Ci belonging to C
“1. Ci depends directly on at least one other constraint belonging to C (Ci is dependent).
“2. There is at least one other constraint Cj belonging to C which depends on Ci (Ci is generative).
“A set C which realises overall closure also realises strict closure if it meets the following additional condition:
“3. C cannot be split into two closed sets.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 186.
“… one general property of closure is that it must include at least one constraint for which τs(Ci) – τd(Ci) > 0 and another for which τs(Ci) – τd(Ci) < 0: the resulting organisation, therefore, is not only multiscale but also requires the realisation of both slow and fast dependence between constraints.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 186.
“… we claim that constraints subject to closure constitute biological functions. Within this framework, performing a function is equivalent to exerting a constraining action on an underlying process or reaction. All kinds of biological structures and traits to which functions can be ascribed satisfy the definition of constraint given above, albeit at various different temporal and spatial scales. In addition to the vascular system and enzymes mentioned above, some intuitive examples include, at different scales, membrane pumps and channels (which constrain both the inward and outward flow of materials through the membrane) and organs (such as the heart which constrains the transformation of chemical energy into blood movement). Closure is then what grounds functionality within biological systems: constraints do not exert functions when taken in isolation, but only insofar as they are subject to a closed organisation.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 186.
“… once the constraints have been included, the organisation of dependencies between them must be described. This can only be done by abstracting them from the physical time in which they occur, since closure cannot be described at a given point in time, but rather requires us to consider a set of processes taking place at different time scales (some processes may not be permanent, but rather may occur cyclically as is the case with heartbeats, for example). Thus, the whole network of dependencies should be considered as one ‘block’ extended over multiple time scales. Accordingly, closure consists of an interdependent relational network of dependencies, extracted from the dynamics of the system in physical time.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 187.
“In the absence of complete descriptions, closure should only be ascribed to maximally closed systems, i.e. those systems which include all mutually dependent constraints, in the available description. Maximally closed systems therefore constitute the lowest boundary of closure ascription: in principle, no subsystem of collectively dependent constraints that can be shown to belong to an encompassing closed system can be said to realise closure.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 188.
“Let us now turn to all those cases in which two or more biological organisms establish a form of mutual dependence due to stable interactions between them, such that each of them can be said to rely on the other(s) for its own maintenance. In these situations, in which a fundamental organisational continuity exists between the interacting organisms, the upper boundaries of closure ascription seem to extend beyond each organism, insofar as the notion of maximally closed system applies only to the encompassing system which contains all (known) constraints subject to closure. If we were to limit ourselves to this analysis, it would be impossible to descibe systems including different nested levels of organisational closure and systems belonging to closed systems (and specifically mutually dependent organisms) would not themselves realise closure as discussed above. Moreover, since biological organisms are systematically involved in such interactions it would follow that most of the time individual organisms cannot be said to realise closure. The main theoretical upshot would be a serious weakness for any account based on closure, which could not be considered a distinctive property of organisms in many biologically relevant cases.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 188.
“As mentioned above, closure is usually considered a Boolean property.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 188.
“Let us choose an arbitrary volume of space ν (included inside one of the cells, for example) and consider the processes and constraints taking place inside this volume. We use K(ν) to refer to the number of dependencies between constraints subject to closure in the encompassing system which take place in ν….
“The assessment of organised complexity is completed by considering K(ν,l) , which, is defined as above, except that we select the dependencies occurring on a given spatial expanse l (a spatial scale). Note that the sum of K(ν,l) over all l equals K(ν).
“A procedure to represent the boundaries between the interacting cells can be implemented by relying on this measure of complexity. Let us presuppose some a priori knowledge of the localisation of the considered cells in space, which guides the choice of the initial volume. Any increase of ν will lead to an exploration of the spatial domain of the system…. The quantity that we propose to represent with this procedure is δK(ν,l), i.e., the increase in the number of dependencies which corresponds to the increase in volume δν….
“We submit that the δK(ν,l) is a measure of the tendency to closure of the organisms involved…. It should be noted that since δK(ν,l) is a quantitative measure of the dependencies subject to closure (and not just individual constraints), its value will be highly dependent on those constraints which are involved in many dependencies. A good example are membranes, which are involved in so many dependencies that their inclusion in the graph would dramatically enhance the tendency to closure of the considered volume.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. pp. 188-9.
“The tendency to closure is a measure of the degree of organisational integration of organisms and, as well as, an operational tool for drawing the boundaries between them, even when they establish functional dependence. It is worth emphasizing, in this respect, that such a measure comes in degrees, for example, one can conjecture that the tendency to closure is higher for a unicellular eukaryote than for a cell in a metazoan. Similarly, the tendency to closure of a biofilm is arguably weaker than that of an individual bacterium, or a metazoan.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 189.
“Thus, overall, it seems that cells do not usually act as constraints individually, but only collectively, when they are assembled in tissues and organs. Consequently, it follows that in most cases there is no mutual dependence between each cell and the encompassing system, enabling their respective closures to be separated, even though they realise a nested hierarchy (the closure of the cells is nested within the closure of the encompassing system). In a sense, this implies that the internal functional aspects of the cells can be separated from those aspects that matter for the organism’s organisation. The separation between nested closures provides a straightforward basis for drawing the boundaries between organisms.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 190.
“We conjecture that a relationship between two closures of constraints which involves both separation and a nested hierarchy provides the theoretical basis for characterising, in our framework, a distinction between levels of organisation if they are both separated and hierarchically nested; accordingly, cells and multicellular organisms constitute two different levels of organisation.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 190.
“As argued above, closure takes place in a temporal interval, and can be described by abstracting the network of closed dependencies from the time flow. In this formal framework, the claim according to which closure constitutes an ‘invariant’ of biological organisation technically means that a description of closure is possible for any interval long enough to describe a sufficient set of constraints and their mutual dependencies. In other words, given a minimum duration, closure is realised for any interval of equivalent duration chosen in the system’s lifetime. The stabilisation of biological phenomena results specifically from the continuous control exerted over processes and reactions by functional constraints, whose maintenance in the long run depends in turn on their mutual dependence through closure. The invariance of closure grounds the stabilisation of the functional organisation.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 190.
“On the other hand, biological systems may (and do) undergo functional changes both throughout their lifespan and over the generations. These changes affect the structure and the function of one or more constraints, which in turn result in a modification of the organisation. Functional variations are related to many factors, including the life cycle and the interactions with the environment, as well as random changes. In some cases, functional variation threatens the viability of the whole system, and may possibly lead to its break-up. The crucial thing to bear in mind in this respect, however, is that functional variation is not merely an obstacle for the maintenance of the biological organisation; rather, it is also a crucial requirement for the adaptivity, increase in complexity and ultimately the long-term sustainability of life. Indeed, in addition to their functional role within a specific organised system, constraints also play a role in enabling the emergence of new constraints, new organisations and new behaviours, typically at the evolutionary and populational scales. Reciprocally, functional variation alters the organisation and yet must be subject to closure in order to be sustained over time….
“As biological systems undergo functional variations, their organisation maintains closure, albeit realised in different variants, because of the continuous acquisition of some functions, and the loss of others. In this sense, the invariance of closure takes place at a level of description which is higher than that at which each specific organisation (instantiated by an individual system) occurs. Understood in this way, the invariance of closure may be said to be complementary to its functional variation, with both being constitutive principles for biology.” Montevil, Mael & Matteo Mossio. 2015. “Biological organisation as closure of constraints.” Journal of Theoretical Biology. 372:179-191. doi: 10.1016/j.jtbi.2015.02.029. p. 190.
“The idea of nature or essence as internal and standalone [as in atoms] is noteworthy because of the unacknowledged assumptions it uncritically accepts. Essence as internal represents a refusal to acknowledge that interactions and relations play a role in a thing’s nature; it also refuses to recognize that relational properties like coordination, integration, and context embeddedness are real. It ignores both the past and current circumstances. It underpins, in short, a worldview that dismisses time and place–context in general–from reality.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 5.
“In contrast [to the Aristotelian tradition], influenced by modern atomists such as French thinker Pierre Gassendi and English experimentalist Robert Boyle, modern scientists and philosophers prioritized analysis over synthesis, parts over the whole. In doing so, the philsophical problem of identity was transformed from ‘How does essence in-form matter and confer on it its identity?’ into ‘How do primary properties cohere into complex wholes’” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 9.
“Newton himself was aware of this so-called three body problem, an example of environmental influence completely transforming a system’s dynamics. The puzzle was an early hint that context should not be so readily dismissed, but modern science and philosophy ignored its warning.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 14.
“Efficient causality cannot account for how parts become interwoven into interdependencies that bind together coherent wholes and persist despite turnover or deletion of component parts.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 15.
“To repeat, complex systems are simultaneously constrained and constraining coordination dynamics….
“…collective coordination dynamics”. Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 23, 25
“This will be a work of speculative metaphysics. It presents an unabashedly ontological worldview by proposing that, in response to constraints, the cosmos partitions and sorts flows of matter, energy, and information into real coherent dynamics, and not just in living things.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 32.
“… constraints are critical to coherence making. Autocatalysis and feedback loops, for example, produce long-range correlations and interweave patterns of matter and energy flow that display novel properties.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 37.
“By interactions, complexity theorists mean relations other than the reversible bumping and jostling of Newtonian forceful impacts.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 39.
“Constrained interactions leave a mark. They transform disparate manys into coherent and interdependent Ones.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 39.
“Coherence might be a better term for the unity relations of complex systems like snowflakes, tornadoes, lichens, living things, homeostasis, ecosystems, human practices, and cultures. Each of these is nothing other than a coordination pattern formed by different constraints with different stringencies, operating in different contexts. Critically, each of these overarching patterns is held together by a set of interlocking constraints; as a result, each displays qualitatively different emergent properties. Synchronization, coordination, and entrainment are instances of coherent organization, defined as a particular regime or logic of interlocking constraints. Coherence so understood marks a qualitatively novel form of organization and order that is absent in either isolated elements or clumped aggregates. Coherence is real; it is a relational and systemwide dynamic brought about by interdependence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 39.
“Complex order is a multiply realizable dynamic of constrained and constraining interactions. Elements in complex systems do not dissolve into a homogeneous medium or fuse into undifferentiated blocks. Rather, coherence consists of articulated and heterogenous interdependencies and covariances into which diverse elements are entrained and which now govern their behavior.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 40.
“Constraints are entities, processes, events, relations, or conditions that raise or lower barriers to energy flow without directly transferring kinetic energy.
“Constraints bring about effects by making available, structuring, channeling, facilitating, or impeding energy flow. Gradients and polarities, for example, are constraints; others include catalysts and feedback loops, recursion, iteration, buffers, affordances, schedules, codes, rules and regulations, heuristics, conceptual frameworks, ethical values and cultural norms, scaffolds, isolation, sedimentation and entrenchment, and bias and noise, among many others.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 40.
“Spatial constraints, that is, organize the world according to place or location. Here, there, inside, out, up, and down are all products of constraints that encode relational spatial arrangements and configuration as conditional probabilities.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 41.
“Constraints sculpt a rugged and multidimensional landscape, the possibility and probability space of what can happen at all, what will most likely happen, and, when it cannot, can or must happen.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 46.
“On a cosmic scale, gravitational and electromagnetic fields are examples of primordial context-independent constraints at work.
“As mentioned, gradients of inclined planes are examples of constraints. Slopes of gradients in general, including those of cosmic expansion and gravity, operate as context-independent constraints. They establish nonuniform background conditions along with energy flows…. Polarities are constraints that organize a landscape such that energy flows only in certain directions.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 49.
“The point is a general one: conditions that promote or impede energy flow need not be material walls; they are inhomogeneities in possibility space…. Gradients and fields, for example, bias whether, how much, and in what direction energy is more or less likely to flow.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 50.
“Context-dependent constraints are defined as constraints that take particles of matter and streams of energy flow away from independence from one other.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 57.
“In populations where a widespread and effective immunization program reaches herd immunity, free riders really do get away with avoiding vaccination; their own risk of contracting the disease is dramatically lowered despite not using masks, practicing social distancing, or being inoculated themselves–because others did get inoculated, are masked, and do practice social distancing. To phrase it crudely, no individual is a percentage; herd immunity is a property of the population as a whole, a property that is measured in percentages. But that emergent, population-level property significantly mediates the way the disease plays out in individuals. Incidence suddenly depends on prevalence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 63.
“Unequal distribution in possibility space, as we saw, is a prerequisite of information and order. We turn now to context-dependent constraints, those that take conditions away from independence. These weave together events and processes such that their interactions become mutually conditional on one another and on the history and context in which they formed. They now covary. The likelihood of events and processes influenced by contextual constraints is measured with conditional probability: X is more or less likely to happen, given the presence of constraint Y, in context Z.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 67.
“In contrast to context-independent constraints that take conditions away from equilibrium, context-dependent constraints therefore take conditions away from independence by intertwining isolated elements and processes; long-range correlations and interdependencies result. From these transitions there emerge novel, smeared out entities with different properties–in this case, a web [from unclear example of tying buttons together a few at a time]. Enabling constraints, in short, transform separate entities into coordination networks characterized by relations and organization.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 68.
“Electron orbits of two nearby atoms, in turn, might have entrained in a constructive interference pattern, an even more metastable and self-reinforcing waveform we know as a molecular orbital. Just as water molecules behave differently in the context of a rolling Benard column, atoms behave differently in the context of molecular orbitals. Context constrains. On the far side of each of these phase transitions, constituents are no longer separate and independent entities; they become relata and components of a new systemwide interdependence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 69.
“Coherence-making by constraints takes place in physical and biological complex systems small and large, from Benard cells to human organizations and institutions, from family units to entire cultures. Entities and events in economic and ecosystems are defined by such covarying relations generated by enabling constraints. These mutually dependent relations are held together by interlocking constraints that can be called constitutive-governing constraints.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 70.
“Adam Smith understood this bottom-up and top-down flow responsible for the interdependent (not merely aggregative) and persistent dynamic of economic systems…. Bottom-up, individual interactions intertwined by enabling constraints generate a coordination pattern of relational behavior. Once the population-level dynamic coalesces, the actions of individuals entrained in it change as a result of the resulting dynamic’s constitutive constraints, as well as the history and circumstances that brought these about. Consequently, agents become consumers, producers, traders, and regulators; they act and respond differently to the embedding constitutive constraints in which they are caught up. We call the constitutive constraints that define this coordination its invisible hand….
“Oligopolies, however, show that such interdependencies can also have a negative aspect: when product prices set by one firm are dependent on prices set by the other, and vice versa, the interdependencies of their constraint regime enact a loop that is difficult to break.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 70-1.
“Enabling constraints are context-dependent constraints that irreversibly link and couple previously separate and entities at the same scale as the constraints. By lowering barriers to energy, matter, and information flows such that independent entities become conditional on each other, enabling constraints drive parts-to-whole phase transitions to emergent coordination patterns, realized as mutually dependent relations.
“Enabling constraints are nature’s mechanism for coherence-making, generalization, and emergence. The rolling columns of fluid that constitute a Benard cell are nothing other than interdependent, coherent dynamics generated by enabling constraints.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 71.
“Phase locking, resonance, synchronization, and entrainment are emergent properties of coherently organized interdependent dynamics.
“Enabling context-dependent constraints are therefore constraints that make the probability of one event conditional upon another.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 71.
“Complex entities formed by context-dependent constraints under conditions of nonequilibrium are coherent and persistent. Those interdependencies satisfy the second law: energy, matter, and information flow with greater ease as coordinated interdependencies than separately….
“Not all constraints may be simultaneously satisfied, but those actual economies, or Benard cells, or ecosystems that do exist satisfy numerous constraints simultaneously; they are the outcomes of multiple constraint satisfaction, a process of continuous adjustment of rates, weights, timing, and so on that satisfies as many constraints as possible.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 72.
“Constraint satisfaction is an important form of ‘causality’ that has been systematically ignored by modern science and philosophy. It can explain the generation and persistence of coherence. The effects of population-level properties on components, members, and stages of those interdependencies are also real. In response to multiple constraint satisfaction, components acquire new relational roles and properties–as members, periods, stages, and so on of a reconfigured dynamic with distinct population-level properties.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 72-3.
“Prior to the introduction of context-dependent constraints, cardinality (quantity) was the only metric available. The clumps grow in size. More and less, bigger and smaller are about increasing magnitude, mass, or agglomeration, which are effects of context-independent constraints such as gradients….
“Spatial and temporal constraints, in contrast, produce indexical ordering. Indexically defined relations explicitly refer to the spatiotemporal context that generated them and the emergent properties that govern them. Ordinality, the position of an event in a sequence, is an indexical property that emerges when temporal, context-dependent constraints weave together a set of local interdependencies in time…. Significantly, this distinction is possible only because individual steps in temporally constrained sequences are not independent of each other. The burst of entropy with which irreversible phase transitions are paid marks a qualitative transition to a now temporally organized phase space. This new space represents a novel four-dimensional landscape, a new distinct constraint regime organized by time as well as space.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 75.
“… the interlocking interdependencies of constraint architectures can bring about mereological effects, top down. Remarkable new powers are among the emergent properties of the new relational landscape generated by enabling constraints. Laser beams cauterize wounds, which individual photons cannot. Molecules subtend the world of chemistry, which atoms on their own do not. A vaccinated population acquires protective powers, and entrained pendulums generate waveforms that regulate individual swings. Liquids with zero viscosity (superfluid) can flow without loss of kinetic energy; electrical resistance vanishes in superconductors.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 79.
“Top-down causality is possible because constitutive constraint architectures of complex interdependencies generated by enabling constraints do double duty as governing constraints. Top down, from the invisible hand’s coordination dynamics to its individual traders and firms, governing constraints in general exert control on their components and behavior in cascades of mutual constraint satisfaction, often as negative feedback loops.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 79.
“The coordination displayed as an overall harmonic pattern of synchronized pendulums persists in response to the top-down constraints the virtual governor applies to each pendulum’s amplitude and phase. As always, such correlated and constrained patterns of energy flow simultaneously satisfy and retard the second law.
“In order words, governing constraints of context-dependent coherent dynamics generated by enabling constraints keep mutually dependent relations coherent. They regulate component processes top down such that the overarching dynamic remains metastable….. In short, behavior controlled top down ensures it stays true to type as defined by the constitutive constraint regime that embodies its emergent properties.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 80.
“Arising concomitantly with the closure of enabling (bottom-up) context-dependent constraints that integrate separate parts into coherent wholes, top-down governing constraints (of those emergent wholes on their components) are therefore specificatory; they go from whole to parts, from general to particular, from constitutive constraint regime of the emergent interactional type to its actualized tokens. In the marching example, the synchronization pattern itself not only can collapse the bridge; it also acts as a global governing constraint on the tempo of the individual soldiers’ cadence, whose steps become entrained into the beat. That is, the rhythm of the stepping is confined to that state space that constitutes the beat.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 80.
“It is important to underscore that constitutive and governing constraints should not be reified; they are not spatiotemporally other than the components and constraints from which they were formed and which they control. Because they operate from whole to parts (from extant, coherent interdependencies to token components, or to next step), governing constraints are in fact second-order context-dependent constraints that bring about specific effects and actions.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 81.
“Whether enacting homeostasis, a newly learned skill, or values, constitutive constraints shape new phase spaces and set the order parameters of emergent coordination dynamics. Then, acting as governing constraints, constitutive constraints operate as limiting constraints; they confine options to a subregion in state space. Like the narrowing chute of attractors in epigenetic landscapes, governing constraints carve stable basins of attraction to which the range of potential tokens and their behaviors (the actual clocks and phenotypes) are restricted.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 83.
“Discovering how feedforward, positive feedback, iteration, and recursion, acting as constraints, can precipitate phase transitions to coordination dynamics with emergent properties has been among the important contributions of complexity theory.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 87.
“Folding-back-on-themselves processes such as feedforward and feedback loops are also catalysts. Iteration and recursion are two such examples. Often used as a synonym of repetition, suggesting a simple context-independent constraint, iteration feeds back information from the output of one run into the initial conditions of the next. Iteration thus acts as a temporal constraint that changes the likelihood of the next output. The process repeats.
“In recursive iteration, full sequences are fed back on themselves. This looping causes processes and sequences to become self-referential; recursive iteration blurs the distinction between parts and wholes.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 88.
“They [living things] are autonomous because, by realizing endogenously self-determining and persistent loops of constraints, not simply loops of processes, they not only self-assemble and self-maintain in response to externally set constraints. They self-constrain. It is in virtue of interdependencies bound together as loops of constraints, not just of processes, that living things also realize a novel form of constraint, constraint closure. The three authors claim that closure of constraint generates a novel type of phenomenon, Life.
“Closure of constraint binds together several local and shorter catalyzed reactions into an extended and catalyzing loop, all without injecting additional energy into the process. The loop itself becomes a virtual governor, a second-order constraint that catalyzes other more local constraints (not just other reactions) and thereby generates an extended and mutually interdependent dynamic, a hypercatalyst (not just a hyper-cycle). This overarching dynamic becomes a self-reinforcing governing and catalyzing constraint. In doing so, constraint closure turns the process self-determining.
“Self-determination as self-constraint is absent in systems characterized solely by process or catalytic closure for which externally set boundary conditions are still significant.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 93; references: Mossio, Montevil, Moreno.
“The received view of causality contends that wholes are nothing but aggregates and therefore epiphenomenal and that efficient causes are other than their effects. We cannot overemphasize the point that interdependencies that realize closure of constraint are not spatiotemporally ‘other than’ the local constraints, and yet as a coherent unit, the loop exerts constraining influences on its component reactions that individual constraints do not. The effect of its influence is the realization of a higher-order dynamic with the novel property of self-constraint. Clearly falsifying the classical prohibition against mereological self-cause, interdependence among constraints reveals a relation that is simultaneously constraining and constrained, from whole to parts and parts to whole.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 95.
“In addition to gradients, catalysts, feedback, replication, redundancy, and reproduction, density, isolation, and buffers are constraints that also increase the stability of a system’s existing default governing constraints and thereby prolong its existence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 111.
“Buffers are conditions that alter possibility space such that energy flows more readily in one direction than another–or does not flow at all. Buffers are not forces; they are add-on constraints that reinforce existing governing constraints by shielding complex systems from intrusion by extraneous forces.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 115.
“To summarize: isolation and buffers are constraints that support persistence by protecting a system’s zone of metastability and continued existence, which they do by acting as shields against threatening input.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 117.
“Once again, it is tempting to conjecture that the universe is characterized by a general trend, from rigid boundaries and physical gaps to interactive interfaces operating as gating constraints. Just as rigid walls of prokaryotes gave way to more permeable membranes of eukaryotes, so too moats and Great Walls of China gave way to … safe conduct letters of transit and visas?… If this conjecture were confirmed, it would be worthwhile to study the role context-dependent constraints played in that trend. Increasing complexity suggests increasing reliance on context dependence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 117.
“Niches and habitats–abiotic, natural, and social–are co-constructed contexts; they are coordination dynamics interwoven by constraints.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 119.
“Affordances are relational properties that function as constraints by weaving together an organism’s capabilities and propensities and its world. Affordances are the products of enabling constraints that create novel interdependencies and opportunities. Like biological niches, they structure an organism’s psychological ecology, dispositions, and behavior patterns such that it can act more effectively in that world.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 120.
“In this sense [as ‘fitted arrangements’], frameworks are like affordances and principles of conceptual organization; they format behavior by presetting definitions, parameters, and category boundaries–in short, by initializing cognitive and behavioral constraint spaces within which certain ideas and actions will be possible or viable, and others not.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 121.
“The stabilizing power of scaffolds is key. Scaffolding’s simultaneously enabling and stabilizing constraints make it more likely that goal-directed activity will reach conclusion.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 122.
“By preventing backsliding and allowing movement only in the forward direction, ratchets make it easier to reach the next step. Ratchets and scaffolds thus reinforce sequential enabling constraints that make advancing easier by providing a steadily growing platform from which to launch the next step.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 122-3.
“By affording nearby ‘points of stability’ from which to continue building or growing in the right direction and at the right pace, scaffolds and ratchets are also like affordances; they embody context-dependent constraints that bias the likelihood of which future events become possible, can occur more readily, or be performed or structured in a particular way. They set up interdependencies whose joint probabilities prevent disruptive perturbations from waylaying long-term projects. In doing so, they contribute to the formation and persistence of new interdependencies. They contribute to coherence-making.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 123.
“From regulatory genes to yearly family rituals or once-in-a-lifetime ones like baptism, temporal constraints generally provide time-based scaffolding and affordances that help complete processes and keep social dynamics coherent.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 124.
“Alternating between external and internal scaffolding is a common pattern in nature. The transition from external to internal can be a form of coopting, as when external constraints are brought onboard and their function is internalized. Moreno and Mossio characterize the process of internalizing or coopting previously external boundary conditions as shanghaiing them and incorporating them as internal ones. When mitochondria were engulfed into bacteria, the former’s enabling constraints for energy production were effectively coopted. The resulting interdependencies and new governing constraints became a new type of organism, eukaryotes.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 127.
“Once again, it is not entirely unreasonable to conjecture that such cooptation and shanghaiing of external constraints [e.g. mitochondria in eukaryotes or earlier exo-skeletons than were moved inside organisms] might represent a general trend that goes from externally set and rigid and impermeable boundary conditions of Benard cells to endogenously generated and more malleable, porous, and internalized constraints whose most recent manifestation is the emergence of self-constraint in living things.
“If so, closure of constraints in living things, as described earlier, constitutes the emergence of a form of self-scaffolding.
“More-making makes more tokens of a coherent type, but closure of constraints ratchets the process to one that self-scaffolds as self-constraint. Closure of constraints self-constrains, self-scaffolds, self-constructs, and self-maintains interdependent processes in dynamic but steady nonequilibrium.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 127, 128.
“Once reached, thermal equilibrium lasts, but there is no-thing that persists at thermal equilibrium. White noise is no-thing; equiprobability is no-macrostate….
“… the second law could therefore also be characterized as ‘the survival of no-thing’ since at thermal equilibrium there are no constraints and consequently no stored information that is qualitatively other than the aggregate or sum of the equally likely microstates. There is no stored information because there are no covarying interdependencies. There are no covarying interdependencies because there are no constraints. Thermal equilibrium carries no information and can do no work. Unconstrained equilibrium (white noise) is a statistical description, but it is a macrostate in name only. There is no ‘it’ that persists as itself over time. Thermal equilibrium is not identical to persistence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 131-2.
“Local pockets of constrained and enduring inhomogeneities in nonequilibrium are neither improbable and unexplained initial conditions nor observed coincidences…. Interactional types as conceived here are not universal or eternal. They are induced by context-dependent constraints and realize self-reinforcing, persistent forms that are multiply realized as distinct path-dependent histories and trajectories.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 135.
“Persistence in nonequilibrium open systems is realized as dynamic kinetic stability (DKS), not thermal equilibrium. According to the two authors [Pascal & Pross], the source of DKS’s persistence is exponential growth such as the growth driven by autocatalysis….
“From the perspective of this book, DKS represents the persistence of coherence, that is, of multiply realizable interdependencies brought about by intertwined enabling constraints and preserved by governing constraints under nonequilibrium conditions.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 136.
“Constraints not only facilitate the emergence and persistence of coherence; constraints can also sediment and even entrench, thereby strengthening the metastability that keeps established, coherent structures from going to thermal equilibrium. In contrast to scaffolding, which commonly aids in the successful completion of a dynamic process, sedimentation and entrenchment preserve existing equilibria in the face of perturbations, actual or potential. Sedimented and entrenched constraints can be defined as constraints that are more difficult than usual to relax or otherwise modify. Difficult here means it takes more energy to become dislodged than to persist. It takes more energy to get over the hillock of the attractor in which a system is embedded and into a neighboring one.
“Sedimented and entrenched constraints therefore strengthen existing governing constraints by making their attractors in possibility space deeper and more pervasive. In living things, sedimented and entrenched constraints reinforce habits and significantly increase the likelihood that only a smaller subset of possible behaviors or phenotypic traits becomes actual.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 143.
“Because constraints generate path-dependent dynamics, interdependencies woven together by contextual constraints are also forms of memory….
“Memories can thus become incorporated into governing constraints on possibility space. By reinforcing an existing constraint regime, memories contribute to the persistence of existing dynamics. As records of real constraints, memories also weight and bias future events–even as they are themselves updated in the process….
“As an example, epigenetic processes such as higher neuronal methylation levels preserve and sediment information of trauma into future generations. They harden the constraints of existing possibility space. As noted earlier, obsessive-compulsive behavior betrays a constraint regime that lacks that capacity to be modified.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 144.
“Epigenetic disruptions such as trauma or starvation early in pregnancy often cause miscarriages. Generatively entrenched developmental constraints protect against that scenario by imposing stringent context-independent constraints early in gestation; these ensure that the fundamental structure of the phyla’s morphological features (its basic radial or bilaterally symmetrical body plan, for example), is strictly satisfied. Once that bauplan is secured, those inflexible constraints relax and others more responsive to current context are enabled. Mutations and epigenetic influences later in developmental processes are often not seriously deleterious; indeed, it can be argued that the flexibility supported downstream during ontogenesis allows phenotypic possibility space to be explored and new structural and behavioral variations to be generated. Generative entrenchment thus narrows and even closes off options altogether early in a diachronically constrained dynamic while simultaneously facilitating unanticipated interactions and other enabling constraints to appear and operate downstream. The process makes room for flexibility, but ensures it only happens downstream.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 152.
“Order parameters best describe such systems [collective properties of complex dynamics that include vorticity, frequency, and different forms of metastability like social cohesion]. These are relatively low-dimensional variables that capture the significant emergent properties of those new interdependencies. Order parameters measure, for example, the degree of cohesion of a system’s interdependencies, a continuous property that is qualitatively distinct from properties of the relata separately.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 156.
“In other words, organisms register internal and external signals as recoded in terms of their contribution to the emergent properties of the organism’s overarching constraint regime.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 158.
“One theory maintains that covalent bonds are constituted as constructive interference patterns between atomic orbitals (Nordholm & Bacskay). Iterated resonance integrates the initially separate reverberations and oscillations of atomic orbitals into expanded patterns of constructive interference, the novel and coherent coordination dynamic we know as molecular orbits. Once entrained into this more encompassing dynamic, the motions of erstwhile separate components align in the service of the new collective dynamic. Rephrased, covalent bonds are coarsened interfaces of a more encompassing, contextually constrained attractor or energetic pathway.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 159; reference: Nordholm, S. & G.B. Bacskay. 2020. “The basics of covalent bonding in terms of energy and dynamics. Molecules. 25:2667.
“Many-to-One transformations everywhere are nature’s way of streamlining through coherence-making by constraints, once again in satisfaction of the second law.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 159.
“… differences in strength, manner, speed, and degree of coupling commonly indicate the presence of a boundary or an interface between hierarchical levels [e.g. across a membrane].” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 184.
“Allen and Starr remark in passing that speeding up certain processes in physical chemistry might have led to the origin of life. This new take on the origin of life suggests that overly assertive holons (perhaps due to the influence of autocatalysis, positive feedback, and constraint closure) might have slipped the control of geophysical constraints and acquired sufficient self-determination and autonomy to loosen the physicochemical context’s control over them.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. pp. 190-1; reference: Allen, T.F.H. & T.B. Starr. 1982. Hierarchy. U of Chicago Press.
“… this book has attempted to articulate the manner in which enabling constraints generate those very self-other interdependencies and practices that are at the heart of the 4E approach. Context-dependent constraints create the phase space, attractors, coherences, and mutual dependencies that the 4E approach emphasizes. Constraints are also the source of the emergent properties of those interdependencies, among which, this book has maintained, are intensional content [here or there significance], qualia, and phenomenal awareness, which in turn and acting as governing constraints produce, regulate, and modulate socially required, task-appropriate, and context-sensitive behaviors.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 207.
“Accounting for how constraints take conditions away from equilibrium and/or away from independence gathers habits, repetitive drills, sedimentation, self-sustaining interdependencies, and the rest of the conceptual tools of the 4E approach under the general framework of constraints….
“In short, Context Changes Everything has aimed to explain the sources of the 4Es, embeddedness, embodiment, enaction, and ecological coherence and interdependence.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 208.
“The clearing we have opened–and it is only a clearing, not the final destination–is one where interdependencies woven together through multiple constrained interactions turn out to be as fundamental as the allegedly standalone things and indivisible particles that for millennia served as the ontic basis of Western philosophy and modern science.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 233.
“The one prerequisite [for a world of coherences]: conditions must be open and away from thermal equilibrium. Context-independent constraints take conditions far from homogeneity and equilibrium and establish background inhomogeneities. Doing so satisfies this first requirement. Next, context-dependent constraints take conditions away from independence by making previously separate entities conditional upon one another. Working together in open conditions far from equilibrium, context-independent and context-sensitive constraints bring about mutually dependent interactions and relations. The processes now covary because, acting as enabling conditions and constitutive/governing regimes, constraints have woven individual processes and particles into integral wholes. The book calls them interactional types. Parts and wholes, tokens and types, can finally be understood as two aspects of a shared and interdependent dynamic.
“A new coherence.
“Coherence is not other than individual particles and processes that comprise it; types are not other than the tokens that realize it.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 233.
“… evolution is not the unfurling of pre-established potentialities. Each new coherence is a genuine creation, the product of path-dependent multiple constraint satisfaction under open nonequilibrium conditions. Coherence making thus brings about major transformations to emergent dynamics. Constraints make creativity possible; emergent coherent dynamics are the creative outcome of mutually constraining and constrained interactions.” Juarrero, Alicia. 2023. Context Changes Everything: How Constraints Create Coherence. MIT Press. p. 235.
“In a nutshell, the theory of biological autonomy holds that a system is an agent if it is capable of interacting with its environment in such a way that its behavior is, first, enabled by its own constitutive organization and, second, contributing to maintain that very organization.” Virenque, Louis & Matteo Mossio. 2023. “What is Agency? A View from Autonomy Theory.” Biological Theory. 10.1007/s13752-023-00441-5. p. [page numbering uncertain] 2.
“Insofar as organizational closure implies thermodynamic nonequilibrium, living beings as autonomous systems are not autarkic or independent but, rather, they must continuously interact with their surroundings. The interaction itself is controlled by functional parts and subsystems subject to organizational closure: hence, interactive capacities are themselves intrinsically purposive. Such purposive, functional interactive capacity performed by the living being realizing organizational closure is agency within the theory of autonomy. Agency, in other words, consists in the (inherent) interactive dimension of organizational closure, in those functional capacities of a living being devoted to purposively governing the relationship with the environment.” Virenque, Louis & Matteo Mossio. 2023. “What is Agency? A View from Autonomy Theory.” Biological Theory. 10.1007/s13752-023-00441-5. pp. [page numbering uncertain] 4-5.
“An adaptive system is a system that is able to undergo functional modifications so as to deal with internal or external perturbations. In turn, an adaptive system is an adaptive agent if such modifications specifically affect its interactive capacities. Compared to minimal agency, adaptive agency involves more sophisticated skills, including higher-order regulation and anticipation, as well as the possibility to shift to different and new organizational regimes. As claimed by Moreno and Mossio, an organizationally closed adaptive agent is an autonomous system and, thereby, a living system. As a matter of fact all living systems, be they unicellular or multicellular, meet ex hypothesi the characterization in terms of adaptive agents. As Moreno and Mossio point out, ‘Auto-nomy here is not just the maintenance of the current condition of existence, but the fact of promoting its own existence on behalf of a more fundamental (and less contingent) identity.’ The identity of the system is less contingent because adaptive agency enables (continuously) changing its own current organization and behavior to keep existing.” Virenque, Louis & Matteo Mossio. 2023. “What is Agency? A View from Autonomy Theory.” Biological Theory. 10.1007/s13752-023-00441-5. pp. [page numbering uncertain] 6-7; reference: Moreno, A. & M. Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Dordrecht: Springer.
“This is called the reductive mode of the [citric acid] cycle. If an organism has access to high-energy electrons like those produced by geochemical processes, in fact, it can thrive with the cycle exclusively in the reductive mode…. In the reductive mode, the input is chemical energy, carbon dioxide and water, and the output is a more complex molecule.
“This must have been the way the cycle operated on the early Earth … because we see it operating this way today in some anaerobic organisms that seem to have preserved this aspect of the biochemistry of their ancestors. In the reductive mode, the cycle provides a way for high-energy electrons to flow down the chemical hill.” Trefil, James, Harold J. Morowitz & Eric Smith. 2009. “The Origin of Life: A case is made for the descent of electrons.” American Scientist. 97:206-213. p. 211.
“A fundamental challenge for enactive theory and other radical varieties of non-representational ‘E cognition’ is to reconceive the end-directed character of cognitive activity in naturally emergent but also experientially adequate terms. In short, it is necessary to show how cognitive activity is motivated.” Barrett, Nathaniel. 2020. “On the nature and origins of cognition as a form of motivated activity.” Adaptive Behavior. 28(2):89-103. 10.1177/1059712318824325. p. 89.
“But the phenomenon of emergent cognitive behavior suggests that the scope of cognitive explanation needs to be expanded to include accounts of how functional capacities ‘self-organize’ to perform a particular task within a particular situation.
“This is a very different kind of explanatory demand: it calls for something much more ‘radical’ than the shift from representational to dynamical kinds of explanation. In abstract terms, it implies that cognitive explanation must be expanded to include not just descriptions of the particular order that obtains when a cognitive task is executed–for example, dynamical descriptions of a functional capacity–but also accounts of how such orders emerge…. …we see that to establish a new paradigm of cognitive explanation based on dynamical systems it is not enough simply to replace computational descriptions with dynamical descriptions, as the latter do not account for the self-organization of the particular form of dynamics that constitutes this rather than that form of engagement….” Barrett, Nathaniel. 2020. “On the nature and origins of cognition as a form of motivated activity.” Adaptive Behavior. 28(2):89-103. 10.1177/1059712318824325. p. 95.
“… studies of other dissipative structures such as Benard cells indicate that complex order is ‘preferred’ only within the confines of certain parameters (e.g. above certain thresholds of the energy gradient, Benard cells are replaced by turbulence).” Barrett, Nathaniel. 2020. “On the nature and origins of cognition as a form of motivated activity.” Adaptive Behavior. 28(2):89-103. 10.1177/1059712318824325. p. 99.
“First, as I have suggested, life might be understood as an end-directed system that helps to determine its own ends by controlling the parameters of its own processes of dissipative adaptation….
“Second, cognition might be understood along the same lines as a form of self-controlled adaptive dissipation that is directed toward more particular, situation-specific ends.” Barrett, Nathaniel. 2020. “On the nature and origins of cognition as a form of motivated activity.” Adaptive Behavior. 28(2):89-103. 10.1177/1059712318824325. p. 101.
“IF (the world) selects the pathway or assembly of pathways that minimizes potentials or maximizes the entropy at the fastest rate given the constraints (LMEP [law of maximum entropy production]),
“AND IF ordered flow produces entropy at a faster rate than disordered flow (the balance equation of the second law),
“THEN the world can be expected to select order from disorder whenever and as soon as it gets the chance.” Swenson, Rod. 2010. “Selection is Entailed by Self-Organization and Natural Selection Is a Special Case.” Biological Theory. 5(2):167-181. p. 173.
“The fundamental scenario is a field (formal cause) of possibilities (available material causes), where a momentary configuration or fluctuation elicits/enables an action (efficient cause) that releases local events resulting in a global increase in physical entropy (final cause) as well as changed situations locally. It is my view that the Second Law of thermodynamics in an expanding universe instantiates the importance of final causality in science.” Salthe, Stanley N. 2018. “Perspectives on Natural Philosophy.” Philosophies. 10.3390.philosophies3030023. p. 2.
“The general perspective of natural science has been, and is, externalist. The scientist almost universally examines a system from (or as if from) the outside, and is not a part of it, as observed. There have been some exceptions (e.g., the physiologist John Scott Haldane–Wikipedia), while some Buddhists claim to practice an internalist ‘science’. Internalism is an attempt to understand a system from within, with the inquirer being a part. Internalism in this sense (not in the mode of the ‘humanities’) ought to be modest in scope, and focused only locally, as things are happening, and would most appropriately be reported in the present progressive tense.” Salthe, Stanley N. 2018. “Perspectives on Natural Philosophy.” Philosophies. 10.3390.philosophies3030023. p. 2.
“The main philosophical reason for taking the internalist stance in my opinion would be that generativity cannot be approached externally. In the externalist context, nothing radically new is produced except by error. Internally, chance would not differ from choice. Internally, dynamical tendencies are continually under construction during the activities of system self-organization….” Salthe, Stanley N. 2018. “Perspectives on Natural Philosophy.” Philosophies. 10.3390.philosophies3030023. p. 3.
“‘By general Semantic Closure I mean the relation between two primitive constraints, the generalized measurement-type constraints that map complex patterns to simple actions and the generalized linguistic-type constraints that control the sequential construction of the measurement constraints. The relation is semantically closed by the necessity for the linguistic instructions to be read by a set of measuring devices to produce the specified actions or meaning.’” Pattee, Howard. 1985. “Universal principles of measurement and language functions in evolving systems.” In: Casti, J.L. & A. Karlqvist (eds). Complexity, Language, and Life: Mathematical Approaches. pp. 268-281. Springer. p. 272. Quoted in Umerez, Jon. 2001. “Howard Pattee’s theoretical biology – a radical epistemological stance to approach life, evolution and complexity.” BioSystems. 60:159-177. p. 166.
“For our purposes, memory can be defined as experience-dependent modification of internal structure, in a stimulus-specific manner that alters the way the system will respond to stimuli in the future as a function of its past. This requires a labile yet stable medium, to provide the necessary latency…. In essence, sensory memory is a message to one’s future self–a view reminds us that memory is thus another instance of biological communication.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 2.
“One of the best candidates for mechanisms underlying information processing at the single cell level is the cytoskeleton, which has all of the necessary properties: it is a large, complex structure that is readily modified by a variety of molecular pathways (writing data), is interpreted by numerous motor proteins and other machinery (reading data), and implements a rich set of discrete transition states that could implement computational operations.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 4.
“Another medium for information processing is within chemical networks, such as reaction-diffusion (RD) dynamics that underlie pattern formation in embryogenesis. Recent work has revealed that RD systems and similar excitable chemical media can be designed so as to execute specific computations, and are being used for the design of minimal cognition controllers and other kinds of computation including planning.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 4; references for “work” above: Kondo, S. & T. Miura. 2010. “Reaction-diffusion model as a framework for understanding biological pattern formation.” Science. 329:1616-1620; Dale K. & P. Husbands. 2010. “The evolution of reaction-diffusion controllers for minimally cognitive agents.” Artif. Life. 16:1-19.
“Gene regulatory networks can be modeled as neural networks, with genes representing nodes and functional links representing inductive or repressive relationships among those genes. That landmark study showed that changes to the connections in the regulatory net represent a kind of Hebbian plasticity (as genes whose expression is up-regulated in specific environments tend to become co-regulated and thus expressed together). In part due to this fire-together-wire-together process, a GRN will develop an associative memory of phenotypes selected in the past.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 4; referred “study”: Watson, R.A., C.L. Buckley, R. Mills & A. Davies. 2010. “Associative memory in gene regulation networks.” Proceedings of the Artificial Life Conference XII. Odense. 194-201.
“Embryos make use of genetically encoded cellular memory, for example in the case of HOX gene expression patterns, which constitute a form of positional memory – ‘an internal representation by a cell of where it is located within a multicellular organism’, and hysteresis in Hedgehog protein signaling, all of which are used to guide the subsequent activity of cells as a function of prior ‘experience’.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 4.
“Additional memory media include the extracellular matrix and chromatin complex markings, both of which area ideal media for recording traces representing specific environmental and/or physiological events. These are examples of internal stigmergy – activity that leaves traces in a labile intracellular or extracellular medium which can be read as memories in the future by cells making decisions for migration, differentiation, apoptosis, or signaling.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 4.
“… plant cells have many features which are considered neuronal, including plasma membrane excitability supporting action potentials, acentriolar microtubules, motile Trans Golgi Networks, and synaptic-like actin-enriched cell-cell adhesion domains. Especially cells in root apices are very active in these neuronal-like activities and act as brain-like command centers, navigating growing roots in their search for water and mineral nutrients in soil, and active root avoidance or escape from toxic, stressful and dangerous situations.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 6.
“A number of non-neural cells have been shown to exhibit memory, with respect to somatic position or differentiation, implemented via long-term stable changes in bioelectric state and transcriptional profile. These are now beginning to be understood via physiological modeling and dynamical systems theory that views memories as attractors in transcriptional, bioelectric, or epigenetic state space.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 7.
“Embryogenesis, regeneration, and metamorphosis stop precisely when the correct anatomical shape has been produced; this is a process akin to goal-directed behaviors, in the sense that the system can pursue multiple paths toward the same (anatomical) goal state, can accommodate unpredictable external perturbations (is not hardwired but flexible), and rests when it is satisfied (can recognize when its goal is achieved). All of these examples show the remarkable information processing that cells carry out, in order to create and maintain specific shapes…. While the brain operates muscles and glands in service of activity in ecological space, the computational processes of non-neural somatic networks control cell behaviors (differentiation, migration, proliferation) to optimize the body’s movement through morphospace.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 8.
“What mechanisms underlie the ability of tissues to measure large-scale shape, detect deviations from a ‘remembered’ correct target morphology, implement remodeling toward repairing that shape, and know when to stop? Recent work has shown that as in the brain, these control networks make use of ion channels, gap junctions (electrical synapses), and neurotransmitters.” Baluska, Frantisek & Michael Levin. 2016. “On Having No Head: Cognition throughout Biological Systems.” Frontiers in Psychology. 7:902. 10.3389/fpsyg.2016.00902. p. 8.
“An allosteric enzyme has two binding sites: a sensory site at which binding a molecule alters the enzyme’s conformation and an effector site that is a production mechanism that catalyses a reaction. On our view, the allosteric enzyme makes a decision as it selects, based on the interaction with a molecule at the sensory site, how the effector site functions. This decision determines the rate of the reaction. Moreover, the allosteric enzyme does so in accord with a norm that is realized in the constitution of the allosteric enzyme itself. This norm is not something represented or selected by the enzyme itself, but incorporated into it. The reason to identify the constitution of the allosteric enzyme as embodying a norm is that it determines how the enzyme will act…. Through its actions it is making decisions for the organism. Selecting the kinetics of a reaction is a minimal example of making a decision…. But this example suffices to illustrate our characterization of decisions as requiring making measurements and applying norms to make selections.” Bechtel, William & Leonardo Bich. 2021. “Grounding cognition: heterarchical control mechanisms in biology.” Philosophical Transactions of the Royal Society: B. 376:20190751. 10.1098/rstb.2019.0751. p. 2.
“This thesis, for which Heschl coined the name ‘Life = cognition Thesis’, maintains that the dimension of a living organism interacting with its environment and modifying itself internally without losing its identity coincides with cognition.” Bechtel, William & Leonardo Bich. 2021. “Grounding cognition: heterarchical control mechanisms in biology.” Philosophical Transactions of the Royal Society: B. 376:20190751. 10.1098/rstb.2019.0751. p. 4; reference: Heschl, A. 1990. “L=C a simple equation with astonishing consequences.” J. Theor. Biol. 145:13-40. 10.1016/50022-5193(05)80532-6.
“We embrace the view that cognitive activities are performed by all living organisms…. And we focus on what is distinctive about these activities–they involve the exercise of control over metabolic and agential activities….
“Decision-making occurs when, in the face of alternative modes of operation, a system detects and integrates information procured from multiple sources (measurement), based on this information evaluates alternative modes of operation and, depending on that evaluation, selects a mode of operation.” Bechtel, William & Leonardo Bich. 2021. “Grounding cognition: heterarchical control mechanisms in biology.” Philosophical Transactions of the Royal Society: B. 376:20190751. 10.1098/rstb.2019.0751. p. 5.
“Quorum sensing provides a way for individual bacteria to regulate their activities depending on the number or state of other bacteria, whether of the same species or of relevant other species, available nearby for collaborative activities. This involves individual bacteria synthesizing and releasing a molecule, an autoinducer, into the environment and then regulating its own gene expression in response to the concentration registered by its own receptors…. Conceptually speaking, the basic mechanism involves two processes that are already performed in many bacteria–synthesizing a molecule for release into the environment and measuring concentrations of molecules in the environment.” Bechtel, William & Leonardo Bich. 2021. “Grounding cognition: heterarchical control mechanisms in biology.” Philosophical Transactions of the Royal Society: B. 376:20190751. 10.1098/rstb.2019.0751. p. 6.
“The ability of cyanobcteria and other organisms to maintain an internal model of the light-dark cycle of their environment posed a challenge: what kind of mechanism could track daily time? Ishiura et al. identified three genes that were necessary for circadian rhythms in the cyanobacterium Synechoccus elongatus. Nakajima et al. reported circadian rhythms in a preparation involving just ATP and the three Kai proteins, suggesting a cycle of phosphorylation and dephosphorylation….
“For this mechanism to satisfy our account of a control mechanism, two further requirements must be met. First, it must actually track the light-dark cycles in its environment. This requires some means by which the oscillator can be entrained to that cycle. Since Synechococcus elongatus has no photoreceptors, it uses proxies to detect the light-dark cycle. For example, when the bacterium is engaged in photosynthesis, quinones are in a reduced state. With darkness they oxidize rapidly, bind to both CikA and KaiA [genes required for circadian thythms], and cause them to degrade. By delaying phosphorylation of KaiC, the metabolic state that results when photosynthesis ceases with darkness acts to reset the clock. Second, the circadian mechanism must act in some manner on the production mechanism of gene expression. When SasA is bound to KaiC, it phosphorylates itself and transfers this phosphate to RpaA. Phosphorylated RpaA acts as a transcription factor, binding to approximately 100 Class 1 promoters, upregulating expression of approximately 170 genes. Eight of these genes are also transcription factors which upregulate yet other genes.” Bechtel, William & Leonardo Bich. 2021. “Grounding cognition: heterarchical control mechanisms in biology.” Philosophical Transactions of the Royal Society: B. 376:20190751. 10.1098/rstb.2019.0751. p. 7.
“By combining simple catalytic building blocks together, either in cooperation or competition, we can construct the more complex functional entities, such as logic gates, computational units or network motifs. In the above description, in which the TjTk dimers are catalysts for the formation of Ti [a monomer], we consider four possible catalytic mechanisms in which i = j = k, i≠ j = k, i ≠ j ≠ k, or i = j ≠ k. These mechanisms are essentially the following network catalytic building blocks: 1) the autocatalytic building block, in which, for example, the dimer T3T3 catalyzes the formation of T3; 2) the homodimeric cross-catalytic block, in which, for example, the dimer T1T1 catalyzes the formation of T3 ; 3) the heterodimeric cross-catalytic block, in which, for example, the dimer T1T2 catalyzes the formation of T3; and 4) the combined auto-cross-catalytic building block, in which, for example, the dimer T1T3 catalyzes the formation of T3. We note that these building blocks are themselves functioning logic gates, namely that the autocatalytic and homodimeric cross-catalytic blocks are examples of IF (YES) gates, while the heterodimeric cross-catalytic and combined auto-cross-catalytic blocks are examples of AND gates.” Wagner, Nathaniel & Gonen Ashkenasy. 2009. “Systems Chemistry: Logic Gates, Arithmetic Units, and Network Motifs in Small Networks.” Chem. Eur. J. 15:1765-1775. 10.1002/chem.200801850. p. 1767.
“Some purely physical or chemical systems are characterized by a closure of processes, where one process influences another in a circular way. For instance, consider the hydrologic cycle in prebiotic Earth. In simple terms, here, a set of processes generates, under certain boundary conditions, a cycle of causal relations in which each of these processes contributes to the maintenance of the whole, and is, in turn, maintained by the whole: the sun evaporates the water of a lake, forming clouds. When rising at higher levels these clouds get colder and generate rain; the rain, in turn, contributes to generate a spring, which gives rise to a river, which contributes to generate a lake, which regenerates clouds and so on.” Nunes-Neto, Nei, Alvaro Moreno & Charbel N. El-Hani. 2014. “Function in ecology: an organizational approach.” Biology and Philosophy. 29(1):123-141. 10.1007/s10539-013-9398-7. p [unclear page numbers]. 129.
“… a first, tentative definition of function in ecology could be put in the following terms:
“An ecological function is a precise (differentiated) effect of a given constraining action on the flow of matter and energy (process) performed by a given item of biodiversity, in an ecosystem closure of constraints….
“In our definition, function is embedded in a control hierarchy, with two levels: the level of the items of biodiversity which constrain the flow of matter and energy, and the level of the flow of matter and energy itself, to which we refer here as processes.” Nunes-Neto, Nei, Alvaro Moreno & Charbel N. El-Hani. 2014. “Function in ecology: an organizational approach.” Biology and Philosophy. 29(1):123-141. 10.1007/s10539-013-9398-7. p [unclear page numbers]. 131.
“According to one familiar story, atomism was finally vindicated after centuries of speculation early in the 20th century with Einstein’s and Perrin’s work explaining Brownian motion, Bjerrum’s explanation of the abnormal specific heat ratio for diatomic molecular gases in terms of the absence of vibrational motion at normal temperatures and other developments associated with the Old Quantum Theory. Shortly after, the first microtheories of the bonding between atoms underlying chemical combination were developed in the famous 1916 paper in which Lewis indicated how then current insights concerning atomic structure might be adapted to provide a foundation adequate for conceptions of bonding in organic and inorganic chemistry, he set out his notion of ionic and covalent bonds.” Needham, Paul. 2014. “The source of chemical bonding.” Studies in History and Philosophy of Science. 45:1-13. 10.1016/j.shpsa.2013.10.011. p. 1; reference: Lewis, G.N. 1916. “The atom and the molecule.” Journal of the American Chemical Society. 38:762-785.
“The bonds of classical structure theory [for chemical bonds] represented by the lines aligning valencies ascribed to atoms in molecules were a complete mystery in the 19th century. The widespread scepticism about whether there really was any atomic theory is hardly surprising. A picture of kinds began to emerge when Lewis understood bonds to be constituted of electrons taken from the bonded atoms. This addressed the question of what bonds are, but how they work remained a puzzle. His representation of covalent bonds as static electrons was easy prey for Bohr in his 1922 Nobel acceptance speech, although orbiting electrons were equally in conflict with classical theory. Heitler and London’s application of Schroedinger’s newly discovered wave mechanics was a decisive step forward in suggesting that electron pairing leads to the creation of a covalent bond, which works by virtue of the quantum mechanical nature of the indistinguishable electrons. But further developments showed these answers wanting.
“We saw that the valence bond approach which built on Heitler and London’s work and sought to retain basic insights of the ball-and-stick models of classical structural theory gave way to molecular orbital theory in mid-century. This was the time when theoretical chemists began questioning the wisdom of holding on to what might have been valuable starting points from the classical scheme. Coulson declared ‘a chemical bond is not a real thing: it does not exist: no-one has ever seen it, no-one ever can. It is a figment of our own imagination.’ Mulliken, as we saw in the Introduction, had already come to this conclusion in 1931….
“Construing the status of the chemical bond as an issue of existence is, perhaps, an unfortunate formulation. What exists are entities such as molecules, atoms and electrons, whereas bonding is something they do. The question is How? The Heitler and London analysis seemed to confirm Lewis’s idea that this was somehow to do with the pairing of electrons. But the existence of the stable H2+ molecule ion shows that electron pairing is not essential for covalent binding.” Needham, Paul. 2014. “The source of chemical bonding.” Studies in History and Philosophy of Science. 45:1-13. 10.1016/j.shpsa.2013.10.011. p. 11; references: Heitler, W. & F. London. 1927. “Wechselwirking neutraler Atome und Homoeopolare Bindung nach der Quantenmechanik.” Zeitschrift fuer Physik. 44:455-472; Coulson, C.A. 1955. “The contributions of wave mechanics to chemistry.” Journal of the Chemical Society. 2069-2084; Mulliken, R.S. 1931. “Bonding power of electrons and theory of valence.” Chemical Reviews. 9:347-388.
“Lange’s account of explanation by constraint is motivated by these cases [impossibility of crossing all Koenisberg’s bridges only once and of dividing 23 strawberries evenly among 3 children] and it contains two main features. First, he suggests that (1) constraints explain in virtue of exhibiting a strong from of necessity, which makes the explanatory target inevitable. This necessity allows the constraint to explain why various outcomes strictly ‘couldn’t’ happen or alternatively ‘that the explanandum had to be’….
“Second, according to Lange, (2) constraints necessitate their outcomes in a way that is stronger than standard causal laws and, because of this, they provide non-causal explanations.” Ross, Lauren. 2023. “Causal Constraints in the Life and Social Sciences.” Philosophy of Science. 10.1017/psa.2023.165. p. 2; reference: Lange, Marc. 2018. Because Without Cause: Non-Causal explanations in Science and Mathematics. Oxford UP.
“Lange is firm in his stance that ‘explanations by constraint are not causal explanations’ as they ‘work not by describing the world’s causal relations’ and they ‘do not reflect causal processes’. This is further supported by his claims that Woodward’s interventionist account–arguably the most influential account of causal explanation in current literature–is unable to capture these constraint-based explanations. On Woodward’s account, some property X is a cause of property Y, if there are hypothetical changes to X that produces changes in Y, in some set of background conditions. Lange argues that interventionism does not accommodate constraint-based explanations, because these explanations have ‘no obvious variables to be changed’.” Ross, Lauren. 2023. “Causal Constraints in the Life and Social Sciences.” Philosophy of Science. 10.1017/psa.2023.165. p. 3; references: Lange, Marc. 2018. Because Without Cause: Non-Causal explanations in Science and Mathematics. Oxford UP; Woodward, J. 2003. Making Things Happen. Oxford UP.
“This example involves an on/off switch that is electrically wired to one of two possible downstream systems, either a bell that rings or a light bulb that shines. Notice that if we intervene on the switch (turning it on/off) we control whether a downstream system is on/off, but we do not control which one. And if we intervene on the electrical wire connection (controlling whether it connects to one system or another), we control which system can be turned on, but not when exactly this happens. Dretske highlights the unique role of each factor by referring to the switch as a triggering cause and the wire as a structuring cause.” Ross, Lauren. 2023. “Causal Constraints in the Life and Social Sciences.” Philosophy of Science. 10.1017/psa.2023.165. p. 6; reference: Dretske, F. 1988. Explaining Behavior. MIT Press. p. 42.
“The neural pathway, vascular pathway, and social structure factors are genuinely causal because they meet the criteria of interventionist causation. These factors are all ‘difference-makers’ for an effect of interest because manipulating them provides control over an effect. However, part of what is revealed by these examples is that causes are not all created equal–factors that meet interventionist causality can differ in significant and important ways. I am going to suggest that these factors should be understood as causal constraints in the sense that they have additional features, beyond those specified by interventionism. Causal constraints are causes that: (i) limit the possible values of the explanatory target, (ii) are external to the process they limit, (iii) are viewed as relatively fixed compared to other explanatory factors, and (iv) guide the explanandum outcome as opposed to triggering it.” Ross, Lauren. 2023. “Causal Constraints in the Life and Social Sciences.” Philosophy of Science. 10.1017/psa.2023.165. p. 6.
“… physical information, i.e. embodied as a spatiotemporal pattern of matter, directs the unfolding of the universe, gives objects their existence and constrains forces to enable physical work to be done. Things happen this way or that because of the relative positions of all the particles that interact at time t to cause the ensuing dynamics. If we consider the set of positions of all labelled particles , then Z(t) embodies information and is particularised by that information and it is that information which constrains the unfolding dynamics to be what it is, rather than any other. Given this view, information is a fundamental aspect of physical reality.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 2.
“Information, as pattern, can be embodied in a wide range of media, e.g. electrical and magnetic fields, pressure variation in a fluid, colour pattern, or the shape of a solid, or of a molecule such as a catalytic protein…. To that extent, information is embodied at different spatiotemporal scales and in different ‘bases’ (I will use the term ‘basis’ to avoid confusion with nucleotide base), each defined by the pattern (i.e. motif) that provides the elemental unit for forming a higher level pattern…. The most relevant examples [of motif] are those of DNA and RNA where the basis is the codon and polypeptide where the basis is the amino acid…. The set of structures into which RNAs and polypeptides can fold into secondary, tertiary and quaternary patterns, provides a set of bases for information embodiment that is equivalent to a set of component parts for a machine. In a language of physical forms, the semantic meaning is the formation of functional wholes, composed of the component parts. Putting together an engine is making a meaningful statement in this language, autopoiesis of a cell is both a physical fabrication and assembly and the construction of a meaningful statement in the language of molecular form motifs.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 2.
“… for correlation of pattern to transmit information or perform efficient cause, the media of embodiment must match, which is trivial if the medium does not change, but where it does (e.g. from sound to axon voltage pulses), the process must depend on one of relatively few physical phenomena having effects in both media.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 2.
“Each combination of medium, scale and basis constitutes a domain for information embodiment, e.g. the frequency and modulation mode for a radio transmission, the codon for DNA/RNA embodied information, the individual components of an iron bridge (where the information is embodied in the component forms and the rules of their assembly) and the electric field near the active site of an enzyme, where the basis is its shape at the atomic scale. In this sense, a domain is the combination of medium, basis and scale in which information is embodied. Medium is the physical substrate, basis is the elemental unit of pattern and scale is the spatiotemporal extent of the basis.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 2.
“The idea of domain in communications leads naturally to the term ‘language’, here used in the general sense of code theory. For this, we define both code and cypher as a mapping from one domain A to another B so that f : A -> B, where f is a subset of all the possible ordered pairs F ⊆ A X B that includes only those {a, b}, such that b = f(a), where a ∈ A and b ∈ B. Then A and B are each languages with a set of symbols (each of a ∈ A and each of b ∈ B) and we need the code f to translate between them.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 2.
“It is no coincidence that the mapping f : A -> B used for code translation is the same as that used for efficient cause…. Crucially it is a kind that links one domain of formal cause embodiment with another. This special kind of efficient cause consists of an empowered formal cause, specifically a configuration of matter, which is at least in part a member of both domain A and B. That is most clear in the case of a tRNA which has one part matching the domain of amino acids and another matching that of codons. A microphone, which transforms pressure fluctuations into electrical, is an assembly of material (a form) having a causal link to both the kinetic and electrical physical domains.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 3.
“Semiotic causality has only indirect ‘causal power’ enabled by pre-determined response within a receiver to a particular signal from the transmitter. Cybernetic causality arises when information directly affects other information by computation (a network of logical relations implemented as correlations within a common domain). Formal constraint occurs when information as pattern in the distribution of matter constrains, hence specifies, the direction and strength of physical forces.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 3.
“With the exception of dissipating heat, energy is transformed from one form to another by an engine; obviously the combustion engine, but also e.g. the dynamo and the chloroplast are engines. By analogy, information (which must be physically embodied) can only be transformed from one domain into another by means of a transducer. Transducers necessarily involve either a cypher or a code and include adaptor molecules and coupled receptors, as well as sensory cells such as those found in the cochlea and eye.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 3.
“The translation complex for transforming RNA information into a polypeptide chain exemplifies a transducer matching one basis to another. A microphone translates from one medium to another and heterodyne circuit from one scale (radio frequency) to another. An olfactory cell translates all three: medium, basis and scale from molecular shape to neuronal axon pulse. In information terms, most transducers perform a reversible linear transformation (i.e. it applies equally over the domain) and so can be represented as a cypher. This sort of transducer embodies little constraining information: just one mapping rule that applies equally to all patterns in the basis. These cypher transducers are essentially physical: their transformation is a causally inevitable force-mediated process, exemplified by the vibrating needle leaving its impression in hot vinyl to make a record….
“In contrast, code transducers embody particular and arbitrary constraints on the relation between one domain of information embodiment and another. One of the defining characteristics of code, as opposed to cypher, is that the set of transformations {f} is arbitrary, not inevitable, not thermodynamically determined, but established by selection (natural or otherwise) and the reinforcement wrought from repetition, both of which imply function and with it, teleonomy, or even teleology, especially of communications within biological systems…. In other words, life requires both the ‘function’ and ‘symbol’ sides of Pattee’s epistemic divide and these are ‘bridged’ by codes.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. pp. 3-4.
“Emphasizing that autonomy is not absolute, but rather a continuum, Froese et al. identified behavioural and constitutive autonomy as two distinct dimensions of variation. Since behavioural autonomy concerns the degree of self-control for a system, I term it cybernetic independence and use constitutive independence for the degree to which a system is responsible for its own constitution.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 4; reference: Froese, T., N. Virgo & E. Izquierdo. 2007. “Autonomy: a review and a reappraisal.” In: European Conference on Artificial Life. Springer. pp. 455-464. 10.1007/978-3-540-74913-4_46.
“… all three of the questions above: (a) the extent to which responses to the environment are mediated by inner mechanisms, (b) the extent to which the (inner) controlling mechanisms are self-generated rather than provided by an exogenous source and (c) the extent to which these inner mechanisms can be appraised and modified from within, to better suit the objectives of the system in the light of the current situation – i.e. are adaptable. The last of these implies a third axes of freedom for a cybernetic system: there must be more than one possible action and there must be at least one level of meta-control to determine which action is taken. In general every additional level of meta-control adds degrees of (controlled) freedom to the cybernetic system, so belongs in the same conceptual category as the range of possible actions and I term this concept cybernetic freedom (the scope for choice).
“Autonomy therefore consists of (a) freedom from direct exogenous control, (b) self-constitution (autopoiesis) of the mechanisms of internal control and (c) adaptation of those mechanisms to suit a changing environment. These are attributes of all living cells and of every living organism and they are conceptually distinct. It is possible to have any one or two of them without the other. Each of them can be quantified by a ratio: (a) internal/external control, (b) endogenous/ exogenous constitution and (c) flexibility/fixation (which can be quantified by degrees of freedom). This enables autonomy to be quantified by a position in a three dimensional space, where each of these ratios is an axis. For illustration, a star is self-made to a limited extent, but has no cybernetic control, so is placed at zero on the two cybernetic axes. Automata and computers are entirely dependent constitutively, but have some independence of cybernetic operation and they range in degrees of freedom from very little (the automaton) to large (the universal computer). Organisms being autopoietic systems have significant constitutive independence and being self-regulated have very considerable cybernetic independence, but they vary in cybernetic freedom from rather little (the microbe) to the great flexibility of behaviour seen in e.g. octopus.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. pp. 4-5.
“Generally, when physical forces are constrained by the configuration of particles, energy flow is organised to do physical work (as opposed to entropic processes such as free gas pressure), e.g. the constraint of chamber and piston in a steam engine, or the configuration of proteins in the muscle fibre. This is the empowerment of the particular configuration (by the general and universal forces (energy flow) to enact efficient cause… He [Hofmeyr] generalises that to ‘without being informed by formal cause the efficient cause has operator potential but no agency’. The Farnsworth (2022 [paper]) interpretation starts with formal cause as pure information that has no agency until it is empowered by physical forces, hence efficient cause is the outcome of physically empowering formal cause….
“Removing the empowerment of force from efficient cause, leaves formal cause, the latent constraint that is embodied information. Separating this formal cause from physical force, protects and preserves it and is achieved by translating it into a different domain of embodiment. Practical examples of this separation include the data on a silicon chip ‘memory stick’ and the genetic program embodied in the relatively inert and protected double stranded DNA molecule (opened to efficient cause by separating the strands) and the paper tapes or punch cards of early computers, Jacquard looms and pianolas. All of these are embodiments of information which act as sources of formal cause (constraint) only within the special circumstances of being an input to a transducer that (a) transforms their information into a domain where it can be empowered by physical force and (b) protects it from the larger forces of efficient causes within the system that it constrains.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 6; references: Hofmeyr, J.-H.S. 2018. “Causation, constgructors and codes.” BioSystems. 164:121-127. 10.1016/j.biosystems.2017.09.008; Farnsworth 2022 is paper up above here.
“But to reproduce, a system must copy itself and there are essentially two solutions to the logical problem that poses.
“The first is found in systems that do not use template information to enable organisational invariance: the preservation of organisational information despite material turnover. These systems follow purely ‘compositional inheritance’…. Non-template replicators have no independent formal cause to preserve their organisational information: all their embodied information has to be simultaneously functional and formal (the specifying information that is duplicated in autopoiesis), as it is in metabolism-first models of proto-life…. That is sufficient for minimal fabrication of component parts, but it cannot address the assembly of the parts into an organised whole…. But assembly into an organised whole, that is not spontaneously produced by thermodynamic gradients, requires a formal template. Needing a formal template implies the need for code, since encoding into a different domain is the only way to ensure formal cause remains formal – by isolating it from the rest of the system.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 8.
“Once proto-life began to exploit the tremendous catalytic power of proteins, their chemistry was no longer entirely thermodynamically directed, in particular the (nearly perfect) thermodynamic equivalence of amino-acid sequences makes information necessary to ensure the correct sequence is followed in fabricating polypeptides. Polypeptides certainly can reproduce themselves, as accumulating evidence has shown ever since Kauffman demonstrated that in principle a reflexively autocatalytic subset of polypeptides can emerge from a sufficiently large set of interacting ‘protoenymes’. Selection of a viable reflexive autocatalytic set from among all possible reactions, among all possible polypeptides, is equivalent to gaining Shannon information (reducing system entropy). This information is what is needed to specify the organisation of the autocatalytic set. As the reaction network complexity and the variety and individual size of polypeptides increases, the autocatalytic set becomes increasingly specific, improbable and rare. As its sophistication increases, there must come a point where the likelihood of a system is so low that without the ‘crutch’ of an independent source of information (a template molecule) to act as a working memory for its evolution, it cannot be found. Eventually, the information needed to specify cascades of enzyme mediated reactions and their timing and possibly branching to match a varying environment, is too much to contain in compositional inheritance. Thus the increasing adaptive sophistication of protein catalysis networks brought with it the requirement for separate formal cause.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 8.
“Reproduction involves transforming the coded information from formal cause into efficient cause – bridging the epistemic gap between symbols and actions. The physical reason for this gap is that the template is embodied in a domain that is different from that of the rest of the system, hence the need for code-translation. Keeping the template in a different domain protects it from the efficient causes that could change the information (but allows special efficient causes to repair errors and maintain the integrity of the template); it keeps the information as formal cause and it keeps it external to the system, solving the logical conundrum of a system maintaining a copy of itself. The template constitutes embodied information that is replicated separately from the information embodied in the form of the system (including membranes, cytoplasm, ribosomes and all the proteins and other biomolecules).” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 8.
“… it would be wrong to think of the template as pure formal cause. Since all information is physical (the pattern of spatiotemporal configuration of particles) pure formal cause cannot physically exist, for example the charge pattern in a silicon chip and the nucleotide sequence of DNA themselves carry a physical forcefield. But we can call template information ‘formal cause’ because the forcefields do not correlate with those of other components in the system except for the code translation apparatus.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 8.
“… mRNA is a relatively fragile molecule which relies on the information-rich structure of the translational machinery of the cell to enact the fabrication of polypeptides without being destroyed by the process. As mRNA bases thread through the ribosome and are met with charged tRNAs moving from A to E to P biding sites, a fairly complicated sequence of conformation change in both ribosomal subunits constitute a constraining mechanism that is both firm enough to ensure repeatable accuracy and delicate enough to preserve the information molecules. Obviously it is only in the context of ribosome and charged tRNAs that mRNA can be cause and there it acts as formal cause for the selection of charged tRNAs according to codon-anti-codon pairing in a way analogous to the tape of the pianola, but the mechanism for transferring its relatively weak forces to the stronger forces (peptide bonds) that elongate the polypeptide is considerably more complicated.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 9.
“Some strikingly simple and well known features arise from coding that enables template replication. Firstly, like the pianola tape, mRNA is a linear structure (notwithstanding its propensity to form secondary and tertiary structure) which makes it far easier to ‘read’ than if the information were embodied in e.g. the three dimensional shape of folded protein. Also it is of indeterminate length, so able to embody any amount of information, whereas a (finite sized) protein molecule would set a specific limit….
“Secondly, mRNA is digital, i.e., it is the sequence of bases, not their chemical structure that embodies information and that gives it near immunity to corruption by interaction with other biomolecules (by analogy, digital communications systems are far less prone to noise and interference than their analogue counterparts, though when digital does go wrong it is usually with far more dramatic effect).” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 9.
“Autonomous systems are of little biological interest if they are causally isolated (as e.g. clocks are); organisms are sensitive to their environment, including other organisms, so that they can adapt and interact in ways likely to benefit their biological fitness. For that, they need to perceive attributes of their environment and interpret their perceptions as signs upon which either to act or not. That requires the effect of information to be strictly semiotic, in the sense that it has causal power, but no direct causal effect via constraining forces (formal constraint) or even cybernetic control via formal cause. Restricting perception to semiotic influence leaves organisms free to be autonomous in the senses of cybernetic independence and freedom. To describe semiotic influence, we adopt the conventional language of ‘source’ and ‘receiver’ communicating information that could be interpreted as ‘signs’.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 10.
“Strictly, the sign vehicle only becomes a sign on interpretation by the receiver. More generally, when the source S is in some state S, it produces the sign-vehicle (s) which is correlated with S. Thus, the sign perceived by the receiver depends on the state of the source, via s which is the information that can propagate to the receiver. Since s is a subst of S, we can more directly refer to the source state S from here on.
“Only by special arrangement of both source and receiver (a communications channel), can the sign-vehicle become formal cause for the receiver. At the receiver, this formal cause carrying information about S informs the receiver’s cybernetic system (which constrains the states of the receiver R) so that some part of R correlates with S. The sign-vehicle is therefore a formal cause (S) only if the communication channel permits it and its effect is restricted to a subset of the response repertoire of the receiver. The communication channel is a matching of information domain from source to receiver, represented by a mapping f(⋅), which matches s to S and R to s. Because a sign is relational, depending on the receiver’s perception of the sign-vehicle, it is a function of both S and R. Perception is effectively the correlation between R and S made possible by matching the domain of S to that of R.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 10.
“Autonomous systems are free to interpret signals in their environment as it suits them (either by design, or adaptation)…. [In figure] we see a source S broadcasting a sign-vehicle s which is interpreted differently by two different receivers. We can imagine this as e.g. the stripes of a wasp that indicate danger to R1 and food to R2. Again, a transducer is needed to transform the sign-vehicle into the domain of each receiver’s internal logic. At minimum, each has a different domain, so requires a different transducer configuration: g1 for R1 and g2 for R2 (e.g. two radio receivers, each tuned into a different frequency). In a biological example, each transformed sign will be logically combined with other formal causes within the receiver to give a different interpretation. This could include correlation with a memory of being stung by a wasp, or with a search image for a food item. Both of those internal conceptions are formal causes, embodied as e.g. patterns in the firing of neurons on a neural network. The important point here is that S does not control any of the receivers: it does not exert efficient cause, nor even formal cause (since that is generated by each receiver internally). Instead, we see only semiotic influence, since the responses are entirely determined by the receivers, which only utilise the broadcast information for internal computation.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 11.
“Taking Peirce’s definition of a sign as anything that is determined by a source, which acts as an interpretation (the interpretant) in some other system, then the formal cause S = f(R|S) is not a sign unless the receiver interprets it. The ‘interpretant’ is normally considered equivalent to the meaning of the sign, so a sign is that which communicates a meaning from a source to a receiver. The meaning cannot be the sign-vehicle, i.e. what Peirce termed the ‘representamen’; the term ‘sign’ is reserved for an interpreted sign-vehicle. The sign-vehicle consists of embodied information, which may be embodied as part of the source, or free from the source, though generated by it. The information embodied in the sign-vehicle is always distinct from the meaning, which must be information embodied by the receiver alone. Interpretation is the formation of meaning from information….
“… every physical configuration has an associated forcefield shape which is always available to influence (by its physical action) any other. But semiotic influence strictly depends on the receiver system having within it a configuration specifically arranged (by design, evolution or learning) to correlate with the disempowered (pure formal) information. For example, the black and yellow stripes of a wasp can only produce a reaction in another organism if that organism embodies information configured to correlate with the signal produced in its detector when perceiving the coloured pattern (i.e. there is a neural network excitation pattern matching the stripes of a wasp, using a neural code).” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 11; reference: Peirce, C. 1998. The Essential Peirce: Selected Philosophical Writings, Vol. 2 (1893-1913). Indiana U. Press.
“Codes are a quintessential part of biological systems, since it is only by coding information that (a) Von Neumann’s infinite regress problem can be solved, enabling closure to efficient causation and self-reproduction; (b) cause-effect links can be transformed into signal-response links, freeing agents of exogenous control (cybernetic independence) and (c) causes can be logically combined to form unboundedly elaborate cybernetic systems enabling the cybernetic freedom of organisms. Accordingly, the autonomy of organisms would not even in principle be possible without their use of codes.” Farnsworth, Keith D. 2023. “How biological codes break causal chains to enable autonomy for organisms.” BioSystems. 232: 105013. 10.1016/j.biosystems.2023.105013. p. 12.
“The most profound historical influence was John von Neumann. His 1966 discussion of self-reproducing automata suggested that efficient control of dynamical construction requires a non-dynamic ‘quiescent description’, and this I interpreted as equivalent to an epistemic cut between objective dynamical laws and subjective non-dynamic symbolic constraints describing the ‘self’. Von Neumann also asked a question that I found to be closely related to Pearson’s question [How can life be conceptually distinguished from the lifeless by the motion of inorganic corpuscles? – Karl Pearson, 1892: ‘Why are the basic macromolecules of organisms so much larger than the fundamental particles of physical theory?’]” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 11; reference: von Neumann, John. 1966. In: Burks, A.W. (ed.) Theory of Self-reproducing Automata. U. of Illinois Press; Pearson, Karl. 1892. The Grammar of Science.
“Equally influential was von Neumann’s discussion of the necessity of an epistemic cut in any measurement process showing that the function of measurement is necessarily irreducible to the dynamics of the measuring device. This logic is closely related to the necessary separation of symbols and dynamics for control of self-replication since measurement and control are inverse processes, i.e. measurement transforms physical states to symbols in memory, while memory-stored controls transform symbols to physical states.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 11; reference: von Neumann, John. 1955. The Mathematical Foundations of Quantum Mechanics. Princeton UP.
“Three closely related epistemic conditions are fundamental for this type [the determinism inherent in Newton’s laws] of dynamical description and need to be emphasized:
“1. To begin this type of description, the world must be separated into the states and the laws that change the states. The detailed (microscopic) laws are expressed as rate-dependent differential equations that define families of orbits in a state space. This means that the paths from states to states are unambiguously deterministic and reversible.
“2. Only when a particular system is located in this space by the act of measurement (determining its initial conditions, i.e. the positions and velocities of all particles at a particular time) do the equations lead to any observable consequences and allow an actual orbit to be calculated by integrating the equations of motion.
“3. Finally, and most importantly, this form of description can claim to be objective only if the act of measurement does not influence the form of the laws, and if the laws do not influence the act of measurement.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 12.
“The first extension of this model [3 points above] was to solid bodies that can be pictured as many point masses held together by fixed (non-dynamic) forces. The nature of these forces was a mystery to Newton. We now attribute them to electromagnetic, quantum, or fundamental particle forces that in principle may also be described in more detail by dynamical laws. Usually, these internal forces do no work and therefore play no role in the dynamical laws of the solid body. They may be interpreted as fixed, thereby greatly reducing the number of variables (degrees of freedom) that enter into the equations of motion. These internal (reactive or geometric) forces are called forces of constraint. What we call more or less rigid structures, from natural molecules, crystals, and rocks, to artificial tables, buildings, and bridges are held together by forces of constraint.
“However, there are also flexible forces of constraint that hold together the innumerable articulated assemblies of rigid structures we call machines, as well as labile assemblies of not-so-rigid structures like the biopolymers that execute measurement and control processes in organisms.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 12.
“It is still [post quantum and relativistic corrections to physics] required that (1) the laws and the initial conditions be crisply separated, (2) initial conditions be determined by measurements, and (3) measurement and laws not influence each other.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 12.
“Of course, many aspects of our physics theories are conventional social constructs, but other aspects appear inexorably objective and have withstood far more rigorous and severe challenges from within the skeptical and competitive physics community than have been offered by the social constructivists.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 12.
“As Gell-Mann has observed: ‘the effective complexity [of the universe] receives only a small contribution from the fundamental laws. The rest comes from the numerous regularities resulting from ‘frozen accidents’.’ I would add that to be effective in evolution, these regularities from frozen accidental constraints must be heritable. That means they must be reconstructible from a memory.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 13; reference: Gell-Mann, M. 1994. The Quark and the Jaguar. NY: W.H. Freeman. p. 134.
“The only useful description of memory or heredity in a physical system requires introducing the possibility of alternative pathways or trajectories for the system, along with a ‘genetic’ mechanism for causing the system to follow one or another of these possible alternatives depending on the state of the genetic mechanism. This implies that the genetic mechanism must be capable of describing or representing all of the alternative pathways even though only one pathway is actually followed in time. In other words, there must be more degrees of freedom available for the description of the total system than for following its actual motion… Such constraints are called non-holonomic.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 13.
“What is historically amazing is that this common type of constraint [non-holonomic or non-integrable constraints as flexible, allosteric, or configuration-changing structures that couple an explicit memory structure with rate-dependent laws] was not formally recognized by physicists until the end of the last century. Such structures occur at many levels. They bridge all epistemic cuts between the controller and the controlled, the classifier and the classified, the observer and the observed. There are innumerable types of non-integrable constraints found in all mechanical devices in the forms of latches, and escapements, in electrical devices in the form of gates and switches, and in many biological allosteric macromolecules like enzymes, membrane channel proteins, and ciliary and muscle proteins. They function as the coding and decoding structures in all symbol manipulating systems.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 14.
“The apparent arbitrariness of the placement of the epistemic cut arises in part because the process cannot be completely or unambiguously described by the objective dynamical laws, since in order to perform a measurement, the subject must have control of the construction of the measuring device. Only the subject side of the cut can measure or control.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 15.
“What is the simplest epistemic event? One necessary condition is that a distinction is made by a subject that is not a distinction derivable from the object. In physical language, this means that a subject must create some form of distinction or classification between physical states that is not made by the laws themselves (i.e. measuring a particular initial condition, removing a degeneracy or breaking a symmetry). In the case of the cell, the sequences of the gene are not distinguished by physical laws since they are energetically degenerate. Where does a new distinction first occur? It is where this memory degeneracy is partially removed, and that does not occur until the protein-folding process. Transcription, translation, and copying processes treat all sequences the same and therefore make no new distinctions, but of course, they are essential for constructing the linear constraints of the protein that partially account for the way it folds. The folded protein removes symbol vehicle degeneracy, but it still has many degenerate states (many conformations) that are necessary for it to function as a non-integrable constraint.
It is important to recognize that the details of construction and folding at this primeval epistemic cut make no sense except in the context of an entire self-replicating cell. A single folded protein has no function unless it is a component of a larger unit that maintains its individuality by means of a genetic memory. We speak of the genes controlling protein synthesis, but to accomplish this, they must rely on previously synthesized and organized enzymes and RNAs. This additional self-referent condition for being the subject-part of an epistemic cut I have called semantic (or semiotic) closure.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 16.
“Controlling predictable physical laws is only part of the problem of survival. There are additional physical conditions for evolvability. These are not abstract principles but specific requirements on how efficaciously the epistemic cut is actually bridged. I will only mention three of three conditions. Evolution depends critically on (1) how easily gene sequences corresponding to functional proteins can be found, (2) how reliably these sequences can control construction of proteins, and on (3) how smoothly or gradually variations in the sequences can produce adaptation of function. In other words, evolvability depends on the many physical and statistical details of how the actual epistemic bridge from symbols to dynamics is executed.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. pp. 16-17.
“… the very concept of a ‘physics of symbols’ is completely foreign. We have come to think of symbol systems as having no relation to physical laws….
“The computer is a prime example of how the apparently physics-free function or manipulation of memory-based discrete symbol systems can easily give the illusion of strict isolation from physical dynamics….
“This apparent isolation of symbolic expression from physics is born of an epistemic necessity, but ontologically, it is still an illusion.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 17.
“Physics largely ignores the exceptional effects of individual (subjective) constraints and boundary conditions and focusses on the general dynamics of laws. This is because constraints are assumed to be reducible to laws (although we know they are not reducible across epistemic cuts) and also because the mathematics of complex constraints is often unmanageable.” Pattee, Howard H. 2001. “The physics of symbols: bridging the epistemic cut.” BioSystems. 60:5-21. p. 19.
“In his [Schroedinger’s 1944] metaphor of an aperiodic crystal as the carrier of this information he both foreshadowed Claude Shannon’s (1948) analysis of information storage and transmission and Watson and Crick’s (1953) discovery of the double helix structure of the DNA molecule. So by 1958 when Francis Crick first articulated what he called the ‘central dogma’ of molecular biology it was taken for granted that that [sic] DNA and RNA molecules were ‘carriers’ of information. By scientific rhetorical fiat it had become legitimate to treat molecules as able to provide information ‘about’ other molecules…. By describing a sequence of nucleotides in a DNA molecule as information and DNA replication as the essential defining feature of life, information was reduced to pattern and interpretation was reduced to copying. What may have initially been a metaphor became difficult to disentangle from the chemistry.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. pp. 537-8.
“Though it is common shorthand to treat portraits as icons and thermometers as indices, this has more to do with what they were created for and what a community assumes is their ‘proper’ interpretation. But when an art critique recognizes the style of a particular portrait and infers from it who it was painted by, it is an index, and when a thermometer reminds someone of a drinking straw, it is an icon. This demonstrates that if we equate semiotic properties with sign vehicle properties or with the multitude of different uses that are possible, we are forced to say that portraits and thermometers are at the same time each both icons and indices.
“This leads to a principle that will frame the remainder of this essay. Perhaps it could be (ironically) described as the central dogma of semiotics. It can be stated as follows:
“Any property of a physical medium can serve as a sign vehicle of any type (icon, index, or symbol) referring to any object of reference for whatever function or purpose because these properties are generated by and entirely dependent upon the form of the particular interpretive process that it is incorporated into.
“Thus, we should not ask what it is about some sign vehicle that makes it an icon, index, or symbol. These are not sign vehicle intrinsic properties. Intrinsic properties are not what make something semiotic. Sign vehicle properties aren’t irrelevant, of course. But intrinsic properties are merely semiotic affordances. They may or may not be utilized for any semiotic purpose. Often the semiotically relevant property of a sign vehicle is only one of its many attributes, and not necessarily the one most salient. What maters is how the relevant property is incorporated into an interpretive process, because being interpreted is what matters.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. p. 539.
“The model I will use for this purpose [to how a physical process could come to treat a molecule as information about something else] is a hypothetical but physically realizable minimally complex molecular process….
“It is modeled after virus structure. In this respect it is not an idealization, just an as yet physically unrealized chemical system. It can be described as a non-parasitic virus that can reproduce autonomously. In this regard it is an autogenic virus, able to autonomously generate copies of itself….
“These two processes–reciprocal catalysis and self-assembly [as in a virus capsid]–are chemically complementary to one another because they each tend to produce conditions that are necessary for the other to occur. So reciprocal catalysis produces high locally asymmetric concentrations of a small number of molecular species while self-assembly requires persistently high local concentrations of a single species of component molecules. Likewise, self-assembly produces constraint on molecular diffusion while reciprocal catalysis requires limited diffusion of interdependent catalysts in order to occur. In this way reciprocal catalysis and self-assembly are molecular processes that each produce the boundary conditions that are critical for supporting each other….
“As a result, catalysts that reciprocally depend on one another to be produced will tend to be co-localized, and prevented from diffusing away from one another. While contained, catalysis will quickly cease when substrates are used up, but in the case that the capsid is subsequently damaged and spills its contents, more catalysts and capsid molecules will be synthesized if there are additional substrate molecules nearby….
“This constitutes what can be described as an autogenic work cycle. A work cycle consists of a linked sequence of thermodynamic processes that involve transfer of work into and out of a system… and that eventually returns the system to its initial state (paraphrased from Wikipedia)….
“It is in this way that each of these self-organizing processes produces the extrinsic boundary conditions that the other requires. As a result the critical boundary conditions are internalized and constantly available to channel the work necessary to maintain and reproduce these same constraints. The two self-organizing dynamics are in this sense co-dependent…. An autogen is therefore self-individuated by this intrinsic co-dependent dynamical disposition, irrespective of whether it is enclosed or partially dispersed.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. pp. 541, 542, 543, 545.
“To summarize the argument so far: there are 5 holistic properties that even a simple autogenic system exhibits that are not reducible to the physical-chemical properties of its components and are emergent from the intrinsic dispositions of the whole integrated system. They are 1. individuation (it intrinsically maintains an unambiguous self-non-self distinction); 2. autonomy (it intrinsically embodies and maintains its own boundary conditions for each other); 3. recursive self-maintenance (it repairs and replicates the critical boundary conditions that are required to repair and replicate these same critical boundary conditions); 4. normativity (it is disposed to produce these results but can fail); and 5. interpretive competence (by being able to re-present its own boundary conditions in new instantiations it intrinsically re-presents and reproduces its own conditions of existence).
“How can we characterize this most basic and simple interpretive competence in semiotic terms? The point of this model system is to establish what can be considered the ground of interpretive competence. In this respect it is effectively a ‘zeroth’ level semiotic process. As such it ‘interprets’ the most basic semiotic distinction: i.e. between self and non self. Thus disruption of integrity is a sign of non self and the dynamics that ensures and reconstitutes the stable state is the generation of an interpretant which actively reconstructs this self/ non self distinction. So a cycle of autogenic disruption and self-repair treats every form of disruption as indistinguishable from each other–i.e. as iconic–because the system can only produce one form of interpretant. In this respect, iconism is the most basic semiotic operation because it marks the limit of what can be interpretively distinguished.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. pp. 546-7.
“An additional capacity beyond self-interpretation involves the ability to interpret different environmental conditions with respect to their relevance to the recursive self-maintenance of the interpreting system….
“This slightly more complex interpretive capacity is exemplified by an autogen that is electively sensitive to its environment because 1. the capsid surface has structures (epitopes) onto which potential substrate molecules will tend to bind, and 2. capsid integrity is made increasingly fragile as the number of surface-bound substrates increases. This will make containment more likely to fail and release catalysts in reproductively supportive conditions….
“So to develop the analogy further, in semiotic terms, the number of substrates bound to the autogenic capsid effectively indicates the presence or absence of extrinsic supportive conditions for persistence and reproduction of this same interpretive capacity. In this respect the interpretive process provides normative information about the environment that can potentially benefit the perpetuation of this same interpretive capacity.
“This analogy is instructive in another sense. It demonstrates that the competence to interpret immediate conditions to be about correlated conditions is dependent on the more basic interpretive competence to re-present self. It is the self-correcting, self re-presenting capacity of simple autogenesis [icon] that enables the correlation between changes in capsid fragility to be about the value of the environment for that self [index] and its interpretive capacity.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. p. 547, 548-549.
“Consider the following enhancement of simple autogenesis. If another of the side products produced by autogenic reciprocal catalysis is a molecule like the nucleotides ATP and GDP that can acquire and give up energy carried in pyrophosphate bonds, the availability of this generic free energy could potentially facilitate more effective catalysis and drive otherwise energetically unfavorable reactions. This could provide a sort of energy-assisted autogenesis which would tend to out-perform spontaneous autogenesis and be favored by natural selection. This could also enable a wider variety of potential substrate molecules to be useful, because the energy to drive reciprocal catalysis would not need to be derived from substrate lysis….
“So energetic phosphates could cause potential damage during the inert phase of autogenesis. To be preserved safely and intact so they can be available when again catalysis is required they need to be somehow stored in an nonreactive form.
“Nonreactive mucleotide-based molecules are of course well-known. They are DNA and RNA molecules. In these nucleotide polymers the phosphate residues serve as the links between adjacent sugars and so are nonreactive. By linking them into a polymer with phosphates unexposed, they can be effectively ‘stored’ for later use via depolymerization. In this evolutionary scenario, then, the initial function of polynucleotide molecules is presumed to be energetic, and only later in evolution do they become recruited for their informational functions….
“As the number of molecular species that need to interact increases linearly, the number of possible cross-reactions that could occur between members of the set increases geometrically…. This will decrease the efficiency and impede reproduction. So autogenic systems like the ones described above have limited evolvability, making autogenic evolution improbable beyond very simple forms. So unless non-supportive reactions can be selectively suppressed, autogenesis cannot lead to more complex forms of life.
“But looked at from the perspective of living organisms, the suppression of all but a tiny fraction of possible chemical reactions is one way to view the function of the template molecules of life, the nucleic acids RNA and DNA and their roles in orchestrating cellular chemistry. In simple terms nucleic acids limit the kinds of proteins that are present in the cell, which in turn strongly biases the types of chemical reactions that tend to take place. Death of the cell or organism allows the myriad of previously suppressed chemical reactions to be re-expressed. So, although we generally tend to conceive of DNA-based synthesis of proteins as a generative process, it can also be considered to be the principle constraining influence that keeps deleterious reactions at bay….
“Since there will be both catalysts and polynucleotides within the inert autogen capsid, free catalysts will tend to associate with free nucleotide polymers with respect to these structural complementarities. The attached catalysts will therefore tend to be arranged into distinct sequences along the length of an extended nucleotide.
“The spatial correlation relationships between catalysts aligned along a nucleic acid polymer will thereby tend to constrain the probability of particular catalytic interactions, increasing some and suppressing others. In this way the structural constraints of the template molecule can bias and constrain the interaction probabilities of the catalysts….
“Because it is supported by template structure and not by any catalyst-intrinsic interaction tendencies that shifts the source of interaction constraints from catalyst properties to template properties.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. pp. 549-550, 551, 552.
“In summary: these variations on the autogenic model system exemplify a three tiered interpretive logic by which referential and instructional information can be derived and evolved. First there is simple autogenesis which is entirely determined by holistically embodied isomorphic (similarity) constraints distributed in its many components that preserve their own codependence despite damage and substrate replacement. Second there is context sensitive autogenesis which is determined by an augmentation of simple autogenesis in which the capsid surface presents structures with forms that are similar to the forms of useful substrates facilitating their binding to the surface where binding weakens capsid integrity. And third there is template-mediated autogenesis in which catalyst interaction constraints become offloaded onto a molecular structure.” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. p. 554.
“The logic of the autogenic approach, though not able to directly account for the evolution of the DNA-to-amino acid ‘code,’ provides something more basic. It provides a ‘proof of principle’ of a sort, showing step-by-chemically-realistic-step how a molecule like RNA or DNA could acquire the property of recording and instructing the dynamical molecular relationships that constitute and maintain the molecular system of which it is a part. In short, it explains how a molecule can become about other molecules…. Rather than thinking of the problem from an information molecule first perspective (how nucleic acid structure came to inform protein dynamics), it might be instructive to ask the question the other way around (how protein dynamics came to be reflected in nucleic acid structure).” Deacon, Terrence W. 2021. “How Molecules Became Signs.” Biosemiotics. 14:537-559. 10.1007/s12304-021-09453-9. p. 557.
“… the current practice of developmental biology is still guided by the metaphoric use of the mathematical concepts of information, program, and signal, particularly the idea of a teleonomic genetic program, shaped by natural selection. Determination of the organism follows from this program and thus is extrinsic to the developing organism as such…. This genocentric view, which endows genes with a privileged causal role, suffers from many weaknesses. It falls short of providing an understanding of how a complex, fully organized biological entity will systematically be formed from this putative ‘program,’ where such a program is located, and how it is executed. One main reason behind these shortcomings is that while there is a close relationship between a DNA sequence and the corresponding protein, there is no such correspondence between genes and phenotypes because the possible properties of phenotypes are not prestatable. Consequently, the relationship between genes and forms is not straightforward.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. pp. 264-5.
“In the 1970s while molecular biologists aspired to reduce biology to chemistry, advances in the understanding of dissipative non-equilibrium physical systems that self-organize influenced theoretical biologists interested in biological organization. Many of these thinkers, such as S. Kauffman, H. Maturana, and F. Varela, went beyond the notion of far from equilibrium systems and were inspired by the Kantian concept of biological organization that stressed the interrelatedness of the organism and its parts and the circular causality implied by this relationship (an organism is the cause and effect of itself). Recognizing that Kantian organization does not correspond to the spontaneous self-organization of physical systems, they worked out a new regime of circular causation. In this circular organizational regime, the parts depend on the whole and vice versa; this regime not only produces and maintains the parts that contribute to the functioning of the whole integrated system, but the integrated system also interacts with its environment to promote the conditions of its own existence.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. pp. 265-6.
“Biological specificity does not negate the idea that aspects and parts of organisms are endowed with a kind of restricted genericity, namely, limited invariance. We call these elements constraints. And example of a constraint is the structure of articulations between bones which preclude certain movements and allow others.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. p. 267.
“A theoretical principle of biological ‘inertia,’ the default state of cells. A method used to develop a theoretical framework consists of positing what take place when nothing is done to a system, that is, when discussing default states. For example, the inertial state of classical mechanics corresponds to the trajectory of an isolated object. In biology, we posit that the default state of cells is proliferation with variation and motility. It is based on the cell theory, and it relates to the specific materiality of the alive. The default state is a manifestation of the agency of living objects and, thus, a cause….
“The principle of organization by closure of constraints….
“The principle of variation…. By contrast, the principle of variation posits that biological objects are specific, and therefore relevant invariants and symmetries typically change over time….
“Overall, these three principles provide a framework for understanding both general aspects of biology and particular biological situations.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. pp. 268, 269.
“Specifically, breast epithelial cells need a support to crawl on since they do not have a flagellum or a functionally analogous set of constraints. Notably, they use fibers [from other breast cells] to which they can attach and that they can pull in order to move. Moreover, cells are not simple mechanical structures that remain invariant over time; they react in a diverse manner to a mechanical force, depending on their history and normativity. For example, mechanical compression induces the expression of a set of genes…. Once embedded in a matrix, breast epithelial cells emit projections, like filopodia and pseudopodia, which are used for motility….
“Cells that touch each other, whether as a result of migration or after cell division, can attach to each other. Adhesion, and more specifically the physicochemical structures involved, constrain cell movements.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. pp. 272-3.
“The use of information metaphors drives experimenters to search for causality in discrete structures such as molecules. Additionally, ignoring the circular interdependency of the organism and its parts while embracing the idea that explanations need to uncover ‘molecular’ mechanisms precludes the identification of physical ‘constraints’ which causally contribute to the generation and maintenance of the organism.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. p. 279.
“Rather than applying the usual procedure of transferring mathematical structures developed for the understanding of physical phenomena into biological ones, we model biological processes from a biological theoretical framework. Here we base our approach on two principles (default state and principle of organization) of the three principles proposed as foundations for a theory of organisms….
“In fact, the two principles (default state and constraints leading to closure) were sufficient to show the formation of ducts and acini. Cells generated forces that were transmitted to neighboring cells and collagen fibers, which in turn created constraints to movement and proliferation.” Montevil, Mael & Ana M. Soto. 2024. “Modeling Organogenesis from Biological First Principles.” From: Organization in Biology. Mossio, Matteo (ed). pp. 263-283. Springer. p. 280.
“In particular, the very status of closure as a causal regime with distinctive properties remains somehow controversial since, to date, no explicit account of the relations between closure and other kinds of causal regimes at work in physics and chemistry has been offered.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 2.
“Constraints subject to closure constitute the biological organisation and, accordingly, make an essential contribution to determining the identity of the system. Biological individuality, we think, has much to do with organisational closure, to the extent that one may conjecture that closure in fact defines biological individuality.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 23.
“Closure is a sort of organisational general invariant: it is the common property of each specific organisation that an individual system may instantiate.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 24.
“Although he [Rosen] was probably not the first author to have used the term ‘closure’ to refer to a distinctive property of biological systems, he was certainly the first one to have explicitly seen and claimed that a sound understanding of closure in biological organisation should make the distinction between two causal regimes at work in biological systems and should locate closure within the relevant regime. In this sense, we acknowledge the intellectual debt we owe to Rosen’s work, and see our work, in many ways, as an attempt to further develop his ideas and insights.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 26.
“The second way of handling perturbations is regulation, which is based on a qualitatively different form of organisation. Regulation requires that the closed organisation possesses a set of constraints exclusively operating when closure is being disrupted by a deleterious variation…. By definition, therefore, regulatory constraints are different (and complementary) with respect to constitutive ones….
“As an example, consider the lac operon system, which regulates the metabolism of lactose in bacterium E. coli. In normal circumstances, E. coli metabolises the glucose taken in the environment. When the level of glucose becomes very low, and lactose is abundant, a mechanism called lac-operon is activated: the detection of lactose disinhibits the expression of a cluster of genes that enable lactose metabolism…. In turn, the lac operon becomes operational when a perturbation (the decrease of glucose levels) occurs and the maintenance of the organisation is menaced: the lac operon re-establishes closure by modifying the constitutive organisation (which shifts from glucose to lactose metabolism), and bridges then the gap between the activity of the system and its conditions of existence. Accordingly, the lac operon mechanism is regulatory.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 33-4.
“… we claim that regulatory constraints are second-order constraints that, unlike constitutive ones, exert their causal actions on changes of other constitutive constraints of the organisation.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 34.
“One important implication [of the separation of the constitutive from the regulatory regime of constraints] is that, since they do not participate to constitutive closure, regulatory actions are triggered when the relevant (class of) perturbations occur. Therefore, a conceptual distinction can be made between the ‘constitutive’ processes that maintain the regulatory functions (as for instance those which maintain the cluster of dormant genes responsible for the glucose/lactose switch in the lac operon case) and the processes (or changes) that trigger their action (as the increase of lactose and decrease of glucose in the environment). The triggering processes, ultimately due to an external or internal perturbation, may take many specific forms: in particular, it is worth noting that they are in many cases completely distinct from the constitutive ones, as for the lac operon…. Not only does regulation not contribute to constitutive closure but typically it is not even triggered by (changes of) processes involved in the constitutive closure….
“The regulatory subsystem (R), when activated (R/P) by a triggering perturbation (P), governs the transition from one constitutive organisation (C1 … Cn) to another one (C1’… Cj). In this specific case, the difference between the two constitutive organisations consists in the replacement of the constraint Cn with Cj.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 34.
“In particular, they [regulatory constraints] govern the transition between two organisations, the one whose closure is collapsing (the glucose-based one, in the example of the lac operon), and the one that they contribute to establishing (the lactose-based one): regulatory constraints depend on the (constitutive constraints of the) former, and enable the (constitutive constraints of the) latter. We argue that, accordingly, regulatory constraints are subject to a second-order closure between both themselves and the whole set of organisations among which they govern the transitions.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 35.
“The view according to which closure constitutes a distinctive feature of biological organisation seems to require the adoption of a non-reductivist stance, according to which biological systems realise a regime of causation that is irreducible to (and then distinct from) those at work in other classes of natural (i.e. physical and chemical) systems.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 39.
“As has been recently argued, when they are subject to closure, constraints correspond to biological functions: performing a function, in this view, is equivalent to exerting a constraining action on an underlying process or reaction in an organised system. All kinds of biological structures and traits to which functions can be ascribed satisfy the above definition of constraint, although at very different temporal and spatial scales…. The emergence of closure is then the emergence of functionality within biological organisation: constraints do not exert functions when taken in isolation, but only insofar as they are subject to a closed organisation.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 51.
“… we advocated the idea that a coherent defence of closure as an emergent and irreducible causal regime does not need to invoke nested causation. Closed organisations can be understood in terms of causal (possibly inter-level) interactions between mutually dependent (sets of) constraints, without implying upward or downward nested causal actions between the whole and its parts. Biological emergence, accordingly, is logically distinct from nested causation, and one can advocate the former without being committed to the latter.
“Again, we by no means wish to exclude the possibility that biological organisation might involve nested causation.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 61.
“The central idea is that functionality, in addition to teleology and normativity, includes a third dimension, that of organisation. Functions, we submit, involve the fact that self-determination is achieved through the interplay of a network of mutually dependent entities, each of them making different yet complementary (and also hierarchical, as in the cases of regulation and control…) contributions to the maintenance of the boundary conditions under which the whole system can exist. In other words, to ascribe functions we must distinguish between different causal roles in the system, a division of labour among the parts.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 71-2.
“‘Functionality’, ‘closure’, and ‘organisation’ are then mutually related concepts, which refer to the very same causal regime; in other words, in the autonomous perspective an organisation is by definition closed and functional.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 72.
“Since what matters in the case of organisational self-maintaining systems is the fact that they use their own constitutive organisation to exert a causal influence on the maintenance of (at least part of) their own conditions of existence, then the organisation of the ‘encompassing system’ made up by a reproducer and a reproduced system itself fits the characterisation of a closed self-maintaining organisation. Reproduction, in this sense, simply constitutes one of the functions through which the organisation succeeds in maintaining itself beyond the lifespan of individual organisms.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 80.
“Nonfunctions refer to the effects of traits which do not comply with the norms generated by closure, and do not therefore contribute at all to maintaining the organisation. A kidney that does not filter blood, for instance, is nonfunctional rather than malfunctional. The distinction between nonfunctions and malfunctions also serves to highlight the fact that malfunctionality is a matter of degree.” While functions are all-or-nothing concepts, malfunctions admit degrees….” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 82-3.
“Biological systems, first and foremost, (self-)maintain their coherence and identity as the closure between their constitutive constraints, which is also regulated by second-order constraints, so as to handle deleterious variations. Yet, the constitutive dimension of organisation is not ipso facto autonomous. In this chapter, we argue that autonomy involves also an interactive dimension, enabling biological systems to maintain themselves in an environment. We will refer to this interactive dimension as agency. A system that realises constitutive closure (metabolism) and agency, even in a minimal form, is an autonomous system, and therefore a biological organism.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 89.
“… an autonomous system exists insofar as it maintains specific interactions with its surroundings, and therefore an adequate inward and outward flow of energy and matter.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 89.
“More technically, constitutive and interactive dimensions correspond to two nested classes of functions, both subject to closure. Accordingly, interactive capacities are a subset of constitutive functions…. Interactive functions are, then, a set of constraints subject to closure, whose specificity lies in the fact that their effects are exerted on the boundary conditions of the whole system.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 90.
“… actions [as agency] are performed according to a certain goal or norm. In contrast to mere ‘effects’ of the system on the environment actions are supposed to have goals and comply with norms. Actions have teleological and normative dimensions. Again, the autonomous perspective captures these requirements by deducing them, in a principled way, from the fact that actions are a class of functions. As such, they are subject to closure, which implies, in particular, that they possess the teleological and normative dimensions generated by the realisation of closure….
“…just like any class of functions, agency requires the interplay of mutually dependent constraints, each of which makes a different yet complementary contribution to the maintenance of the whole system.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 93.
“Since part of the genome is composed of a set of metabolically decoupled gene strings, the adaptive mechanism consists of the activation and deactivation of genes in order to switch between metabolic pathways in accordance with certain environmental conditions. Agency here takes rather the form of self-transformation than of a direct modification of environmental conditions. A similar case is that of some bacteria that, under harsh conditions, transform into spores in order to better resist heat and dehydration….
“For example, adaptive agency takes place when a whole subsystem of biochemical pathways not involved in the constitutive metabolic network supports detection-action coordination. In this case, regulatory chemical pathways act directly on the interaction between the system and the environment.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 102.
“We submit that agents, i.e., in an extended form, systems realising a regulated closed agential emergent organisation, in the technical sense developed throughout these four chapters, are autonomous systems and therefore biological organisms….
“What is the logic behind this definition? Its central purpose consists in showing that autonomy is inherently grounded in, and yet not equivalent to, organisational closure…. Closure … is the technical concept that captures this capacity. Yet, closure is not autonomy: the inherent complexity of biological systems requires also appealing to regulation and agency.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 104.
“… minimal autonomy does capture the essential features of biological systems, and therefore, we believe the concept of organism itself. In particular, minimal autonomy can be pertinently applied to account for the principles of organisation of unicellular organisms.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 105.
“The highly stable nature of DNA, as well as its dynamic decoupling from the metabolic processes, enables us to view changes in DNA sequences as largely independent of the metabolic organisation itself. Ultimately, the decoupling of template functions from the metabolic dynamics is the expression of the inherent insertion of organisms, as autonomous systems, into a historical-collective dimension where the ‘slow’ processes of creation and modification of evolutionary patterns take place, and where the mutual dependence between individual organisation and the eco-evolutionary dimension is better established.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 132.
“When dealing with inherently intertwined multicellular biological systems, however, the question of the boundaries of closure may become much more complex, insofar as forms of strong (both intra- and inter-level) interactions between closed systems are considered. In spite of these difficulties, however, we do maintain that closure is a useful conceptual tool for identifying biological systems and, in particular, for distinguishing relevant levels of biological organisation. While we have previously discussed the realisation of different orders of closure (in relation to regulatory capacities), here we address the issue of levels of closure, each level consisting of a set of closed constraints which is either made of constituents or included in an encompassing system, themselves realising closure.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 143.
“Realising that there is a trade-off between the capacity for movement and the capacity for reproduction in single cells, Buss suggests that the appearance of gastrulation – where a hollow ball of cells is transformed into a multi-layered structure including diverse patterns of differentiated cells – was a crucial step in the origin of multicellular organisms. The idea was inspired by the observation that the cells of a metazoan can be either ciliated or prone to divide, but not both. In other words, the gastrula would be the ‘solution’ to this problem, with the cells on the surface remaining ciliated while those inside lose their cilia, so they can divide. Through gastrulation, cells begin to live in a more specific and spatially-organised environment, where migrated cells are surrounded by still-ciliated ones, which stay at the periphery of the group and provide the material and energy inflow required for the proliferation of the internal cells.
“Buss’ account, being consistent with natural selection (since cells find a way to maintain themselves and proliferate), can then be said to show that differentiation and integration processes go together.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 150-1.
“Inter-cellular signalling mechanisms….
“The plasticity, modularity, and robustness of the network…
“The degree of internal metabolic control over cell differentiation and cell division….
“Taken together, these features provide a relevant measure of the degree and kind of control exerted by higher-level functions on the development and differentiation of individual cells. In turn, this gives an indication of the ‘taking over’ of biological functions by the higher-level of organisation and, ultimately, of the degree of functional integration of the multicellular system as a whole. What matters from the autonomous perspective is that only those multicellular closed systems that have attained a sufficient threshold of collective functional integration are complex enough to realise higher-level autonomy. In particular, multicellular autonomous systems are those systems whose higher-level closed organisation includes the classes of functions required for autonomy, i.e. agential and regulatory.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 152, 153.
“… the relative dynamical decoupling of the nervous system means that the metabolism generates and sustains a dynamical system, while at the same time minimising its functional interactions with it.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 175.
“… the constitutive organisation of the organism underdetermines the activity of the nervous system, which rather depends on its internal dynamics and its embodied sensorimotor couplings with the environment. In a word, the biophysical specificity, high connectivity, embodiment, and situatedness of neural electrochemical dynamics make them largely independent (at least at the time scales relevant for describing functional sensorimotor interactions) from the underlying metabolic organisation….
“As a result, no other intercellular system even comes close to having the nervous system’s capacity to functionally correlate so many elements and, at the same, time to selectively modify their states so quickly. In this respect, the specificity of the nervous system is therefore its ability to generate an enormous variety of states (configurations) per unit of time, and to coordinate an immense number of state transformations simultaneously.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 175.
“In vertebrates, an important part of neural resources is devoted to controlling the metabolism through the ANS [autonomic nervous system], (through direct neural modulation of the functioning of different viscera, such as the circulatory and respiratory systems). In particular, the ANS can modify the pressure and flow of nourishing blood in different body areas and organs by means of direct neural control, contracting or dilating the vessel wall or adjusting pump (heart) functioning. The cardio-circulatory system, as mentioned, allows muscles to work in a quicker and more efficient way, which improves animal movements: as a consequence, the ANS allows the muscular system to mobilise a large body mass with speed and strength. This also implies a better control (through the highly efficient circulation of hormones, peptides, and other regulatory substances) of the metabolism of other internal organs (viscera), as well as a better modulation of different organs and their functions: digestion, respiration, sexual activity, etc…. Reciprocally, the development of this kind of circulatory system provided the adequate energetic maintenance of big neural concentrations, and, in particular, of encephalisation.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 181.
“From the perspective of the evolution of agency, the functional differentiation within the nervous system is what sets the conditions for conciliating its embodiment in the metabolism and the further increase of it dynamical decoupling….
“The differentiation between the ANS and SMNS [Sensorimotor nervous system] subsystems requires the establishment of new forms of coordination between them, which includes complex interactions with the environment, as well as with visceral and metabolic states.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 182, 183.
“… the appearance of emotion-based control in the organisation of the nervous system seems to be consistent with the claim put forward by Christensen according to which what is under selection when agency increases in complexity is the set of factors that account for the evolution of high-order control….
“According to this second author [Damasio], being aware of something would be the process of linking the sense of ‘self’ to a given stimulus or action. In other words, an animal is conscious as soon as it is aware that its actions and perceptions are related to its own body.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 184; references: Christensen, W.D. 2007. “Volition and cognitive control.” In: D. Spurrett, H. Kincaid, L. Stephens & D. Ross (eds). Distributed cognition and the will: individual volition and social context. pp. 255-287. MIT Press; Damasio, A.R. 1999. The Feeling of What Happens. NY: Harcourt Brace & Co.
“Two distinct structures of the nervous system play a crucial role in the emergence of consciousness: the limbic and the thalamocortical system. The first is fundamentally related with the regulation of the body, since it controls all information relayed from the body to the brain (and vice versa), including control of emotions. The second controls mainly sensorimotor tasks. The thalamus connects a variety of subcortical areas and the cerebral cortex, and its functions are related to the control of the sensory systems (except for the olfactory system), such as the auditory, somatic, visceral, gustatory, and visual systems. As mentioned above, the joint action of these two brain structures coordinate (by exerting a higher-level control over) the relations between the ANS and SMNS, allowing increasingly inclusive forms of functional integration of many local neural dynamics.
“How do these two systems actually achieve such global functional integration? A key concept is what Edelman calls ‘re-entrant signalling’, which synchronises these different neural ensembles. Their global functional integration results in the formation of a ‘coherent perceptual scene’ associated with emotional states.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 185; reference: Edelman, G.M. 1992. Brilliant Air, Brilliant Fire: On the Matter of Mind. NY: Basic Books.
“… we have argued that the development of an increasingly complex nervous system was enabled by a very specific body plan, namely, the vertebrate body plan, which allows fast, plastic, and strong movement at a larger size…. At a given stage of this evolutionary process (primary) consciousness appeared, which provided the capacity for a higher degree of hierarchical control over, and integration of, neural dynamics.
“As we shall explain next, once this evolutionary stage is reached, the closed organisation of the nervous system itself realises a distinct level of autonomy.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 187.
“… neurodynamic autonomy, consists in a self-regulated closed network of dependencies between neurodynamic structures. On the one hand, this closed network is linked to the sensorimotor couplings and, on the other hand, it monitors the body processes. The neurodynamic organisation must be able to perform these functions simultaneously while maintaining its own coherence by itself, likewise through internal higher-level control.
“In our own view this neurodynamic closed organisation satisfies also the criteria of autonomy because, (1) this neurodynamic closed organisation is self-regulated (it selectively modulates the neurodynamic structures); and (2) it is at the same time inextricably linked to the aforementioned conscious agency (the neural constraints governing sensorimotor couplings normatively contribute to the self-maintenance of the autonomous neurodynamic domain)….
“Now, following Barandiaran and Moreno, we claim that neurodynamic autonomy is the organisational ground for the cognitive domain. When neurodynamic autonomy is realised, the self-determination of the neural dynamic organisation becomes the source of the specific teleological and normative dimensions of its constitutive, agential, and regulatory functions of this domain, that is, the ‘locus’ of identity shifts from the metabolic and developmental level of organisation to the neural one….
“At least in its most minimal sense (that involving perception, memory, and emotion), cognition requires the adequate and complex balance between decoupling, embodiment, and control provided by neurodynamic autonomy.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. pp. 188-9; reference: Barandiaran, X. & A. Moreno. 2006. “On what makes certain dynamical systems cognitive.” Adaptive Behavior. 14:171-185.
“Social interaction has been defined as:
“a co-regulated couplinig between at least two autonomous agents, where: (1) the co-regulation and the coupling mutually affect each other, consituting an autonomous self-sustaining organisation in the domain of relational dynamics and (2) the autonomy of the agents involved is not destroyed (although its scope can be augmented or reduced).” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 190: subquote: De Jaegher, H., E. Di Paolo & S. Gallagher. 2010. “Can social interaction constitute social cognition?” Trends in Cognitive Science. 14:441-447. pp. 442-3.
“Conscious agency is the expression of a new form of autonomy because the structure of the regulatory controls that govern the behaviour of the animal is itself dependent on the maintenance of the functional sensorimotor actions triggered by them. Here again we see that ‘the being’ (in this case, the conscious mind) is ultimately dependent on its ‘doing’ (conscious, higher-level environmental sensitivity and goal-directed sensorimotor behaviour). But the maintenance of coherency between ‘being’ and ‘doing’ requires that the actions fulfil (species-dependent) epistemic norms.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 192.
“Our main claim is that the distinctive feature of biological organisms, which distinguishes them from any other natural system, is their autonomy…. In turn, the circular (teleological) relation between the existence and activity of the system provides a naturalised ground for normativity: its conditions of existence are the norms governing its activity. That is why biological organisms are literally auto-nomous, they generate by themselves – at least in part – the norms that they are supposed to follow.” Moreno, Alvaro & Matteo Mossio. 2015. Biological Autonomy: A Philosophical and Theoretical Enquiry. Springer. p. 196.
“According to functionalism (or externalism), living matter is a fundamentally passive entity that owes its organization either to external forces (functions that shape organs) or to an external agent (natural selection). Structuralism (or internalism), is the view that living matter is an intrinsically active entity that is capable of organizing itself from within, with purely internal processes that are based on mathematical principles and physical laws.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 412.
“The distinction between spontaneous and manufactured molecules allows us to divide the period that preceded the origin of the first cells into two great phases: a first period of chemical evolution during which organic compounds were formed exclusively by spontaneous reactions, and a second period of postchemical evolution, that started with the appearance of the first molecular machines and of the first manufactured molecules…. All spontaneous reactions are completely described by physical quantities (space, time, mass, temperature, etc.), whereas manufacturing processes can be fully accounted for only if we take into account additional observables like sequences and codes. Postchemical evolution, in short, is a stage of the history of life that came after chemical evolution but had not yet acquired the full characteristics of biological evolution.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 413.
“The simplest molecular machines that could appear spontaneously on the primitive Earth were bondmakers, molecules that could stick monomers together in a random order and produce statistical polymers….
“Statistical polymers could also be formed spontaneously, of course, but bondmakers had at least two important advantages. One is that they could produce polymers at an almost continuous rate thus enormously increasing their number on the primitive Earth. The other is that some bondmakers could acquire the ability to join monomers together no longer at random but in the order provided by templates. Those bondmakers, in short, started making copies of the templates and became copymakers…. with potentially unlimited numbers of copied molecules, in particular of nucleic acids.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. pp. 413-4.
“What is particularly important is that in most cases the functions of the RNAs are greatly enhanced by the attachment of even short peptides, and it is that combination that provides the real functional units. This is why all molecules formed by RNAs and by their combinations with peptides and proteins (ribopeptides and ribonucleoproteins) have been referred to as ribosoids, and the collection of all ribosoids in a system has been called the ribotype of that system….
“RNAs and peptides evolved together because one class of molecules provided bondmakers for the other.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 416.
“Ribonucleic acids and proteins can give origin not only to ribonucleoproteins and to large assemblies of ribonucleoproteins like ribosomes. They can also make giant scaffoldings made of tens of thousands of molecules and produce supramoleclular systems whose dimensions can reach the size of a small cell. The formation of these supramolecular clusters is based on self-organizing processes, so it could well have taken place in primeval solutions, particularly when these became enriched by RNA-driven synthesis of proteins and by protein-driven synthesis of RNAs. The limits to the dimensions of such clusters are anybody’s guess but the best example that we have today is represented by the nucleoli, and for this reason they have been given the name of nucleosoids….
“… clusters of ribosoids provide microenvironments which trap molecules and localise their interactions.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 417.
“The nucleosoids are, by definition, aggregates of ribosoids, but the statistical nature of their reactions implies that many other types of molecules could appear in them. As long as these non-ribosoidal components had only a temporary association with the nucleosoids, their presence was a sort of random noise and can be ignored. Eventually, however, some ‘contaminations’ proved to be useful for quasi-replication purposes, and that set in motion a process that turned them into stable components of the system. The nucleosoids evolved in this way into structures that became permanently associated with non-ribosoidal components, a process that can be summarized by saying that the nucleosoids became heterogeneous nucleosoids or heterosoids….
“In addition to DNA, there was at least another class of molecules that was likely to become associated with nucleosoids [lipids].” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 418.
“One of the most important characteristic of the lipid membranes is their ability to act as catalysts in a variety of reactions such as ion transport and signal transduction. In particular, they can incorporate pigment molecules that capture the energy of light and set in motion those chains of energy transduction processes that eventually led to photosynthesis and respiration.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 419.
“… let us reacall that amino acids are divided into four great groups (acidic, basic, hydrophilic and hydrophobic) by the chemical properties of their side chains, and it is the sum total of these groups that determine the overall chemical properties of the proteins….
“Statistical proteins could not function as specific enzymes, but could provide structural support, could modify the local microenvironment, and above all could maintain the systems in a state of continuous metabolic activity. In those circumstances, a change in the coding rules would have changed the overall physico-chemical conditions of the primitive systems and therefore their ability to grow and to split. Different RNAs, for example, would have favoured the synthesis of different families of statistical proteins, thus promoting group-properties rather than individual features….
“We conclude that in the last phase of postchemical evolution, the first genetic code probably arose as a set of rules that were affecting the collective properties of the primitive systems.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 421.
“The RNAs and the proteins that appeared spontaneously on the primitive Earth produced a wide variety of ribosoids, some of which were synthesizing ribosoids whereas others were ribogenes and others were riboproteins (or ribozymes). The systems produced by the combination of all these molecules, therefore, had a ribotype, a ribogenotype and a ribophenotype. Eventually, evolution replaced the ribogenes with genes and the riboproteins with proteins but the synthesizing ribosoids of the ribotype have never been replaced. This shows not only that the ribotype is a distinct category of the cell but also that it is a category without which the cell simply cannot exist.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 423.
“It is an experimental fact, at any rate, that every cell contains a system of RNAs and ribonucleoproteins that makes proteins according to the rules of an organic code, and that system can be described therefore as a code-and-template-dependent-protein-maker, i.e., as a codemaker. That is the third party that makes of every living cell a trinity of genotype, phenotype, and ribotype.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 424.
“In transcription, a DNA sequence is used as a template to assemble an RNA sequence, and in this case a normal biological catalyst (an RNA polymerase) is sufficient, because each step requires a single recognition process. In translation, instead, two independent recognition processes must be performed at each step (one for a codon and the other for an amino acid), and the assembling system (the ribosome) needs special molecules, first called adaptors and then transfer RNAs, in order to associate codons to amino acids.
“This conclusion should now be generalized. We are accustomed to thinking that all biochemical processes are catalyzed reactions, but in reality we should sharply distinguish between catalyzed and codified reactions. Catalyzed reactions are processes (like transcription) that require only one recognition process at each step, whereas codified reactions require (like translation) two independent recognition processes at each step and a set of coding rules.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 424.
“… any code is a set of rules that create a correspondence between the objects of two independent worlds, which means that it is necessarily implemented by structures that perform two independent recognition processes at each step. The genetic code, for example, is a set of rules that link the world of nucleotides to the word of amino acids, and its adaptors are the transfer-RNAs. The adaptors are required because there is no necessary link between the two worlds, and a set of rules is required in order to guarantee the specificity of the correspondence.
“The adaptors, in short, are the key molecules in all organic codes.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 424.
“It is an experimental fact, at any rate, that Archaea, Bacteria and Eucarya have three different types of membranes and three distinct signalling systems, and this brings us to the idea that the three cell domains came into being by the combination of the universal genetic code with three distinct signal-transduction codes. This amounts to saying that a modern cell design requires at least two organic codes: a genetic code for protein synthesis and a signal transduction code for a context-dependent behaviour. The three primary kingdoms of life, in other words, were the result of three independent attempts performed by the descendants of the common ancestor to evolve a signal transduction code.
“We realize in this way that the genetic code was instrumental to the origin of life and that the signal transduction codes were instrumental to the origin of the modern cell designs. In these two cases, in other words, there has been a deep relationship between organic codes and the great events of macroevolution.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. pp. 425-6.
“The molecules responsible for HGT are nucleic acids (RNAs and DNAs) that are produced by copying and that survive by invading any system that is capable of copying them. They represent a form of life based on ‘copying alone’ and since this is the logic of the viruses we can give them the collective name of ‘viroidea’. Archea and bacteria are cellular systems that are based on copying and coding, but have adopted a streamlining strategy that prevented them from developing new organic codes. They represent a second form of life, known as ‘prokarya’, and is based on ‘copying and limited coding’. Other cells, the ‘eukarya’, have maintained the potential of the ancestral precellular systems to explore the coding space and represent a third form of life based on ‘copying and unlimited coding’.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 432.
“It [autopoiesis] does not explain, for example, the fact that during embryonic development the cells become different from their progenitors. It does not tell us why cells can do something that is very distant from autopoiesis: they can suicide themselves.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 433.
“We know virtually nothing of the common ancestor, but the molecular data tell us that it had at least three types of RNAs one of which was able to join peptides together into polypeptides. Before the origin of the genetic code, that ancestral ribonucleoprotein system, or ribotype, was still in the process of evolving its coding rules and was therefore a code exploring system. After the origin of the genetic code, however, the situation changed dramatically. No other modification in coding rules was tolerated and the cell became a code conservation system. From that moment onwards, the quintessential point, the true constant in the history of life, was the imperative to conserve the rules of the genetic code.
“Some cells, furthermore, maintained the potential to develop other coding rules and gave origin to a new code exploring system. The ancestral Eukarya, for example, had a code conservation part for the genetic code, but also a code exploring part for the splicing code. This tells us that the eukaryotic cells had to solve two distinct problems:
“(1) the first is a code conservation problem: the cells managed to conserve their organic codes for billions of years despite the fact that all their genes were subject to continuous mutations,
“(2) the second is a code exploring problem: some cells managed to maintain the potential to explore the coding space and to give origin to new organic codes.
“We realize in this way that what is really important in the cell is two things: one is the ability to conserve its organic codes and the other is the potential to evolve new ones. This gives us an entirely new definition of the cell that can be expressed in this way: ‘the cell is a system that is capable of creating and conserving its own codes’.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 433.
“A variation in a coding rule changes instead the meaning of that rule. The great difference that exists between copying and coding, and therefore between natural selection and natural conventions, comes from the difference that exists between ‘information’ and ‘meaning’.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 435.
“There are, in short, three major differences between copying and coding: (1) copying acts on individual objects whereas coding acts at the collective level, (2) copying modifies existing objects whereas coding brings new objects into existence, and (3) copying is about biological information whereas coding is about biological meaning. All of which means that there are two distinct types of evolutionary change in life: evolution by natural selection, based on copying, and evolution by natural conventions, based on coding.” Barbieri, Marcello. 2012. “Code Biology – A New Science of Life.” Biosemiotics. 5:411-437. 10.1007/s12304-012-9147-3. p. 435.
“The long, flat portion of the supply curve [global output on x axis and average prices adjusted for inflation on the y axis] corresponds to the introduction of incremental productive capacity from emerging economies [little vertical rise in prices]. Think of this as the early days of a country engaging with the world economy with a deep bench of untapped labour. As global demand grows and the accessible store of previously unused labour declines, the supply curve eventually turns up [prices rise but output does not increase that much]. The easy gains go away and things become more expensive.
“Much of the growth in the early stages comes from moving surplus labour in traditional sectors such as agriculture into the modernising urban sector. Productivity jumps as people cross that boundary. But eventually any country, no matter the size, runs out of surplus labour. The range in which the declining supply of surplus labour produces an upturn in the supply curve is called ‘Lewis turning point’, named after the Noble Laureate economist Sir W. Arthur Lewis, whose work illuminated these patterns.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. pp. 66-7.
“Ageing economies account for the vast majority of the global economy today, delivering 78 per cent of global economic output with only 34 per cent of the global population.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. pp. 67-8.
“If the goal is to delay the arrival of the global version of the Lewis turning point – a moment when economic growth gets trapped, slows, or worse, declines – then the biggest opportunity to restore global growth momentum lies in lower income countries, many of which are in Africa. In a supply-constrained world, this would be mutually beneficial for both consumers seeking price relief and African economies hoping to grow incomes and enter into the global economy.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. pp. 68-9.
“It is puzzling why more countries have not pursued the model of a formal ‘national economic council’ (NEC) that resides in the executive branch of government alongside less insular central bank decision-making. The key function of an NEC-like structure is to inform, influence and, in some instances, impose outcomes on the multiple agencies that implement bottom-up individual economic policies on a daily basis.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 164.
“In the same way that from 1945 to the 1970s tariffs and fixed currencies limited the spread of globalisation in advance of the era of hyper-globalisation that opened the world up to a free-for-all, now new tariffs and non-tariff barriers are once again defining the limits and extent of globalisation.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 202.
“A 2021 report from the Financial Stability Board estimates that NBFIs [non-bank financial intermediaries operating outside the jurisdiction of financial authorities like the Federal Reserve with depositor funds unprotected and balance sheets mostly escaping supervision and regulation] account for roughly 50 per cent of global financial assets worth more than $200 trillion dollars. This is one graveyard the world can’t afford to whistle past.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 260.
“Asymmetric information has been the cause of, or the contributing factor to, multiple crises. In the run-up to the Global Financial Crisis [2007-8], different stakeholders with different degrees of information on bad debt, problematic leverage and terrible market bets capitalised on the lack of information held by the counterparty.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 261.
“What the world desperately needs is a vision of a well-managed globalisation.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 281.
“It’s time to build economic resilience – a product of the proposals just covered… which will in turn leave the world better prepared for more frequent and violent external shocks. And the cost of sustainability must be calculated in fiscal policy. We know the price tag of a more sustainable economy – that’s a more than $4 trillion annual bill…. The cost of inaction is far greater than action, and this reality must shape how the world spends.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 291.
“We need to first recognise what it really means when we no longer think of ourselves just as a set of national economic islands sufficient unto ourselves but rather part of a global system that has to be made to work.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 292.
“The World Bank can and should expand its mandate to take on global public goods, a mission which will necessitate an expanded capital base. The IMF must broaden its scope beyond lender of last resort and better perform the all-critical function of global surveillance body. Both institutions must shed the feudal practice of reserving their leadership positions for certain nationalities. The G20 should have a durable secretariat that ensures better continuity as the presidency rotates from country to country. And the WTO and UN Security Council should be reformed to less resemble a Western-led club and instead a truly global coalition.” Brown, Gordon, Mohamed A. El-Erian & Michael Spence. 2023. Permacrisis: A Plan to Fix a Fractured World. London: Simon & Schuster. p. 293.
“Briefly, in this paper, (i) we demonstrate the self-assembly of large RNA catalytic molecules from constituent smaller fragments inside charge-rich coacervates (ii) this assembly can be achieved in both self-autocatalytic and collective cross-catalytic fashion, allowing us to form ACSs [autocatalytic reaction networks] within coacervates, (iii) these ACS confer a chemical compositional identity to the coacervate compartments, and (iv) despite the lack of an impermeable boundary, the compartments transiently protect the enclosed reaction networks (and by extension, the chemical identity) from external perturbation. Altogether, by combining RNA autocatalytic networks with dynamic phase-separated coacervate compartments, our work opens the possibilities for reacting primitive chemical units, that can participate in self-reproduction, growth, and division and adaptive evolution.” Ameta, Sandeep, Manoj Kumar, Nayan Chakraborty, Yoshiya J. Matsubara, Prashanth S, Dhanush Gandavadi & Shashi Thutupalli. 2023. “Multispecies autocatalytic RNA reaction networks in coacervates.” Communications Chemistry. 6:91. 10.1038/s42004-023-00887-5. p. 2.
“The Azoarcus ribozyme, WXYZ, is an ~200 nucleotide RNA which can be split into inactive RNA fragments of varying lengths (two fragments, four fragments, five fragments). These fragments can covalently assemble in full-length active ribozymes in the presence of Mg2+ ions using both catabolic and anabolic approaches via recombination reactions. The assembly occurs in an autocatalytic manner i.e. the self-assembled ribozymes catalyze the subsequent assembly of fragments into other functional ribozymes to form autocatalytic networks capable of collective reproduction.” Ameta, Sandeep, Manoj Kumar, Nayan Chakraborty, Yoshiya J. Matsubara, Prashanth S, Dhanush Gandavadi & Shashi Thutupalli. 2023. “Multispecies autocatalytic RNA reaction networks in coacervates.” Communications Chemistry. 6:91. 10.1038/s42004-023-00887-5. p. 2.
“Integrating RNA autocatalytic reaction networks with coacervate compartments, brings together four important conceptual frameworks related to the emergence of a protocell from a ‘primitive’ chemical system: (i) the RNA world hypothesis or more broadly, the dynamics of sufficiently long, information carrying catalytic molecules capable of participating in complex reactions and evolving in complexity, (ii) autocatalytic reaction networks, which possess all the attributes required of a simple chemical system to display the properties of robustness, heritability and evolvability, (iii) dynamic compartmentalization via coacervation which serves to spatiotemporally localize chemistries, and (iv) proposition from Freeman Dyson that the Oparin-like compartments could endow self-reproducing reaction networks and undergo Darwinian evolution.” Ameta, Sandeep, Manoj Kumar, Nayan Chakraborty, Yoshiya J. Matsubara, Prashanth S, Dhanush Gandavadi & Shashi Thutupalli. 2023. “Multispecies autocatalytic RNA reaction networks in coacervates.” Communications Chemistry. 6:91. 10.1038/s42004-023-00887-5. p. 7.
“The aim of this paper is to show that information has not its own causal power besides that of matter…. The rationale is based on two arguments:
“1. Causation can produce (and erase) information, but causal chains cannot go across spatial scales.
“2. Assuming that information can flow over many spatiotemporal scales, it cannot produce causation.
Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. p. 4.
“Information can be collected, stored, transmitted, and copied, but causation cannot.” Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. p. 4.
“We can never return to the same event in time. The primary difference between cause and reason is the fact that cause is an event that directly leads to something, whereas reason is a logical explanation for why something happened in the past and can happen in the future. What follows is that causal reasoning requires counterfacturals of the sort ‘what if’ while every particular cause occurs in the observer’s present (‘just now’) and is unique in the physical world that has no counterfactural worlds. Thus, we must distinguish between an ontological cause (a matter of being) and an epistemic reason (a matter of knowledge) inferred logically.” Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. p. 4.
“Ironically speaking, an observer, knowing only the atomic (or quantum) scale, could not in principle become a biologist.” Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. p. 9.
“Water is a weakly emergent property of hydroxides. Two or more hydroxide molecules are not sufficient to produce water. Their number must be large enough in order to cause emergent self-organization (very primitive but above Brownian motion in gas) that is responsible for fluidity and viscosity.” Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. p. 11.
“A canonical example [of weak emergence] is the murmuration of starlings, each placed in the elementary basis of observation. As the behavior of each bird at the microscale depends on the behaviors of its neighbors in this elementary basis, there is no autonomy for them there. The trajectory of any single member would show only chaotic behavior. Autonomy and self-organization emerge spontaneously from their collective dynamics at the macroscale as if having a ‘life of its own.’
“In this case, biological relativity or, more generally, all theories of strong emergence should argue that upward causation originates from the given elementary basis, whereas downward causation comes from the environment, or even that the flock’s self-organized ‘life of its own’ can have causal power over any single starling. Is it the case? No. This form of strong emergence occurs only in the eyes of an observer where information generates an illusion of causal power acting on the flock. Varley, for example, calls this form of (weakly) emergent autonomy and self-organization, balancing on the edge between the flock and its environment, ‘flickering’. It is enough for all the starlings to suddenly scatter in separate directions, each flying on its own (perhaps in response to a swooping hawk), and the flock’s autonomy and self-organization observable at the macroscale will vanish together with spurious upward/downward causation by merely breaking down to the elementary basis….
“The ‘flickering effect’ of the murmuration of starlings is probably the best example showing that information does not produce causation. The murmuration results from synergistic information that emerges from the spontaneous self-organization produced by the relationships among the birds.” Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. pp. 17, 22; reference: Varley, T.F. 2023. “Flickering Emergences: The Question of Locality in Information-Theoretic Approaches to Emergence.” Entropy. 25:54.
“Ultimately, weak emergence amounts to triviality with respect to the fact that the universe itself we live in and observe is a hierarchically organized emergent phenomenon. There are no complex systems at the fundamental Planck scale. All things, minds, and events emerge at larger scales.” Yurchenko, Sergey B. 2023. “Is information the other face of causation in biological systems?” BioSystems. (Preprint) 10.31219/osf.io/5avr6. p. 27.
“The key point is that the first genetic code was necessarily ambiguous because nothing could prevent a codon from coding two or more amino acids. This means that a sequence of codons was translated some time into a protein and some other time into a different protein, and the apparatus was inevitably producing statistical proteins.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 12.
“Ribosomes are formed by self-assembly from their components, and it has been possible to discover the contribution of individual ribosomal proteins by studying what happens when ribosomes are reassembled without anyone of them in turn. These experiments have shown that the ribosmal proteins fall into three major groups: some are necessary for function, others are required for self-assembly, and those of the third group have a stimulating effect but are fundamentally disposable.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 12.
“The ambiguity of the genetic code, in other words, was the limiting factor that determined how many families of statistical ribosomal proteins could reappear in the descendants. Which means that only by lowering the ambiguity of the code it was possible to promote the evolution of the ribosomal proteins….
“It will be noticed that the evolution of the ribosomal proteins was not about this or that protein or this or that protein function. It was involving all ribosomal proteins at the same time. It was not about individual features but about collective relationships. It was the evolution of a systems as a whole, an evolution that went on until the ambiguity of the genetic code was completely removed and biological specificity in protein synthesis came into existence.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 13.
“The modern genetic code is a mapping between 64 codons carried by transfer-RNAs and 20 amino acids carried by 20 aminoacyl-tRNA-synthetases, each of which attaches one amino acid to one or more tRNAs. The synthetases are specific proteins that can be produced only by an apparatus that already has a genetic code, and this gives us a class chicken-and-egg paradox….
“A possible solution is that the modern apparatus of protein synthesis was preceded by an ancient apparatus where the amino acids were attached to the transfer-RNAs not by proteins but by RNAs. The modern genetic code, in other words, was preceded by an ancient genetic code based on RNA-synthetases that were later replaced by protein-synthetases….
“Whatever did happen in the optimization phase, it seems that the introduction of protein synthetases in protein synthesis not only replaced the ancient genetic code with the modern one, but provided the conditions for optimizing its performance, a process that gave origin to a genetic code of extreme virtuosity and the accuracy of protein synthesis became so high as to be virtually error-free.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 13.
“When the ambiguity of the genetic code was completely eliminated, the ancestral systems acquired the ability of producing specific proteins. At that point they could have employed these proteins for the same functions as the previous statistical proteins, but in reality they did something completely different. They started using specific proteins for entirely new functions or for functions that were previously performed by the RNAs, and in this way initiated a revolution that eventually transformed the ancient RNA world into the modern protein world. Once in existence, in other words, the genetic code set in motion a massive change in macroevolution, a true major transition in the history of life.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 13.
“The genetic code is the set of rules that the apparatus of protein synthesis employs to make proteins, and yet there is a profound difference between the evolution of the genetic code and the evolution of the apparatus of protein synthesis. The genetic code has been highly conserved since its origin almost 4 billion years ago, whereas the apparatus of protein synthesis has continued to evolve and to change.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 14.
“We need therefore to understand how does the brain produce the mind and today the major scientific theories that have been proposed on this issue can be divided into four groups.
“(1) The computational theory is the idea that lower-level brain processes are transformed into feelings and instincts by neural processes that are equivalent to computations.
“(2) The connectionist theory maintains that the brain is solving problems by means of neural networks that operate with explorative strategies, and feelings and instincts arise as side-effects of these networks.
“(3) The emergence theory states that higher-level brain properties emerge from lower-level neurological phenomena, and mind is distinct from brain because any emergence is accompanied by the manifestation of new properties.
“(4) The code theory is the idea that there has been a neural code at the origin of mind as there has been a genetic code at the origin of life….
“According to the code theory, feelings and instincts are not the side-effects of neural networks (as in connectionism), they do not come into existence by emergence, and they are not the result of computations. They are manufactured from lower-level brain processes according to the rules of the neural code just as proteins are manufactured from amino acids according to the rules of the genetic code. In the framework of the code theory, in other words, feelings and instincts are manufactured brain artifacts, whereas according to the other theories they are spontaneous brain products.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 14.
“The nervous system is made of three types of neurons: (1) the sensory neurons transmit to the brain the signals produced by the sense organs, (2) the motor neurons deliver signals from the brain to the motor organs (muscles and glands), and (3) the intermediate neurons provide a bridge between them. In some cases the sensory neurons are directly connected to the motor neurons, thus forming a reflex arch, a system that produces a quick stimulus-response effect known as reflex action….
“Once in existence, however, in addition to transmitting electrical signals they started processing them and this new function fuelled their evolution into increasingly complex systems. This is because the behaviour of an animal must take into account a variety of cues from the environment, and to that purpose it is necessary that a motor organ receives signals from many sense organs and that a sense organ delivers signals to many motor organs.
“The intermediate neurons solved that problem by developing multiple connections between sensory inputs and motor outputs….
“It must be underlined that all sense organs send to the brain the same electrical signals (in the form of trains of action potentials) and could, in principle, evoke the same reactions. Today this does not happen because in embryonic development the intermediate neurons go through processes of differentiation that allow them to respond in different ways to the same signals that come from different organs.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. pp. 14-5.
“The diversification in embryonic development is necessary because it is only that process that allow the intermediate neurons to respond in different ways to the same electrical signals that come from different sense organs. This incidentally, has an outstanding theoretical implication: the fact that the intermediate neurons diversify their responses during embryonic development means that those responses can be modified according to need and are therefore based on arbitrary rules; which amounts to saying that a neural code does exist in the intermediate brain.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 15.
“This [the first person experience of seeing a tree in the outside world rather than on the retina or in the brain] tells us that first-person experiences are nothing elementary and indivisible. On the contrary, they are the result of complex operations where highly differentiated cells act in concert to create a physiological short-circuit between body and brain, between observer and observed, between senders and receivers of neural signals….
“The origin of the neural code, in other words, set in motion a true biological revolution, a major transition that transformed the unconscious brain of the ancestral animals into the feeling brain of the modern animals. The result was an absolute novelty: it was the origin of consciousness, the origin of subjectivity, the origin of first-person experiences, in short, the origin of mind.
“This is the code theory of mind, the idea that there has been a neural code at the origin of mind as there has been a genetic code at the origin of life.” Barbieri, Marcello. 2019. “A general model on the origin of biological codes.” BioSystems. 181:11-19. 10.1016/j.biosystems.2019.04.010. p. 16.
“The eponymous two-component signaling pathway contains a sensor histidine kinase and a cognate response regulator. Upon receipt of a stimulus, the histidine kinase typically catalyzes an autophosphorylation reaction on a conserved histidine residue. This phosphoryl Group is then transferred to a conserved aspartate on a cognate response regulator. Phosphorylation of the regulator usually drives a conformational change that activates its output response, often leading to changes in gene expression.” Capra, Emily J. & Michael T. Laub. 2012. “The Evolution of Two-Component Signal Transduction Systems.” Annu. Rev. Microbiol. 66:325-347. 10.1146/annurev-micro-092611-150039. p? (bootleg). 326.
“Changes in response regulator outputs may also frequently occur after duplication or lateral transfer events. For gene duplication, changes in the output response of one or both regulators is likely a critical step in the establishment of new functions and, consequently, the maintenance of the duplicated proteins. For instance, in E. coli, a duplication event likely gave rise to the paralogous systems NarX-NarL and NarQ-NarP which respond to nitrate and nitrite in anaerobic conditions. While the regulators NarP and NarL share significant similarity and even recognize highly similar consensus binding sites, divergent evolution has enabled each response regulator to recognize different promoter architectures and to activate different genes. The duplication of the Nar two-component system has thus led to an increase in complexity of the transcriptional control of genes necessary for growth in anaerobic conditions.” Capra, Emily J. & Michael T. Laub. 2012. “The Evolution of Two-Component Signal Transduction Systems.” Annu. Rev. Microbiol. 66:325-347. 10.1146/annurev-micro-092611-150039. p? (bootleg). 333.
“CH4 + 2O2 -> CO2 + 2H2O + energy (heat and light)
“… this chemical energy is due to the instability of the arrangements of the elements in CH4 + 2O2 compared with those of CO2 + 2H2O. (Chemical energy is, in fact, an electrostatic storage of energy in relatively unstable bonds.)” Williams, R.J.P. & J.J.R. Frausto da Silva. 2006. The Chemistry of Evolution: The Development of our Ecosystem. Elsevier. pp. 78-9.
“Atoms can also be ordered by forming compounds which restrict their motion, so that a compound of many atoms such as a polymer of An units is more ordered than n.A separate A units. Even in a reaction such as the formation of ammonia
N2 + 3H2 ⇄ 2NH3
there is less order in N2 + 3H2 than in 2NH3 since there are more units to the left to be disordered. The compound NH3 has more bound atoms per molecular unit; however, it has also a higher binding, chemical stability, related to the electrostatic interactions of electrons and nuclei. At low temperature, NH3 is the more stable state. In fact, there can be nearly 100% NH3 if this molecule is at a low enough temperature. At higher and higher temperatures, as disorder of all molecules increases, the weighted disorder of the state N2 + 3H2 is more favoured.” Williams, R.J.P. & J.J.R. Frausto da Silva. 2006. The Chemistry of Evolution: The Development of our Ecosystem. Elsevier. p. 81.
“However, since late antiquity, especially since the writings of Galen, an ‘organic body’ was understood as an integrated system in which the parts mutually depend on one another.” Toepfer, Georg. 2024. “‘Organization’: Its Conceptual History and Its Relationship to Other Fundamental Biological Concepts.” From: Organization in Biology. Mossio, Matteo (ed). pp. 23-40. Springer. p. 24.
“Starting with mechanistic models of vital processes in the second half of the seventeenth century, ‘organization’ and ‘life’ were increasingly used interchangeably. Since the end of the eighteenth century, ‘organization’ has thus predominantly been understood as a characteristic of living beings, becoming a signal word for the animate world and its scientific analysis.” Toepfer, Georg. 2024. “‘Organization’: Its Conceptual History and Its Relationship to Other Fundamental Biological Concepts.” From: Organization in Biology. Mossio, Matteo (ed). pp. 23-40. Springer. p. 24.
“In the 150 years between 1650 and 1800, which could be viewed as the formative period of biology, the ancient principle of life, the ‘soul,’ was gradually replaced by ‘organization.’” Toepfer, Georg. 2024. “‘Organization’: Its Conceptual History and Its Relationship to Other Fundamental Biological Concepts.” From: Organization in Biology. Mossio, Matteo (ed). pp. 23-40. Springer. p. 27.
“According to Polanyi, an organism has the same general makeup as a machine: its bodily structure serves as a boundary condition harnessing physical-chemical processes.” Toepfer, Georg. 2024. “‘Organization’: Its Conceptual History and Its Relationship to Other Fundamental Biological Concepts.” From: Organization in Biology. Mossio, Matteo (ed). pp. 23-40. Springer. p. 35; reference: Polanyi, M. 1968. “Life’s Irreducible Structure.” Science. 160:1308-1312.
“Thus, morphology, the study of forms, is the fundamental explanatory principle of biology. It has always been fairly easy for biologists to identify functions in living beings….
“Organic forms, then, are the mediators for the realization of biological organizations. They instantiate these organizations in specific living bodies; in their function as particular ‘constraints,’ they enable the causal interdependence of the components and the self-referentiality of the whole system. Thus, ‘organization’ and ‘form’ are two complementary aspects of living bodies: the first refers to the causal pattern that constitutes the unity of the system and the second to the individuality of the system and the specific material ‘constraints’ by which this causal pattern is realized and instantiated in concrete living beings.” Toepfer, Georg. 2024. “‘Organization’: Its Conceptual History and Its Relationship to Other Fundamental Biological Concepts.” From: Organization in Biology. Mossio, Matteo (ed). pp. 23-40. Springer. p. 36.
“Our discussion of Canguilhem and Kant, which calls for a focus on logic in matters relating to organization in biology, suggests that the crisis of ‘knowledge about’ requires a more critical viewpoint on what can be qualified as a knowing subject. Insofar as one wishes to take on board the Kantian premise that the knowable is always for us, never in itself, the most straightforward move to make is to include, in the heart of conceptuality, the knowing subject’s participation in living dynamics. More precisely, both the living organism and the knowing subject seeking to describe the living organism [another organism; the predicate or object of knowing] appear to be characterized by an internal logic of reciprocity.” Van de Vijver, Gertrudis & Levi Haeck. 2024. “Judging Organization: A Plea for Transcendental Logic in Philosophy of Biology.” From: Organization in Biology. Mossio, Matteo (ed). pp. 59-84. Springer. p. 61.
“[Canguilhem:] ‘One cannot defend the originality of the biological phenomenon, and consequently the originality of biology, by demarcating within the physico-chemical territory–that is, within the milieu of inertia, of externally determined movements–enclaves of indetermination, zones of dissidence, or foyers of heresy. If one is to assert the originality of the biological, this must be in terms of the originality of one realm over the whole of experience, and not over islets of experiences. In the end, classical vitalism was, paradoxically only in its excessive modesty, in its reluctance to universalize its conception of experience. Once one recognizes the originality of life, one must comprehend matter within life, and the science of matter–which is science itself–within the activity of the living.’” Canguilhem, G. 2008. “Aspects of vitalism.” In: P. Marrati & T. Meyers (Eds.) Knowledge of Life. pp. 59-74. Fordham UP. p. 70; taken from: Van de Vijver, Gertrudis & Levi Haeck. 2024. “Judging Organization: A Plea for Transcendental Logic in Philosophy of Biology.” From: Organization in Biology. Mossio, Matteo (ed). pp. 59-84. Springer. p. 67.
“One of Kant’s central ideas in the first Critique is that analysis always presupposes synthesis: if we are to analyze the material world, we have to presuppose that it is always already synthesized following certain rules…. In other words, if knowledge of an object can generally be dissected into a conceptual constituent on the one hand and a sensory constituent on the other, this means that an object is as such made possible by a synthesis of sensibility and conceptuality….
“Turning the manifoldness of our sensory representations into an object is only possible by making an appeal to the opposite thereof, namely, the unity of concepts. Thus, the concept is constitutive of the object on account of the fact that it unifies the manifold of intuition delivered in sensibility. Objectification requires overcoming heterogeneity while being indicative of it. It is only through objectification that heterogeneity itself is retrospectively revealed…. Kant stresses quite elaborately in this respect that the act of homogenizing is a matter of judgment: judgment is the activity that relates concepts to sensible intuitions.” Van de Vijver, Gertrudis & Levi Haeck. 2024. “Judging Organization: A Plea for Transcendental Logic in Philosophy of Biology.” From: Organization in Biology. Mossio, Matteo (ed). pp. 59-84. Springer. pp. 71-2.
“While attempting to formulate objective judgments about living organization, we must not trivialize the assumption that our capacity to judge is (self-)organized too. It involves an internal reciprocity between heterogeneous elements, which highlights a certain purposefulness in its tendencies. A structural drive to connect our sensible representations with conceptual ones in judgments functions as the motor behind our rational endeavors and intentions. In this regard, Canguilhem’s theory of the ‘broken judgment’ eloquently captures to what extent judgment is structurally torn between a conceptual, universal realm (the reality judgment) and a sensible, singular one (my judgment). Confronted with nature’s infinite specificity and particularity (not excluding self-organizing beings), the attempt to unify sensible representations according to concepts or universal laws ultimately fails. This then breaks judgment in two and leaves us, as Kant would have it, with the distinction between ‘reflective’ and ‘determinative’ judgements.
“In this regard, our take-home message is that the judging, knowing human being–according to the philosophical tradition, the conscious holder of all sorts of intentions–is subject to, rather than a subject over and above, its rational capacities. The subject is perhaps not so much an agent that simply makes use of these capacities in view of acquiring knowledge about the world–for instance, while judging organization in nature. Rather, it is condemned to use these capacities on the grounds that it is a judging organization.” Van de Vijver, Gertrudis & Levi Haeck. 2024. “Judging Organization: A Plea for Transcendental Logic in Philosophy of Biology.” From: Organization in Biology. Mossio, Matteo (ed). pp. 59-84. Springer. pp. 81-2.
“‘Organization’ has a narrow and a wide usage. In its narrow usage – n-organization – it means possessing internal, nested correlations of the general sort illustrated above in the Krebs cycle and car engine. In its wide usage, ‘organization’ means no more than ‘is in some respect, to some degree, systematic,’ as in having a well-organized work desk.” Hooker, Cliff. 2024. “On the Organizational Roots of Bio-cognition.” From: Organization in Biology. Mossio, Matteo (ed). pp. 85-102. Springer. p. 87.
“… self-organization is best conceived as a process leading to the emergence of new constraints, whether or not they produce n-organization and whether or not there is an active self involved.” Hooker, Cliff. 2024. “On the Organizational Roots of Bio-cognition.” From: Organization in Biology. Mossio, Matteo (ed). pp. 85-102. Springer. p. 87.
“Essential work [for living things as thermodynamic engines] is of three kinds: (i) the repair or replacement of internal infrastructure, including of any enclosing membrane, and of the capacity for suitable work, (ii) the support of action in the environment, and (iii) the export (elimination) of wastes. This is already an n-organizational arrangement, focused around two cycles, an external interaction cycle with the environment comprising resource extraction and waste elimination and internal action cycle comprising repair and replacement.” Hooker, Cliff. 2024. “On the Organizational Roots of Bio-cognition.” From: Organization in Biology. Mossio, Matteo (ed). pp. 85-102. Springer. p. 89.
“Self-directedness and anticipativeness are two fundamental cognitive capacities harbored by autonomy. Mutually supporting one another, these capacities form the central cognitive process of self-directed anticipative learning (SDAL). SDAL in turn provides the foundation of the deepest, most powerful forms of problem-solving, that is, of cognition, and of tracking, that is, of intentionality. Thus, intention and cognition are provided their common n-organizational root.” Hooker, Cliff. 2024. “On the Organizational Roots of Bio-cognition.” From: Organization in Biology. Mossio, Matteo (ed). pp. 85-102. Springer. p. 93.
“Reflex and random actions aside, every action anticipates its outcome. At its most primitive, anticipation is the forming (learning) of a simple association between current features and an outcome of an action. The bee dance anticipates re-locating ephemeral nectar supplies as outcome; it would not be attended to unless that outcome and its attendant resource availability were frequently enough the consequence of the dance.
“Anticipative learning is where the organism learns to anticipate a goal achievement by employing an action sequence, thus associating receiving goal satisfaction with doing an action sequence.” Hooker, Cliff. 2024. “On the Organizational Roots of Bio-cognition.” From: Organization in Biology. Mossio, Matteo (ed). pp. 85-102. Springer. p. 94.
“We argue that from an organizational perspective, development is a regulatory process that changes the number or types of functions of a regime of closure of constraints.” Bich, Leonardo & Derek Skillings. 2024. “There Are No Intermediate Stages: An Organizational View on Development.” From: Organization in Biology. Mossio, Matteo (ed). pp. 241-262. Springer. p. 243.
“Accounts of development focused on achieving reproductive capabilities as the end point of the [life cycle] process fail to be satisfactory when dealing with integrated symbiotic assemblages. These are systems where developmental phenomena appear to be present in the more comprehensive system (the assemblage) but that do not reproduce at the level of the comprehensive system.” Bich, Leonardo & Derek Skillings. 2024. “There Are No Intermediate Stages: An Organizational View on Development.” From: Organization in Biology. Mossio, Matteo (ed). pp. 241-262. Springer. pp. 248-9.
“Development is qualitatively different from other regulatory processes because it does not operate only on available functions but also changes the set of functions available to the system. At each developmental step, some new functional traits are generated, such as in the appearance of new tissues, organs, or limbs…. Functional traits might also be shed. Think of the transition between tadpole and frog, with the appearance of legs and lungs and the disappearance of gills and tail. These changes are different from the activation or inhibition of mechanisms which are already present in the system, and they affect the way the multicellular organization maintains itself in its new regime of closure.
“Developmental regulatory change on this picture is not necessarily irreversible. Not does it imply that development necessarily tends toward some future adult state.” Bich, Leonardo & Derek Skillings. 2024. “There Are No Intermediate Stages: An Organizational View on Development.” From: Organization in Biology. Mossio, Matteo (ed). pp. 241-262. Springer. pp. 256-7.
“… the information about a variable Y provided by two predictors X1 and X2, denoted by I(X1,X2,;Y), can be decomposed via the information chain-rule as
I(X1,X2;Y) = I(X1;Y) + I(X2;Y|X1),
where I(X1;Y) corresponds to the information provided by X1, and I(X2;Y|X1) refers to the information provided by X2 when X1 is already known. Taking this idea one step further, the PID [partial information decomposition] framework proposes to decompose each of these terms into information atoms as follows:
I(X1;Y) = Red(X1,X2;Y) + Un(X1;Y|X2)
and I(X2;Y|X1 ) = Un(X2;Y|X1) + Syn (X1,X2;Y),
where Red(X1,X2;Y) represents the redundant information about Y that is contained in both X1 and X2, Un(X1;Y|X2) and Un(X2;Y|X1) correspond to the unique information that is conveyed by X1 or X2 but not the other, and Syn(X1,X2;Y) refers to the synergistic information that is provided by X1 and X2 together but not by each of them separately. For example, consider our two eyes as sources of visual information about the environment. The information that we still have when we close either eye is redundant (e.g. information about colour), while the extra information we derive from combining them (e.g. stereoscopic information about depth) is synergistic.” Mediano, Pedro A.M., Fernando E. Rosas, Andrea I. Luppi, Henrik J. Jensen, Anil K. Seth, Adam B. Barrett, Robin L. Carhart-Harris & Daniel Bor. 2022. “Greater than the parts: a review of the information decomposition approach to causal emergence.” Philosophical transactions of the Royal Society: A. 380:20210246. 10.1098/rsta.2021.0246. p. 3.
“We are being urged from every side to become efficient rather than intimate.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. xvii.
“A soul mate is someone to whom we feel profoundly connected, as though the communicating and communing that take place between us were not the product of intentional efforts, but rather a divine grace. This kind of relationship is so important to the soul that many have said there is nothing more precious in life. We may find a soul partner in many different forms of relationship–in friendship, marriage, work, play, and family. It is a rare form of intimacy, but is not limited to one person or to one form.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. xvii.
“The spirit of detachment makes sense from a spiritual point of view. It’s important to clear the decks and to be free of everyday worldly concerns in order to explore fully the realm of the spirit. The world can easily distract from this higher endeavor. But the soul has an equal task and commitment, to find the treasures and explore the ins and outs of life by being attached. Just as there is spiritual practice in search of the highest and most refined reaches of human potential, so there is soul practice in pursuit of the juices and nutriments of life’s entanglements.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 16.
“We are given the illusion that it’s possible to understand ourselves and others. But it seems to me that these expectations ignore soul. The soul is always complicated. Most of its thoughts and emotions could never be expressed in plain language.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 29.
“Sometimes it appears that there is more moralism in the field of psychology than there is in religion.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 30.
“New ideas about psychology often lead to suggested programs of self-improvement, but such programs work against the soul. For one thing, self-improvement is full of ego and conscious intention, but the whole idea of soul embraces much that is unknown, and in order to be soulful, we need some way of allowing for the unknown….
“Another problem with the idea of self-improvement is that it implies there is something wrong with who we are. Everyone wants to be someone else, but getting to know and love yourself means accepting who you are, complete with your inadequacies and irrationalities. Only by loving the soul in its entirety can we really love ourselves. This doesn’t mean that we can’t hope to live a fuller life or become a better person, but there is a difference between self-improvement and the unfolding of the soul.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. pp. 40, 41.
“It’s more difficult to look at marriage as we actually experience it, taking note of its deep fantasies, its hidden emotions, and its place in the life of the soul; not looking for perfection, but asking what the soul is doing when it entices us toward such a demanding form of relationship….
“We approach its soul when we understand that marriage is a mystery, a sacrament, as some religions say–a sacred symbolic act.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 46.
“Marriage seems to be about relationship with another person, but … marriage is also more mysterious,… it is a strange but fulfilling union with the world of dream and fantasy.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 50.
“In the soulful marriage cynicism and disillusionment are replaced by an appreciation for the impersonal powers at work in what we imprecisely call human relationship. The Native American story [Cochiti story about eligible maiden who is enticed into marriage with a coyote who dances in human outfit with black currants in his hand and who has little coyote babies with him and manages to crawl into a tiny hole to live with him under the ground] reminds us that the ‘other’ in marriage is not only a human being. It is also an animal, and a special animal at that–a tricky, resourceful, earthy, dark, untamable coyote, who brings to a marriage the potential for joy and fun as well as fear and power. In a marriage cognizant of soul, the partners find a brand of intimacy that is deeper than personal trust and mutual understanding. Oddly, it is rooted in mistrust and lack of understanding, in a distance that allows the soul of the other and of the marriage to be unpredictable and inexplicable. Oscar Wilde once said, ‘Only the shallow know themselves.’ The same could be said about marriage partners.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. pp. 59-60.
“The fatefulness that surrounds the beginning of a profound relationship suggests an intentionality far beyond the ken of the people involved. In acknowledging this turn of fate, we may find some peace and grounding, and also some humility as the relationship continues to offer unexpected challenges.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 60.
“When we respect the genius of our marriage, we focus as much on its own creativity as on our intentions for the relationship.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 62.
“To care for its [marriage’s] soul, it is more important to honor its mystery than to try to outwit its intentions for what we, with our small minds, may think is a better outcome. If you want to ensure the soulfulness of your marriage, it would be infinitely better to build a shrine to it, find its god or goddess, and tend its image than to follow the ‘manual’ and do it all properly and intelligently.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 69.
“The fundamental problem with the family is one of imagination. We need an appreciation of the family shadow–the tensions, differences, antagonisms, and clashes–that plays a constitutive role in the family soul. It’s often a struggle for family members to forge a new imagination of what they are, especially as various members go through their individual rites of passage and life transitions. But if they have the courage to reimagine themselves continually as a family, while remaining loyal to their traditions, they will be caring for the family soul. They may not discover happiness–happiness pure and simple isn’t the goal of soul-work anyway–but they may find the deep, rich rewards of meaning, belonging, direction, and history simply by honoring the soul of the family.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 75.
“With the scientific discoveries of the past hundred years, and with continuing technological inventions, it is evident to all that we live in a ‘global village.’ Apparently it is not yet evident that we could live in a ‘global family,’ with all the feelings of connectedness, support, security, love, and community that a genuine family can provide.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 82.
“… imagine how radically our social structures would change if we made friendship our highest priority and considered our functional purposes secondary.
“When we make the effort to place soul at the center of our concerns, … values shift significantly. In every gathering of people, from business to politics, community would be considered more important than organization, and friendship more valuable than productivity.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 91.
“Conviviality is not the heavy onus of taking responsibility for the rest of the world, but rather the pleasure of living within a web of relationships.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 106.
“We can apply two tests to discover if a group is really a community: (1) Is there a working together, affection and discord, and commonality? (2) Are the members truly individuals, or are they expected to think alike, have shared goals and values, speak the same language, or hold to a party line? Community is born when individual and group are no longer felt to be two independent realities.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 106.
“If we could imagine chastity as an essential ingredient in the sexual life, we would not get so caught up in various excesses and repressions…. Chastity increases pleasure and actually reveals beauty, which might otherwise be drowned in lust, playing a necessary role in the full range of the convivial sexual life.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 109.
“The paradox [in finding our independent will and strong sense of self] is that the source of independent existence we all crave is set infinitely deep in the soul, so that no amount of muscle-flexing egotism can waken it. Only the surrender of the very idea of self can evoke the soul’s rare gift of self-reliance.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 111.
“But what passes for communication can be to relationship what information is to education–a soulless exchange of facts.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 115.
“What matters is not how much you expose about yourself in conversation, but that your soul is engaged.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 118.
“The soul seems to prefer talk that is close to life and yet not only pragmatic and technical. Its favorite modes are reverie, reminiscence, reflection–those re- words that point to the soul’s task of working imagination into past experience.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 119.
“From Emerson’s point of view, conversation is a way of coming to oneself, a mode of relating to oneself as much as to another. Maybe this is one of the reasons why conversation can be so pleasurable: we become reacquainted with ourselves.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. pp. 119-120.
“Conversation is the sex act of the soul, and as such it is supremely conducive to the cultivation of intimacy.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 124.
“People who have to be perfect, or who can’t admit to each other the difficult or impossible situations life presents, can hardly be intimate. What they share is the common artifice of perfection, but they overlook the fuller soul, which prospers in the failure of perfection. Humor allows us to entertain failure and inadequacy in life without being literally undone by them.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. pp. 130-1.
“In our childish attachment to romance, we are championing the way of the soul–its thirst for pleasure, and its inescapable need for experiences that may or may not be conducive to productive lives.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 145.
“In his book Three Faces of God, on the trinity as a structure in all of life, David Miller discusses the necessity of the triangle in all loves. ‘There is one man, one woman, and love. If this fails, then perhaps there will be one man, one woman, and a pet animal or a mutual hobby. Or there may come a time when she notes, not without appropriate jealousy, that he seems wed to his work, which is now a third in the marriage.’ All love is a menage a trois, Miller concludes.
“The third, I would say, is always the soul. traditionally the soul was always considered the third factor between mind and body, between spirit and matter. It is the medium, the mediating element, that holds everything together.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 147.
“To arrive at the life that stirs in romantic love requires finding a way through the power plays to the person we love, through the pains that almost always accompany such love to a pure experience of love, through the things we are intentionally looking for in love and in another, to the life and vitality that have been generated by means of love’s illusions.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 152.
“From a Hermes point of view, sex offers guidance toward soulfulness, especially toward the deep places of the soul where strong emotions arise. For instance, we might look closely at shifts in our sexual fantasies for signals of what is going on deep in the soul, as though these fantasies were herms [stacks of rocks for Hermes, but like a phallic rock pile] showing us the way. Our usual tendency is to judge these fantasies, or to move quickly into either repressing them or acting them out; we don’t think to take them as indications of movements in the soul. Yet it’s quite evident that the soul has its own sexual poetics….
“Indeed sex is one of the means Hermes uses to make these magical relationships. The worst thing would be to replace Hermes by ‘using’ sex for communication or by intellectualizing it. The only thing required is to be open to Hermes in sex, and let him do his work. We could develop an awareness allowing us to distinguish when we are manipulating and forcing, and when we are letting ourselves be revealed and communicated. This passive form, ‘being communicated,’ is a pious way of letting the god have his way with us.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. pp. 161, 163.
“In ancient Rome people believed that Priapus, the god of sexual vigor and vitality, was also the god who visited in impotence. These two sides of sex–vitality and impotence–have equal legitimacy and importance, and both are divinely sanctioned. If we try to achieve one by defending ourselves against the other, we will never know the fullness of sexual pleasure.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 169.
“Discussing sex, Patricia Berry says that married people usually lose the polymorphous quality of childhood sexuality, and therefore suffer from an excessively adult notion of sex.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 172.
“Eros is a mystery because it is never fully satisfied, and yet it is always finding satisfactions; it seems to be identical with love, and yet it has an essential relationship with hate. If we identify desire only in relation to what we want, then we overlook the fact that when we struggle amid feelings of hatred, there may also be an erotic element involved.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 173.
“When moral sensitivity and respect for eros merge, the two are so close the result might be called ‘erotic morality.’ This is a finely tuned ethical sense that recognizes the fact that soul is frequently set in movement by desires that may be initially confusing, but later may prove to be all-important in shaping life for the better. This kind of morality is life-affirming rather than prohibiting, and respectful of eros rather than suspicious. It trusts desire, and therefore, paradoxically, it doesn’t breed compulsion.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 179.
“Religion in the deepest sense takes shape as we learn through pain and loss that the creativity we exercise over our lives is finite, a mere participation in a greater creative act.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 196.
“… the ending of a relationship doesn’t have to be read as literal failure, but can be seen vertically, as a means toward a new level of experience. That is the meaning of initiation, and that is why initiation rites around the world employ funereal imagery.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 199.
“Divorce and diversion are closely related, both coming from the Latin divertere. This etymology suggests that divorce is not a failure of the parties to maintain their commitments, but rather evidence of the tendency of fate to spin us in different directions. When our thoughts about endings are based on moralistic judgment, we create a culture filled with guilt, fantasies of impossible perfection, and the wrong kind of responsibility….
“Divorce is a word filled with opprobrium, while diversion is light to the point of irresponsibility.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 199.
“I would never recommend that a person express whatever anger they feel. Raw emotion has almost no access to soul. On the other hand, emotion is the raw material for grounded feeling….
“We have seen that when anger is broken down into more subtle feelings and fantasies, it can be assimilated in a number of ways: as firmness, strength, certainty, authority, self-knowledge, confidence, vision, and grounding. These refined versions of anger do have impact in life, and are drawn into the soul as elements of character–not momentary flashes of expression, but available resources.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 217.
“The only possible way that is in tune with the soul is in the direction of the symptom.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 224.
“Running away from something is no way to find what is needed. To put it another way, defending against loneliness is no way to establish a relationship. We may have to befriend our loneliness and even our loveless life. Any other move goes contrary to what the soul is presenting. Besides, the ‘poor me’ attitude in these expressions of lovelessness suggests a certain kind of narcissism, a whining for one’s own wishes, while what is required in soul-work is a widening of heart and mind and an opening to fate. Narcissism is always a hint that we’re not loving the soul in some essential way. It may be that we don’t like the yin and yang of love and loss, and so we narcissistically moan and complain. But what the soul asks of us is a vision of human life sufficiently grand and profound as to embrace these contraries and appreciate their wisdom.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. pp. 224-5.
“Pathology is the voice of a god or goddess trying to get our attention. The Greek dictionary says that pathos means the opposite of ‘do’; it means ‘to have something done to you,’ and it is also the passive form of poiein or poetry. We are made poetry by our pathologies. Our lives are made into stories, and the most soulful moments may well feel unusually dramatic. Soul is the poetry of our lives, most strongly felt when the god is asking to be admitted. We are the stuff on which the soul’s themes are imprinted. If our thinking is largely secular, we will think of love’s pathologies as problems and assume that we’re doing something wrong; but if we have a sense of the sacredness of relationship, then we might see the pathological moments as an opportunity for soul, as a visitation from eternity where relationship is seeded and at least in part crafted.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 228.
“Our problem in relationships is how to have an ongoing, intimate life with another person at the same time as we invite this completely unpredictable depth to have a significant place in our lives. It isn’t easy to live with the power and mystery of another’s soulful personality. For one thing, you can’t depend on what the person promises, since soul isn’t willing to be chained to intentions or even to commitments. If the individual doesn’t understand everything going on in the soul, how one can [sic] who is close, whose life is seriously wrapped up in the other, have even the remotest understanding?
“The only solution to this problem I know is for both parties to respect soul, to acknowledge the mystery that is inescapably contained in the soulful life, and to come to treasure that very unpredictability. This may entail a radical shift in values. Ordinarily without thinking about it, we honor commitments, promises, fidelities, and reliable habits. When these values are trespassed against, we become indignant and complain about a failure in relationship. If, on the other hand, we had a larger picture in mind and honored the tendency of the soul to move in mysterious ways, we might see that the unpredicted developments that come from the soul can have a positive effect on a relationship. They demand a great deal of adjustment and allowance, but they also offer continuous deepening of the connection and a grounding of the attachment in soul rather than in any one person’s will. Besides, individual willfulness is usually laced with fear and manipulation, and is hardly solid ground for the building of intimacy.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 235.
“Our culture puts a great deal of trust in facts, experiment, and experience, but all three of these can be dangerous to imagination if they are used one-dimensionally for their weight of proof rather than as a stimulus for discussion. One aspect of this cultural bias toward fact is our habit of treating relationships factually.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 247.
“A relationship problem may be like the piece of marble Michelangelo confronted with his hammer and chisel: the inner figure waiting to be sculpted out is not easy to perceive and is certainly invisible except to a poetic eye.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 250.
“Living soulfully requires that we allow hope, faith, and love to be open-ended; we do not know what to hope for, may not believe in any particular thing, and will love whatever it is we receive. Soul also embraces the shadow sides of these ‘virtues,’ so that it is important to experience despair, to sink into doubt, and even to fight sometimes against the presentations of fate.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 252.
“As sweet as it sometimes sounds, care of the soul is a radical departure from modern notions of living correctly and successfully–at all levels: moral, theological, psychological, social. The same could be said of soulful relationships: they are not necessarily the healthy ones, the successful ones, or the peaceful ones.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 252.
“Relationship is not a project, it is a grace. The difference between these two is infinite, and since our culture prefers to make everything in life a project,… it is not easy for us to treat intimacy as a grace.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 256.
“We may well be preoccupied with the theme of interpersonal relationship precisely because we are stuck in a shallow pool of love, unable to arrive at the mystic’s view in which the divine is the only satisfying lover, the only true soul mate.
“What is divinity? What is the nature of this ultimate relationship? He who speaks, the Tao te Ching says, does not know…. We could turn to the religions of the world, a vast source of poetry, confession, prayer, and ritual, to be instructed in this dimension of relationship, but ultimately we will find this divine undercurrent in all our relationships in our own unique way.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 258.
“For this is what relationship is about: the discovery of the multitude of ways soul is incarnated in this world….
“If we can find the whole world in a grain of sand, we can also find the soul itself at the small point in life where destinies cross and hearts intermingle.” Moore, Thomas. 1994. Soul Mates: Honoring the Mysteries of Love and Relationship. NY: HarperPerennial. p. 259.
“… I think we are now on the threshold of answering Schroedinger’s question [what is life?], and the answer will usher in a whole new era of science.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 1.
“The impressive data-storage properties of DNA have created something of a cottage industry among scientists uploading poetry, books and even films into the DNA of microbes (without killing them). Craig Venter pioneered the field by inserting ‘watermarks’ in his creation, including a pertinent quotation by the physicist Richard Feynman embedded into the customized genome of a microbe that he re-engineered in his lab.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 39.
“… information is about what you know, and entropy is about what you don’t know.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 40.
“Organisms are awash with information, from DNA up to social organization, and it all comes with an entropy cost. No surprise, then, that evolution has refined life’s information-management machinery to operate in a super-efficient manner. Organisms need to have perfected the art of storing and processing information or they would quite simply cook themselves to death with waste heat.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 62.
“Control kernels seem to be a general feature of biological networks. So in spite of the great complexity of behaviour, a network’s dynamics can often be understood by looking at a relatively small subset of nodes.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 99; source?: Kim, Hyunju, Paul Davies & Sara Imari Walker. 2015. “New scaling relation for information transfer in biological networks.” Journal of the Royal Society Interface. 12(113): 20150944. 10.1098/rsif.2015.0944.
“It would be wrong of me to give the impression that information flow in biology is restricted to gene regulatory networks. Unfortunately, the additional complexity of some other networks makes them even harder to model computationally…. On top of that, the number of components skyrockets when it comes to more finely tuned functions like metabolism. The general point remains: biology will ‘stand out’ from random complexity in the manner of its information patterning and processing, and though complex, the software account of life will still be vastly simpler than the underlying molecular systems that support it, as it is for electronic circuits.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 99.
“Cancer is the most studied subject in biology, with over a million published papers in the last fifty years. It may therefore come as a surprise to the reader to learn that there is no agreement on what cancer is, why it exists and how it fits into the great story of life on Earth. Very little attention has been given to understanding cancer as a biological phenomenon, as opposed to a disease to be annihilated by any means at hand….
“It goes without saying that cancer is a disease of bodies; it makes little sense to say that an isolated bacterium has cancer.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. pp. 131, 132.
“In summary, our view of cancer is that it is not a product of damage but a systematic response to a damaging environment – a primitive cellular defence mechanism. Cancer is a cell’s way of coping with a bad place. It may be triggered by mutations, but its root cause is the self-activation of a very old and deeply embedded toolkit of emergency survival procedures….
“… in technical jargon, it is an atavistic phenotype.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. pp. 137, 138.
“In his Dublin lectures Schroedinger identified life’s ability to buck the trend of the second law of thermodynamics as a defining quality. Living organisms achieve this entropy-defying feat by garnering and processing information and directing it into purposeful activity. By coupling patterns of information to patterns of chemical reactions, using demons to achieve a very high degree of thermodynamic efficiency, life conjures coherence and organization from molecular chaos.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 166.
“How did life begin? Because living matter has both a hardware and a software aspect – chemistry and information – the problem of origins is doubly difficult.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 166.
“To conclude: time doesn’t pass.
“Well, what does pass, then? I shall argue that it is the conscious awareness of the fleeting self that changes from moment to moment. The misconception that time flows or passes can be traced back to the tacit assumption of a conserved self. It is natural for people to think that ‘they’ endure from moment to moment while the world changes because ‘time flows’…. At each moment, the you appropriate to that world-state interprets the correlation with that state as ‘now’. It is indeed ‘now’ for ‘that you’ at ‘that time’. That’s all!
“The flow-of-time phenomenon reveals ‘the self’ as a slowly evolving complex pattern of stored information that can be accessed at later times and provide an informational template against which fresh perceptions can be matched. The illusion of temporal flow stems from the inevitable slight mismatches.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 195.
“Although Galileo, Newton and their contemporaries were influenced by Greek thought, their notion of physical laws owed much to monotheism, according to which an omnipotent deity ordered the universe in a rational and intelligible manner. Early scientists regarded the laws of physics as thoughts in the mind of God.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 210.
“From a computer science perspective, one might say that the physical world can be thought of as being modelled by two distinct components: the program and the data. But in the biological world, the program is the data, and vice versa.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 213.
“The possibility that there may be new laws, or at least systematic regularities, hidden in the behaviour of complex systems, is by no means revolutionary. Several decades ago it was discovered that subtle mathematical patterns were buried in a wide range of chaotic systems. Physicists began to talk about ‘universality in chaos’. What I am proposing here is universality in informational organization, in the expectation that common information patterns will be found in a large class of certain complex systems – patterns that capture, at least in part, something of the features of living organisms.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 214.
“The appearance of anything new in the universe is always an amalgam of laws and initial conditions. We simply don’t know the conditions necessary for biological information to emerge initially, or, once left to get going, how strong a role natural selection plays versus the operation of informational laws or other organizational principles that may be at work in complex systems. All this has to be worked out.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 216.
“Two contrasting views of life’s origin are the statistical fluke hypothesis championed by Jacques Monod and the cosmic imperative of Christian de Duve. Monod appealed to the flukiness of life to bolster his nihilistic philosophy…. In responding to Monod’s negative reflections, de Duve wrote, ‘You are wrong. They were [universe and biosphere were pregnant with life],’ and proceeded to develop his view of what he called ‘a meaningful universe’. Boiled down to basics, the issue is this. Is life built into the laws of physics? Do those laws magically embed the designs of organisms-to-be? There is no evidence whatever that the known laws of physics are rigged in favour of life; they are ‘life-blind’. But what about new state-dependent informational laws of the sort I am conjecturing here?…
“These speculative notions are very far from a miracle-working deity who conjures life into being from dust. But if the emergence of life, and perhaps mind, are etched into the underlying lawfulness of nature, it would bestow upon our existence as living, thinking beings a type of cosmic-level meaning.
“It would be a universe in which we can truly feel at home.” Davies, Paul. 2019. The Demon in the Machine: How hidden webs of information are solving the mystery of life. Penguin. p. 217.
“The functions of the body, the interactions of organisms, the development of life, and the life of the mind did not yield to purely mechanical analogies [in the late 18th century]. The specter of purpose was difficult to exorcise….
“This state of affairs led to a schizophrenic approach to life: On one hand, a mechanistic approach had undeniably yielded important insights into how life worked; on the other hand, this approach seemed insufficient to account for what made matter alive.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 31.
“Efficiency is best achieved when we do not stray too far from equilibrium, because large movements cause friction and, consequently, rapid degradation of low-entropy energy. Life chooses the middle road: By staying away from equilibrium, we stay alive. By staying close to equilibrium, we increase efficiency.
“Life is a near-equilibrium, tightly controlled, open, dissipative, complex system.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 87.
“Life must begin at the nanoscale. This is where complexity beyond simple atoms begins to emerge and where energy readily transforms from one form to another. It is here where chance and necessity meet. Below the nanoscale, we find only chaos; above this scale, only rigid necessity.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 91.
“In a nutshell, cooperativity means that a structure cannot form unless a certain number of molecules ‘cooperate’ to form the structure….
“Cooperativity, the observation that some structures form only when a minimum number of molecules cooperate, is ubiquitous throughout biology.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. pp. 105, 106.
“If oil is placed into water, water molecules form a kind of cage around an intruding oil molecule, trying to maximize hydrogen bonding to their own kind. The cage structure they form induces order in the water and therefore decreases entropy…. Trying to put oil into water comes at high (entropic) cost….
“The hydrophobic force, which is responsible for the separation of oil and water, is therefore another example of an entropic force.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 111.
“If all bonds in the molecules of living organisms are too strong, there can be no motion or change. If they’re too weak, there can be no stability…. The solution that life has found is to capitalize on the cooperativity of many bonds [e.g. DNA]. As we saw earlier, many weak bonds cooperating make a molecule very strong, while individually, the bonds can easily be broken, allowing for rearrangement when needed.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 116.
“The stability of DNA is therefore the result of bond cooperativity, complementarity of the two strands, and active repair by the cell’s machinery.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 117.
“Cooperativity is almost inevitable when you have many entities interacting with each other.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 117.
“Once water is squeezed to just a few molecular layers between the surface and the tip, it becomes difficult for the water molecules to move out of the way of the approaching tip [of AFM or atomic force microscope]…. When confined to the nanoscale, many molecules have to move in concert to create a hole into which the tip will move–water molecules have to cooperate to move out of the way. What is truly remarkable about these results is that it takes water molecules extremely long, of the order of seconds, until they randomly happen to move in a coordinated manner to create a hole. That is a million billion times longer than the average time between water molecule collisions. A crude calculation indicates that thirty to forty molecules–not very many–would have to be involved in the collaborative motion to create such a long time scale. Cooperativity can create not only sharp transitions, but also large changes in time scales, making even molecular processes take second or even minutes.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 120.
“Cooperativity leads to switching. Yesterday everything was fine; today the economy has crashed. A second ago, lipid molecules were happily floating around, and then, suddenly, they form micelles, and osmotic pressure drops precipitously.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 121.
“Changes in a molecule’s shape are driven by cooperativity of many bonds, and the shape change, often sudden and dramatic, can be driven by a relatively small external change. This behavior allows for the creation of molecular switches, molecules that can effect large changes in response to small causes, such as the binding of a small molecule.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 121.
“… only at the nanoscale are many types of energy, from elastic to mechanical to electrostatic to chemical to thermal, roughly of the same magnitude.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 122.
“In chemical reactions, molecules must change shape to combine in novel ways. These changes in shape are driven by a reduction in free energy….
“During any chemical reaction, thee is an awkward moment when molecules no longer have their original shapes, but neither do they have their final shapes. They form an intermediate state between their initial state (reactants) and their final state (products). This intermediate state, called the transition state, tends to be uncomfortable for the molecules.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 146.
“Binding a control molecule changes an enzyme’s shape, with part of the enzyme moving relative to other parts.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 153.
“… each turn of the motor [ATP synthase rotary protein] would perform a different step of the ATP synthesis: binding an ADP and a phosphate, attaching the phosphate, releasing ATP. All of these steps would happen in the same enzymatic pocket. The rotation would somehow modify this pocket during each turn so that it would be most suitable for the particular reaction step it was assisting. Having three such multifunction pockets would allow three ATPs to be produced per full turn of the machine.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. pp. 196-7.
“Note that even though the ribosome is more complex than the other molecular machines we have encountered, almost all of them have one thing in common: They move along a track. Kinesin moved along microtubules, myosin along actin filaments, helicase and RNA polymerase along DNA, and the ribosome moves along mRNA.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 209.
“Evolution is not random: It is the collaboration between a random process (mutation) and a nonrandom, necessary process (selection). It is the result of the balance of chance and necessity. This is not unusual–all of nature is the result of this balance.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 222.
“In our cells, directed motion, ‘purposeful’ activity, is created by the action of molecular ratchets–molecular machines, enzymes, and motors, which by degrading free energy and due to their asymmetric structures, can rectify the random motions of the molecular storm to create order. Evolution is also a ratchet: It rectifies the random input from mutations into the creation of an ever larger number of possible creatures. This rectification is achieved by natural selection. Thus there is a pleasing analogy between evolution and its products, our molecular machines.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 225.
“Kinesins consist of one or two similar motor domains, which process ATP and bind to microtubules. In addition to the motor domain, kinesins can contain a number of other domains to bind cargo, to bind to specific locations, or for regulation. In the cargo-carrying motor kinesin-1, the cargo-binding domain also serves a regulatory function, as it would be wasteful to have motor proteins running around in the absence of cargo. After all, they use up ATP. How is kinesin regulated? When no cargo is around, the kinesin molecule folds up, such that the cargo-binding domain can bind loosely to the motor domains. In effect, the molecule puts on its parking brake. If the cell wants to activate the motor, it sends two control molecules, which bind to the cargo domain and release it from the motor domains. The process essentially takes off the parking brake. This is not the only way kinesin-1 is regulated. For instance, the cell can control which microtubule a kinesin walks on using various proteins that bind to the microtubule. Some will ‘attract’ kinesin, and some will inhibit its motion on the tract. Another set of regulatory proteins controls the binding and release of cargo.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 232.
“We can understand many things about molecules by determining their atomic structure, but the quark structure is already too far removed to yield much insight or even a useful explanation for the properties of a molecule. As we move further along, these links become ever more tenuous, until there is really no meaningful conceptual connection between a highly complex entity and the most fundamental levels of matter and energy.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. p. 240.
“‘But how do you predict a cow from particle physics?’ A great question! [asked by friend of author’s, Sean Gavin]
“Is it just too complicated to predict the existence of cows from particle physics, or is it fundamentally impossible to predict a cow from the properties of quarks and electrons?…
“Particle physics may be necessary to make a cow (because we need atoms and molecules), but it is clearly not sufficient.” Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. Basic Books. pp. 241, 242.
“… I suggest in this chapter that some scientific explanations (which I dub ‘explanations by constraint’) work not by describing the world’s causal relations, but rather by describing how the explanandum involves stronger-than-physical necessity by virtue of certain facts (‘constraints’) that possess some variety of necessity stronger than ordinary causal laws possess.” Lange, Marc. 2018. “Because Without Cause: Scientific Explanations by Constraint.” From: Explanation Beyond Causation: Philosophical Perspectives on Non-Causal Explanations. Reutlinger, Alexander & Juha Saatsi (eds). pp. 15-38. Oxford UP.
“In vision, the nerve nets of the brain can learn to anticipate the identity of an object in the world–to supplement the raw information coming from the retina with its knowledge of images it has seen before. Boiled down, this means that much of perception is not just a fixed response to the visual scene but is learned.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 3.
“A transient cell [among the retinal ganglion cells, those that come after the initial cones and rods and after the bipolar connector neurons] responds mainly when a visual image first appears, then falls almost silent afterward. It is essentially a change detector. Clearly, you would not use the signals transmitted by a transient cell to recognize a face in a crowd. The face would disappear in an instant, after a few hundred milliseconds. You would not have time to register the configuration of its eyes, nose, mouth, et cetera. To see the face with a steady gaze, you, as the brain, would do better relying on the output of sustained cells. On the other hand, imagine that the shape of a pterodactyl suddenly swoops across your retina. That is something that the retina should report to you (the brain) as vividly and quickly as possible. This is what a transient cell is good for. Such a cell is silent most of the time. But its glory is to tell the brain about the sudden appearance of an object within its receptive field. Advertisers know that a flashing sign is more powerful than a steady one, and the transient cells explain why….
“Within transient cells, some respond when their receptive fields encounter an increase in brightness; these are transient ON cells. Some ganglion cells respond when a light goes off; these are transient OFF cells.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 36-7.
“But edges embody a central principle that controls many, many aspects of vision. The pixels of the natural world are far from random. The natural visual world occurs in structures–lines, angles, curves, surface. What that means is that the occurrence of certain pixels is influenced by what’s around them. A truly random visual world looks like television snow. Your visual system is arranged so that it emphasizes the structures where change is happening and downplays places in the image where not much is happening–the middle of the sky, the interior of a solid-colored surface….
“Lateral inhibition increases the strength of responses of ganglion cells near an edge. Because of lateral inhibition, the difference between the signal that the brain receives from the back edge and from the white edge is greater than it would otherwise be.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 39.
“So far I have told you a major principle: the resolution of all vision is controlled by the mosaic of retinal ganglion cells, in the same way that the density of pixels on a screen determines the screen’s resolution. The more densely packed the retinal ganglion cells, the more sharply the person or animal can see.
“And you also know some principles about the types of information that get transmitted to the retina: some ganglion cells respond mainly at the onset of light, some when the light disappears, some only transiently, others sustainedly….
“Recent estimates suggest that in most mammals there are more than thirty different types of ganglion cells, each tuned to a different aspect of the visual stimulus.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 77-8.
“The most famous of the ‘smart’ ganglion cell types is directionally selective: it responds to movement of a stimulus in one direction, and not to movement of the same stimulus in the opposite direction. It responds, in other words, to the direction of movement itself–independent of the particular visual object….
“We know something of what this cell is good for: it helps control the position of our eyes when we move…. In fact, you cannot by force of will prevent your eyes from following the moving scene; they drift backward, then jump forward again to meet the moving image….
“Your retina’s directionally selective neurons are largely responsible for this reflex. If you hold your eyes still, the image of the objects outside moves on your retina. The direction-selective neurons are activated: they tell the brain that the image is slipping, and which direction it is moving in. A nucleus in the brain receives that information and sends a precise message back out to the eye muscles, telling them how to contract to make the image stand still on the retina….
“We have the same problem when we walk,, and the motion is far more complicated. We walk–in effect, we bounce–from point to point. Our eyes must compensate for that exotic trajectory. Your directionally selective retinal ganglion cells help you compensate for these complexities by holding your gaze steady while you’re walking.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 78, 79.
“A second type of smart retinal ganglion cell is the local edge detector. It likes very slow movement of a tiny spot within its receptive field. Big stimuli do not excite this cell…. Levick, who discovered this type of cell in the rabbit retina, suggested that this is an evolutionary adaptation to the rabbit’s life as a prey animal. For what it’s worth, he pointed out that the tiny moving spot is just the stimulus that would be generated on the retina by a hawk circling slowly high in the sky. This type of ganglion cell is found in great numbers in ground-dwelling rodents, and the implication is that the retina of a rabbit or mouse needs to survey the sky for danger.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 80; reference: William Levick with no further reference.
“Humans have about one million retinal ganglion cells.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 81.
“Every point in the visual scene is reported to the brain by around thirty different analyzers (ganglion cells), each describing a different feature of the world at that point.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 83.
“Before the 2000s, the retina was thought of as a simple neural system, with only a few major cell types. It was a shock to find that there were twenty-nine kinds of amacrine cell [neurons connecting two bipolar cells that are themselves between rod and cone cells and the downstream retinal ganglion cells] and thirteen types of bipolar cell.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 85.
“… specific small patches of the temporal lobe lit up when the subject saw a face….
“In people and monkeys there are six such patches, arranged along the surface of the temporal lobe….
“Each cell of a given face patch responds best to specific parts of the face…. The cells don’t so much ‘recognize’ faces as measure parameters of the stimulus that is potentially a face, and then somehow sum them up to decide whether the stimulus is a face.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 112, 115.
“A clever variation on dark-rearing was to deprive animals during early life of the ability to see motion. The experimenters did this by rearing cats in an environment lit only by very brief strobe flashes. This allowed the cats to see the usual world, but the flashes were too short for any meaningful movement of objects across the retina to occur–in other words, these animals’ cortices were deprived of visual movement. What happened? These animals grew up without direction-selective neurons in their cortex.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 122.
“… Donald Hebb had proposed that groups of neurons that fire together have their connections strengthened….
“Donald Hebb predicted that vision is to a major extent learned: complex perceptions are formed from experience, by association, because objects in the world occur in clusters of individual features.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 123-4.
“Most neurons of the retina and visual portions of the brain are not very interested in objects that are unchanging. They respond well when a new object is shown, but gradually stop responding if the image shows no change at all. This is useful; it means the brain doesn’t spend energy on things that carry no new information. But a side effect is that images are prone to fade from perception if they don’t move. The resting tremor of the eye counteracts that process by making the image slip back and forth across the retina (again, in movements too small for us to perceive), so the neurons do not fatigue and the object is continuously visible. But the experimental contact lens nullified those small eye movements so that whenever the eye moved, the image moved as well.
“As you might have guessed, when the experimental contact lens was used, the image disappeared because there was no tremor to stabilize it. But to Hebb, the critical result was not that it disappeared. What was most important was what happened while it disappeared. The stabilized image did not disappear in an unorganized way–for example, decomposing into a scatter of dots. Instead, it disappeared in chunks. A whole square might disappear at once. Alternatively, an outline square might initially lose one of its four sides but keep the other three, then lose two more sides, and finally lose the last remaining line.
“Hebb postulated that these chunks correspond to the concurrent activation of groups of neurons in the brain. These he called ‘cell assemblies,’ his version of the most basic nerve net.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 132-3.
“Nerve nets are distributed through many regions of the brain. If a nerve net is not tightly localized but widely spread out, it could explain why individual memories don’t have a fixed location. If a cell assembly consists of a very large number of neurons, all interconnected, losing a few would not hurt us much…. Because of nerve nets, the brain becomes what engineers call ‘fault tolerant.’” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 136.
“But there is a subtler, deeper meaning of perceptual learning, and this is the one that interested Hebb: the neurons of your sensory system adjust themselves to the stimulus. In fact, Hebb believed–in 1949, before the advent of information theory–that neural reorganization in response to the regularities of the natural world was not just icing on the cake but a fundamental basis of perception itself.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 142.
“In fact, there are very few visual inputs in our world that are not redundant. A truly nonredundant scene, again, looks like snow on a television screen.
“In terms of the demands that vision puts on your nervous system, this is a very big deal. It means that your perception does not really need to evaluate every pixel in a scene. It can use the regularities of the scene to predict what neighboring pixels contain, and insofar as the brain knows those regularities ahead of time (because it has created cell assemblies representing them), it can save itself work.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 143.
“… a global idea of how the [visual] system is designed. Here it is:
“I. Visual systems are not neutral, bias-free recorders of their inputs. At every level, their responses are distorted to match the regularities of the natural environment.
“II. In some cases this match is embedded in the genetic code, but in many it is accomplished by nerve net learning. This goes all the way from basic regularities such as sensitivity to edges and lines to complex perceptions such as faces.
“III. The coarse connections between the brain’s visual areas are made using molecular cues–the kind of cues nature uses during infant development to build a hand or a liver. These are mostly chemical pathfinding signals; they lead axons to target areas in the brain, and help them form a rough topographic map of the visual field in each. But the wiring that underlies perceptions of specific objects–object recognition–is created by neural plasticity.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 173.
“The complex cell is thought to be created in just the same way as the simple cell: the convergence of earlier neurons, in this case the simple cells converging on the complex cell.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 179.
“The pixels [formed by input of neurons] of a face do not occur at random. The two dark holes representing nostrils occur more often in pairs than by chance, and they also occur more frequently above the line of pixels that define a mouth than by chance. The individual elements that define a face become linked–if you will, they make a cell assembly.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. p. 182.
“Eyes, noses, chins, and hairlines do not occur at random in a young monkey’s visual world. They occur together, the prerequisite for perceptual learning….
“… it means that the brain of an individual animal is linked in the very wiring of its cells to the natural world in which that animal lives. Because of perceptual learning, our visual brains contain a built-in copy, a distillation, of our natural environment.” Masland, Richard. 2020. We Know It When We See It: What the Neurobiology of Vision Tells Us About How We Think. London: Oneworld Publications. pp. 190, 191.
“A necessary physical condition [for sufficient conditions for biological informational concepts like signs, symbols, memories, instructions, and messages] is that all informational vehicles are material boundary conditions or constraints acting on the lawful dynamics of local systems.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p. 9.
“Classical physicists did not worry about the role of the observer in making measurements. This naive realism allows us to avoid explicit separation of the subjective model from its referent object; but historically this separation has always been lurking as a conceptual ‘loose end’ and it is still lurking in philosophy, physics, biology, cognitive science, and psychology.
“In both relativity and quantum theory the necessity of this separation of the observer and the observed became a foundational issue. I call this separation the epistemic cut, following physicists’ recognition of this essential distinction. The separation is epistemic, by definition, but the cut is one of the modern physicists’ metaphors. It is a metaphor because what is actually involved in separating knowledge of the world from the world itself is not simple like a cut, but a profoundly complex process that philosophers and modern physicists still actively puzzle over. Plato made this cut between the men carrying implements and their shadows in his cave, and the cut mislead Descartes to believe in ontological dualism. Today, physicists can’t explain measurement in terms of laws, and brain theorists can’t explain consciousness in terms of physics because of the complexity and obscurity of this metaphorical cut. For convenience I call the problem of bridging all levels of epistemic cuts the symbol-matter problem.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. pp. 9-10.
“In order to keep this discussion at a reasonable length, I characterize four hierarchical levels of biological information: (1) syntactic information, meaning information described by Shannon’s Communication Theory that is about the logical and statistical limits of storing, sending, and receiving messages in the presence of noise without regard to symbol definition, interpretation, or use of the message, (2) heritable information, meaning the information evolved and stored in genes or other heritable structures that arises by replication, variation, and natural selection, (3) non-heritable sensory and cognitive information, meaning, information stored in nervous systems and brains, and acquired by observation and instruction, or created by cognitive variation and individual or cultural selection, and (4) measured information, meaning experimental observation or measurement of a physical system in the context of a theory of natural laws.
“Notice that these levels form a dependency hierarchy. That is, although syntactic information is meaningless, (1) all semantic information must conform to the logical limitations of syntactic communication – even human thought. (2) All non-heritable information depends on the heritable information that has evolved nervous systems, sensorimotor controls, and brains. (3) All experimental measurements in physics depend on non-heritable information that creates theories of natural laws, and the language and mathematics in which theories can be expressed.
“There is also a temporal scale hierarchy of information that covers an enormous range (over 30 orders of magnitude), and therefore requires a hierarchy of dynamical models. The oldest heritable information is probably more than a billion years (~1017 sec.) old and is still expressed in DNA sequences in present organisms including humans. Non-heritable recorded information has a relatively short span and covers time scales from thousands of years (~1011 sec.) from the origin of writing to individual human memory span that includes long term (~109 sec.) and short term time scales. Time scales for non-heritable and non-recorded or dynamic information, as in sensorimotor control, is in milliseconds for organisms, and much shorter for artifacts. Time scales for information obtained by measurements is at the femtosecond (~10-15 sec.) time scale. In many ways this parallels the dependency hierarchy because it follows an evolutionary sequence. For example, millisecond dynamic sensorimotor information depends on molecules synthesized from 100 million-year-old heritable information.
“I believe that these information hierarchies are also unavoidable semiotic hierarchies, and that all signs are forms of information that fall within these hierarchical levels. What I want to emphasize is that the acquisition, execution, interpretation, and meaning of information (and signs) is different at all these levels, even though there are common requirements for all levels. These common requirements include, (1) all information and sign vehicles are executed or interpreted by acting as constraints on a lawful dynamics, (2) there must be an epistemic cut between the information and what it is about, (3) the information must satisfy the statistical limits of communication theory, and (4) the information must satisfy the physical limits on execution of information required by the nature of constraints and natural laws.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. pp. 11-12.
“What is a complete language? This should be a foundational issue for biosemiotics. Lacking a clear answer we can still recognize some conditions for a complete language: (1) It has the expressive power to generate endless novelty – in genetic language this includes all varieties of life, and in human language all varieties of thought. (2) It uses only a small stable set of elements like molecules or alphabets that occur in discrete sequences. (3) It has a small stable syntax like codes or grammars. (Stable means slow to change relative to the rate of productions in the language.)… Nevertheless, genetic and human languages are the only known symbol systems that satisfy these criteria for a complete or general purpose language.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 12.
“The most common view is that information indicates a difference or makes a distinction. What is the most primitive distinction? Or put another way, what kinds of universes would allow an agent to make distinctions? The physicist Eugene Wigner thought about these extremes. At one extreme, think of a universe that is totally disordered in every detail without any regular events. In total disorder one cannot imagine distinguishing anything, let alone signs and life. At the other extreme, consider a universe that is totally ordered and strictly deterministic in every detail. In this total order no alternatives can exist to distinguish, so information and life would also be impossible.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 13.
“It was Newton who first clearly recognized that events must be separated into the regular laws of motion that do not depend on the state of the observer, and the non-regular initial conditions that depend on the choice of an observer of what and when to measure….
“It turns out, then, that our intuitive concept of semantic information makes sense only if our models of the universe reflect two complementary modes of description that we associate with necessary events and events of choice…
“Physics formally distinguishes these complementary modes as laws and initial conditions. Laws are necessary, but measurements of initial conditions are made by choice of an observer or agent. This choice is undeterminable by laws. No two individuals directly perceive their detailed environments (their initial conditions) in exactly the same way, if only because they are in different locations; but objectivity requires that all individuals must agree on the necessary laws that are those relations that are common to all observations (all initial conditions). Wigner expressed how we should think about a natural law: ‘We should always have the impression that it could not be otherwise.’ Consequently, information is meaningful only for those events that could be otherwise. In fact, information capacity is defined by the logarithm of the number of ‘otherwise’ physically accessible alternatives.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 14; reference: Wigner, Eugene. 1967. “The problem of measurement.” In: Symmetries and Reflections. Bloomington, Indiana: The University Press.
“Laws are energy-based and initial conditions are information-based. In physics, information vehicles must have distinguishable alternative states, and for optimal information capacity these states must have the same energy. They are called degenerate states….
“It is for these reasons that the epistemological concept of information requires vehicles that belong in the category of initial conditions and local boundary conditions, as was explained by Polanyi. Information vehicles, which include all signs and symbols, are a special type of local boundary condition physicists call constraints. A constraint is any local physical structure that limits or alters lawful dynamics…. In physical terms, all information and sign vehicles, both discrete and continuous, are executed or interpreted by acting as constraints on a lawful dynamics.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 14; reference: Polanyi, M. 1968. “Life’s irreducible structure.” Science. 160:1308-1312.
“Constraints make no sense outside the context of the law-based physical dynamics which they constrain. This is also the case for information and signs. The concepts of information and signification make no sense outside the context of the physical system which they inform or signify.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 15.
“From this physical point of view, life can be described as the result of an optimum level of constraint – a fortuitous balance of determined and undetermined behaviors that is available to matter only within a very narrow range of cosmic energies that allows local stable heritable structures (memory) to constrain state-determined (memoryless) dynamical laws.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 15.
“The statement: ‘Life consists of individual cells that exert control in a universe of uncontrollable universal laws’ sounds paradoxical unless you understand that cells do not control the laws themselves but only the initial conditions that laws leave undetermined. The separation of inexorable universal laws and an organism’s control of local initial conditions is recognized explicitly in physics by the necessity of clearly separating the organism’s detection or sensing structures from the system being detected. This separation is the lawfully undeterminable epistemic cut.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 15.
“There is also a formal argument to justify epistemic duality. All the fundamental most detailed (microscopic) laws are expressed as rate-dependent equations that are reversible (time-symmetric). However, any measurement is conceptually irreversible. That is, conceptually the results of a measurement cannot exist before the measurement. Also, a measurement cannot be perfectly exact. A single model cannot be both reversible and irreversible. One must therefore always make a decision where to separate the measurement itself from the system being measured – an agent must make an epistemic cut. The point is that where the cut is made is arbitrary, and therefore not a consequence of objective laws.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 16.
“The empirical evidence of evolution is that about 4 billion years ago there emerged cells with heritable information in the form of simple molecules that gradually evolved complex nervous systems and eventually human brains. Only at this human level can we think about how all these earlier emergent forms of matter came about – the most basic question being: When can we objectively say that matter acts as a sign?…
“Of course the origin of life is still mysterious, but from our knowledge of physics it is possible to imagine how organized molecules can become symbols that instruct replication. But from our knowledge of physics it is not possible to imagine how organized symbols can become molecules [criticizing Hoffmeyer].” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. pp [unsure page numbering, not final version]. 17-18; reference: Hoffmeyer, J. 2008. Biosemiotics. Scranton, PA: U of Scranton Press.
“What measuring (reading) the DNA must do is to distinguish the base sequence structure that stores the information from all the non-informational support structures. I argued that only the specificity of substrate binding of enzymes and RNAs could execute such a classification. In this case, if the cell is an autonomous agent, the enzyme’s chemical specificity amounts to the cell’s choice of what to measure.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 19.
“In addition to von Neumann’s logical conditions for open-ended evolution, evolvable informational constraints must also satisfy these additional conditions:
“(1) energy degenerate memory structure (storage)
“(2) replication and transmission of this structure (copying)
“(3) syntactic translation of information (coding)
“(4) activation of information (e.g., protein folding, a symbol-matter bridge)
“(5) specific, local rate control by the informational constraints (execution semantics)
“(6) coordination of controls to replicate and maintain the integrity of the organism (pragmatics)
“(7) reliability enough to prevent error catastrophe
“(8) variability enough to evolve.
“These last two competing conditions are not easy to satisfy as evidenced by the fact that most species have become extinct.
“Energy degeneracy, stability, and random access memory implies time and rate independence. More precisely, the events of such memory have no temporally coherent relation to the dynamical time of the systems they control. This means the process of reading and interpreting symbolic memory structures, like genes, texts, logical and mathematical expressions, and computer programs are essentially rate-independent, unlike physical laws. For example, the same protein results from a given gene whether its synthesis is fast or slow.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. pp [unsure page numbering, not final version]. 20-21.
“The fact that genetic information defines a unique source of order that is crucial for evolution does not mean that it is the only source of order. Physical laws and many non-genetic, self-organizing, and developmental constraints are necessary at every stage of the execution of genetic information.
“The best analogy to genetic information I know is the information in the score of a symphony. The score is an essential part of the music, but a very small part compared to its execution in an actual performance. The symbols of the score uniquely define the opus but the score indicates nothing of the complexity of execution and the effects on the audience…. However, this analogy is too simple and breaks down because of the complexity of epigenetic and developmental feedback networks that continually and strongly affect the expression of the genes. Musicians are all reading the same page of the score. In an organism each cell can turn to a different page of its genome.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 21.
“Natural selection is a complex unpredictable process that affects every level of biological organization. It is also a never-ending process that includes all present and future statistical biases that alter a population distribution. Since there can be no experimental evidence of ‘all present or future biases’ we can predict very little about evolution.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 22.
“One can think of heritable information as the minimum amount of constraint that allows survival. This is certainly not the case for human information. Some language is necessary for culture, but we do not know how much information is actually biologically or culturally adaptive. In our ‘information age’ most human information has now become so cheap and biologically irrelevant that selection is no longer effective. Many historians and social observers doubt that our information is even culturally adaptive, and some claim it is evidence of cultural decadence. Uncontrolled growth of information like uncontrolled growth of cells is likely to become malignant.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 22.
“In the context of the cell, folding [a protein sequence] is the primordial case of bridging an epistemic cut. Folding removes the energy degeneracy of one-dimensional information vehicles and allows the quiescent symbolic information to control the enzyme’s dynamics in a three-dimensional world of energy and rate-dependent physical laws.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 22.
“At this folding process [of a protein sequence] we lose any clear definition or unique means of measuring information in the molecule because the non-dynamic informational constraints of the linear genetic sequence become inseparably incorporated into the physical dynamics….
“Fortunately, the continuous dynamics of enzyme-catalyzed reactions increases rates so enormously that their description can be usefully simplified by representing them as discrete switching events.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 23.
“Folding is just the first step of interpretation. A second level of interpretation is the enzyme’s recognition of the substrate (another metaphor) and catalysis. A third level of interpretation is in the metabolic network in which the enzyme functions – and so forth, from the cell’s interpretation to the organism’s, to the ecosystem’s, and to the final interpretation by natural selection. These increasing levels of material complexity form a structural hierarchy, but the information itself is not hierarchical because information flow goes in all directions forming an interpretative network with connections between nodes at all levels…. Interpretive networks allow many forms of meta-language and recursive self-reference. This is another condition for a complete language. At the same time it makes even partial interpretation extremely complex, and because natural election is open-ended there can be no final interpretation or final meaning of life.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 24.
“The differences between genetic and human language are as important as their fundamental similarities, as would be expected after 4 billion years of evolution. The fact that genetic information is heritable and cognitive information is not, makes a profound difference in how we think about its acquisition and interpretation. The defining difference is that variation in genetic information must be expressed before selection can begin. Natural selection operates only through the phenotype, not directly on the genotype. Human brains, in contrast, have the enormous advantage of being able to acquire, evaluate, and select information before expression. In other words, humans can think before they act.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 24.
“However, any science of biosemiotics must incorporate the evidence that all signs and meaning, throughout the entire course of evolution, and including human thought, must satisfy certain conditions. These include: (1) Information is physically executed by acting as local structural constraints on a lawful dynamics, (2) there are logical and statistical limits on storage and communication of information, (3) there are physical restrictions on the type of constraints that execute information, (4) all information and sign vehicles are interpreted by autonomous agents defined by semiotic closure, and (5) these agents must establish a cut separating the information vehicle from what the information is about. This epistemic cut is not a paradox. It distinguishes symbol from matter, information from natural laws, and the living from the lifeless. It is a necessary condition for life and knowledge to have meaning.” Pattee, Howard. 2013. “Epistemic, Evolutionary, and Physical Conditions for Biological Information.” Biosemiotics. 6:9-31. 10.1007/s12304-012-9150-8. p [unsure page numbering, not final version]. 26.
“… we borrow from physics the idea of a reference frame (RF), a standard or coordinate system that assigns units of measurement to observations, and thereby renders them comparable with other observations. Clocks, meter sticks, and standardized masses are canonical physical RFs. We show … that organisms must implement internal RFs to enable comparability between observations, and make explicit the role of RFs in predictive-coding models of cognition….
“A ‘difference which makes a difference’ must, clearly, be recognized as a difference, i.e., as being different from something else. The ‘something else’ that allows differences to be recognized is an RF. Choosing an RF is choosing both a kind of difference to be recognized, e.g., a difference in size, shape, color, or motion, and a specific reference value, e.g., this big or that shape, that the difference is a difference from.” Fields, Chris & Michael Levin. 2020. “How Do Living Systems Create Meaning.” Philosophies. 5:36. 10.3390/philosophies5040036. p. 3.
“We suggest that, while memories may be stored either internally or externally, the mechanisms and consequences of access are the same. The distinction between ‘individual’ and ‘public’ memories is, therefore, unsustainable.” Fields, Chris & Michael Levin. 2020. “How Do Living Systems Create Meaning.” Philosophies. 5:36. 10.3390/philosophies5040036. p. 3.
“… the concept of an RF was originally developed within physics to formalize the pragmatic use of clocks, measuring sticks, and other tools employed to make measurements. In E. coli, however, we see an internal state being employed as an RF. This situation is completely general: any use of an external system as an RF presupposes the existence of an internal state that functions as an RF. An external clock, for example, can only register the passage of time for an observer with an internal RF that enables comparing the currently-observed state of the clock to a remembered past state.” Fields, Chris & Michael Levin. 2020. “How Do Living Systems Create Meaning.” Philosophies. 5:36. 10.3390/philosophies5040036. p. 5.
“How did evolution get from systems like E. coli that are restricted to tasting an environment that they may move in, but do not otherwise detect or represent, to systems like humans equipped with RFs for three-dimensional space and linear time, as well as RFs capable of identifying thousands of individual objects and tracking their state changes along multiple dimensions? This is the fundamental question for an evolutionary theory of cognition, one that goes far beyond what is standardly called ‘evolutionary psychology’….” Fields, Chris & Michael Levin. 2020. “How Do Living Systems Create Meaning.” Philosophies. 5:36. 10.3390/philosophies5040036. p. 6.
“If distributed cognition is taken as a credible paradigm for cognitive science, this in turn presents a challenge to volition because the concept of volition assumes integrated information processing and action control…. The apparently centralized decision and action control processes of volition would be an illusion arising from the competitive and cooperative interaction of many relatively simple cognitive systems. Here I will make a case that this conclusion is not well-founded….
“According to the high-order control model, control competency is distributed across multiple systems, but systems are also organized hierarchically such that one or more high-order systems control multiple low-order systems, which are responsible for organizing effector output. Perceptual information flows to both low- and high-order control systems, and low-order controllers can be capable of generating action without higher order input. It is assumed that the architecture is the product of an evolutionary process in which higher order control has been progressively added to low-order controllers, which thus have substantial preexisting control capacity. Low- and high-order controllers are differentially specialized: low-order controllers for low-order control problems, and high-order controllers for high-order problems. High-order controllers provide flexible orchestration of low-order controllers, and increased specification and refinement of low-order competencies. For simple or routine activity high-order controllers may be minimally active. High-order controllers become maximally active in novel situations and for problems requiring complex information processing and action coordination.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. pp. 255-7.
“In fact the frame of reference [for the question of whether cognition is distributed or centralized] has been largely shaped by the advocacy of rival theoretical paradigms within cognitive science: the cognitivist symbolic computation paradigm, the connectionist artificial neural network paradigm, the behavior-based robotics paradigm, the dynamical systems paradigm, and the situated cognition paradigm. Collectively the latter four propose conceptions of cognition that are distributed in comparison with the cognitivist model.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. p. 257.
“The central type of evidence that a theory of cognitive architecture should explain, then, is large-scale patterns in the evolution of sensorimotor organization and behavior in metazoa….
“When measured against these conceptual and empirical criteria, the distributed cognition paradigm fares poorly. It does not provide a clear positive account of what cognition is and offers little purchase on the problem of specifying the nature of variations in cognitive ability. Consequently it doesn’t provide a structured basis for explaining the empirical distribution of cognition. To be fair, distributed cognition was not framed with these questions in mind; as noted above, it has rather been focused on drawing a contrast with the cognitivist paradigm.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. pp. 258, 259.
“Clearly, articulated action control can confer advantages by improving action targeting. I will refer to the relative advantage of more differentiated action production when there is selection for improved action targeting as articulation pressure….
“The effect of sustained articulation pressure is complexification. Increased complexity through differentiation and specialization permits more complex production processes through interaction between differentiated components. This allows more resources of greater variety to be brought to bear on action production. The list of adaptive benefits of complexity includes:
“Power….
“Specificity….
“Diversity….
“Accuracy….” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. pp. 263, 264.
“At the same time the cost of failing to achieve global coherence increases. This is because increases in functional complexity inherently tend to increase functional interdependency, but increased interdependency increases the likelihood that a functional failure somewhere in the system will propagate to downstream processes, resulting in a cascade of dysfunction. Thus, while the advantages of functional complexity depend on integration, increases in complexity make integration harder to achieve, and the costs of failing to achieve integration increase. I will refer to the escalating need for integration as complexity increases as integration pressure.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. pp. 264-5.
“Nervous systems first appeared in Cnidaria, carnivorous radially or biradially symmetric animals with a sac-like body and a single body opening (the mouth) surrounded by tentacles. The evolution of neurons from ectoderm constituted a major advance in regulatory capacity by permitting the specialization of sensory function (through sensory neurons), and by permitting the rapid and precise transmission of signals to muscle cells (through motor neurons). Sensory discrimination could become more sensitive, precise, and functionally differentiated (e.g., into different modalities). The addition of an intermediate layer of specialized communication between sensory function and motor output allows point-to-point, longer range information transmission, and creates the potential for divergence and convergence of information flow. Divergent signal paths allow a sensory neuron or sensory area to broadcast to many distant parts of the animal, permitting a rapid, coordinated whole-organism response to a sensory stimulus. Convergent signal pathways allow a given muscle cell to be sensitive to many different sensory neurons, and to the activity of other muscle cells. Thus, early neural evolution made possible much greater behavioral complexity and integration.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. p. 271.
“To casual observation the continuous unconscious bodily adjustments of the autonomic system might seem like a marvelous example of distributed organization…. When assessed in terms of anatomy and function, rather than in comparison with conscious control, the autonomic system is a centrally organized high-order control system. Invertebrates lack a specialized regulative system of comparable complexity and have much more limited capacity for coordinated bodywide physiological changes. Thus the autonomic system can be seen as a regulatory adaptation to the integration pressure posed by the complexity of vertebrate bodies and lifestyles.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. pp. 272-3.
“A notable feature of this hierarchy [of cognitive control under the prefrontal cortex] is that higher levels perform more complex forms of integration. Sensory control requires the least information, activating a stored motor program in response to an innate or learned stimulus. Contextual control is more demanding: information provided by the nature of the stimulus is not sufficient to determine what response is appropriate. It is necessary to draw on memory of the context in which the stimulus occurs. Episodic control is more complex again, requiring information both about context and current circumstances in order to determine the appropriate response…. This is counterevidence to the distributed cognition prediction that brain organization should feature multiple control centers with no significant hierarchical organization.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. pp. 278, 279.
“Taken together, these lines of research support the view that the PFC [prefrontal cortex] is a highest order executive control system with the kinds of properties that would be expected on the basis of the model of the evolution of high-order control described previously in this chapter. To reiterate, the highest level of control should integrate the greatest amount of information, have the widest control scope, and be responsible for the most complex action control problems. This conclusion is at odds with current distributed cognition principles. In light of the theoretical considerations outlined earlier, and the empirical evidence presented, there is a basis for suggesting that these principles should be reexamined. A reasonable conclusion to draw form the evidence is that the major claims of no significant hierarchical structure and no central system are falsified. There is certainly no central system of the kind envisioned by classical cognitive science, but a central system nevertheless. Yet in other respects the account developed here can be seen as supporting and extending the basic distributed cognition approach.” Christensen, Wayne. 2007. “The Evolutionary Origins of Volition.” Pp. 255-287. From Ross, Don, D. Spurrett & H. Kincaid. Distributed Cognition and the Will: Individual Volition and Social Context. MIT Press. p. 280.
“Stated simply, the allostery concept harkens back to the Roman deity Janus…. symbolized by his two faces and noted for presiding over all kinds of transitions. In this book, we will take a broad view of allostery as the phenomenon in which a molecule has more than one state of activity…. with the relative probabilities of those different states controlled by some effector(s).” Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery. Princeton UP. p. 3.
“… the interesting regulatory behavior of these molecules is that the binding of a ligand can change the relative probabilities of the inactive and active states. Specifically, the binding affinity of the ligand for each state is different, resulting in a shift in the relative probabilities of the inactive and the active conformations when the ligand concentration is changed.” Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery. Princeton UP. p. 4.
“The puzzle faced by early investigators of proteins that were subject to inhibition and activation was how a battery of regulatory molecules could be fine-tuned to fit into the active sites of their binding partners…. The simple answer is that often they don’t. Rather, groups in Paris and Berkeley realized that a different regulatory strategy could be ‘action at a distance,’ in which the binding of a regulatory ligand in one part of a macromolecule could lead to a conformational change elsewhere in the molecule such that the activity of the enzyme was changed. This thinking has been codified in the so-called Monod-Wyman-Changeux (MWC) model.” Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery. Princeton UP. p. 16.
“A central theme of the book is the power and beauty of coarse-grained descriptions that intentionally suppress reference to the microscopic degrees of freedom. A corollary of this point of view will be that sometimes we will have a measured indifference to the molecular particulars of a given problem.” Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery. Princeton UP. p. 28.
“A hallmark of cellular signaling and regulation is combinatorial control. Whether we are thinking about the enzymes of the glycolysis pathway or the transcription factors that control transcriptional networks, multiple inputs into the same pathway often give rise to a much richer response than can be achieved through single-input functions. That is, the response of a given signaling or regulatory architecture depends on the presence of more than one molecular species.” Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery. Princeton UP. p. 303.
“Part of the intent of this book is a tentative attempt at seeing how far we can go with a worldview that self-consciously eliminates molecular details. The thinking presented here attempts to intentionally coarse grain away things which we know to be true about the underlying molecules but for which we might not have to account.” Phillips, Rob. 2020. The Molecular Switch: Signaling and Allostery. Princeton UP. p. 396.
“Biological organisms ranging from bacteria to humans possess an enormous repertoire of genetic response to ever-changing combinations of cellular and environmental signals.” Buchler, Nicolas E., Ulrich Gerland & Terence Hwa. 2003. “On schemes of combinatorial transcription logic.” PNAS. April 29, 2003. 100(9):5136-5141. p. 5136.
“The transcription machinery can be regarded as a molecular computer, because it is capable of complex logic computations. Specifically, the molecular components (TFs and RNAP [transcription factors and RNA polymerase]) satisfying the two ingredients of regulated recruitment, i.e., continuously tunable protein-DNA-binding strengths and glue-like contact interaction between proteins and further supplemented by distal activation and/or repression mechanisms, constitute a flexible toolkit, a kind of molecular Lego set, that can be assembled in different combinations to perform the desired computations. This machine is a general-purpose computer, because its function can be ‘programmed’ at will through choices and placements of the protein-binding DNA sequences in the regulatory region of any gene. This should be contrasted with an alternative strategy of transcription control based on dedicated, complex (e.g., allosteric) protein-protein interactions: In the latter, complexity of the system is derived from the complexity of proteins, whereas in the former, complexity is derived combinatorially from the composition of the regulatory sequences (the ‘software’) alone without the need of tinkering with the proteins (the ‘hardware’). A notable advantage of encoding combinatorial control in the regulatory region, as opposed to in the regulatory proteins, is evolvability: unlike the regulatory proteins, each cis-regulatory region controls the expression of a given gene and hence can be programmed with minimal pleiotropic effects.” Buchler, Nicolas E., Ulrich Gerland & Terence Hwa. 2003. “On schemes of combinatorial transcription logic.” PNAS. April 29, 2003. 100(9):5136-5141. pp. 5139-40.
“A neural network can be ‘trained’ to perform complex tasks by adjusting its synaptic strengths. Similarly, the regulatory system we discuss can fine-tune or modify its control function by adjusting molecular interactions through a combination of the programmable protein-DNA and protein-protein interactions.” Buchler, Nicolas E., Ulrich Gerland & Terence Hwa. 2003. “On schemes of combinatorial transcription logic.” PNAS. April 29, 2003. 100(9):5136-5141. p. 5140.
“The organicists sought to offer a ‘third way’ into the mechanist-vitalist dispute that served as a middle ground between the austerity of the mechanists and the extravagance of the neovitalists….
“For the organicists, organization marked the decisive feature for demarcating living phenomena from non-living physico-chemical phenomena. Unlike the neovitalists, however, the organicists did not hold organization to be inscrutable, but rather an important explanandum of biological study.” Eronen, Markus I. & Daniel Stephen Brooks. 2023. “Levels of Organization in Biology.” Stanford Encyclopedia of Philosophy. pp. 4-5.
“The basic conclusion that Potochnik and other levels skeptics draw from this [previous discussion] is the following. The levels concept precludes a sophisticated discussion of philosophical and scientific issues by imposing an overly simplistic representation of science and nature. So, although perhaps no one would deny the attractiveness of ‘levels’ in seeking to make complex natural systems tractable to analysis, depicting these systems using the concept seems to do far more harm than good.” Eronen, Markus I. & Daniel Stephen Brooks. 2023. “Levels of Organization in Biology.” Stanford Encyclopedia of Philosophy. p. 22; reference: Potochnik, Angela. 2021. “Our World Isn’t Organized into Levels.” pp. 61-76. Brooks, Daniel S., James DiFrisco & William C. Wimsatt (eds). Levels of Organization in the Biological Sciences. MIT Press.
“The most striking general property of these molecules [large, biological molecules] is the specificity of their activity.” Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.” Nature. May 8. 4097:707-9. p. 707.
“Specificity is shown in a striking way by antibodies…. They have he power of combining specifically with the material (the antigen) that led to their production, and of neutralizing or incapacitating the antigen. Thus an antitoxin is able to neutralize its homologous toxin….” Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.” Nature. May 8. 4097:707-9. p. 708.
“A very high degree of specificity [for selecting an antibody] can be obtained if the surface area over which the complementariness of structure is exercised is great enough to include a good number of interacting structural units [positive charges in the chain in close proximity to negative charges in the antigen, and… hydrogen-bond-forming groups].” Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.” Nature. May 8. 4097:707-9. p. 708.
“Chemists are accustomed to using the process of crystallization as a method of purification: a crystal growing in a complex mixture of molecules is able to select from the mixture just the molecules of one kinds, rejecting all others. Thus pure crystals of sugar may deposit from a jam in which there are molecules of thousands of different substances. The specificity of crystallization is the result of the same striving toward complementariness and the operation of the same interatomic and intermolecular forces that are responsible for the specificity of antibodies.” Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.” Nature. May 8. 4097:707-9. p. 708.
“I believe that the same mechanism, dependent on a detailed complementariness in molecular structure, is responsible for all biological specificity.” Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.” Nature. May 8. 4097:707-9. p. 709.
“I believe that it is molecular size and shape, on the atomic scale, that are of primary importance in these phenomena, rather than the ordinary chemical properties of the substances, involving their power of entering into reactions in which ordinary chemical bonds are broken and formed.” Pauling, Linus. 1948. “Nature of Forces between Large Molecules of Biological Interest.” Nature. May 8. 4097:707-9. p. 709.
“Substances [at the time of the separation of organic chemistry from inorganic chemistry] were viewed as ‘organic’ if they irreversibly changed upon heating, and ‘inorganic’ if they reverted to their original forms when cooled.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 2.
“Many of the more recent definitions of life begin with seven key characteristics that must co-exist for something to be considered truly living: reproduction, growth and development, metabolism, biological evolution, a cellular basis and response….
“Koshland has targeted a separate set of seven pillars: program, improvisation, compartmentalization, energy, regeneration, adaptability and seclusion.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 2; reference: Koshland Jr, D.E. 2002. “The seven pillars of life.” Science. 295(5563):2215-2216.
“A different molecular perspective, that of ecosystem chemistry, has been advanced by Muchowska et al., who suggest that cellularity may merely represent a way of partitioning ecosystem- or planetary-scale metabolism in order to respond to resource heterogeneity across local environments.
“Thus, ecosystem chemistry may be more important than cellular partitioning.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 2; reference: Muchowska, K.B., S.J. Varma & J. Moran. 2020. “Nonenzymatic metabolic reactions and life’s origins.” Chem. Rev. 120(15):7708-7744.
“The first law of thermodynamics relates to quantity, and states that while energy can change from one form to another, the total amount of energy remains constant. The second law of thermodynamics relates to quality, stating that processes occur in the direction of decreasing quality of energy, from high quality with low entropy, such as solar radiation, to low quality with high entropy, such as heat. The second law of thermodynamics has three unique features. Firstly, it is the only physical law dealing with order. Secondly, it states that time has an arrow that tracks irreversible processes. Finally, it predicts the future as statistical probabilities, not certainties.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 3.
“Bauer [in Bauer’s principle of permanent non-equilibrium of living systems] defined life as follows: ‘We call living organisms any body system that is not in equilibrium in a given environment and is so organized that it transforms the energy of its environment into such forms of energy, which act in the given environment against the establishment of an equilibrium state’.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 3; subquote: Bauer, E. 1920. “Die Grundprinzipien der rein wissenschaftlichen Biologie und ihre Anwendungen in der Physiologie and Pathologie.” Vortaege und Aufsaetze ueber Entwicklungsmechanik der Organismen. Herausgegeben von Wilhelm Roux. Heft XXVI. Springer. p. 10.
“Interestingly, this latter definition [of life] fails to embrace viruses, nor obligate parasites as living, as neither are self-reproducing nor, for parts of their lifecycle, self-contained.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 4.
“Skene (2020) suggests that the central dogma acts as an entropy transition mechanism, ‘with increasing internal information entropy (as the genetic code is continuously randomized), and with increasing external entropy production (as increasingly more complicated structures and functions are produced in the form of new protein morphologies, again determined by the bioenergetic context). The loss of information at the genetic level results in potential gains in information at the protein level’….
“Skene (2020) referred to this as the genetic entropy paradox, wherein DNA increases in internal information entropy, as the genetic code is randomized through mutation, and yet has the potential to increase external entropy production, as increasingly more complex structures and functions are produced, along a path of increasing entropy in the form of new protein morphologies and metabolic pathways and increasing organismal complexity, allowing greater access to ecological space and therefore greater potential for entropic output.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 5; references: Skene, Keith R. 2020. “In pursuit of the framework behind the biosphere: S-curves, self-assembly and the genetic entropy paradox. Biosystems. 190(104101).
“Arango-Restrepo et al. demonstrate that while enzymatic evolution can be seen to enhance kinetics, more fundamentally, it maximizes total entropy production.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 6; reference: Arango-Restrepo, A., J.M. Rubi & D. Barragan. 2018. “Enzymatic Evolution Driven by Entropy Production.” bioRxiv. 319814.
“The supply chains upon which a particular individual organism requires, potentially including a mate for sexual reproduction, mean that there is an obligate interaction with many components within the Earth system. This is what results from existing far-from-equilibrium in an entropic universe
“We propose that the glue holding the various components together, be they lichen, mycorrhiza, or food webs, is the increased dissipation of free energy achievable through such interactions. Thus, ‘altruism’ is driven by the second law of thermodynamics as are the many other relationships found throughout the Earth system.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 7.
“Self-organization can be defined as the difference between the information the system receives (input) and the information the system produces (output).” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 8.
“In their native states, natural proteins are not optimized for thermal stability. This is thought to be because this would impact on the ability to degrade proteins when necessary. Interestingly, a similar principle relates to designing long-life products in manufacturing. While they may reduce the need for material turnover in replacing short life products, the energetic and chemical demands in ultimately recycling them would be extremely high. Thus, generally in the Earth system, rapid turnover is favourable, freeing up resources and allowing access to otherwise locked-up materials.” Skene, Keith R. 2024. “Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.” BioSystems. 236(105123):1-15. 10.1016/j.biosystems.2024.105123. p. 10.
“Warren Weaver (1894-1978), one of the pioneers of machine translation and co-author with Shannon of The Mathematical Theory of Communication, supported a tripartite analysis of information in terms of
“1) technical problems concerning the quantification of information and dealt with by Shannon’s theory;
“2) semantic problems relating to meaning and truth; and
“3) what he called ‘influential’ problems concerning the impact and effectiveness of information on human behaviour, which he thought had to play an equally important role.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 2.
“The life cycle of information typically includes the following phases: occurrence (discovering, designing, authoring, etc.), transmission (networking, distributing, accessing, retrieving, transmitting, etc.), processing and management (collecting, validating, modifying, organizing, indexing, classifying, filtering, updating, sorting, storing, etc.), and usage (monitoring, modelling, analysing, explaining, planning, forecasting, decision-making, instructing, educating, learning, etc.).” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 4.
“During this span of time [12 millennia from beginning of Neolithic to 2000], Information and Communication Technologies (ICTs) evolved from being mainly recording systems – writing and manuscript production – to being also communication systems, especially after Gutenberg and the invention of printing – to being also processing and producing systems, especially after Turing and the diffusion of computers.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 4.
“In many respects, we are not standalone entities, but rather interconnected informational organisms or inforgs, sharing with biological agents and engineered artefacts a global environment ultimately made of information, the infosphere. This is the informational environment constituted by all informational processes, services, and entities, thus including informational agents as well as their properties, interactions, and mutual relations.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 9.
“Augmenting appliances have instead interfaces that allow communication between different possible worlds. For example: on one side, there is the human user’s everyday habitat, the outer world, or reality, as it affects the agent inhabiting it; and on the other side, there are the dynamic, watery, soapy, hot, and dark world of the dishwasher; the equally watery, soapy, hot, and dark but also spinning world of the washing machine; or the still, aseptic, soapless, cold, and potentially luminous world of the refrigerator. These robots can be successful because they have their environments ‘wrapped’ and tailored around their capacities, not vice versa. This is why it would be a silly idea to try to build a droid, like Star Wars’ C3PO, in order to wash dishes in the sink exactly in the same way as a human agent would. Now, ICTs are not enhancing or augmenting in the sense just explained. They are radically transforming devices because they engineer environments that the user is then enable to enter through (possibly friendly) gateways, experiencing a form of initiation. There is no term for this radical form of re-engineering, so we may use re-ontologizing as a neolgism to refer to a very radical form of re-engineering, one that not only designs, constructs, or structures a system (e.g. a company, a machine, or some artefact) anew, but that fundamentally transforms its intrinsic nature, that is, its ontology. In this sense, ICTs are not merely re-engineering but actually re-ontologizing our world….
“To return to our distinction, while a dishwasher interface is a panel through which the machine enters into the user’s world, a digital interface is a gate through which a user can be present in cyberspace. This simple but fundamental difference underlies the many spatial metaphors of ‘virtual reality’, ‘being online’, ‘surfing the web’, ‘gateway’, and so forth. It follows that we are witnessing an epochal, unprecedented migration of humanity from its ordinary habitat to the infosphere itself, not least because the latter is absorbing the former. As a result, humans will be inforgs among other (possibly artificial) inforgs and agents operating in an environment that is friendlier to informational creatures.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 10-12.
“… in the near future, the very distinction between online and offline will disappear. The common experience of driving a car while following the instructions of a Global Positioning System clarifies how pointless asking whether one is online has become. To put it dramatically, the infosphere is progressively absorbing any other space.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 16.
“But in advanced information societies, what we still experience as the world offline is bound to become a fully interactive and more responsive environment of wireless, pervasive, distributed, a2a (anything to anything) information processes, that works a4a (anywhere for anytime), in real time. Such a world will first gently invite us to understand it as something ‘a-live’ (artificially live). This animation of the world will then, paradoxically, make our outlook closer to that of pre-technological cultures, which interpreted all aspects of nature as inhabited by teleological forces….
“… we shall be living in an infosphere that will become increasingly synchronized (time), delocalized (space), and correlated (interactions).
“… we shall see that we should probably be working on an ecology of the infosphere, if we wish to avoid foreseeable problems.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 17, 18.
“Over the past decades, it has become common to adopt a General Definition of Information (GDI) in terms of data + meaning.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 20.
“The General Definition of Information (GDI)
“σ is an instance of information, understood as semantic content, if and only if:
“σ consists of n data, for n ≥ 1;
“the data are well formed;
“the well-formed data are meaningful.
“…‘well formed’ means that the data are rightly put together according to the rules (syntax) that govern the chosen system, code, or language being used. Syntax here must be understood broadly, not just linguistically, as what determines the form, construction, composition, or structuring of something.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 20-21.
“For the presence of a white page is still a datum, as long as there is a difference between the white page and the page on which something is or could be written. Compare this to the common phenomenon of ‘silent assent’: silence, or the lack of perceivable data, can be as much a datum as the presence of some noise, exactly like the zeros of a binary system…. This clarifies why a datum is ultimately reducible to a lack of uniformity.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 22-23.
“First, data can be lacks of uniformity in the real world. There is no specific name for such ‘data in the wild’. One may refer to them as dedomena, that is, ‘data’ in Greek. Dedomena are not to be confused with environmental information, which will be discussed later…. They are pure data, that is, data before they are interpreted or subject to cognitive processing.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 23.
“Environmental information = two systems a and b coupled in such a way that a’s being (of type, or in state) F is correlated to b being (of type, or in state) G, thus carrying for the observer of a the information that b is G.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 33.
“Whether environmental or semantic, instructional information is not about a situation, a fact, or a state of affairs ω and does not model, or describe, or represent ω. Rather, it is meant to (contribute to) bring about ω.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 35.
“After Shannon, MTC [mathematical theory of information] became known as information theory…. The term ‘information theory’ is an appealing but unfortunate label, which continues to cause endless misunderstandings. Shannon came to regret its widespread popularity, and I shall avoid it in this context.
“MTC is the theory that lies behind any phenomenon involving data encoding and transmission. As such, it has had a profound impact on the analyses of the various kinds of information….
“MTC treats information as data communication, with the primary aim of devising efficient ways of encoding and transferring data.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 38.
“Compression procedures, such as those used to reduce the digital size of photographs, work by reducing data redundancy, but redundancy is not always a bad thing, for it can help to counteract equivocation (data sent but never received) and noise.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 43.
“… MTC is not a theory of information in the ordinary sense of the word. In MTC, information has an entirely technical meaning. For a start, according to MTC, two equiprobable ‘yes’ answers contain the same amount of information, no matter whether their corresponding questions are ‘is the battery flat?’ or ‘would you marry me?’. If we knew that a device could send us, with equal probabilities, either this book or the whole Encyclopedia Britannica, by receiving one or the other we would receive very different amounts of bytes of data but actually only one bit of information in the MTC sense of the word.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 44.
“… since MTC is a theory of information without meaning (not in the sense of meaningless, but in the sense of not yet meaningful), and since [information – meaning = data], ‘mathematical theory of data communication’ is a far more appropriate description of this branch of probability theory than ‘information theory’. This is not a mere question of labels. Information, as semantic content, can also be described as data + queries. Imagine a piece of information such as ‘the earth has only one moon’. It is easy to polarize almost all its semantic content by transforming it into a [query + binary answer], such as [does the earth have only one moon? + yes]. Subtract the ‘yes’ – which is at most one bit of information – and you are left with all the semantic content, with all the indications of its truth or falsity removed.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 44-5.
“The informational and the thermodynamic concept of entropy are related through the concepts of probability and randomness. ‘Randomness’ is better than ‘disorder’, since the former is a syntactical concept, whereas the latter has a strongly semantic value, that is, it is easily associated to interpretations…. Entropy is a measure of the amount of ‘mixedupness’ in processes and systems bearing energy or information. It can also be seen as an indicator of reversibility: if there is no change of entropy then the process is reversible. A highly structured, perfectly organized message contains a lower degree of entropy or randomness, less information in the Shannon sense, and hence it causes a smaller data deficit, which can be close to zero [e.g. same response no matter what].” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 47.
“MTC is not interested in the meaning, reference, relevance, reliability, usefulness, or interpretation of the information exchanged, but only in the level of detail and frequency in the uninterpreted data that constitute it.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 48.
“Knowledge and information are members of the same conceptual family. What the former enjoys and the latter lacks, over and above their family resemblance, is the web of mutual relations that allow one part of it to account for another. Shatter that, and you are left with a pile of truths or a random list of bits of information that cannot help to make sense of the reality they seek to address. Build or reconstruct that network of relations, and information starts providing that overall view of the world which we associate with the best of our epistemic efforts. So once some information is available, knowledge can be built in terms of explanations or accounts that make sense of the available semantic information.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 51.
“Thermodynamics and information theory are often allies sharing one goal: the most efficient use of their resources, energy, and information.
“Their potential degree of efficiency might seem to be boundless: the better we can manage information (e.g., extract or process more information with the same or less energy), the better we can manage energy (extract more, recycle more, use less or better), which can then be used to improve information processes further, and so forth.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 62.
“… data in the wild were described as ‘fractures in the continuum’ or lacks of uniformity in the fabric of reality.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 69.
“First, it will be useful to recall that there are three main ways of talking about information:
“(a) Information as reality, e.g. patterns, fingerprints, tree rings;
“(b) Information for reality, e.g. commands, algorithms, recipes;
“(c) Information about reality, i.e. with an epistemic value, e.g. train tables, maps, entries in an encyclopaedia.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 74.
“Rather, genes are instructions, and instructions are a type of predicative and effective/procedural information, like recipes, algorithms, and commands. So genes are dynamic procedural structures that, together with other indispensable environmental factors, contribute to control and guide the development of organisms…. Dynamic procedural structures are a special type of informational entities, those that are in themselves instructions, programs, or imperatives.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 79-80.
“In imperative programming, statements change a program state and programs are a sequence of commands for the computer to perform. Each step (each base) is an instruction, and the physical environment holds the state that is modified by the instruction. The relation between instructions (genes, imperative programs, recipes) and the outcome is still functional, causal, and based on laws, but no semantics needs to be invoked…. Biological information, in the predicative sense of the world [= ‘word’?], is procedural: it is information for something, not about something.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 80.
“A living system is any anti-entropic informational entity, i.e. an informational object capable of instantiating procedural interactions (it embodies information-processing operations) in order to maintain its existence and/or reproduce itself (metabolism).” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 82.
“… it should become clear what information ethics amounts to. It is an ecological ethics that is still patient-oriented but replaces biocentrism with ontocentrism. It suggests that there is something even more elemental than life, namely being – that is, the existence and flourishing of all entities and their global environment – and something even more fundamental than suffering, namely entropy. The latter is most emphatically not the concept of thermodynamic entropy…. Entropy here refers to any kind of destruction, corruption, pollution, and depletion of informational objects (mind, not just of information as semantic content), that is, any form of impoverishment of reality. Information ethics then provides a common vocabulary to understand the whole realm of being informationally. It holds that being/information has an intrinsic worthiness. It substantiates this position by recognizing that any informational entity has a right to persist in its own status, and a right to flourish, i.e. to improve and enrich its existence and essence. As a consequence of such ‘rights’, information ethics evaluates the duty of any moral agent in terms of contribution to the growth of the infosphere and any process, action, or event that negatively affects the whole infosphere – not just an informational entity – as an increase in its level of entropy and hence an instance of evil.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. pp. 112-3.
“By then [2020], it is estimated that the carbon footprint of ICTs will be higher than that of aviation. However, according to recent studies, ICTs will also help to eliminate almost 8 metric gigatons of greenhouse gas emissions annually by 2020, which is equivalent to 15% of global emissions today and five times more than the estimated emissions from ICTs in 2020.” Floridi, Luciano. 2010. Information: A Very Short Introduction. Oxford UP. p. 120.
“RNA’s building blocks, nucleotides, are complex substances as organic molecules go. They each contain a sugar, a phosphate and one of four nitrogen-containing bases as sub-subunits. Thus, each RNA nucleotide contains 9 or 10 carbon atoms, numerous nitrogen and oxygen atoms and the phosphate group, all connected in a precise three-dimensional pattern. Many alternative ways exist for making those connections, yielding thousands of plausible nucleotides that could readily join in place of the standard ones but that are not represented in RNA. That number is itself dwarfed by the hundreds of thousands to millions of stable organic molecules of similar size that are not nucleotides.” Shapiro, Robert. 2007. “A Simpler Origin for Life.” Scientific American. June. Pp. 129-136. p[?]: 131.
“The theories [for an alternative definition of life] employ a thermodynamic rather than a genetic definition of life, under a scheme put forth by Carl Sagan in the Encyclopedia Britannica: A localized region which increases in order (decreases in entropy) through cycles driven by an energy flow would be considered alive.” Shapiro, Robert. 2007. “A Simpler Origin for Life.” Scientific American. June. Pp. 129-136. p[?]: 133.
“The exquisite selectivity of enzyme catalysis was recognised as early as 1894 by Emil Fischer, who demonstrated that the enzyme which hydrolyses sucrose, which he called ‘invertin’, acts only upon α-D-glucosides, whereas a second enzyme ‘emulsin’ acts only upon β-D-glucosides.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 1.
“At the same time as the discovery of enzymes in the late 19th and early 20th centuries, a class of biologically important small molecules was being discovered which had remarkable properties to cure certain dietary disorders. These molecules were christened the vitamins, a corruption of the phrase ‘vital amines’ used to describe their dietary importance (several of the first-discovered vitamins were amines, but this is not true of all the vitamins)….
“Many of the vitamins are in fact co-enzymes: small organic co-factors which are used by certain types of enzyme in order to carry out particular classes of reaction.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 3.
“If there is an essential enzyme found uniquely in a certain class of organisms or cell type, then a selective inhibitor of that enzyme could be used for selective toxicity against that organism or cell type. Similarly, if there is a significant difference between a particular enzyme found in bacteria as compared with the same enzyme in humans, then a selective inhibitor could be developed for the bacterial enzyme.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 6.
“Enzymes are giant molecules. Their molecular weight varies from 5,000 to 5,000,000 Da, with typical values in the range of 20,000–100,000 Da. At first sight this size suggests a bewildering complexity of structure, yet as we shall see that enzymes are structurally assembled in a small number of steps in a fairly simple way.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 7.
“One of the hallmarks of enzyme catalysis is its high substrate selectivity, which is due to a series of highly specific non-covalent enzyme-substrate binding interactions. Since the active site is chiral, it is naturally able to bind one enantiomer of the substrate over the other, just as a hand fits a glove. There are four types of enzyme-substrate interactions used by enzymes, as follows:
“1) Electrostatic Interactions….
“2) Hydrogen Bonding…. The strength of hydrogen bonds depends upon the chemical nature and the geometrical alignment of the interacting groups. Studies of enzymes in which hydrogen-bonding groups have been specifically mutated has revealed that hydrogen bonds between uncharged donors/acceptors are of energy 2.0–7.5 kj mol-1, whilst hydrogen bonds between charged donors/acceptors are much stronger, in the range 12.5–25 kJ mol-1.
“3) Non-Polar (Van der Waals) Interactions. Van der Waals interactions arise from interatomic contacts between the substrate and the active site. Since the shape of the active site is usually highly complementary to the shape of the substrate, the sum of the enzyme-substrate Van der Waals interactions can be quite substantial (50–100kJ mol-1), even though each individual interaction is quite weak (6-8 kJ mol-1). Since the strength of these interactions varies with 1/r6 they are only significant at short range (2-4 Å), so a very good ‘fit’ of the substrate into the active site is required in order to realise binding energy in this way.
“4) Hydrophobic Interactions. Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. pp. 17-19.
“Enzymes are highly selective in the reactions that they catalyse.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 27.
“It is worth at this point distinguishing between selectivity, which is the ability of the enzyme to select a certain substrate or functional group out of many; and specificity, which is a property of the reaction catalysed by the enzyme, being the production of a single regio- and stereo-isomer of the product.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 28.
“In thermodynamic terms, catalysis of a chemical reaction is achieved by reducing the activation energy for that reaction, the activation energy being the difference in free energy between the reagent(s) and the transition state for the reaction. This reduction in activation energy can be achieved either by stabilisation (and hence reduction in free energy) of the transition state by the catalyst, or by the catalyst finding some other lower energy pathway for the reaction….
“It is important at this point to define the difference between an intermediate and a transition state: an intermediate is a stable (or semi-stable) chemical species formed during the reaction and is therefore a local energy minimum, whereas a transition state is by definition a local energy maximum.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 28.
“However, the secret to the extra-ordinary power of enzyme catalysis lies in the fact that the reaction is taking place as the substrate is bound to the enzyme active site. So what was in the non-enzymatic case an intermolecular reaction has effectively become an intramolecular reaction.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 29.
“Intramolecular reactions generally proceed much more rapidly and under much milder reaction conditions than their intermolecular counterparts, which makes sense since the two reacting groups are already ‘in close proximity’ to one another. But how can we explain these effects?
“A useful concept in quantitating proximity effects is that of effective concentration. In order to define the effective concentration of a participating group (nucleophile, base, etc.), we compare the rate of the intramolecular reaction with the rate of the corresponding intermolecular reaction where the reagent and the participating group are present in separate molecules. The effective concentration of the participating group is defined as the concentration of reagent present in the intermolecular reaction required to give the same rate as the intramolecular reaction.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 30.
“The binding of substrates and cofactors at an enzyme active site of defined three-dimensional structure brings the reagents into close proximity to one another and to the enzyme active site functional groups. This increases the probability of correct positioning for reaction to take place, so it speeds up the reaction…. Recent studies have concluded that the thermodynamic origin of this kinetic advantage in enzyme catalysis is primarily enthalpic, rather than entropic. Nevertheless, the catalytic power of proximity effects, or ‘preorganisation’, has been demonstrated by the synthesis of host-guest systems which mimic enzymes by binding substrates non-covalently.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 32.
“… in order to achieve optimal catalysis, enzymes should selectively bind the transition state, rather than the substrate. Hence it is not advantageous for enzymes to bind their substrates too tightly.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 33.
“Enzymes also have the ability to carry out bifunctional catalysis: protonation of the substrate at the same [time?] as deprotonation in another part of the molecule.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 38.
“Remember that the over-riding factor in achieving rate acceleration in enzyme-catalysed reactions is the difference in free energy between the ES [intermediate complex of enzyme and substrate upon binding] complex and the transition state of the enzymatic reaction. If the enzyme can somehow bind the substrate in a strained conformation which is closer to the transition state than the ground state conformation, then the difference in energy between the bound conformation and the transition state will be reduced, and the reaction will be accelerated.
“How can an enzyme bind its substrate in a strained conformation: Is that not energetically unfavourable? The answer to these questions is that if the substrate is of a reasonable size, the enzyme can form a number of enzyme-substrate binding interactions, and the total enzyme-substrate binding energy can be quite substantial. In some cases, in order to benefit from the most favourable overall binding interactions, the substrate must adopt an unfavourable conformation in a part of the molecule. That part of the substrate may happen to be where the reaction is going to take place! In thermodynamic terms, the enzyme uses its favourable binding energy in the rest of the substrate to compensate for the adoption of an unfavourable conformation in the strained part of the molecule.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 44.
“For extremely efficient enzymes, the rate of reaction becomes limited by the rate at which a substrate can diffuse onto its active site and diffuse away into solution – the so-called diffusion limit.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 46.
“Examination of protein structure in solution by NMR spectroscopy has revealed that there is a significant amount of internal motion in a protein on a timescale of 1-10 nanoseconds, and also slower movements of loops and domains which take place on timescales of 0.1-100 microseconds. Such internal motion could transmit kinetic energy from a distant part of the protein to the active site, in order to assist in catalysis (typical kcat values are 0.1-100 s-1, so a typical turnover would take 10-10,000 milliseconds). It has been proposed that dynamic fluctuations in the protein structure are used by enzymes to organise the enzyme-substrate complex into a reactive conformation.” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 47.
“The final group of enzymatic transformations that we shall meet are the isomerisation reactions: the interconversion of two isomeric forms of a molecule. The interconversion of enantiomers is catalysed by racemase enzymes….” Bugg, T.D.H. 2012. Introduction to Enzyme and Coenzyme Chemistry: Third Edition. A John Wiley & Sons. West Sussex: UK. p. 213.
“… we will demonstrate how teleological processes in biology can arise from the organization of local dynamical processes that reciprocally produce each other’s boundary conditions. As a result, critical field effects [e.g., while a gradient might be quickly used up, the continual production of a capsid-forming protein by a catalyst might keep the capsid forming despite decay] external to each component process are produced intrinsic to the whole [i.e. in their example a thought experiment “autogen” composed of two reciprocal catalysts in an appropriately substrate-supplied environment and where of them is a capsid-forming molecule as for a virus]and can thereby counter external background field effects….
“By contrast to terminal processes, the processes that we will call ‘targeted’ or ‘target-directed’ only ‘terminate’ [as with the autogen example] with respect to internal boundary conditions…..
“‘Targeted’ or ‘target-directed’ processes are genuinely teleological.” Deacon, Terrence W. & Miguel Garcia-Valdecasas. 2023. “A thermodynamic basis for teleological causality.” Philosophical Transactions of the Royal Society: A. 381:20220282. 10.1098/rsta.2022.0282. p. 6.
“Although self-organizing processes require a constant source of externally provided energy and material resources and must offload entropy into the environment, this is what enables them to reduce local entropy.” Deacon, Terrence W. & Miguel Garcia-Valdecasas. 2023. “A thermodynamic basis for teleological causality.” Philosophical Transactions of the Royal Society: A. 381:20220282. 10.1098/rsta.2022.0282. p. 7.
“Moreover, the boundary conditions that can support or inhibit a particular form of self-organizing dynamics are environmental constraints on the energy and material flows that support it. Consequently, it should be possible to identify distinct self-organizing processes that each reciprocally generate each other’s permissive boundary conditions, and collectively prevent each other from reaching terminality at equilibrium.
“By impeding each component self-organizing process from reaching its terminal state, such a system will be disposed to develop toward a target state that preserves the terminal dispositions of each process but also prevents them from reaching termination. Such a system of linked self-organized processes will tend to preserve the local constraints that each process generates before the whole system depletes its resource base. In other words, the system will develop toward a target state that is not a terminal state. But when perturbed away from this target state the collective actions of the component self-organizing processes will tend to return the system to that state again. This might be described as a basic form of self-repair.” Deacon, Terrence W. & Miguel Garcia-Valdecasas. 2023. “A thermodynamic basis for teleological causality.” Philosophical Transactions of the Royal Society: A. 381:20220282. 10.1098/rsta.2022.0282. p. 9.
“Although an autogen could be superficially described as a version of an autopoietic system, it is its thermodynamic organization, not its behavioural properties–such as autonomy or constraint closure–that defines it….
“An autogenic process is produced by the synergistic coupling of two or more terminal processes. These terminal processes must be far-from-equilibrium self-organizing processes that each produces the supportive and limiting boundary constraints for the other. As a result, the local entropy-decreasing dynamic of each is facilitated while their tendency to develop self-termination is prevented. The co-dependent coupling of these self-organizing dynamics thereby creates a higher-order dynamical synergy with a disposition to repair damage to its integrity and to reconstitute its individual unit if damaged, despite radical material replacement. The model we describe demonstrates that at least two co-dependently coupled self-organizing processes are both necessary and minimally sufficient to produce a locus of teleological causality.” Deacon, Terrence W. & Miguel Garcia-Valdecasas. 2023. “A thermodynamic basis for teleological causality.” Philosophical Transactions of the Royal Society: A. 381:20220282. 10.1098/rsta.2022.0282. pp. 9, 11.
“Although not fully understood, the MEPP [maximum entropy production principle] principle is frequently used to study non-equilibrium complex processes in physics, chemistry, biology, ecology, etc. It is proposed that the MEPP governs not only the evolution of non-equilibrium physical and chemical processes but ‘guides’ also biological evolution since it was observed that it is closely connected to multiple hypotheses in evolutionary biology. For example, in 1922, A. Lotka proposed that evolution occurs in such a direction as to make the total energy flux through the system as maximal as possible; and in 1976, H.T. Odum and E.C. Odum wrote that the system using the greatest amount of energy and consuming it in the most efficient way survives in competition with other systems.” Vitas, Marko & Andrej Dobovisek. 2019. “Towards a General Definition of Life.” Origins of Life and Evolution of Biospheres. 49:77-88. 10.1007/s11084-019-09578-5. p. 79; references: Martyushev, L.M. 2013. “Entropy and entropy production: old misconceptions and new breakthroughs.” Entropy. 15:1152-1170; Lotka, A. 1922. “Contribution to the energetics of evolution.” Proc. Natl. Acad. Sci. USA. 8:147-151; Odum, H.T. & E.C. Odum. 1976. Energy basis for man and nature. NY: McGraw-Hill Book Company.
“… Freeman Dyson established that before the emergence of replication processes (making exact copies), a metabolic system must have reproduced (making similar copies), progressively increasing the accuracy of its pathways before allowing a spin-off system to initiate replication. Furthermore, it was shown that autocatalytic sets are capable of evolution by natural selection, even in the absence of specific information-carrying molecules. The idea of collectively autocatalytic sets was introduced as a ‘metabolism-first’ scenario in the context of the origin of life. In this scenario, life supposedly started as a functionally closed, self-sustaining reaction network in which several molecules collectively supported each other’s production from basic nutrients through mutually catalysed chemical reactions. Large, complicated and extremely complex early prebiotic metabolisms have been proposed. A partition network into potentially growing sub-networks could be proposed, with a simultaneous understanding that natural selection acts on the variation in any mechanism that consumes energy from the environment. This, in turn, includes molecular interactions and a metabolism. On this basis we can assume that the evolutionary development of the networks of autocatalytic reactions that occurred in the primordial world is possible on the Darwinian paradigm without having information stored digitally in template homopolymers e.g. DNA or RNA.” Vitas, Marko & Andrej Dobovisek. 2019. “Towards a General Definition of Life.” Origins of Life and Evolution of Biospheres. 49:77-88. 10.1007/s11084-019-09578-5. pp. 81-2. Reference: Dyson, Freeman. 1985. Origins of Life. Cambridge UP.
“Life is a far from equilibrium self-maintaining chemical system capable of processing, transforming and accumulating information acquired from the environment.” Vitas, Marko & Andrej Dobovisek. 2019. “Towards a General Definition of Life.” Origins of Life and Evolution of Biospheres. 49:77-88. 10.1007/s11084-019-09578-5. p. 84.
“Macromolecules are as processual as living systems. But in order to convincingly make the case for this thesis, philosophers need to look not only at theoretical models in biology, but also at the details of scientific practice at the level of the laboratory bench. If we follow such a shift in philosophical methodology, it will be possible to show that whilst molecules appear to be substance-like, they are in fact processual entities that are made to look like substances. This is achieved through the use of a set of research practices, in particular of what I will refer to as ‘energy-level management’ (ELM) practices.” Guttinger, Stephan. 2021. “Process and Practice: Understanding the Nature of Molecules.” HYLE – International Journal for Philosophy of Chemistry. 27:47-66. p. 49.
“Once aware of the importance of disorder researchers quickly found that it [constant structural change, or disorder] is not a rare feature as up to 50% of proteins are now thought to contain disordered elements. This new class of proteins was labelled ‘intrinsically disordered proteins’ or ‘IDPs’.
“The discovery of IDPs clearly posed a challenge for the traditional picture of proteins as represented by the SSF [sequence-structure-function] paradigm.” Guttinger, Stephan. 2021. “Process and Practice: Understanding the Nature of Molecules.” HYLE – International Journal for Philosophy of Chemistry. 27:47-66. p. 53.
“In protein chemistry the expression ‘protonation state’ is used to refer to the numbers of protons present in a protein….
“The protonation state of a protein can change because many amino acids contain protons they can give off to a proton acceptor (making them so-called ‘proton donors’) or because they have free electron pairs that can be used to bind an additional proton. As a consequence, protons are constantly exchanged between the protein and the molecules that surround it (primarily the bulk water molecules).
“This exchange depends, among other things, on the pH of the surrounding solution: as the pH is nothing but a measure for the concentration of protons in a solution an increase or decrease of the pH means that more protons are pushed onto the protein or removed from it.
“Because of this, the number of protons (and hence the atomic microstructure) of the protein can change whilst its amino acid sequence remains the same.” Guttinger, Stephan. 2021. “Process and Practice: Understanding the Nature of Molecules.” HYLE – International Journal for Philosophy of Chemistry. 27:47-66. p. 57.
“ELM [energy-level management] practices come in many shapes and forms, from cooling down a solution to creating a vacuum in a test tube. They all have one goal: to control and manipulate the energy landscape in an experimental setup.
“The key practice used to keep the protonation state of a protein stable is buffering….
“A buffered solution is a specific mixture of an acid or a base and its corresponding salt, dissolved in water. What this solution can do is to absorb extra hydrogen ions that are added to the system (or to compensate for the addition of hydroxide ions, which can trap free hydrogen ions). A buffer can thereby keep the pH stable even though protons are added to or removed from the solution….
“If this buffer is set, for instance, to pH 9 it will remain at this level if protons are added (which would normally lead to a lowering of the pH).
“Apart from buffered solutions the practicing biologist will use other tools to control the stability of their protein of interests, such as tightly controlled temperature (protein solutions are usually handled on ice and stored at -20 or -80 degrees Celsius) or the salt concentration of the solution. All of these practices are part of ELM practices, as they are ultimately about the control of the energy landscape the protein is exposed to in the experimental setting.
“Importantly, ELM practices are boundary-making practices: by setting a specific pH (and temperature etc.) the researcher fixes the protein in a specific state (in our example the protonation state).” Guttinger, Stephan. 2021. “Process and Practice: Understanding the Nature of Molecules.” HYLE – International Journal for Philosophy of Chemistry. 27:47-66. p. 59.
“… proteins are made to look and behave like substances through the use of specific practices, in particular those that I have labelled ‘energy-level management’ practices.” Guttinger, Stephan. 2021. “Process and Practice: Understanding the Nature of Molecules.” HYLE – International Journal for Philosophy of Chemistry. 27:47-66. p. 61.
“In their analysis, Levy and Bechtel point to several categories of mechanism where the machine analogy breaks down. These include:
“1. Mechanism whose parts are not discrete entities but are large collections of entities.
“2. Mechanisms where the organization of parts is not fixed.
“3. Mechanisms whose parts change over time.
“4. Mechanisms with porous boundaries.
“5. Mechanisms that exist only transiently.” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. p [of bootleg copy] 11; reference: Levy, A. & W. Bechtel. 2020. “Beyond Machine-Like Mechanisms.” Philosophical Perspectives on the Engineering Approach in Biology: Living Machines? Holm, Sune & Maria Serban (eds). NY: Routledge.
“Historically, studies aimed at understanding the mechanism of enzyme action have generally fallen into one of three areas of investigation:
“kinetic investigations – the study of reaction rates, and their dependence on experimental variables
“chemical investigations – the study of the molecular rearrangements that transform reactants into products
“dynamics investigations – the study of the non-covalent protein structural changes that play causative roles in the transformation of reactants into products….
“These three distinct areas of investigation led to three distinct conceptions of the reaction intermediate and to three distinct mechanistic accounts of enzyme action:
“Kinetic Mechanism – the energetic landscape that defines the passage of intermediates from substrates to products….
“Chemical Mechanism – the molecular rearrangements that transform substrates into products….
“For enzyme-catalyzed reactions, intermediates may exist along the reaction pathway that arise from the formation of covalent bonds between the enzyme and substrate….
“Dynamics Mechanism – the protein conformational changes required for substrate turnover”. Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. pp [of bootleg copy] 15, 16, 17.
“What is the relationship between the three aspects of mechanism and the actual mechanism?
“Our discussion of enzyme reaction intermediates helps us answer this question. The key concept that will help us here is to view the enzyme-mediated transformation of substrate into product as the evolution, or temporal progression, of intermediate states, where this evolution will always be characterized by the energetic coupling between chemistry and protein dynamics….
“To say that two reactions are coupled is to first say that they occur in a concerted, synchronous fashion. But more than that, coupled reactions occur with one reaction proceeding at an accelerated rate at the energetic expense of the other reaction.” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. p [of bootleg copy] 19.
“The mechanism of an enzyme-catalyzed reaction is the integration of the three aspects of mechanism.” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. p [of bootleg copy] 21.
“In Machamer, Darden, and Craver [as author criticizes the New Mechanists], we see this presupposition made explicit in their endorsement of a dualistic ontology of entities and activities, telling us: ‘Both activities and entities must be included in an adequate ontic account of mechanisms. Our analysis of the concept of mechanism is explicitly dualist’….
“Indeed, I submit that it is impossible to decompose a macromolecular reaction into entities and activities, and from this decomposition, construct a mechanism that accurately reflects what science teaches us about these reactions.” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. p [of bootleg copy] 25, 26l; subquote: Machamer, P., L. Darden & C.F. Craver. 2000. “Thinking about Mechanisms.” Philosophy of Science. 67:1-25. p. 4.
“We now see that a molecule maintains its identity through time, not because it is static and unchanging but rather because it is a dynamic system exhibiting a stability-pattern through time.” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. p [of bootleg copy] 28.
“Contemporary theories of molecular transformation do not allow simple decomposition of the mechanism of molecular change into entities and activities. This apparent melding of entities and activities was hinted at by Machamer, Darden, and Craver, when they asserted that ‘entities and activities are … interdependent.’” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. p [of bootleg copy] 29; subquote as above, p. 6.
“As a protein in solution, an enzyme does not exist as a stable, unchanging entity, but rather as an ensemble of conformers…. Thus, the enzyme should not be viewed as static substance, but rather as an entity in constant flux, with a complex internal structure that allows it to respond relational to its environment.” Stein, Ross L. 2022. “Mechanisms of Macromolecular Reactions.” HPLS. 44(11) 10.1007/s40656-022-00492-0. pp [of bootleg copy] 31-2.
“Our theories, our hypotheses, are our adventurous trials. Admittedly, most of them turn out to be errors: under the impact of our tests their falsity may be revealed. Those theories that we cannot refute by the severest tests, we hope to be true. And, indeed, they may be true; but new tests may still falsify them.
“This method of bold, adventurous theorizing, followed by exposure to severe testing is the method of life itself as it evolves to higher forms: it is the method of trials and of the exposure and elimination of errors through tests.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. pp. 6-7.
“The tendency of statistical averages to remain stable if the conditions remain stable is one of the most remarkable characteristics of our universe. It can be explained, I hold, only by the propensity theory; by the theory that there exist weighted possibilities which are more than mere possibilities, but tendencies or propensities to become real: tendencies or propensities to realize themselves which are inherent in all possibilities in various degrees and which are something like forces that keep the statistics stable.
“This is an objective interpretation of the theory of probability. Propensities, it is assumed, are not mere possibilities but are physical realities. They are as real as forces, or fields of forces. And vice versa: forces are propensities. They are propensities for setting bodies in motion.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 12.
“I had stressed that propensities should not be regarded as properties inherent in an object, such as a die or a penny, but that they should be regarded as inherent in a situation (of which, of course, the object was a part). I asserted that the situational aspect of the propensity theory was important, and decisively important for a realist interpretation of quantum theory.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 14.
“… the relative or conditional probability statement
“(2) p(a, b) = r
to be read: ‘The probability of the event a in the situation b (or given the conditions b) equals r’.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 16.
“Our very understanding of the world changes the conditions of the changing world; and so do our wishes, our preferences, our motivations, our hopes, our dreams, our phantasies, our hypotheses, our theories. Even our erroneous theories change the world, although our correct theories may, as a rule, have a more lasting influence. All this amounts to the fact that determinism is simply mistaken: all its traditional arguments have withered away and indeterminism and free will have become part of the physical and biological sciences.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 17.
“But with the introduction of propensities, the ideology of determinism evaporates. Past situations, whether physical or psychological or mixed, do not determine the future situation. Rather, they determine changing propensities that influence future situations without determining them in a unique way.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. pp. 17-8.
“Just like a newly synthesized chemical compound, whose creation in turn creates new possibilities for new compounds to synthesize, so all new propensities always create new possibilities. And new possibilities tend to realize themselves in order to create again new possibilities. Our world of propensities is inherently creative.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 20.
“All this means that possibilities – possibilities that have not yet realized themselves – have a kind of reality…. The future is, in this way, actively present at every moment.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 20.
“A brief closing passage from the preface to a book of mine may apply all this to the education of young scientists.
“I think that there is only one way to science – or to philosophy, for that matter: to meet a problem, to see its beauty and fall in love with it; to get married to it and to live with it happily, till death do ye part – unless you should meet another and even more fascinating problem or unless, indeed, you should obtain a solution. But even if you do obtain a solution, you may then discover, to your delight, the existence of a whole family of enchanting, though perhaps difficult, problem children, for whose welfare you may work, with a purpose, to the end of your days.” Popper, Karl R. 1990. A World of Propensities. Bristol, UK: Thoemmes. p. 26.
“The production of whole organisms from divided germs is possible with many other animals. Even identical twins, which occasionally appear in man, are produced in a similar way; they are, so to speak, a Driesch experiment performed by nature herself.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 5.
“Every organism represents a system, by which term we mean a complex of elements in mutual interaction.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 11.
“Atomic physics everywhere encounters wholes that cannot be resolved into the behaviour of elements considered in isolation. Whether atomic structure or structural formulae of chemical compounds or space-lattices of crystals are investigated, problems of organization always arise and appear to be the most urgent and fascinating of modern physics…. An atom or a crystal are not the result of chance forces but of organizational ones; yet it was thought possible to explain the organized things par excellence, the living organisms, as chance products of mutation and selection.
“The task of biology, therefore, is to establish the laws governing order and organization within the living.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. pp. 14-5.
“We can therefore summarize the leading principles of an organismic conception in the following way: The conception of the system as a whole as opposed to the analytical and summative points of view; the dynamic conception as opposed to the static and machine-theoretical conceptions; the consideration of the organism as a primary activity as opposed to the conception of its primary reactivity.
“These principles enable us to overcome the antagonism of the mechanistic and vitalistic conceptions.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. pp. 18-9.
“It seems to be the task which is set to our age, to accomplish in biology that ‘Copernican revolution’ which, in the sciences concerned with inanimate nature, took place with the transition from the Aristotelian world-system to modern physics.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 22.
“Individual means something ‘indivisible’; how can we call these creatures individuals when they are in fact ‘dividua’ and their multiplication [unicellular organisms] arises precisely from division? The same holds good for asexual reproduction by fission and budding, as is found in many of the lower metazoa. In the face of experimental evidence, the term ‘individual’ becomes inapplicable. Can we insist on calling a hydra or a turbellarian worm an individual, when these animals can be cut into as many pieces as we like, each capable of growing into a complete organism?” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 48.
“It is easy to produce a double-headed polyp by making an incision at the anterior end. Afterwards the two heads compete: if a water-flea is caught, both heads quarrel about the booty, although it does not matter at all which one takes it–in any case it goes down into the common gut, where it is digested and so benefits all parts. The question whether we have to deal with ‘one’ or ‘two’ individuals here becomes meaningless.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 48.
“Strictly speaking, there is no biological individuality, but only a progressive individualization, both phylogenetic and ontogenetic, which is based upon progressive centralization, certain parts gaining a leading role and thus determining the behaviour of the whole. Individuality is a limit which is approached but not reached, either in development or in evolution.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 49.
“Complete individuality, i’e., centralization, would make impossible reproduction, which presupposes the construction of a new organism out of parts of the old. On the other hand, it is precisely the main central systems–brain and heart–which break down first in the natural course of senescence, and are therefore the organs of death.
“Thus the notion of the individual is, biologically, only to be defined as a limiting concept.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 50.
“The stream of life is maintained only in the continuous flow of matter through all groups of organisms.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 52.
“There will be a time when the mechanistic and atomistic conception is entirely overthrown in clever brains, and all phenomena will appear as dynamic and chemical, and will thus testify ever more the divine life of nature.” Goethe, J.W. von quoted in: Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 55; subquote: 1812. Tagebuch.
“Some four main problems [with Darwinism] can be distinguished: first, the origin of the multiplicity of forms within a given type of organization or bauplan, that is, the origin of the lower systematic units, of races, subspecies, species, perhaps also of genera; secondly, the origin of these types of organization themselves, that is, of the higher systematic units; thirdly, the origin of ecological adaptations to definite environments; fourthly, the origin of the complex morphological and physiological integration within the organism as a whole. It is, of course, impossible to draw sharp border lines between these problems. Problems 1 and 2 concern the origin of the multiplicity of organic forms, 3 and 4 that of the ‘fitness’ of the organism.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. pp. 84-5.
“The pros and cons of the theory of selection have been discussed on countless occasions. Indeed, the controversy with more or less noteworthy ‘objections,’ constitutes a main part of every presentation of the theory–a procedure that would be looked for in vain in a treatise on, say, physics or physiology.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 86.
“Like a Tibetan pray-wheel, Selection Theory murmurs untiringly: ‘Everything is useful.’ But as to what actually happened and which lines evolution has actually followed, selection theory says nothing, for the evolution is the product of ‘chance,’ and therein obeys no ‘law.’” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 92.
“If selection represents a necessary condition of evolution, it does not follow that it indicates a sufficient condition.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 93.
“Organisms are characterized by three principal attributes: organization, dynamic flow of processes, and history.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 109.
“Schroedinger, however, clearly feels that this conception of the organism as a ‘mechanism’ or ‘clockwork’ is inadequate, as it is also refuted by organic regulation. Thus, there remains for him recourse only to an ego ‘that supervises the movements of atoms.’” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 145.
“Perhaps it can be said that in the modern dynamic conception a theory of systems may play a role similar to that of Aristotelian logic in Antiquity. For the latter, classification was the basic attitude, and thus the doctrine of the relation of universals in their subordination and superordination appeared as the basic scientific organon. In modern science, dynamic interaction is the basic problem in all fields, and its general principles will have to be formulated in General System Theory.” Bertalanffy, Ludwig von. 1952. Problems of Life: An Evaluation of Modern Biological Thought. NY: Wiley. p. 201.
“As we noted, a mechanistic explanation accounts for one causal process in terms of the causal processes of the mechanism’s components. But as Machamer, Darden, and Craver argue, this strategy cannot be iterated indefinitely; at some point this process must bottom out. Lacking a metaphysical foundation to end the regress, one that at some point explains causation without resorting to the next mechanistic level down, leaves a cause having a given effect as simply a brute, unexplained fact. We term this the mysteriousness problem…. Woodward himself has conceded that his view is intended merely as an account of ‘how we think about, learn about, and reason with various causal notions and about their role in causal explanation’; he explicitly denies that his account is intended to solve the sort of bottoming-out problem that mechanists have been concerned with.” Winning, Jason & William Bechtel. 2018. “Rethinking Causality in Biological and Neural Mechanisms: Constraints and Control.” Minds & Machines. 28:287-310. 10.1007/s11023-018-9458-5. p. 289; subquote: Woodward, J. 2008. “Response to Strevens.” Philosophy and Phenomenal Research. 77(1):193-212. p. 194; reference: Machamer, P., L. Darden & C.F. Craver. 2000. “Thinking about mechanisms.” Philosophy of Science. 67:1-25.
“We argue that the causal organization of a system consists exactly in its spatiotemporal organization combined with the operative constraints.” Winning, Jason & William Bechtel. 2018. “Rethinking Causality in Biological and Neural Mechanisms: Constraints and Control.” Minds & Machines. 28:287-310. 10.1007/s11023-018-9458-5. p. 294.
“Consider an example from Cliff Hooker:
“‘a skeleton is a disabling constraint, for example limiting the movements of limbs (cf. an octopus), but by providing a jointed frame of rigid components for muscular attachments it also acts to enable a huge range of articulated motions and leverages, transforming an organism’s accessible niche, initiating armour and predator/prey races, and so on.’” Winning, Jason & William Bechtel. 2018. “Rethinking Causality in Biological and Neural Mechanisms: Constraints and Control.” Minds & Machines. 28:287-310. 10.1007/s11023-018-9458-5. p. 294; subquote: Hooker, Cliff. 2013. “On the import of constraints in complex dynamical systems.” Foundations of Science. 18:757-780. p. 761.
“Each protein in an organism is like a skeleton in this sense; a structure that will resist certain forces while translating the directions of other forces, re-routing forces, displacing forces, etc. all by virtue of how it is constrained. The tendency or capacity to resist, re-route, displace, etc. various forces is just what it is to be a causal power. Thus, on our view, when constraints enable objects to have novel, emergent behaviors, this is tantamount to the emergence of causal powers.” Winning, Jason & William Bechtel. 2018. “Rethinking Causality in Biological and Neural Mechanisms: Constraints and Control.” Minds & Machines. 28:287-310. 10.1007/s11023-018-9458-5. p. 294.
“To perform work, as Atkins shows in discussing the Carnot engine, a system must be able to selectively filter the flow of energy so as to shape its response properties:
“Here is an essential asymmetry of the engine: it possesses a directional response to the impacts it receives. The face of the piston is, in effect, a screen: it picks out and responds to the motion of particles that happen to be traveling perpendicular to it; and it rejects (by not responding to) components of motion that happen to be parallel to it. Engines, in effect, select certain motions of the particles within them. The directionality of the movement of an actual piston in an engine is a consequence of this asymmetry. Our exploitation of heat to achieve work is based on the discovery that the randomness of thermal motion can be screened and sorted by asymmetry of response.” Winning, Jason & William Bechtel. 2018. “Rethinking Causality in Biological and Neural Mechanisms: Constraints and Control.” Minds & Machines. 28:287-310. 10.1007/s11023-018-9458-5. pp. 295-6; subquote: Atkins, P.W. 1984. The Second Law. NY: Scientific American Books. p. 83.
“The notion of constraints serving as filters clarifies respects in which machines are intrinsically passive and respects in which they are intrinsically active. They are intrinsically passive in that they must make use of free energy from the environment to perform work. They are intrinsically active in that they filter and shape the flows of free energy from the external and internal environment. All mechanistic operations are, among other things, energy flow operations filtered and shaped by constraints.” Winning, Jason & William Bechtel. 2018. “Rethinking Causality in Biological and Neural Mechanisms: Constraints and Control.” Minds & Machines. 28:287-310. 10.1007/s11023-018-9458-5. p. 296.
“First, from an evolutionary perspective consciousness, as understood at the higher levels, does not appear to have any necessary role in any individual organism being alive.” Pattee, Howard. 2015. “The Physics of Symbols Evolved Before Consciousness.” Cosmos and History: The Journal of Natural and Social Philosophy. 11(2):269-277. p. 270.
“Interpreters of quantum mechanics very often do not distinguish the unique quantum mechanical problems from the general epistemic problems that apply to all knowledge. Here are four important general examples: (1) the subject-object epistemic cut, (2) reversible vs. irreversible models, (3) deterministic vs. probabilistic models, and (4) general complementarity of models.” Pattee, Howard. 2015. “The Physics of Symbols Evolved Before Consciousness.” Cosmos and History: The Journal of Natural and Social Philosophy. 11(2):269-277. p. 271.
“It is the subject/object distinction that stands out in the measurement problem in quantum mechanics because the object requires a quantum description and the subject requires a classical description. Where this essential distinction is made Heisenberg called the Schnitt, John Bell called the shifty split, and I call the epistemic cut to emphasize that it is not an ontological dualism.
“What is often not understood is that the subject-object distinction and the epistemic cut is not just a problem of quantum mechanics. Born, von Neumann, and others have explained why there must be an epistemic cut in any measurement process. The reasons are: First, no laws can tell you what to measure or when to measure it. Second, measuring devices are special boundary conditions, and like initial conditions they are not derivable from or reducible to laws. Von Neumann explained that lumpnig system S and measurement apparatus M as one system (S + M) without a cut would require a new M1 to measure new initial conditions – a process leading to an infinite regress.
“Von Neumann’s point was that this regress can be terminated only by choosing, seemingly arbitrarily, an epistemic cut – a separation of the system and measuring device, or more specifically, the separation of the record of a measurement (a symbol) from the physical event the symbol represents. This is not just QM. It is a requirement for any empirically testable theory.” Pattee, Howard. 2015. “The Physics of Symbols Evolved Before Consciousness.” Cosmos and History: The Journal of Natural and Social Philosophy. 11(2):269-277. p. 271.
“QM has nothing to do with the necessity of an epistemic cut.” Pattee, Howard. 2015. “The Physics of Symbols Evolved Before Consciousness.” Cosmos and History: The Journal of Natural and Social Philosophy. 11(2):269-277. p. 272.
“There is no model of everything. For example, you cannot formally derive a probabilistic model from a deterministic model, or an irreversible model from a reversible model, or a discrete model from a continuous model. The hierarchy principle requiring different models at different levels applies to both classical and quantum theory….
“In spite of much evidence, the idea of the necessity [of?] two irreducible and often inconsistent models is often rejected on philosophical grounds. It still surprises me that the necessity of general complementarity of models is so controversial, because it is evident that one universal model of reality does not exist, and everyone uses more than one model of their experiences even in everyday life. Nevertheless, much of the literature in many scientific fields is full of unproductive arguments over which of several complementary models is correct or superior to the others.” Pattee, Howard. 2015. “The Physics of Symbols Evolved Before Consciousness.” Cosmos and History: The Journal of Natural and Social Philosophy. 11(2):269-277. p. 273.
“One should note here, following Auletta’s terminology, that there is a significant difference between having causal power (to concur in producing a certain effect) and having causal effectiveness (which, in ideal situations, would suffice to bring about an effect, given the other conditions). Formal causes, for example constraints, only have causal power but not causal effectiveness. For example, the structure of a forest (the way the trees are disposed) together with other environmental items (rocks, plants, rivers, and so on) will affect (have causal power on) the way natural agents (like wind or fire) will propagate. For instance, wind may be more canalized in some parts and blocked in other ones. However, what is here causally effective is the wind (or the fire), not the structure of the forest, which would remain completely ineffective (not operative) and unable to concur in any causal process without an effective causal agent. All formal constraints have this character. Top down causation as considered here means having causal power over lower levels, channeling causal effectiveness at those levels. Ellis, G. F. R. 2008. “On the nature of causation in complex systems.” Transactions of the Royal Society of South Africa. 63(1): 69–84. 10.1080/00359190809519211. p. [unsure numbering] 74; reference: Auletta, G. 2007. “How Many Causes There Are?” XXI Secolo. 7.
“Most chemical reaction systems have a single steady state, but a few interesting cases are known to oscillate, form spatial patterns, or have multiple stable states. Aside from their intrinsic mathematical and chemical significance, systems with multiple stable states are of particular biological interest because they can retain a ‘‘memory’’ of past inputs and cellular decisions. Bistability is a particularly interesting case of multi-stability, as it leads to switch-like behavior. Chemical stimuli can trigger a state change from one stable state to another. The current state of the chemical system is therefore a ‘‘memory’’ of this earlier stimulus.” Ramakrishnan, Naren & Upinder S. Bhalla. 2008. “Memory Switches in Chemical Reaction Space.” PLOS Computational Biology. 4(7):e1000122. p. 1.
“… memories can occur only in systems that are neither fully ordered nor in thermal equilibrium.” Nagel, Sidney R., Srikanth Sastry, Zorana Zeravcic & Murugappan Muthukumar. 2023. “Memory formation.” The Journal of Chemical Physics. 158:210401. 10.1063/5.0156354. p. 1.
“By contrast [to transcribing new mRNA and translating into protein for cell changes], the events that precipitate transcriptional changes are usually faster, more spatially organized, and less costly in terms of energy expenditure. First, unlike transcription, which is limited to the nucleus where the genomic DNA resides, the cell signaling machinery spans the cell from the external surface of the cell membrane into the nucleus. Indeed, one of the major tasks of many signaling systems is to transduce signals from outside the cell to the interior, where they can modulate intracellular processes such as transcription. A second major difference is in the speed of the response. Many cell signaling events are extremely rapid, capable of switching states in fractions of a second, and the changes induced are often transient and reversible….
“Another difference between cell signaling mechanisms and gene expression is that signaling can be spatially organized and localized. Again, this organization can occur over different scales, from the distance of a few molecules to the diameter of the cell and beyond….
“Finally, most signaling transactions do not expend anywhere near the resources needed to make new proteins, usually requiring the equivalent of a molecule or two of ATP to transmit information from one molecule to another. Because signaling reactions are relatively cheap, it is not a serious disadvantage for the cell to continuously monitor the environment.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 10.
“The idea that some kind of change is essential for information processing cannot be emphasized too strongly.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 11.
“In electronic circuits, there is one universal currency for information transmission, which is the electrons flowing through the circuit. There are relatively few devices that process information, and their inputs and outputs all involve this single currency. In cell signaling, there is a wider variety of signaling currencies, and therefore a wider variety of molecular devices or systems that are able to read one currency and convert it to other output currencies.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 11.
“In cell signaling, the most basic units of information are changes in the state of proteins….
“If information transfer requires change, and proteins lie at the heart of signaling, it follows that changes in the properties of proteins will provide the basis for cell signaling mechanisms.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 12.
“… all signaling inputs must be converted into another form, often many times, in order to generate the appropriate cellular response. It is this concept of conversion of one type of signal into another that led to the widespread use of the term ‘signal transduction’ to describe the field of cell signaling.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 16.
“The basis for protein-protein binding (or the binding of proteins to other macromolecules) is a specific fit, or complementarity, between the two interacting surfaces. The shape of the two surfaces largely determines this fit. Like pieces of a puzzle, two surfaces are more likely to bind if they have complementary shapes, with bumps and ridges on one surface fitting into holes and grooves on the other. Binding is also stabilized by hydrophobic and electrostatic interactions and hydrogen bonds between the interacting surfaces.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 23.
“Protein-protein interaction surfaces can be roughly divided into two categories. In the first, relatively broad surfaces of the two binding partners interact, with each binding surface composed of amino acids that may be widely separated in the linear sequence of the protein. In the second, one of the binding surfaces consists of a relatively short, linear peptide sequence (usually four to eight amino acids in length) that fits into a corresponding groove on the surface of its binding partner.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 24.
“The affinity of an interaction is a measure of the intrinsic strength of the binding interaction. Simply put, if the affinity of the interaction between two species is high, then there is a higher probability of finding the molecules in complex at equilibrium.
“In contrast to affinity, the specificity of an interaction is not an absolute measure but a relative one–it reflects the relative affinity of a particular interaction (between protein P and ligand A) with respect to other possible interactions (between protein P and all other molecules in the cell). Unlike affinity, which is an intrinsic property of two interacting molecules, specificity can only be defined in relation to a particular set of other potential interactions.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 25.
“Biologically important binding reactions can vary widely in their strength, ranging from weak and transient interactions that may be difficult to detect to extremely strong interactions that are nearly as stable as covalent bonds. Thus binding is not an all-or-none phenomenon….” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 25.
“… the overall binding energy [of a ligand] is the sum of many distinct and counterbalancing changes in enthalpy and entropy, both of the interacting proteins and the surrounding solvent, many of which are difficult to quantify precisely on a theoretical basis.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 28.
“However, the specificity described here only reflects the preference of protein P for binding ligand B over ligand A and does not reflect the preference of protein P for binding ligand B over any other competing ligands.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 28.
“The dissociation constant describes the fraction of components bound to each other at equilibrium. In biological systems, however, binding reactions very seldom achieve equilibrium. In fact, it is changes in protein binding over relatively short periods of time that are usually most important for transmitting information during signaling.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. pp. 28-9.
“There is a limit to how large kon can be, however: with rare exceptions, the rate of binding cannot be higher than the random rate of collision of A and B. For typical proteins in aqueous solution, the diffusion-limited rate of collision is on the order of 108–109 M-1 s-1. If kon approaches this rate, then a very high percentage of colliding molecules bind to each other, at least momentarily. The actual on-rates for biological binding reactions are usually considerably lower than this limit, typically 105–106 M-1 s-1.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 29.
“In a process of positive discrimination, the affinity of the protein for one of its ligands can be increased by the formation of additional favorable stereochemical interactions. Whether these new interactions increase specificity, however, depends on their nature. Favorable interactions that recognize chemical features common to all members of a competing ligand family will increase the affinity, but not the specificity, for the given ligand. For example, many relatively nonspecific peptide-binding proteins, such as the MGC molecule described previously, recognize their peptide ligands partly through extensive hydrogen-bonding to the peptide backbone–which, unlike bonding to side chains, is not specific to a particular sequence of amino acids. Positive discrimination will generally increase specificity only if the increase in affinity involves the formation of specific side-chain interactions–elements that are unique to the correct ligand compared with its related competitors….
“Specificity can also be increased via a process of negative discrimination. In this case, affinity for related competitor ligands is decreased while the affinity for one ligand remains unchanged.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. pp. 34, 35.
“Cooperativity refers to an interaction in which binding of one ligand enhances the binding of an additional ligand(s). In thermodynamic terms, cooperativity is observed when the free energy of two ligands binding simultaneously is different from the sum of the free energies of the two ligands binding individually. If the binding of one ligand increases the affinity for an additional ligand, then positive cooperativity is said to have occurred. Here we will focus only on positive cooperativity, although negative cooperativity–when the binding of one ligand decreases the affinity for an additional ligand–does occur. An important consequence of positive cooperativity is that assembly of a complex occurs in more of an all-or-none fashion: the multiple ligands cooperate to assemble the complete complex, and intermediate states of assembly are poorly populated” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 35.
“A common example of cooperativity in intracellular signaling is when one protein is recruited to the membrane by a protein-lipid interaction, thereby increasing its local concentration. This cooperatively increases its effective affinity for another membrane-localized partner.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 36.
“The protein complexes that perform more dynamic roles in signaling are often much less stable and homogeneous. Interactions among the components are likely to be relatively weak, and there can be many possible binding partners for a given binding site. Thus, many different possible combinations of interactions are possible. An important property of such structures is that their interactions are likely to change and reorganize relatively quickly….
“Such complexes, which can be termed dynamic molecular assemblies, differ greatly from more stable macromolecular machines such as the ribosome. This is an important concept to keep in mind when thinking about signaling pathways: although we often loosely refer to the signaling machinery, this analogy should not be taken too literally. The actual complexes that transmit signals can be difficult (if not impossible) to define precisely, and the contributions of a single interaction among many possible interactions can be difficult to tease out. What advantages might there be to signaling mechanisms based on such dynamic molecular assemblies? It may be that because such complexes exist in a wide range of possible states, depending on the specific combinations of binding partners, they are better able to respond to and transmit complex, finely graded signals. The relative instability of such assemblies also allows them to be highly sensitive to rapid and subtle changes in the environment. And since they function in a combinatorial fashion, a relatively limited number of components can participate in an almost infinite variety of pathways having different inputs and outputs.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 38.
“Phosphorylation is the protein modification most frequently used in signaling, while G proteins use conformational changes to transmit signaling information.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 43.
“Because signaling proteins act as relay switches, they are often selected not for optimum catalytic efficiency, but rather for the ability to be regulated.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 44.
“Conformational changes that are induced by upstream inputs such as ligand binding or post-translational modification, and which result in changes in the protein activity, are referred to as allosteric changes. This conformational coupling between an upstream input and a change in protein activity provides a basic mechanism for the protein to propagate signals.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. pp. 44-5.
“Another common feature of signaling enzymes is that they occur as complementary pairs. For example, a specific phosphorylation reaction might be catalyzed by a protein kinase, while the reversal of this modification–the removal of the phosphate group–is catalyzed by a protein phosphatase. The kinase would essentially act as a ‘writer’ element that drives the substrate to a new state, while the phosphatase acts as an ‘eraser’ that returns the substrate to the original state. all information-storage and -transmission systems, be they natural cellular systems or human-made electronic ones, require some sort of mechanism like this to write and erase information in a controllable fashion.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 45.
“There are several general mechanisms that enzymes can use to stabilize the transition state of a chemical reaction, all of which are observed in various signaling enzymes. First, enzymes can lower the transition-state energy by binding and orienting key reactive groups within a substrate (or two different substrates) such that they react with one another in a more favorable fashion. Second, enzymes can provide general acids and general bases to donate or accept protons that are transferred to and from the substrate during the reaction. The use of general acids, bases, and metal ions to activate attacking groups and stabilize charge development can be particularly important for nucleophilic displacement reactions (such as phosphoryl transfer reactions) that require activation of an attacking nucleophile and stabilization of a leaving group. Third, enzymes can provide a binding site that is more complementary to the electrostatic or geometric propeties of the transition state than the ground state; in this case, some of the binding energy of the transition state is used to reduce the free-energy barrier for the reaction….
“Finally, in some cases, enzymes alter the path or mechanism of a reaction, causing the reaction to proceed through a reaction intermediate that does not normally occur in the uncatalyzed reaction.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 46.
“This continuous jostling motion increases with temperature (it is sometimes called thermal ‘breathing’ of the structure), but occurs even at physiological temperature.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. pp. 47-8.
“Many signaling proteins can respond to multiple allosteric inputs, some positive and some negative. In this way, a protein can integrate many different environmental signals through changes in its conformation.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 48.
“G proteins are named for their ability to bind guanine nucleotides–both guanosine triphosphate (GTP) and guanosine diphosphate (GDP). The primary function of G proteins is to serve as conformational switches: they adopt significantly different conformations depending on whether GTP or GDP is bound. In general, the GTP-bound state is the ‘active’ conformation, which is capable of binding and modulating the activity of downstream effectors, while the GDP-bound state is the ‘inactive’ conformation, with much lower affinity for these effectors….
“This system is very useful for signaling, however, because regulatory enzymes can overcome these kinetic barriers. The nucleotide-binding state of G proteins is controlled by two opposing enzymes: guanine nucleotide exchange factors (GEFs), which activate G proteins, and GTPase-activator proteins (GAPs), which inactivate them. GEFs activate G proteins by catalyzing the release of GDP and the subsequent binding of GTP. GAPs inactivate G proteins by catalyzing the hydrolysis of bound GTP to GDP. Thus, these opposiong enzymes form a kinetically controlled ‘writer/eraser’ system analogous to kinase/phosphatase systems….” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. pp. 65, 66.
“Thus, in a sense, the G protein functions to convert a single phosphate difference into a large conformational change.
“In its GTP-bound conformation, a particular G protein often is capable of binding to many different downstream effectors.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 67.
“A typical eukaryotic cell contains well over 150 different G proteins, involved in diverse signaling pathways. These G proteins can be divided into several distinct superfamilies, including two families that play key roles in cell signaling. The first family is the small G proteins: these monomeric G proteins are often referred to as small GTPases. The second family is the heterotrimeric G proteins, which have alpha, beta, and gamma subunits….
“All of the G protein superfamilies have at their core a 20 kD G domain, which binds the guanine nucleotide and can adopt alternative conformations depending on whether GDP or GTP is bound. The small G proteins essentially consist of a single G domain, while the heterotrimeric G proteins contain a G domain in their G-alpha subunits.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 67.
“Heterotrimeric G proteins are activated by G-protein-coupled receptors (GPCRs). In humans, there are many hundreds of distinct G-protein-coupled receptors, making them the most highly represented class of signaling proteins.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 69.
“But in the cell, signaling enzymes do not function individually, but rather are embedded within pathways and networks in which they function as one relay node within a much larger network. These higher-order signal transduction networks are constructed by functionally connecting the individual nodes. This often means that individual signaling enzymes are linked in series into cascades, where the output of one enzyme directly or indirectly regulates the activity of the next enzyme.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. p. 75.
“Among the most prevalent kinase cascades in all eukaryotes are the mitogen-activated protein (MAP) kinase cascades. This is a pathway module composed of three kinases [MAPKKK, MAPKK, MAPK] that act in series, and it is utilized in a remarkably wide variety of cellular responses….
“The large number of related MAPK cascade components, and the potential cross-talk that could occur between these components, raises the issue of how specific signaling responses can be generated in the cell. The very same kinase can play a role in two distinct pathways, in which case the problem of pathway specificity is particularly acute.
“In many cases, such specificity is accomplished through the use of scaffold proteins–proteins that interact with multiple proteins within a pathway, organizing them into a single complex. Not surprisingly, MAPK cascades were one of the first pathways shown to be organized by scaffolds.” Lim, Wendell, Bruce Mayer & Tony Pawson. 2015. Cell Signaling: Principles and Mechanisms. NY: Routledge. pp. 76, 77.
“These are the usual “marks” that are taken in the literature to show that a richer sense of information than Shannon’s has been introduced to biology. But the most crucial difference between the less and more contentious applications of informational concepts is that, in the richer cases, information use is supposed to help explain how biological systems do what they do—how cells work, how an egg can develop into an adult, how genetic inheritance mechanisms make the evolution of complex phenotypes possible.
“At this point, there are a number of options on the table. One is to deny that genes, cells and other biological structures literally traffic in information in ways that explain their behaviour, but to argue nevertheless that this is a useful analogy or model….
“A second option is to argue that genes and other biological structures literally carry semantic information, and their informational character explains the distinctive role of these structures in biological processes. If we think of genes or cells as literally carrying semantic information, our problem changes; who or what could count as composing or reading these messages?…
“A third option is to argue that causal information itself can explain biological phenomena, and no additional concept of information is needed. Biological systems, on this view, can be adapted to send or receive signals that carry causal information.” Godfrey-Smith, Peter & Kim Sterelny. 2016. “Biological Information.” The Stanford Encyclopedia of Philosophy. Zalta, Edward N. (ed.). p. [of Html file] 4.
“…the fact that specific genetic elements (or the genetic system as a whole) have an evolved function is clearly not sufficient for genes to carry semantic information. Legs are for walking, but they do not represent walking. Enzymes are for catalyzing reactions, but they do not instruct this activity. There are things that legs and enzymes are supposed to do, but this does not make them into information-carriers, in a rich beyond-Shannon sense.” Godfrey-Smith, Peter & Kim Sterelny. 2016. “Biological Information.” The Stanford Encyclopedia of Philosophy. Zalta, Edward N. (ed.). p. [of Html file] 5.
“The movement known as Developmental Systems Theory (DST) has often opposed the mainstream uses of informational concepts in biology, largely because of the idea that these concepts distort our understanding of the causal processes in which genes are involved…. These theorists have two connected objections to the biological use of informational notions. One is the idea that informational models are preformationist. Preformationism, in its original form, in effect reduces development to growth…. Preformationism does not explain how an organized, differentiated adult develops from a much less organized and more homogeneous egg; it denies the phenomenon….
“DST theorists think that informational models of genes and gene action make it very tempting to neglect parity, and to attribute a kind of causal primacy to these factors, even though they are just one of a set of essential contributors to the process in question. Once one factor in a complex system is seen in informational terms, the other factors tend to be treated as mere background, as supports rather than bona fide causal actors. It becomes natural to think that the genes direct, control, or organise development….
“Second, DST theorists have often endorsed a “parity thesis”: genes play an indispensable role in development, but so do other causal factors, and there is no reason to privilege gene’s contribution to development. This claim is often buttressed by reference to Richard Lewontin’s arguments for the complexity and context sensitivity of developmental interaction, and his consequent arguments that we cannot normally partition the causal responsibility of the genetic and the environmental contributions to specific phenotypic outcomes. DST theorists think that informational models of genes and gene action make it very tempting to neglect parity, and to attribute a kind of causal primacy to these factors, even though they are just one of a set of essential contributors to the process in question.” Godfrey-Smith, Peter & Kim Sterelny. 2016. “Biological Information.” The Stanford Encyclopedia of Philosophy. Zalta, Edward N. (ed.) p. [of Html file] 9.
“A working definition is, however, suggested: the RNA World hypothesis denotes the view that life incorporated RNA before the emergence of coded proteins and DNA genomes. We argue that sufficient evidence exists to support this view beyond reasonable doubt.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1086.
“A notable example of RNA’s wide functional repertoire is its ability to undergo self-regulation as a function of ligand binding…. At present, there are over 50 classes of riboswitches and there is evidence that some of the contemporary riboswitches possibly evolved from ancient sensors and switches based on RNA that arose during the preprotein stages of evolution.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1088.
“The list of known natural and artificial ribozymes previously mentioned increases the known versatility of RNA, while providing clues about the nature of the ancient RNA World. These findings indicate that functional RNAs in the ancient RNA World might have been capable of phosphorylation, nucleotide synthesis, ligation, alkylation, coenzyme attachment, RNA-dependent RNA polymerization, and more. Perhaps the eventual coupling of amino acid chemistry with functional RNA dynamics facilitated the coevolution of ribozymes and amino acids, leading to the emergence of aminoacylation and peptidyl transferase ribozymes during the birth of primitive polypeptide synthesis.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1088.
“The working definition of the RNA World hypothesis–that life incorporated RNA before the emergence of coded proteins and DNA genomes–requires a distinction between coded proteins and noncoded polypeptides as the former require a genetic decoding apparatus for information flow from nucleic acids to amino acids, and the latter do not.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1089.
“… it is not unexpected that the RNA World and the OoL are both thought to involve the ribosome’s origins. Consistent with this notion is the observation that translation-related genes dominate the set of <100 genes common to all living organisms, termed the Universal Gene Set of Life….
“The observation that the catalytic core of the ribosome is an RNA enzyme is consistent with the RNA-centric and translation-centric nature of the OoL, and was later used to support the view that RNA preceded coded proteins in the early evolution of life.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1089.
“… it has been shown that amino acids joined to single nucleic acids can form template-based dipeptides, without ribosomes.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1090.
“Given the centrality of rRNA and tRNA in translation, it is necessary that the origins of translation involved the ancestors of both molecules.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1090.
“Though much of the evidence for the RNA World hypothesis involves the ribosome, it is important to consider RNA World relics found within the riboswitches, self-splicing introns, and other RNA-based molecular architecture in contemporary life.” Fine, Jacob L. & Ronald E. Pearlman. 2023. “On the origin of life: an RNA-focused synthesis and narrative.” Cold Spring Harbor Laboratory Press. 29:1085-1098. 10.1261/ma.079598.123. p. 1091.
“At the core of the present life system, RNA and protein mutually synthesize each other: ribosomes (RNA) synthesize proteins, and RNA polymerases (protein) synthesize RNA. This suggests that our complex genetic system or the central dogma resulted from a long co-evolutionary process between RNAs and proteins.” Tagami, Shunsuke & Peiying Li. 2023. “The origin of life: RNA and protein co-evolution on the ancient Earth.” Development, Growth & Differentiation. 65:167-174. 10.1111.dgd.12845. p. 167.
For NATO, addressing hybrid threats is paramount, as they directly challenge the alliance’s mission of collective defense and security through non-conventional means, particularly where adversaries can leverage vulnerabilities in NATO member critical infrastructure while maintaining plausible deniability. The sophisticated nature of these threats benefits from a resilience-oriented approach, emphasizing the need for agile, adaptive strategies that can respond to the dynamic and often indistinct contours of hybrid warfare.” Keenan, Jesse M., Benjamin Trump, Eero Kytomaa, Gitanjali Adlakha-Hutcheon & Igor Linkov. 2024. “The role of science in resilience planning for military-civilian domains in the U.S. and NATO.” Defence Studies. 10.1080/14702436.2024.2365218. p. 3.
“It can be argued that the scientific status of chemistry has become established through the move from causal to catalytic models. Likewise, the central explanatory role of cyclical models in biology has made it possible to move from the idea of genetic determination to that of epigenetic negotiation as tfhe core of biological theory.” Valsiner, J. 2014. “Breaking the Arrows of Causality: The Idea of Catalysis in its Making”. In: Cabell, K., Valsiner, J. (eds) The Catalyzing Mind: Beyond Models of Causality. Annals of Theoretical Psychology, vol 11. Springer, NY. 10.1007/978-1-4614-8821-7_2. p. 1.
“Life’s ability to structure matter and make it functional via manipulation of information is very unlike what we see in any other kind of physical system. While this view is gaining increasing traction in a variety of communities, it remains to be proven.” Kim, Hyunju, Gabriele Valentini, Jake Hanson & Sara Imari Walker. 2021. “Informational architecture across non-living and living collectives.” Theory in Biosciences. 140:325-341. 10.1007/s12064-020-00331-5. pp. 325-6.
“‘Anticipatory regulation’ replaces the more familiar ‘homeostatic regulation’–which is supposed to operate by waiting for each parameter to deviate from a ‘set point,’ then detecting the error and correcting it by feedback….
“Anticipatory regulation offers huge advantages. First, it matches overall response capacity to fluctuations in demand–there should always be enough but not too much. Second, it matches capacity at each stage in the system to anticipated needs downstream, thus threading an efficient path between excess capacity (costly storage) and failure from lack of supplies. Third, it resolves potential conflict between organs by setting and shifting priorities. For example, during digestion it can route more blood to the gut and less to muscle and skin, and during exercise it can reverse this priority. Finally, it minimizes errors–which are potentially lethal and also cause cumulative damage.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. xvi, xvii.
“An organ that anticipates need and regulates the internal milieu by over-arching control of physiology would be especially effective if it also regulated behavior.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. xvii.
“… when one part is forced to do two jobs, it can do neither well. An example is the two-stroke engine.
“The operating cycle of a four-stroke automobile engine involves four sweeps of the piston through the cylinder. One draws in the fuel, the next compresses it, the third delivers power as combustion drives the piston outward, and the fourth sweeps out the exhaust. The two-stroke engine discharges the exhaust with the same stroke that draws in fuel at the bottom of the combustion stroke and the beginning of the compression stroke. This serves well for a lawn mower or a power saw because the simpler design avoids the need for a valve gear to separately port fuel and exhaust, giving a better ratio of power to weight. However, the four-stroke engine’s more complicated design delivers much more power per liter of fuel and runs smoother and quieter. Moreover, its more efficient combustion discharges fewer pollutants.
“There are general advantages to providing a separate part for each task. First, each part can be independently tuned for speed, sensitivity, and so forth–without compromise. Second, each part can be regulated independently. Third, more parts provide more opportunities for further refinement, innovation, and improvement–simply because there are more starting points.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 6-7.
“… an animal’s small brain saves energy by efficiently directing the activities of large, power-hungry muscles.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 9.
“A receptor’s binding affinity determines the concentration at which protein synthesis becomes economical.
“For its default fuel E. coli uses glucose. But when glucose is off the menu, it can use lactose. This requires lactose detectors to call for two proteins: a permease to admit lactose and an enzyme, galactosidase, to split it. The genes coding these proteins are adjacent in E. coli’ DNA, comprising an operon (genes that work together). Their expression is blocked by a repressor protein that binds to this stretch of DNA and blocks the entry of RNA polymerase, the molecular machine that transcribes DNA to RNA to initiate protein synthesis. The repressor is the lactose detector which, upon binding allolactose (an isomer that always accompanies lactose) changes shape and releases from the DNA. This allows RNA polymerase to move off and transcribe the operon.
“In effect, the lactose receptor predicts for the organism what it will need to exploit this new resource. By encoding the permease and the digestive enzyme together, one sensory signal can evoke all necessary components in the correct ratios…. This design principle–matching capacities within a coupled system–is a key to the organization of multicellular animals where it is called ‘symmorphosis’.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 12-13.
“E. coli’s working memory is simple: it is imprinted on the receptor protein by means of a negative feedback loop. The activated taste receptor causes an enzyme to attach methyl groups to the receptor complex, decreasing its sensitivity. The number of methyl groups on a receptor indicates how strongly it has been activated, and because the feedback loop is sluggish, the record stretches back into the bacterium’s frantic past–1 s. The mechanism, by using the past to set receptor sensitivity, determines the bacterium’s response in the present–a reasonable definition of memory.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 15.
“But diffusion time increases as the distance squared, so for a Paramecium that is 100-fold longer than E. coli, diffusion from ‘head’ to ‘tail’ would be 10,000-fold slower, about 40 s. Obviously, this is far too slow for receptors at the head to call ‘Reverse!’ to the tail cilia. Electrical signals spread much faster: a change in membrane voltage initiated at the head reaches the tail in milliseconds.
“Electrical signaling for this avoidance response requires several new components. First, a mechanoreceptor is needed to detect the bump. This involves a specialized cation channel inserted into the cell membrane. Stretch on the membrane deforms the channel, opening it to sodium ions that rapidly depolarize the membrane (<100μs). Depolarization opens voltage-sensitive calcium channels that admit a rush of calcium ions–further depolarizing the membrane, opening still more calcium channels, and so on….
“The reason to spread the electrical signal via a calcium channel, rather than a voltage-gated sodium channel (such as used by nerve and muscle), is that a calcium ion can also serve intracellularly as a chemical messenger. In this case the chemical message arrives synchronously at the base of all cilia, saying ‘Reverse beat,’ and their simultaneity adds power to the reversal. As Paramecium backs up, calcium pumps in the membrane vigorously reduce the calcium level, allowing patches of cilia to slip back into ‘forward’–explaining the indecisive twiddle. Once most of the calcium has been extruded and all cilia again beat forward, Paramecium heads off in a new direction.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 18-20.
“The crossover–where multicellular animals arise and dominate (eat the unicellular)–occurs at a size of around 1 mm and a lifetime of days. Then cells specialize and associate to form tissues, tissues form systems, and systems cooperate to form a more versatile organism….
“Coordination demands some mechanism with an overview that enables it to weigh alternatives, set priorities, and then exert ultimate authority to execute. Fortunately, the multicellular design that demands such integration also provides a special class of cells to accomplish it. These cells–neurons–now do what Paramecium could not: provide multiple fast lines for communication. In short, for a multicellular organism a brain becomes necessary, possible, and profitable.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 20-1.
“The worm’s [C. elegans’] brain may be small, but its 302 neurons plus 56 glial and support cells comprise nearly 40% of its body’s entire complement. The figure in humans is close to 1%.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 22.
“The worm builds its oscillator by combining feedback with body mechanics. A burst of activity in motor neurons drives the muscles on one side. Their contraction bends the body and tensions the body’s intrinsic spring–internal hydrostatic pressure. Sensors excited by these forces feed back to inhibit motor neurons, whereupon the muscles relax and the body springs back….
“So by using its biomechanics the worm can dispense with a central pattern generator, thus freeing up brain space. Here, then, is useful design principle for motor systems: lighten the brain’s load by using the body. Engineers call this embodied computation (also embodied intelligence or cognition).” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 25, 26.
“Far from living in the moment like E. coli, the worm uses its brain to associate events over time and thus draw on its experience.
“A worm remembers the temperature at which it was well fed and later seeks this temperature by moving up or down a thermal gradient. Finding the preferred temperature, it hangs there, searching along the isotherm. But dopamine decays promptly; so if the cupboard is bare, preference turns to aversion and the worm crawls off. Upon finding food and thus earning another shot of dopamine, the worm resets its temperature preference.
“The mechanism for this learning resides within the thermal sensor that drives oriented crawling. This neuron senses changes of 0.003̊ C. Its response is minimal at the preferred temperature and rises on either side. The temperature for this minimum is reset by adjustments to the neuron’s internal signaling; this requires protein synthesis and takes several hours. This learning process–chemical reprogramming within a single neuron–changes protein molecules but not synaptic connections.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 32.
“In short, the worm’s behavior demonstrates its reliance on information from three distinct sources; outside, inside, and the past.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 32.
“We distinguish these terms: ‘receptor’ refers to an individual protein molecule that responds to a specific event–like stretch, temperature, protons, or chemical binding; ‘sensor’ refers to an individual neuron that expresses one or more types of receptor. Although neuroscientists understand this difference perfectly well, for historical reasons they often use ‘receptor’ for both the molecule and the neuron.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 33.
“If a set of receptors all lead to the same final action, they share a common sensor….
“This rule explains receptor grouping generally. The worm uses more than 1,700 different types of receptor molecule for chemoreception (taste and olfaction). This considerably exceeds the 800 or so used in mammals, but unlike mammals where each receptor type is typically assigned its own sensor, the worm provides only about 30 separate sensor neurons.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 33-4.
“The worm meets all basic requirements for behavior (sensory pattern recognition, sensorimotor integration, and motor control) with small numbers of neurons. Thirty-eight sensors connect to 82 interneurons (whose processes are confined within the brain) that contact 119 motor neurons (cells whose processes leave the brain to contact the worm’s 100 muscle cells). This reserves about 70 neurons for internal regulation and mating.
“Yet there is a downside to performing several operations in a single cell. A cell’s capacity to handle information is limited by factors such as internal noise, dynamic range, and energy supply. So a sensor that processes inputs from several types of receptor compromises its ability to handle the information from any one receptor type. A dedicated sensor can devote more receptors to its particular modality and thus improve sensitivity and signal-to-noise. This is the engineer’s principle … to prevent one component from doing two tasks suboptimally, complicate.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 34.
“… chemical computing by circuits within a neuron can manage behavior. Moreover, this can be very efficient because chemical signals are orders of magnitude cheaper than electrical signals.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 35.
“As animals emerge from the soil to a wide, less viscous world, the possibilities for foraging expand immensely. A worm explores mainly in two dimensions over an area of 0.01 m2 whereas a honeybee typically covers an area of nearly 10 m2, and a fly somewhat less. So foraging area expands by 109 (1 billionfold). Add the third dimesnion, and the volume to be explored becomes astronomical. Larger animals, such as fish, birds, and mammals, may migrate and thus forage over thousands of kilometers–thus millions of square kilometers.
“Such gigantic territories contain immense resources and, of course, harbor innumerable dangers. For an animal to find the one and avoid the other requires it to rapidly gather vast amounts of information from the environment. To calibrate ‘vast’ with one example, the eye sends the brain about 10 megabits per second, roughly the rate of an Ethernet connection. All sense data reach the brain in the form of tiny patterns–evanescent pieces of a dynamic jigsaw puzzle–and to be of any use, they require assembly to reveal a larger pattern. So if gathering information is to be at all rewarding, the brain must commit resources to assembling larger patterns on spatial and temporal scales that are relevant to behavior.
“Yet, even a larger pattern might be useless until it is compared to a library of stored patterns where it can be identified: edible/toxic, friend/foe, or search item not found. Either outcome provides a basis for behavioral choice. A match allows confident choice: eat or decline, approach or flee. A non-match suggests caution and need to gather more data. Thus, the brain requires ‘pattern comparators,’ and these must couple to mechanisms that select behaviors: feed, fight, copulate, investigate. These, in turn, couple to mechanisms for detailed motor patterns to drive muscles for moving limbs or wings.
“Any given motor behavior might match exactly the action that was ordered: the arrow might strike the exact point at which it was aimed. But often there are errors due to environmental or neural perturbations, and these need to be identified, so that performance can progressively improve. Thus, a brain needs mechanisms to evaluate the mismatch between the orders it gave and the actual motor performance. So, in addition to sensing and processing patterns to discover ‘what’s important out there,’ the brain also devotes considerable resources to sensing and processing its own motor errors, and other errors of internal ‘intentional’ signaling in order to improve the accuracy and efficiency of the next round. This is ‘motor learning.’
“Behaviors are subject to another important class of errors. Every action has both costs and consequences. The costs are partly energetic: how much energy was spent? But also there are ‘opportunity costs’: could the return have been greater and the risk less for some different action? Every behavior, even when perfectly executed, needs to be evaluated from this perspective: wise or foolish? repeat or not? These evaluations of reward prediction, like those for motor errors, are used to update stored knowledge in order to improve the next round of predictions….
“What the brain does for the external environment it also does for the internal environment which has also expanded and complexified. Moreover, the mechanisms for managing the internal and external environments need to couple closely in order to serve each other.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 43-4.
“In fact, all internal regulation, even the mildest sort, is far from autonomous. As the external environment presents opportunity or cause for concern, internal processes must predict what the external environment is about to deliver and must prepare particular responses that will probably be needed in support. For internal processes the goal is not to correct mis-matches but to prevent them.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 46.
“To raise pressure, the heart accelerates and vessels constrict. Also the kidney expands blood volume by pumping more salt water into the circulation.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 47.
“Information is the reduction of uncertainty about some situation X associated with observing any variable Y that is causally correlated with X.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 51.
“Reduction of uncertainty succinctly describes the brain’s purpose. A spike in an ON ganglion cell reduces the brain’s uncertainty that a brighter than average object is located in a particular region of the visual field. And when the brain matches the sensory pattern coded by a patch of ganglion cells to a stored pattern, it reduces a key uncertainty: ‘Friend or foe?’” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 51.
“To convey information, a neuron must represent the state of its input as a distinct output (input and output must be causally related). It follows that a neuron’s capacity to convey information is limited by the number of distinctly different outputs that it can generate. The number of different outputs a spiking neuron can generate in a given time is the number of distinctly different spike trains that it can produce in that time.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 51.
“A symbol that occurs less frequently is more surprising and so more informative. This effect, which Shannon called surprisal, makes a code with fewer spikes more efficient.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 52.
“The inescapable cost of sending any information and the disproportionate cost of sending at higher rates lead to three design principles: send only what is needed; send at the lowest acceptable rate; minimize wire, that is, length and diameter of all neural processes….
“Designs should reduce wire, or course, because wire uses space and energy. But wires also use time for transmission, and that is time lost to processing and action.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 54-5.
“… the SCN [suprachiasmatic nucleus, the master clock] couples to an adjacent region, the hypothalamus, that for its comparatively small extent is extremely well informed. This region monitrors myriad internal parameters, including temperature, blood levels of salt, and metabolites, hormonal signals for ssatiety, hunger, thirst, pain, fear, and sexual state…. To execute, it does not micromanage but instead calls the appropriate pattern of behavior….
“Hypothalamic circuits, designed to anticipate impending needs, generate signals that elicit various ‘motivated behaviors,’ that is, foraging for food, or drink, or sex in response to these integrated signals. As these motivating signals are broadcast to other brain regions, there arises a subjective component that we experience as desire….
“The local pattern generators manage the exact timings of muscle contraction required for coordinated behavior….
“In short, the hypothalamic network is designed to receive executive summaries as input and deliver broad memoranda as output.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 61, 63.
“Design principles dictate that the slowest processes should be governed by the slowest effectors and the least wire. Where signals can be sent with zero wire, that is best. Consequently, the effectors for micromanaging the broad catabolic and anabolic patterns are endocrine glands….
“Each node in the hypothalamic network can call a particular pattern of brain hormones for release into the blood just upstream of the pituitary, thus stimulating it to release its own hormones into the general circulation. The whole endocrine network reaches every cell in the body within seconds. Not blazingly fast, but on the other hand, the messages are broadcast without any wire at all and with zero energy cost above what the heart is already doing.
“The genius of this wireless system lies partly with the receivers. Although all somatic cells are exposed to all hormones, only certain cell types download a given message.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 64, 65.
“Patterned inputs encounter the same constraints as patterned outputs, and to economize, they follow the same principles. First, the inputs deliver what can be computed locally; second, they relay upward only what is needed to assemble larger patterns. Each successive stage of processing sheds unneeded information. These principles also apply to storage: save only what is needed, for as long as it is needed, and in the most compact form.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 83.
“Exemplifying the rule, compute locally, are two types of pressure receptor located on the foot….
“For example, pressing your bare foot on a smooth surface activates an array of low-frequency pressure receptors that excites the pattern generator for limb extension to support your weight. But pressing your foot on a sharp point activates higher frequency pressure receptors that excite the pattern generator for limb flexion to withdraw your weight and for limb extension on the opposite side to support your weight. This occurs faster than you can feel ‘Ouch!’ because the higher frequency pressure responses travel over thick, fast-conducting wires that couple directly to the local pattern generator.
“Such direct functional connections between specific sensory inputs and specific motor outputs were historically termed reflexes. But now the design is seen as coupling each receptor type to the appropriate pattern generator.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 83-4.
“Each motor act is also a beginning: it is a provisional answer to some predicted need. Since needs recur, output patterns might be improved if their effectiveness could be evaluated. Therefore, the brain invests heavily in several systems for evaluation and error correction.
“One system asks, ‘How precisely did the actual output pattern match the intended pattern?’ This system computes the difference between the intended pattern and the actual pattern; then it feeds the error back to command structures that gradually improve performance. This serves motor learning–what is gained from practicing the piano or the golf swing…. Thus, motor learning is subset of intention learning.
“Another system asks, ‘Was the act, however well performed, worth the energy and the risk?’ This system compares the expected payoff from a particular act to what was actually gained. The neural mechanism rewards a better outcome by releasing a pulse of dopamine at key brain sites and punishes a poorer outcome by reducing dopamine and enhancing other chemical signals. This is reward-prediction learning….” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 86-7.
“To identify rotting fruit and detect pheromones, Drosophila invests in about 50 types of olfactory receptor. These are more than are used by the louse that parasitizes humans (10) but fewer than are used by the honeybee (160) and fire ant (400) for their extensive foraging and chemical communication.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 91-2.
“Insect sensory processing resembles mammalian processing in that small patterns collected by sensors are filtered and then assembled into larger patterns.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 93.
“In short, the central complex is aptly named because it is both centrally located and central to the brain’s broad tasks that were indicated… (assemble larger patterns, compare to stored patterns, predict a promising output pattern, and call an integrated output). Thus in many ways the central complex [of a fly, or insects in general] is homologous to the mammal’s basal ganglia. It seems remarkable that the central complex achieves all this with less than 600 neurons.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 98.
“The mushroom body [in insect brains], like mammalian cerebral cortex, participates in olfactory learning, associative learning, spatial learning, visual pattern recognition, attention, and sensory integration. The mushroom body, like cortex, shapes its circuit architecture to view multiple inputs, looking for coincidences to associate with reward or punishment. This suggests a multipurpose cross-correlator that can be wired to evaluate a variety of associations and store the lessons.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 102.
“Thus, most transfer of information from a source neuron to a receiver neuron occurs via chemistry (concentrations, binding reactions) and physics (changes in molecular structure).” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 106.
“A finite-state machine processes information by running through a well-defined sequence of state changes, each triggered by a particular condition, such as the presence or absence of an input, or a conjunction of inputs. This is allostery. As a protein molecule runs through a sequence of state changes, each conditional upon a particular input, it produces an output conditional upon those inputs. Thus, allostery enables a single protein molecule to compute. For example, a single molecule is easily programmed to perform the Boolean operation, AND.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 117.
“The human genome specifies more than 800 different receptor proteins that couple to a G protein and more than 100 different G proteins.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 117.
“Amplification is a form of redundancy since each copy simply repeats a message without adding new information. Thus, multiple G proteins activated by the β2 receptor simply repeat, ‘Adrenalin!,’ ‘Adrenalin!’…. Yet this redundancy is essential for two reasons. To produce a concerted response to adrenalin, the signal must reach many parts of the cell in good time, hence the activation of several G proteins. Second, the system must guard against noise. Because a thermal bump occasionally activates a single G protein molecule, the receptor must activate several molecules to generate a reliable message.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 120.
“Allostery also equips a single protein molecule to compute by operating as a finite-state machine. By running through a well-defined program of state changes, triggered by specific inputs, the molecule completes a program only when it encounters a specific combination of inputs. These properties equip proteins to form circuits of molecules that compute.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 124.
“… information is encoded whenever a source’s change in state registers as a change in state at a receiver. The primary mechanism at the nanometer scale is a protein’s ability to connect specific inputs to specific outputs by, for example, binding molecules, catalyzing reactions, and changing conformation.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 125.
“To understand neural computing at the nanometer scale, one must consider what shapes a protein’s I/O function. What determines, for example, whether it will take a sum or a logarithm, whether it will switch or filter? These functions emerge from a protein’s three-dimensional structure, through its ability to react chemically, mechanically, and electrically, and to change state in response to these inputs–allosterically….
“While the ligand is bound, the protein adopts an active conformation in which it produces its output, for example, it is able to bind a downstream protein or catalyze a chemical reaction. Thus, the protein’s output is proportional the fraction of time it binds the ligand….” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 126, 127.
“Chemical circuits support Turing’s Universal Computation, which means that they can in principle be configured to compute any function.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 131.
“Not only does chemistry compute, it equips the brain to compute over the range of timescales observed in animal behavior–from the microseconds of the electric sense and hearing to a century of memory.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 131.
“Transmission within a chemical circuit is wireless, so space for wires also reaches an absolute minimum and circuits share space seamlessly.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 131.
“To charge the membrane quickly, ions must be driven through channels at high rates. The primary driving force is a concentration gradient maintained across the membrane by ion pumps. Most important is the sodium-potassium pump, which maintains low sodium concentrations and high potassium concentrations inside the neuron. This pump is a molecular machine, a protein complex spanning the membrane which hydrolyzes one ATP molecule to export three sodium ions and import two potassium ions. This asymmetrical exchange generates an outward current of one positive charge per pump cycle and sets up the two concentration differences, [K]in > [K]out and [Na]in < [Na]out. These two gradients power most of the brain’s electrical circuits. Consequently, the sodium-potassium pump consumes 60% of the brain’s energy.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 138.
“With an input energy of 25 kBT joules and an output of 2.4 X 10 kBT joules, a sodium channel opening for 1 ms has a power gain X1,000. Thus, a channel’s combination of sensitivity, fast switching, and gain satisfies the need for speed. But as noted, it comes at a price….
“The gradient is restored by pumping the ion back across the membrane, so when a sodium channel opens for 1 ms and admits 6,000 Na+ ions, sodium-potassium pumps hydrolyze 2,000 ATP molecules to ADP to pump these ions back. The efficiency of the conversion of the chemical energy supplied by ATP to the electrical energy delivered by the channel is reasonably high, 50%. Nevertheless, a channel’s signaling cycle (open, admit ions for a millisecond, close, restore ions) uses 2,000 times more ATP than a G protein’s cycle. This is the price paid for speed over distance.
“In summary, an ion channel changes a neuron’s membrane potential rapidly by operating as a power transistor that is irreducibly small and operates close to thermodynamic limits.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 142.
“A voltage-gated channel opens or closes allosterically, in response to membrane potential. Thus, a voltage-gated channel can be activated within milliseconds by channels opening millimeters away. In addition, a voltage-gated channel amplifies an electrical input.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 147.
“A voltage-gated calcium channel admits an ion that readily binds a protein and changes its conformation…. A calcium ion is especially effective at changing a protein’s conformation because, being divalent, it pulls negatively charged parts of a protein closer together.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 150.
“Calcium is especially effective as a chemical messenger because cells pump it out to keep the internal concentration low, 30-200 nM. This creates a steep concentration gradient, equivalent to a battery of 130 mV that, aided by the -70mV resting potential, drives calcium in through a channel at a rate of ~107 ions per second. With so little internal calcium, the proteins within nanometers of the channel experience a 100-fold increase in calcium concentration within 100 μs. This nanodomain calcium signal has a wide bandwidth because it decays as rapidly as it rises. The puff of calcium injected by a channel vanishes within 500 μs by diffusing rapidly into a large sink, the well-buffered bulk of the cell’s cytoplasm….
“Whereas chemical signaling can send information in a millisecond, but only over 1 μm, passive electrical signaling can send it a millimeter in the same time–1,000-fold faster.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 150.
“Computing by chemistry offers good S/N [signal to noise] at irreducibly low cost in space and energy. Moreover, where the reaction vessel shrinks, the principle of mass action can operate on high concentrations with small numbers of molecules. High concentrations allow low binding affinities to achieve useful signaling rates. Small volumes also shorten distances–over which diffusion is rapid. Also, because concentrations of diffusing molecules decay steeply in space and time, many computations can be accomplished wirelessly–simply by placing detectors at different distances from a source and letting Brownian motion do the math.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 155.
“… overall, the mammalian brain transcribes 5,000 to 8,000 genes and uses alternative splicing to produce 50,000 to 80,000 distinct proteins.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 155.
“Chemical computing works brilliantly across a spatial scale of nanometers to micrometers and a temporal scale of 100 μs to seconds. Yet to serve behavior, computations must retain the same timescale but travel up to 1 millionfold farther. To achieve speed over distance requires recoding the chemical signals to electrical signals. Recoding begins with an allosteric trigger, such as ligand-binding or G protein activation, but allostery must eventually open an ion channel in the membrane to establish an electrical signal. This is one key task for a neuron: use allostery to send an electric signal somewhere fast.
“‘Somewhere fast’ has two parts. First, a chemical signal released by a presynaptic neuron targets a postsynaptic neuron on a short branch (dendrite). The chemical transmitter binding to a protein receptor allosterically opens its ion channel. This initiates an electrical signal that spreads passively along the dendrite toward a central locus (cell body or specialized cable segment) for integration with signals from other dendrites. Second, the integrated electrical signal recodes to an all-or-none pulse that spreads actively down a single cable (axon) toward presynaptic terminals that contact other neurons.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 155, 156.
“A neuron steps up from the nanometer scale of protein circuits to the micrometer scale of a synapse (1,000 fold), then to the millimeter scale of a dendritic tree (1,000-fold), and then to the meter scale of the longest mammalian axons (1,000-fold), ultimately integrating processes that span a 109 range of spatial scale. This greatly increases the cost of space, materials, and energy. A protein molecule allosterically encoding 1 bit occupies about 50 nm3; whereas the smallest neuron cell body encoding 1 bit occupies 109 greater volume; and the largest neuron cell body encoding 1 big occupies 1012 greater volume and correspondingly more materials. The energy cost of encoding 1 bit rises from about 25 kBT to about 109 kBT.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. p. 157.
“Synapses enable neurons to process information in neural circuits by transferring and transforming signals at specific connections. The simplest synapses are electrical, made from proteins that form an array of channels that connect two neurons. Where it serves as a simple resistor, an electrical synapse is as inexpensive and noiseless as a connection can be. This is why electrical synapses are widely used to weakly couple neurons, for example, to compute the mean signal over a patch of retina to reduce redundancy, to synchronize rhythmical activity among the cortical inter-neurons, and to synchronize motoneurons that drive the same muscle. But coupling with a resistor does not equip a circuit to compute much. More transformations are required, and signals must be amplified to produce fast response that are resistant to noise. These requirements are met by chemical synapses, so called because a presynaptic neuron transmits chemically by sending a pulse of neurotransmitter to receptors on a postsynaptic neuron.
“A chemical pulse originates when a vesicle docked to a presynaptic active zone fuses with the plasma membrane and releases transmitter molecules through a fusion pore into the synaptic cleft. The vesicle contains about 4,000 molecules of transmitter concentrated by a transporter protein in the vesicle membrane to roughly 100 mM….
“For vesicle fusion (exocytosis) to work at all requires multiple allosteric processes. And for it to transfer the information encoded chemically to an electrical signal, while preserving temporal precision and S/N, these allosteric processes must couple efficiently as now explained.
“To preserve temporal precision, vesicle fusion must occur promptly as a triggered event. This requires docking it in advance to a specialized active zone and then priming the vesicle with multiple SNAREs, each a complex of four protein molecules. A SNARE, upon binding the vesicle tightly to the presynaptic membrane, adopts a high free energy conformation that is metastable. Consequently, a small signal can push a SNARE over the hump on its energy landscape and trigger fusion.
“The trigger is a surge of calcium ions reaching the docked vesicle through voltage-gated channels clustered at the active zone. When channels open in response to a presynaptic depolarizing electrical signal, several hundred calcium ions enter to raise the local concentration by 50-fold in less than 500 μs. Several calcium ions are bound by the protein synaptotagmin attached to the vesicle, which then binds to the SNARE and pushes it over the energy hump. As the SNARE plummets to a lower energy conformation, the freed energy causes violent tugs on the vesicle. The combined force from three SNAREs suffices to fuse the vesicle to the presynaptic membrane and wrench open a pore with consequence already noted.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 157-158, 160.
“Dendritic biophysics provides cheap and robust analogue processing. For example, by placing input synapses that carry less information distally on the dendrite, they can be given less weight in the final output, whereas signals that carry more information can be given more weight by placing them nearer the cell body. More generally, inward currents from excitatory synapses can be combined with outward currents from inhibitory synapses and potassium channels. Thus, a dendrite serves as an analogue electrical circuit that adds, subtracts, divides, multiplies, and takes logarithms….
“To increase their processing abilities, dendrites complicate their design….
Thus, more complicated dendrites provide two layers of processing, local within a single dendrite and global within the larger dendritic tree.” Sterling, Peter & Simon Laughlin. 2017. Principles of Neural Design. MIT Press. pp. 171-2.
“The terms ‘catalytic force’ and ‘catalysis’ were introduced by Berzelius in 1836 in such a way as to stress the connection between the newly named force and electrochemical affinities. It was not his intention to hypostasize a new causal agency….
“… Liebig responded that he thought the whole idea of the catalytic force is false. Although he was still ridiculing it to Woehler as late as 1839, two years thereafter, in the second of his serialized and anonymously published ‘Chemical Letters,’ Liebig effectively accepted the operation of such a force, though without deigning to use Berzelius’s term.” Caneva, Kenneth L. 1993. Robert Mayer and the Conservation of Energy. Princeton UP. pp. 174, 175.
“As first described classically by Jung, individuation is essentially a process of renewal and widening of the ego-consciousness. It is in this classical sense that I refer to individuation here. As such, it presupposes an ego-consciousness already emerged from the unconscious background through a process of painful and progressive separation from the matrix, the collective unconscious, symbolized by the Mother. As a result of this separation, ego-consciousness gains a necessary distance from the unconscious, and thereby strengthens its boundaries. But, with increased distinctiveness and clarity, ego-consciousness progressively loses its contact with the unconscious matrix. There ensues a condition of imbalance between conscious and unconscious, a dissociation. Symptoms appear. Disconnected from its instinctual source, ego-consciousness is in danger of dying, of becoming rigid and sterile. Consequently, the ego must go back to the unconscious, to the collective matrix, in order to renew itself, to gain access to new archetypal energies and forms. The confrontation between the ego and the unconscious is, in essence, symbolized by the hero myths and tales, by the tales of death and rebirth. In its descent and journey, described by these myths, the ego encounters the various archetypes of the collective unconscious, and, as a result, ego-consciousness is renewed and progressively widened.” McCurdy, Jole Cappiello. 2017. “The Structural and Archetypal Analysis of Fairy Tales.” From: Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales: Volume I. pp. 1-15. Stein, Murray & Lionel Corbett (eds). pp. 1-16. Asheville: Chiron Publications. pp. 2-3.
“Propp identified a total of thirty-one functions in the fairy tale. Naturally, not all the functions are present in every tale. Some isolated functions may be missing, for example, the preparatory section may not appear, or the tale may end when the initial villainy is countermanded. The important fact is that the relationship between functions is always the same; that is, the basic structure is always present…. Furthermore, this network of functions is constant whether or not the tale’s cast includes all of the seven different kinds of typical characters which Propp names. These seven–the villain, the donor, the helper, the sought-for person, the dispatcher, the hero, and the false hero–are identified according to their functions, not according to their attributes, motivations, or feelings.” McCurdy, Jole Cappiello. 2017. “The Structural and Archetypal Analysis of Fairy Tales.” From: Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales: Volume I. pp. 1-15. Stein, Murray & Lionel Corbett (eds). p. 8; reference: Propp, Vladimir. 1958. Morphology of the Folk Tale. Lawrence Scott, translator. Indiana University Research center in Anthropology, Folklore, and Linguistics.
“With the appearance of symptoms, the unconscious begins its disturbing influence; at the same time, consciousness becomes more rigid in order to defend itself. On one side, we have in the tale, following Propp, the interdiction–representing the attempt at conscious defense–and, on the other side, we have the actions of the villain, representing the unconscious now perceived as an enemy. The hero–the ego–finds itself assaulted from two sides: from one side by the moral and rigid interdictions that constitute the persona and, from the other, by the pressure of the unconscious. The hero tries to defend himself or herself, but the villain tests and lures, undermining the defenses. Finally, the hero, explicitly or implicitly, will assent to the villain, giving in to the temptations that come from the unknown other.
“It is interesting that Propp calls this function ‘complicity.’ We recall the story of the Fall, of Eve’s and Adam’s willingness to eat the forbidden fruit. The violation of the interdiction in fact represents the first actively heroic gesture of the hero. With the violation, contact with the unknown other, with the unconscious, is established and the process of development can now begin.” McCurdy, Jole Cappiello. 2017. “The Structural and Archetypal Analysis of Fairy Tales.” From: Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales: Volume I. pp. 1-15. Stein, Murray & Lionel Corbett (eds). p. 11.
“Sometimes a man will embark on ‘men’s work’ but refuse to go underground. Men of this sort become consumers of myths, connoisseurs of fairy tales, judges of the conference leaders, playboys of growth.” Bly, Robert. 2017. “The Dark Man’s Sooty Brother: Male Naivete and the Loss of the Kingdom.” From: Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales: Volume I. pp. 91-101. Stein, Murray & Lionel Corbett (eds). p. 94.
“… it is a state of feeling that avoids the dark side of one’s own motives or the motives of others. Naivete discounts anger, fear, or greed and assumes more goodness in the world than there is. The naive person often refuses confrontation or combat and, if thrown into combat by circumstance, often fails to notice that he has in fact been defeated….
“Naivete seems to be characteristic of American men in the last forty years; we could say that Hemingway represents a successful fight against it–he tried to see defeat as defeat.” Bly, Robert. 2017. “The Dark Man’s Sooty Brother: Male Naivete and the Loss of the Kingdom.” From: Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales: Volume I. pp. 91-101. Stein, Murray & Lionel Corbett (eds). p. 96.
“Where love reigns, there is no will to power; and where the will to power is paramount, love is lacking. The one is but the shadow of the other.” Jung, Carl. 1943. par. 78. On the psychology of the unconscious. Collected Works 7:1-119. Princeton UP. 1966. From: Psyche’s Stories: Modern Jungian Interpretations of Fairy Tales: Volume I. 2017. Stein, Murray & Lionel Corbett (eds). p. 160.
“The difference between a ‘motor’ and a ‘switch’ as basic molecular machine types, for example, is significant because ‘motor’ and ‘switch’ become descriptors of very different types of behavior at molecular length scales, not simply iconic images. A ‘switch’ influences a system as a function of the trajectory of its components or the substrate….
“That is not to say that molecular switches cannot use chemical energy to do mechanical work. They can, but it is undone by resetting the switch to its original state. The key reason why this point is important is that switches cannot use chemical energy to repetitively and progressively drive a system away from equilibrium, whereas a motor can.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 74.
“Even the most efficient nanoscale machines are swamped by its [thermal motion] effect. A typical motor protein consumes ATP fuel at a rate of 100-1000 molecules every second, which corresponds to a maximum possible power output in the region of 10-16 to 10-17 W per molecule. When compared with the random environmental buffeting of approximately 10-8 W experienced by molecules in solution at room temperature, it seems remarkable that any form of controlled motion is possible.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 75.
“Indeed, neither Maxwell nor Thomson saw the demon as a threat to the second law of thermodynamics [as some did later in a reach for energy for free], but rather an illustration of its limitations–an exposition of its statistical nature.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 76.
“Even at the mesoscopic level of bacteria, viscous forces dominate. At the molecular level, the Reynolds number is extremely low and the result is that molecules, or their components, cannot be given a one-off ‘push’ in the macroscopic sense. Thus, momentum is irrelevant. The motion of a molecular-level object is determined entirely by the forces acting on it at that particular instant–whether they are externally applied forces, viscosity, or random thermal perturbations and Brownian motion…. Moreover, the high ratios of surface area to volume for molecules mean they are inherently sticky and this will have a profound effect on how molecular-sized machines are organized and interact with one another.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 78.
“Listed below are what appear to us to be the most significant aspects of biological machines to bear in mind when considering synthetic molecular machine design.
“1) Biological machines are soft, not rigid.
“2) Biological systems operate at near-ambient temperatures (heat is dissipated almost instantaneously at small length scales so they cannot exploit temperature gradients).
“3) Biological motors utilize chemical energy, in the form of covalent-bond breaking/formation of high-energy compounds such as ATP, NADH, and NADPH or concentration gradients.
“4) Biomachines operate in solution, or at surfaces, under conditions of intrinsically high viscosity.
“5) Nature utilizes–rather than opposes–Brownian motion. Biomolecular machines need not use chemical energy to initiate movement–their components are constantly in motion–rather, they function by manipulating (ratcheting) that movement. Furthermore, constant thermal motion and small ‘reaction vessels’ (cells and their organelles) ensure that the mixing of biological machines, their substrates, and their fuel is extremely rapid, in spite of the high viscosity they experience.
“6) The viscous environment and constant thermal motion mean that biological machines have no use for smooth, low-friction surfaces. Genuinely smooth features are not possible on the molecular scale, of course, since the machine-component dimensions are close to the dimensions of the intrinsic unit of matter–the atom.
“7) Biomotors and other mobile machines utilize architectures (for example, tracks) which serve to restrict most of the degrees of freedom of the machine components and/or the substrate(s) they act upon. The molecular machine and the substrate(s) it is acting upon remain kinetically associated during the operation of the machine….
“8) The operation and structure of biological machines are governed by noncovalent interactions (intramolecular and intermolecular), many of which exploit the aqueous environment in which the machines assemble and operate.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 79.
“We choose to distinguish between two overarching classes of mechanism: energy ratchets, which fall into two basic types–pulsating ratchets and tilting ratchets… and information ratchets, which are much less common in the physics literature…. Both energy ratchets and information ratchets bias the movement of a Brownian substrate.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. pp. 80-1.
“In the pulsating and tilting types of energy ratchet mechanisms, perturbations of the potential-energy surface–or of the particle’s interaction with it–are applied globally and independent of the particle’s position, while the periodicity of the potential is unchanged. Information ratchets transport a Brownian particle by changing the effective kinetic barriers to Brownian motion depending on the position of the particle on the surface.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 83.
“By analogy to the stereochemical term ‘conformation’, which refers to geometries that can formally be interconverted by rotating about covalent bonds, the relative positioning of the components in interlocked molecules (and supramolecular complexes) is often referred to as a ‘co-conformation’.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 102.
“To create artificial Brownian machines which are more sophisticated than simple positional switches, control over the kinetics for exchange of the substrate between two sites of the machine must be introduced.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 116.
“Although the development of reaction-driven, field-driven, self-propelled, and scanning-probe-controlled submolecular motion is rapidly gathering pace, it is the design and synthesis of molecular structures–both classical covalent and mechanically interlocked–which restrict the thermal movements of various submolecular components that has been central to the major advancements in molecular-level machines to date. These structural constraints have been successfully combined with external switching of molecular and/or electronic structure to create systems which exhibit a remarkable level of control over both the relative position of units as well as the frequency and even directionality of their motion.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 139.
“… the relative positioning of the components of molecular-level structures can be switched, rotated, speeded up, slowed down, and directionally driven in response to stimuli. In doing so they can affect the nanoscopic and macroscopic properties of the system to which they belong. Whether one chooses to call such structures, ‘motors’ and ‘machines’, or prefers to consider them more classically as specific triggered large amplitude conformational, configurational, and structural changes, is irrelevant.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 163.
“Currently it is fair to say that there are two distinct design philosophies being used to try and prepare synthetic molecular-level machines: The first ‘hard matter’ approach focuses on adapting mechanical principles and designs from the macroscopic world to molecules and is typified by the research efforts on field-driven rotors, molecular gyroscopes, molecular scissors, molecular wheelbarrows, nanocars, etc. In this approach, friction and binding interactions are avoided as much as possible and the molecules are designed to be rigid in all degrees of freedom except those involved in the desired motion. The input energy is designed to provide a directed force that pushes the molecular machine in the desired direction or exerts a torque to cause it to turn. This approach follows directly from that used in the design of macroscopic machines, which are designed to reduce friction and sticking and to eliminate jitter, vibration, and excess motion that dissipate energy and reduce the efficiency of the machine.
“The second ‘soft matter’ approach is more chemical in philosophy and seeks to adapt principles of chemistry (selective stabilization and destabilization of noncovalent bonding interactions, structural symmetry, and kinetic versus thermodynamic control of processes) to achieve efficient and controllable directional motion at the molecular level.” Kay, Euan R., David A. Leigh & Francesco Zerbetto. 2007. “Synthetic Molecular Motors and Mechanical Machines.” Angewandte Chemie International Edition. 46:72-191. 10.1002/anie.200504313. p. 164.
“Contingency is a very important concept in evolution, both prebiotic and biological. Contingency can be defined as the convergence of several parameters or factors, which, although independent of one another, by chance act simultaneously in a given point/time and thus determine the course of the event….
“Is contingency equivalent to ‘chance’? The answer is no.” Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.” Israel Journal of Chemistry. 10.1002/ijch.201400177. p. 2.
“Contingency should not be confused with chance, or random events, nor with stochastic events, because it works on the basis of structural determinism of the growing entity [hypothetical penta-peptide] and the outcome depends on selection chemistry. What is due to chance is which factors and which reaction partners will be around at that given moment. This finally corresponds with the definition of the initial conditions of a reaction.” Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.” Israel Journal of Chemistry. 10.1002/ijch.201400177. p. 3.
“One can see kinetic control as one of the factors of contingency, since it is in a way part of the initial conditions that operate at one particular growth step, but catalysis is conceptually different from contingency, and it is better from the heuristic point of view to see these two effects as separate from each other.” Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.” Israel Journal of Chemistry. 10.1002/ijch.201400177. pp. 6-7.
“I believe that the identification of the criterion of life with the criterion of evolution is wrong. These are ontologically two different things ….” Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.” Israel Journal of Chemistry. 10.1002/ijch.201400177. p. 8.
“More generally, let us conclude these two last sections by saying that concentration can indeed be seen as a chemical constraint in the origin of life, since chemistry cannot operate below a certain threshold of concentration. A very trivial consideration, but, as we stated previously, often ignored in the field.” Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.” Israel Journal of Chemistry. 10.1002/ijch.201400177. p. 10.
“Once we accept contingency as the main driving force for the biogenesis of macromolecules and molecular evolution in general, we are bound to accept that it is impossible to know the way by which our macromolecules of life have been made. Within contingency, as we have illustrated, there are additional constraints, such as kinetic control, a concentration threshold, self-replication, and homochirality; we are dealing in other words with a multi-parameter problem where each of these parameters conceivably have an erratic, unprogrammed appearance.” Luisi, Pier Luigi. 2015. “Chemistry Constraints on the Origin of Life.” Israel Journal of Chemistry. 10.1002/ijch.201400177. pp. 11-12.
“Biological reproduction rests ultimately on chemical autocatalysis. Autocatalytic chemical cycles are thought to have played an important role in the chemical complexification en route to life. There are two, related issues: what chemical transformations allow such cycles to form, and at what speed they are operating. Here we investigate the latter question for solitary as well as competitive autocatalytic cycles in resource-unlimited batch and resource-limited chemostat systems. The speed of growth tends to decrease with the length of a cycle.” Könnyű, B., Szathmáry, E., Czárán, T. et al. 2024. “Kinetics and coexistence of autocatalytic reaction cycles.” Scientific Reports. 14:18441. 10.1038/s41598-024-69267-w. p. 1.
“With the rich supply of diverse organic compounds and the multitude of different physicochemical environments provided by the ocean and the ocean bed, a vast network of loosely connected organic reactions could have emerged. The pathways of this early reaction network must have been channeled mostly by kinetics lacking catalytic aid, or at best by inorganic catalysts. Since these early reaction pathways were not constrained by any functional requirement, the only way they could have produced relatively complex compounds of significance for the earliest stages of chemical evolution towards life was by coincidence, and even so side reactions may have prevailed and turned them into tar.
“A feasible escape route out of the trap of chemical chaos, even in the absence of specific catalysts, is provided by the kinetic dominance of autocatalytic reaction cycles over linear reaction pathways or non-autocatalytic cycles. An autocatalytic reaction cycle is a reaction path that forms a closed loop and includes a reaction producing an extra molecule of one of the loop members, A, while the cycle turns around once. From the viewpoint of this molecule, the self-propagating reaction A → 2A takes place in a single turn of the cycle, under the proper conditions and with all necessary resource compounds for all the reactions of the cycle present. Then the amount of molecule A, and, consequently, of all the other cycle members increase exponentially, which can radically change the dynamics of the network of reactions embedding the autocatalytic cycle: its compounds can persist and dominate in spite of the strong chemical noise in non-catalytic chemical networks. The autocatalytic subsystem increases much faster than it is eroded by side reactions. Such a cycle may also become a source of ‘feedstock’ for the larger network that includes it, as are the biochemical cycles in the cells of all recent organisms: some elements of the Krebs or TCA cycle provide substrates to chemical pathways producing other biomolecules (e.g., amino acids). For each of the best-known autocatalytic cycles with a supposed role in prebiotic (chemical) evolution: the formose reaction, the reverse tricarboxylic acid cycle, and the glyoxylate cycle, it is also true that individual cycle members can plug into a putative pathway for the production of a biomolecule. Thus, autocatalytic cycles may have emerged from the prebiotic chemical mayhem due to their kinetic advantage, and, once in place, they could have provided a continuous supply of biomolecules for the evolution of higher levels
of (pre-)biotic organization. Both of these advantages can be attributed to the potential of autocatalytic cycles to grow exponentially.” Könnyű, B., Szathmáry, E., Czárán, T. et al. 2024. “Kinetics and coexistence of autocatalytic reaction cycles.” Scientific Reports. 14:18441. 10.1038/s41598-024-69267-w. pp. 1-2.
“We attempted to dive into the competitive behavior of small-molecule autocatalytic cycles. This is an important topic for the study of chemical organizations in the realm of systems chemistry, as well as for the investigations of the origins of life where chemical complexification requires dynamical coexistence of an increasing number of different chemical species.
“Unsurprisingly we see parallels with the theory of the selective behavior of template replicators.” Könnyű, B., Szathmáry, E., Czárán, T. et al. 2024. “Kinetics and coexistence of autocatalytic reaction cycles.” Scientific Reports. 14:18441. 10.1038/s41598-024-69267-w. p. 7.
“Evolution produces complex and structured networks of interacting components in chemical, biological, and social systems. We describe a simple mathematical model for the evolution of an
idealized chemical system to study how a network of cooperative molecular species arises and evolves to become more complex and structured. The network is modeled by a directed weighted graph whose positive and negative links represent ‘catalytic’ and ‘inhibitory’ interactions among the molecular species, and which evolves as the least populated species (typically those that go extinct) are replaced by new ones. A small autocatalytic set, appearing by chance, provides the seed for the spontaneous growth of connectivity and cooperation in the graph. A highly structured chemical organization arises inevitably as the autocatalytic set enlarges and percolates through the network in a short analytically determined timescale. This self organization does not require the presence of self-replicating species. The network also exhibits catastrophes over long timescales triggered by the chance elimination of ‘keystone’ species, followed by recoveries.” Jain, Sanjay & Sandeep Krishna. 2001. “A model for the emergence of cooperation, interdependence, and structure in evolving networks.” PNAS. 98(2):543-547. 10.1073/pnas/021545098. p. 543.
We have described an evolutionary model in which the dynamics of species’ populations (fast variables) and the graph of interactions among them (slow variables) are mutually coupled. The network dynamics displays self organization seeded by the chance but inevitable appearance of a small cooperative structure, namely an ACS. In a dynamics that penalizes species for low population performance, the collective cooperativity of the ACS [autocatalytic set] members makes the set relatively robust against disruption. New species that happen to latch on cooperatively to this structure preferentially survive, further enlarging the ACS in the process. Eventually the graph acquires a highly nonrandom structure. We have discussed the time evolution of quantitative measures of cooperation, interdependence, and structure of the network, which capture various aspects of the complexity of the system.
“It is noteworthy that collectively replicating ACSs arise even though individual species are not self replicating. Thus the present mechanism is different from the hypercycle, where a template is needed to produce copies of existing species. Unlike the hypercycle, the ACS is not disrupted by parasites and short circuits and grows in complexity, as evidenced in all our runs. It can be disrupted, however, when it loses a ‘‘keystone’’ species.” Jain, Sanjay & Sandeep Krishna. 2001. “A model for the emergence of cooperation, interdependence, and structure in evolving networks.” PNAS. 98(2):543-547. 10.1073/pnas/021545098. p. 547.
“Our work shows that catalytically-active and chemotactic particles participating in a primitive metabolic cycle exhibit a variety of structural complex collective behaviour.” Ouazan-Reboul, Vincent, Jaime Agudo-Canalejo & Ramin Golestanian. 2023. “Self-organization of primitive metabolic cycles due to non-reciprocal interactions.” Nature Communications. 14:4496. 10.1038/s41467-023-40241-w. p. 1.
“Prigogine’s studies on dissipative matter reconciled the emergence of complex structural order from chaos with the need to increase entropy in accordance with the Second Law of Thermodynamics. The counterpart of structure is often dynamics, and in recent years concepts and methods have been introduced that can directionally drive molecular systems away from a state of equilibrium, powered by non-directional energy sources. These are molecular ratchets. They have their mechanistic origins in the rectification of the random thermal motion of Brownian particles.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 2.
“For molecular-sized bodies, incessant random thermal (Brownian) motion overwhelms inertia such that it is not causing a nanoscale particle to move that requires an input of energy, but rather energy is required for the rectification of its inherent stochastic (Brownian) motion to achieve directionality (and thereby perform tasks). Accordingly, biomolecular motors appear to operate through ratchet mechanisms based on statistical mechanics, not through a manipulation of momentum and inertia.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 3.
“Kinetic gating[:] The kinetic bias to perform a process (chemical or mechanical) that results in forward motion within the chemomechanical (or chemical engine) cycle of the ratchet. Can be divided into chemical gating and mechanical gating.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 4.
“Molecular machine[:] A subset of ‘molecular devices’ (functional molecular systems) in which some stimulus triggers the controlled, large amplitude or directional mechanical motion of one component relative to another, or of a substrate relative to the machine, which results in a net task being performed.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 4.
“Although many different types of molecular system can, in principle, undergo powered directionally biased dynamics, certain architectures are particularly well-suited in this regard: threaded and mechanically interlocked molecules can undergo well-defined, large amplitude, relative motion of the interlocked components; rigid rotors can be repetitively rotated about double and single covalent bonds that connect them to rigid stators; molecular ‘walkers’ can be transported along tracks by successively forming and breaking ‘foothold’ interactions; substrates can be transported through membranes between separated compartments.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 7.
“In terms of their dynamic function, molecular ratchets can be classed as either motors or pumps. Motors perform mechanical work (either directionally biased transport of themselves or a substrate, or repetitive directional 360̊ rotation) and repetitively and progressively dissipate energy through the relative displacement of the components or substrate. Pumps drive substrates away from their equilibrium distribution, creating or sustaining a concentration gradient and thereby storing the energy transduced by the ratchet.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 7.
“There are four fundamental requirements of a molecular ratchet: (i) It should be able to act repetitively, each complete cycle returning the chemical engine to its original state (but not the substrate the ratchet has done work on). (ii) It must transduce energy from one form to another to do work progressively (that is, multiple cycles of the ratchet should do work cumulatively). (iii) The ratchet and the substrate (or track) need to be associated processively (that is, take multiple steps of the engine cycle without dissociating). (iv) The ratchet’s action is to directionally bias an otherwise stochastic, dynamic exchange process.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 7.
“These concepts [physics theories for energy ratchets and information ratchets] formed the basis of a major review of synthetic molecular machinery a year later [work cited above by Kay et al 2007], which broke with the prevalent dogma of technomimetic design strategies (i.e. the mimicking of macroscopic machinery mechanisms) and formalised the requirements for molecular ratchets to perform work and other tasks.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 10.
“The introduction of Brownian ratchet mechanisms into synthetic molecules in the early-mid 2000s marked a turning point in the control of molecular-level dynamics. It showed how physics theories regarding the dynamics of Brownian particles could be adapted to become design principles for molecular ratchets. These scale-relevant principles work through chemistry, not the Newtonian mechanics that govern the operation of macroscopic machinery.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 11.
“Energy ratchets harness modulation of external conditions (either spatially or temporally), for example pH, temperature, addition/removal of metal ions or electrochemical potential, to alter a potential energy surface and raise or lower alternating pairs of energy wells and energy barriers. Reversing the relative depths of the wells changes the equilibrium distribution of the system and causes a statistically biased movement.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 12.
“Information ratchets work by the kinetic selection of reaction pathways. Biomolecular machines operate through information ratchet mechanisms, which do not require modulation of the external conditions, but instead can function progressively and autonomously while supplied with a chemical fuel. Information ratchets achieve directional motion by interacting with a fuel-to-waste process differently depending on their mechanical state, similarly to the way Maxwell’s Demon chooses to open or close the door depending on the nature of the particle approaching it….
“The key aspect of information ratchets is their ability to kinetically differentiate processes depending o the mechanical state of the ratchet, analogous to a dynamic kinetic resolution. A ‘burnt bridges’ mechanism is where the backwards steps are prevented by effectively irreversible chemistry.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 22.
“One of the most important functions of biological motors is to act as pumps, creating transmembrane gradients. In 1992, Kamp and Hamilton discovered that upon addition of fatty acids to the exterior of vesicles, a transmembrane pH gradient was established within seconds, with the interior of the vesicles approximately 0.4 pH units lower than the exterior…. Fatty acids are known to ‘flip-flop’ within lipid bilayers, shuttling between the exterior and the interior of a vesicle, similar to the shuttling of a macrocycle between two equivalent binding sits on a rotaxane shuttle.
“The rate of the fatty acid ‘flip-flop’ is faster when protonated than when deprotonated, effectively constituting a kinetic resolution. When added to the exterior of the vesicles, fatty acids insert into the membrane tail-first, driven by hydrophobic interactions. The fatty acids ‘flip-flop’ to randomise their orientation within the membrane, increasing entropy. This ‘flip-flop’ is faster with a protonated head group, transporting a proton across the membrane. Subsequently, externally orientated carboxylates are protonated while internally orientated acids are deprotonated, generating a pH gradient across the membrane….
“The entropic gain from equilibration of the orientation of fatty acids in the membrane provides the energy that fuels the ratchet mechanism.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. pp. 28-9; reference: Kamp, F. & J.A. Hamilton. 1992. PNAS USA. 89:11367-11370.
“The majority of biomolecular machines are information ratchets, as this mechanism enables machines to operate autonomously rather than relying on alterations in conditions. Chemically fuelled information ratchets universally act as catalysts for the dissipation of a potential energy gradient in a fuel-to-waste process.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 36.
“In molecular ratchets, it is not necessary for barriers to fully prevent movement (or for the absence of barriers to instantaneously allow movement), it is the relative rates of different processes that are important for driving directionally biased motion. Therefore, the important consideration is the difference between the activation energy for unwanted movement past a barrier and the activation energy for the desired movement in the absence of a barrier. This determines how likely a machine is to undergo a series of desired mechanical transitions across the course of a full cycle. The ratio of rates between desired and undesired mechanical transitions makes up the mechanical component of kinetic gating: the mechanical gating.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 37.
“This [the physical principle of microscopic reversibility] states that for any microscopic process, each step is necessarily directly reversible by the same, but opposite mechanistic pathway. That is, if A and B react to form C following some path on a potential energy surface, by following the same pathway in reverse, C can form A and B. This idea originates in the 19th century with Boltzmann and van’t Hoff and was formalised by Lewis in 1925. It is the basis of chemical equilibrium, as for equilibrium to be maintained the rate of the backward reaction must equal the rate of the forward reaction. In practice, thermodynamics often favour one set of products so heavily that practically none of the reverse reaction is observed. Nevertheless, the reverse pathway must be physically possible.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 38.
“In an information ratchet, the pathway for removing the physical barrier must be different to the pathway for forming the physical barrier, so that they can proceed at different rates. This means that across the full cycle of forming and removing a barrier, a chemical change must occur if the system is to have directionality. The component that is changed is acting as a fuel,… while the machine functions as a catalyst for the fuel-to-waste reaction….
“The chemical gating [from example of rotating molecule ratchet where a constraining molecule for rotation has two enantiomeric forms that are changed by the fuel and where one makes the breaking of the constraint to be further rotated than the other so that the fuel effects the likely progression of the rotating part of the molecule to continue] is solely responsible for introducing kinetic asymmetry and driving the biaryl motor as the enantiomeric pairs have, by definition, an equal chemical potential making a power stroke impossible. Motion is achieved by Le Chatelier’s principle as the mechanical equilibria are driven towards the species that react more quickly.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 40.
“As they are not bounded, chemical engines can, in principle, reach almost perfect efficiencies.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 41.
“Thermodynamic efficiency is intrinsically linked to the kinetic asymmetry of a ratchet. However, thermodynamic efficiency is also affected by other factors, such as the incidence of futile cycles, which use fuel without the motor taking a productive step.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 41.
“It has been demonstrated that a ratcheting process can cause heterogeneous catalysis to exceed the Sabatier limit, which is the maximum rate achievable for a surface-catalysed reaction if performed using a conventional passive catalyst. Usually, heterogeneous catalysts that bind and activate a substrate strongly, release the product slowly. Conversely, catalysts that release product rapidly are slower to bind the substrate or activate it to a lesser degree. The Sabatier limit recognises this trade-off and represents the point at which these factors are balanced. Dauenhauer’s approach, however, is to repetitively switch the surface between a form that quickly binds the substrate and activates it strongly, and one that rapidly releases product, for example by applying an oscillating potential across the surface.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 51; reference: Ardagh, M.A., T. Birol, Q. Zhang, O.A. Abdelrahman & P.J. Dauenhauer. 2019. Catal. Sci. Technol. 9:5058-5076.
“Within origin of life research, the problem of maintaining the level of information in a self-replicating system across successive generations is called ‘Eigen’s paradox’, and is a significant challenge to overcome. Ratchet mechanisms, where kinetic selection drives a particular process, can rectify errors. DNA and RNA polymerases and topoisomerases, part of the machinery that proofreads DNA, all function through ratchet mechanisms.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 52.
“Nonequilibrium thermodynamic theory has shown that nonequilibrium steady states are more susceptible to perturbations in their environment than systems at equilibrium. Therefore, nonequilibrium steady states could provide the basis for enhanced sensing ability. Hore has suggested an appealing analogy to illustrate this, by imagining how a block would react to the touch of a passing bee or feather. In its equilibrium resting state the effect on the block would be undetectable, however, if an energy input was used to maintain the block balanced in an unstable state, then even the lightest touch could cause the block to fall over, producing a large detectable response.
“This strategy is employed by some biological sensors for detecting weak stimuli. Migratory birds ‘see’ magnetic fields using a protein-based sensor, which is sustained by a constant light-energy input in a highly responsive diradical steady state. Under these nonequilibrium conditions, even small changes in the magnetic field are sufficient to alter the distribution of states in the chemical engine cycle of this protein, thus allowing the magnetic field to be detected…. Highlighting the importance of this nonequilibrium process, as much as 10% of the body’s total energy budget is used to maintain a resting nonequilibrium steady state in the human brain.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 52; reference: Hore, P.J. & H. Mouritsen. 2016. Annu. Rev Biophys. 45:299-344.
“In a universe where entropy must increase overall, life is a curious spontaneous emergence of localised decreased entropy. This mirrors the behaviour of the simplest ratchet-based molecular machines, which harness energy from a fuel-to-waste process (where entropy increases), to locally decrease the entropy of the machine. Pross’s theory of dynamic kinetic stability describes life as a persistent replicating kinetic entity, which, at a basic level, mirrors the steady states of simple ratchet mechanisms. This is contrasted by England’s theory of dissipative adaptation, which predicts that structures develop to most efficiently dissipate energy, as opposed to Prigogine and Pross’s assertion that dissipative networks tend to evolve to minimise dissipation and reach the most kinetically stable state.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 53.
“Prior to 2007 the design principles for synthetic molecular machines were overwhelmingly based on macroscopic imagery, but it is now generally understood that molecular machines will not behave like their macroscopic counterparts.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 54.
“Mechanically interlocked molecules allow well-defined large amplitude dynamics of the interlocked components, and have thus been helpful for developing and understanding many of the principles that underpin molecular ratchets. Threaded architectures ensure processivity as the macrocycle cannot dissociate from the track. In contrast, molecular walkers can potentially both dissociate from the track (useful for resetting and reusing) and overstep. Such events are problematic for ratchets that process information as they will introduce sequencing errors. Indeed, biomolecular ratchets that have evolved for reading and writing information, such as polymerases and ribosomes, often operate through threaded, rotaxane-like, structures.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 55.
“Walkers may dissociate from the track or overstep, while mechanically interlocked molecules ensure progressivity and processivity. Mechanically interlocked molecules cannot progress past junctions in the track, whereas the progress of walkers is unhindered by the presence of a junction, allowing their incorporation into tracks.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 55.
“How to build an energy ratchet[:]
“Key requirements:
“The ratchet must experience different sets of conditions during its operation cycle
“The conditions must switch the relative depths of pairs of thermodynamic minima.
“The conditions must switch the relative heights of pairs of kinetic barriers.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. pp. 58-9.
“For an information ratchet fuelled by a chemical potential gradient (e.g. between fuel and waste), the ratchet acts as a catalyst for the fuel-to-waste process. The chemical change to the ratchet caused by the fuel must occur via a different mechanistic pathway to that which re-established the initial chemical state of the ratchet by emitting the waste.” Borsley, Stefan, David A. Leigh & Benjamin M. W. Roberts. 2024. “Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.” Angewandte Chemie International Edition. 63:e202400495. 10.1002/anie.202400495. p. 59.
“Even accounts of evolution that challenge the Modern Synthesis and its legacy tend to be centered on organisms, their features and on the Darwinian populations that they form. In contrast, we argue that evolution refers to the set of changes that characterize an evosystem, with only a subset of these changes being related to the distribution of variation within populations, and a (potentially) bigger subset referring to changes regarding the interactions between and within populations as well as other elements of the evosystem (including those that have traditionally been considered part of ‘the environment’). Simply stated, change occurs in complex systems that often involve many Darwinian populations as well as abiotic elements and their interactions. Evosystems are meant to reflect this complexity.” Papale, Francois, Fabrice Not, Eric Bapteste & Louis-Patrick Haraoui. 2024. “The evosystem: A centerpiece for evolutionary studies.” BioEssays. 10.1002/bies.202300169. p. 4.
“Although evolutionary biologists seldom offer a precise definition [of the ‘environment’], it is commonly used to denote ‘the state or quality of being the causal context for something else’. In evolutionary biology, relevant causality related to the environment refers mostly to selective pressures. This means that the environment is the context in which something (a population or lineage) evolves. However, with an evosystem-based approach, the evolutionary context itself becomes the primary focus of investigation. Organisms and the populations within evosystems are then seen as constitutive parts, often interchangeable and functionally redundant, that acquire biological significance solely through their embedment in it. The evosystem is more than the context in which something else evolves. The evosystem is the thing that evolves.” Papale, Francois, Fabrice Not, Eric Bapteste & Louis-Patrick Haraoui. 2024. “The evosystem: A centerpiece for evolutionary studies.” BioEssays. 10.1002/bies.202300169. p. 4.
“For Aristotle, the aliveness of living things was imbued by their soul (psyche). This is not to be confused, although later it would be, with the Christian notion of a soul; rather, it refers to a kind of innate capacity for action. The psyche had no substance in itself, but it was inseparable from the body: it was in the very nature of living bodies.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 21.
“Stability in a time/persistence sense is more fundamental than stability in an energy/entropy sense. Why? Because all systems that are stable in an energy sense are necessarily stable in a time/persistence sense–a system at equilibrium does not undergo further change. But the reverse is not true. Time-stable systems are not necessarily energy stable, making stability in its time facet the more fundamental one.
“The realization that stability’s time facet is more fundamental than its energy facet is significant since it offers new insights into the nature of change in the universe, whether in the biological or the physical world. it allows the formulation of a general principle of nature, the Persistence Principle. The principle, based on logic and supported by mathematics, may be stated as follows: systems will tend from less stable (persistent) to more stable (persistent) forms, or more concisely: nature seeks persistent forms.” Pross, Addy. 2012. What is Life?: How Chemistry Becomes Biology. Oxford UP. p. 194.
“All the same, Berzelius [Swedish chemist in 1812] added a fruitful notion. Rather than postulate some ‘vital force’–‘a word to which we can affix no idea’–we should recognize that ‘this power to live belongs not to the constituent parts of our bodies, nor does it belong to them as an instrument, neither is it a simple power; but the result of the mutual operation of the instruments and rudiments on one another.’ In other words, it is not so much a question of what the molecules are, but of what they do, and specifically, of what they do collectively.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 25.
“In the early twentieth century, the word organization was thrown around as a kind of catch-all invocation of aspects of life barely understood even in broad outline.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 26.
“It’s better to have a vague concept that may act as a bridge across a void of ignorance than to come dejectedly to a halt at the brink.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 26-7.
“The Cartesian mechanistic metaphor is very much alive and well: biologists routinely speak of ‘molecular machines’ such as enzymes, and not without good reason. But such language can morph into a literal view, in which we might really treat microscopic biological entities as though they were cogs and motors that operate in the same way as our technological ones. This, as we’ll see, can be deeply misleading.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 28.
“One of the fundamental messages of this book is that we cannot properly understand how life works through analogies or metaphorical comparison with any technology that humans have ever invented (so far).” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 29.
“So long as we insist that cells are computers and genes are their code, that proteins are machines and organelles are factories, the picture that emerges is a clumsy marriage of the mechanical and the anthropomorphic. Life becomes an informational process sprinkled with invisible magic.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 30.
“We should not make life fit the image of our present-day machines, but we might yet make our machines in the image of life….
“The artificial intelligence algorithms that, by analogy with the brain, we even call ‘neural networks’ are a good example of this. These networks function not by design–doing their job the moment they are switched on–but through learning and training.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 33.
“Meaning is not some mysterious force or fluid that pervades the vacuum. No; life is what creates such meaning as exists in the cosmos.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 36.
“I suspect it is in fact precisely by virtue of being a thing that has autonomous goals, and that can autonomously attribute meaning, that an entity can be said to be alive.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 36-7.
“In an odd way, the popular view of genes with which we have become burdened echoes the flaw in the classic ‘argument from design’ of natural theology in the nineteenth century. The latter asserted that forms and functions as exquisite as those we find in nature, and perhaps in the human body in particular, could not but require an intelligent Creator. They couldn’t possibly happen through blind chance. But natural selection showed how, on the contrary, they could.
“Yet that Darwinian process was then enlisted as a source of a plan that could substitute for God’s work. For surely a body as intricate and reliable as ours could not be produced unless there were some pre-existing blueprint for it? And seemingly, only the genes could encode that, for they were (in the conventional view) all our bodies start with.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 49.
“It’s not so much, therefore, that their [the results of Mendel’s experiments] relevance to genetics and inheritance more generally was only recognized in the early twentieth century; rather, it was only then that such relevance was created.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 58-9.
“In the nucleus of our cells, the [DNA] molecule is packaged up into a substance called chromatin–a filamentary assembly of DNA and proteins–in which only very short stretches of the ‘naked’ helix are fleetingly revealed. There is twice as much protein as DNA in chromatin (as well as typically around 10 percent by mass of RNA, mostly as nascent transcribed chains).” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 70.
“In the first stage of packaging, the DNA is wound around protein disks called histones to form a bead-like structure called a nucleosome…. Each nucleosome bonds around two hundred base pairs of DNA in two coils, and there is very little ‘free’ DNA between adjacent nucleosomes, sometimes as little as eight base pairs. The string of nucleosomes forms fibers about thirty nanometers wide, which is the basic structural unit of chromatin….
“But it’s not simply that: the three-dimensional structure of chromatin is quite carefully controlled in the cell.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 70, 71, 72.
“What happens at a promoter site determines whether transcription can happen; but the chance that it will is influenced by DNA sequences called enhancers, of which there are hundreds of thousands in the human genome, typically fifty to fifteen hundred base pairs long.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 73.
“There is no consensus about whether or when such noncoding DNA sections warrant being called (noncoding) genes–simply because there is no longer any agreement about what, at the molecular level, gene should designate.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 83.
“By making comparisons of the entire genome sequences of the individuals, we can find which genes seem to ‘make a difference’ and which don’t. To state it more precisely, we are looking here for correlations between variations in genes and in traits, but we can’t be sure that this means the genes ‘make’ the difference.
“Such an analysis is called a genome-wide association study, or GWAS. It requires genome data for many people on whom we also have information about traits. Most of the variations between genes that are identified in GWASs are single-nucleotide polymorphissms (SNPs, pronounced ‘snips’), meaning that the alleles differ in just one base pair….” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 86.
“Even for traits that show a strong heritability, such as height, the genetic component derives from the tiny effects of many genes rather than big effects from just a few.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 90.
“What’s more, some diseases and traits might not even have a set of core genes at all. Instead, the ‘global’ activity of the genome sets the state of a cell or tissue such that it is at greater or lesser risk of the disease developing. This complexity of dynamic interactions throughout the genome, along with the ambiguity of what a gene even is as a meaningful functional unit, suggests that perhaps we should really be trying to understand inheritance not on the basis of genes but of what is really passed to offspring: their entire genome.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 92.
“Problems only arise when biologists try to have it both ways: not just to keep the evolutionary and the molecular or developmental gene, but to make them the same thing. The responsibility placed on the molecular gene, if it is to meet the expectations of the evolutionary gene, is simply too great, and can be satisfied only by the alarming gambit of giving it an almost sentient agency it does not possess, turning it into a little ‘replicator’ struggling to survive in a population of other pseudo-organismic little molecules. This idea simply has to go; there’s no question about it. But there’s no reason to fear. We have nothing to lose but our metaphors.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 98.
“Biologists were puzzled to find that in eukaryotic cells, much more RNA seemed to get transcribed than was exported out of the nucleus as mRNA to be translated by the ribosome. Much of this so-called heterogenous nuclear RNA (hnRNA) gets broken down soon after it is made.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 110.
“In this dynamic activity, the real agency operates at the level of regulation of transcription: it’s less a matter of what is transcribed than of when and where that happens.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 113.
“Not all regulatory ncRNAs are long; some are surprisingly small….
“It’s now clear that microRNAs play diverse and important roles in regulating genes, ramping their expression up or down. One estimate suggests that around 60 percent of our genes are regulated by microRNAs. Some of these little molecules bind directly to the chromosomes and stop sections of DNA being transcribed, or alternatively turn on transcriptions. Some of them prevent the translation of a genes’s mRNA product into the corresponding protein by interacting with the mRNA in some way, perhaps labeling it for enzymatic destruction.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 119.
“The universe of regulatory noncoding RNAs is still expanding. There are, for instance, Piwi-interacting RNAs (piRNAs) that are involved in silencing errant transposons–those aforementioned ‘jumping genes.’ They do this in collaboration with so-called Piwi proteins, which play a key role in the differentiation of stem cells and germline cells. There are small nucleolar RNAs (snoRNAs) that steer and guide chemical modifications of other RNA molecules, such as those in the ribosome of the ‘transfer RNA’ molecules that ferry amino acids to the ribosome for stitching into proteins. If cells are stressed, this can trigger the conversion of transfer RNA into molecules called tiRNAs that regulate the cells’ coping mechanisms, and which also have roles in the development of cancer,.
“And so on: RNA seems to be a general-purpose molecule that cells–particularly eukaryotic cells like ours in which gene regulation is so important–use to guide, fine-tune, and temporarily modify its molecular conversations.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 120-1.
“Our understanding of the significance of RNA regulation was transformed by an international initiative called ENCODE, launched in the wake of the Human Genome Project in 2003 to look at how the genome is actually used–which is to say, transcribed–in our cells. ENCODE identified which parts of the entire genome are transcribed in the cells of different tissues, characterizing the human transcriptome….
And indeed, the ENCODE findings seemed to seriously upset the established narrative. The HGP confirmed that just 2 percent or so of our genome consists of protein-coding genes, and most of the rest of the DNA was therefore considered ‘junk’ accumulated across millennia of evolution, with no useful function. But according to ENCODE, transcription is not confined to that small proportion of ‘meaningful’ DNA. Rather, at some point or another our cells appear to transcribe up to 80 percent of the genome.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 122.
“DNA is really a crib sheet for two kinds of functional molecule–proteins and RNA–and there is nothing that should privilege protein-coding genes over segments of DNA that encode ncRNAs [noncoding RNA].” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 125.
“Far from being the mere messenger for making proteins, RNAs are the focus of much of the real action in our cells. Indeed, they are the reason why many proteins exist at all. While proteins have traditionally been segregated into those that exist in compact, soluble form and those that sit within cell membranes, a third major class of proteins in our cells have the role of binding to regulatory RNA.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 125-6.
“The importance of noncoding DNA is greater for us than for simpler organisms. Around 90 percent of the bacterial genome is protein-coding. For C. elegans, that figure is 25 percent. For humans, as we’ve seen, it’s a mere 2 percent at most.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 126.
“One way a gene can be turned on or off is by chemical changes to the genome itself. The most common such alteration is methylation of a DNA base; in mammals it occurs almost exclusively on C nucleotides, especially those adjacent to G, which are denoted CpG segments. Such ‘epigenetic marks’ are very widespread in our genome, being found in around 60-80 percent of the twenty-eight million CpG elements it contains.
“Methylation alters how a gene is expressed, but not in a way that is easily generalized. You might suppose that sticking a methyl ‘bump’ onto the DNA strand will disrupt the ability of RNA polymerase to transcribe it, rather like a scratch or bit of dirt on a cassette tape. But it’s not that simple. For one thing, it depends on where in the gene the modification happens. We saw earlier that the protein-coding part of a gene is accompanied by DNA sequences called promoters where transcription is initiated. As a general (but not inviolable) rule, methylation in the coding part of the gene can boost transcription, whereas methylation of a promoter region suppresses it….
“But methylation is not necessarily forever. There are enzymes that can remove methyl marks too.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 128-9.
“Crudely speaking, the enzyme is thought to interact with the substrate like a lock into which only the right key fits. This is known as molecular recognition….” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 155.
“The popular view that science is the process of studying what the world is like needs to be given an important qualification: science tends to be the study of what we can study.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 160.
“Even so, the vast majority of protein structures obtained so far are for proteins that form crystals–which is by no means all of them. Our portraits of proteins are not representative.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 160.
“This [intrinsically disordered proteins] is rather common phenomenon: one estimate puts the proportion of disordered segments in the entire human proteome at 37-50 percent. What’s more, disorder seems particularly prevalent in many of the most important proteins in the molecular ecology of the cell. That seems to be a characteristic of metazoan proteomes in particular: intrinsically disordered proteins make up just 4 percent or so of many bacterial proteomes. This difference is another clue that human cells don’t really work like bacterial cells.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 161.
“The conformational flexibility conveyed by disorder [of proteins] underscores how important changes in shape are for the way these molecules work. The very notion of ‘protein structure’ is perhaps better regarded as a set of conformations, akin to the choreographed poses through which a dancer continually moves. There’s no guarantee that the pose adopted in a crystal structure is the one that matters most for its biochemical function(s). For example, many enzymes have loops in the polypeptide chain that dangle around or over their active sites, where they bind and transform their ligand targets. The loops are highly flexible and can create different active-site conformations with distinct properties and functions, such as affinity for different ligands.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 163.
“Biochemists Vincent Hilser and Brad Thompson have proposed that disorder is a better way to ensure that a change in one part of a protein can be felt in another part, because it doesn’t require precise ‘engineering’ of a mechanism to couple them. Binding of a ligand produces subtle shifts in the many different conformations to which a disordered protein has access, and these collectively ‘spread the word.’ The floppiness makes such proteins not only able to bind several different ligands but makes them intrinsically and broadly sensitive to what is happening in different parts of the molecule so that the binding event can have knock-on consequences. In this way, disordered proteins can become versatile ‘connectors’ between different chains of interaction that convey signals in the cell, making them excellent hubs in the networks of molecular interactions involved in signal transduction and regulation.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 164; reference: Hilser, V. J. & E. B Thompson. 2007. “Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins.” PNAS USA. 104:8311-15.
“Precisely because disordered proteins are good at mediating molecular interactions, due to their ability to adapt and bind to many other molecules, they have a tendency to stick to one another. Disordered proteins can increase the complexity and versatility of our regulatory networks, but at the cost of increased risk of toxic aggregates formed from misfolded proteins.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 166.
“The splicing of exons is carried out by an assembly of small nuclear (sn) RNA molecules and proteins called the spliceosome. Some of the proteins unite with snRNAs to make so-called small nuclear ribonucleoproteins (snRNPs, pronounced ‘snurps’).” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 167.
“Much of the regulation of splicing–the choice, if you like, or how to stitch exons back together–is accomplished by associations between RNA and so-called RNA-binding proteins (RNABPs), which do what it says on the can [sic]. These proteins constitute another whole network on top of that which regulates gene activity itself, organizing the RNA transcripts in different ways in different tissues. We currently estimate that there are around 1,500-1,900 types of RNABPs in human cells–they are, in addition to soluble globular proteins and membrane proteins, a third major group, whose very existence was unforeseen until just a few years ago….
“A few RNABPs seem, remarkably, to have dual roles. As well as binding to RNA, they might act as regular metabolic enzymes: as clear an indication as any that we can’t glibly assign proteins fixed roles.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 169.
“The reason reshuffling produces proteins that are still capable of doing something useful is that most of their parts, sometimes encoded in individual mRNA exons, are really modules, independently able to fold and to confer some kind of function. These modular units are called domains, and each is rather like a mini-protein in its own right, typically between 50 and 250 amino acids in length. In fact it’s more than a likeness: many of the domains found in the predominantly multidomain proteins of metazoans have analogues amid the single-domain proteins of bacteria. It looks rather as though, as life became multicellular and complex, evolution did not so much find new proteins from scratch as assemble existing ones into composites with new functions.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 172.
“There is a class of proteins called scaffold proteins (SPs) whose job it is to do this [help gather certain proteins together in the same part of cell space].” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 177.
“But alternative splicing, the way it is regulated, and the role of disorder in enabling promiscuous proteins networking, together mean that the information processing of the cell–if we can, with caution, use that loose computational analogy–doesn’t have the architecture we thought it does….”
“There is a loose analogy with the way the computational architectures known as neural networks operate….”
“The analogy is far from perfect, not least because proteins don’t need to be ‘trained’ to acquire their roles: cells could hardly survive if they did. But those roles arise from a complex interplay of the ‘information’ they possess by virtue of the genetic sequence from which they were derived, the processing that takes place during transcription of their mRNA (such as exon splicing), any post-translational chemical modifications, and the way they interact with other proteins and molecules in their vicinity, facilitated by the versatility that disorder supplies. You might say that the proteins have to wait to be told what to do….” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 180, 181.
“That’s one of the problems with a systems approach like this: you can’t simply read out shape and form from a knowledge of which genes are active.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 186.
“Another problem [other than that the gene’s regulatory elements were scattered throughout the genome] was that, for complex organisms like us, the network of interacting molecules–the interactome–sometimes seemed not just absurdly but impossibly complicated. The prevailing idea was that biomolecules speak to one another in intimate, highly selective embraces….
“That problem became simply embarrassing when it came to understanding gene regulation. The components that seemed to be required just kept multiplying, forcing researchers to postulate transient ‘complexes’ made from a dozen or more molecules.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 188.
“In particular, some proteins lack the well-defined shapes necessary for such exquisite molecular recognition to happen–they might bind to a variety of other molecules, with varying degrees of precision and stickiness. What’s more, that kind of promiscuity is particularly common among the molecules at the heart of the interactome: the proteins called transcription factors.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 190.
“If the first challenge to the conventional story of our own biology comes with the recognition that genes don’t relate to traits in any straightforward way, and the second comes from the discovery that our organismal complexity lies not with the genes themselves but with how they are regulated, the third major shift in thinking is that this regulation is not governed by simple switching processes in a precisely delineated interactome network.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 190.
“They [mathematical biologist Erez Liebermann Aiden et al] found that the chromatin seemed to be divided into six distinct ‘compartments,’ which were much the same in different human cell types. Each compartment has a distinct network of ‘contacts’ between different parts of the chromatin–rather like different social networks–as well as a distinct class of epigenetic marks, like friends who share the same tastes in clothing. Each compartment contains many dense clusters of DNA and other molecules, called topologically associating domains or TADs; the fancy name really just means the different molecular components sit together in the same spatial location.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 195.
“In 2014 Robert Tjian and his colleagues measured how long the components actually stay bound to one another in a TAD, and found that this duration is only about six seconds. ‘I was so shocked that it took me months to come to grips with my own data,’ says Tjian. ‘How could a low-concentration protein ever get together with all its partners to trigger expression of a gene, when everything is moving at this unbelievably rapid pace?’ Evidently the committee needs to be very flexible. There might be no seating plan, nor any requirement that all members are present, so long as they have a quorum. The process may be literally rather fluid.
“The current idea is that, rather than forming a precisely structured assembly, all these proteins, RNAs, and bits of looped DNA gather into a kind of liquid blob enveloping the gene being regulated, which is distinct from the watery liquid of the surrounding cytoplasm and has a high concentration of transcription factors and other molecules required for regulating the gene.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 197; reference: Tjian, D., S. Sun & J.T. Lee. 2010. “The long noncoding RNA, Jpx, is a molecular switch for X-chromosome inactivation.” Cell 143:390-403. Quotes are from personal communication with author.
“When gathered into these loose blobs–topologically associating domains [TAD] or chromatin hubs, also called ‘condensates’–the proteins can repeatedly bind to and unbind from one another and from the DNA that the blobs envelop, while remaining in the vicinity rather than diffusing away. Instead of TAD formation relying on the highly unlikely chance encounter of all the right molecules, these molecules have chemical properties that make them likely to co-condense into a long-lived cluster. Their regulatory work would then be a cooperative affair involving many repeated binding events, rather like the committee reaching a decision through many individual conversations among its members, even though they might never manage all to sit down in the same room at the same time….
“But good evidence for droplets forming amid the tangled mass of chromatin in the cell nucleus is difficult to find. Such droplets have been seen in lab experiments on mixtures of biomolecules in test tubes, but those don’t necessarily reflect the physiological conditions in a live cell.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 197-9.
“Earlier I mentioned that one of the classic misnomers of genetic terminology was the gene called BMP, which encodes a protein named bone morphogenetic protein. It is so named because it was found in the 1960s that this protein, introduced to the body in the wrong places at the wrong time, could trigger the formation of bone where bone did not belong. Two decades later it was found that there are several types of BMP protein, and that they can cause stem cells in the early embryo to develop into bone- and cartilage-forming cells. BMPs are themselves members of a larger family of proteins called transforming growth factor β proteins which have a broad range of developmental effects: they are examples of so-called morphogens (‘shape-formers’), which influence the differentiation and arrangements of embryonic cells and tissues….
“It’s possible that making promiscuous, reconfigurable networks doesn’t just convey advantages but perhaps is the only way a complicated system like our cells can work, if it is to be robust against ineluctable randomness and unpredictability in the fine details. The operational principles exemplified by gene-regulating condensates and signaling pathways like the BMP system–with their molecular promiscuity, their combinatorial, fuzzy logic, their versatility for addressing and promoting many different cell states, and their apparent evolvability–may well be a sine qua non for multicellular organisms in which genetically identical cells work together in diverse, specialized states.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 204-5, 211.
“If there’s slack in the system–say, because promiscuous binding allows one protein to substitute for another–it’s possible for the network to develop new functions without losing old ones.
“It seems likely that metazoans have evolved this evolvability. One of the odd features of transcription factors that bind to DNA is that, in eukaryotes, the base sequences that they recognize are often surprisingly short–perhaps six or so base pairs long. This compromises the selectivity of their binding, because, if you pick a six-base sequence at random, it’s likely that you’ll find a lot of copies throughout the genome. But there’s no reason the selectivity has to be this approximate; in prokaryotes the binding sites are longer and the binding is therefore more specific. It seems that eukaryotes have, so to speak, chosen this sloppiness–probably because it allows new regulatory pathways to develop, opening up the potential for variation and evolvability.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 212.
“In collaboration with other researchers, Hoel has investigated how and where causal emergence arises in the networks of protein interactions (the interactomes) of a wide range of organisms. The group looked at around 1,500 species of bacteria, 11 of archaea, and 190 of eukaryotes including humans and other mammals. Using a measure called ‘effective information’ to quantify causation, the researchers searched for ‘informative macroscales’ in the networks–situations where a group or cluster of protein-protein interactions could be replaced by a single ‘macro-node’ in the network that does the same job as the collective. Such macronodes can be considered autonomous units in producing the observed outcome at the level of the phenotype. It’s a bit like dividing up a population geographically into cities and towns: these are not just arbitrary groupings, but ‘real things’ with discrete and identifiable influences. These macro-nodes will function reliably even if there’s some variability or noise among their component parts. They become genuine causal entities that operate at a higher level of organization: agents of causal emergence.
“Hoel and colleagues found that there was significantly more causal emergence–more informative macroscales–for eukaryotes than for prokaryotes. In effect, the more complex multicellular organisms that appear later in evolutionary history tend to assign causal roles to higher levels of organization in their networks.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 218-9; reference: Hoel, E.P., L. Albantakis & G. Tononi. 2013. “Quantifying causal emergence shows that macro can beat micro.” PNAS USA. 110:19790-95.
“They [Lowe et al] considered fragments of genome sequences called nonexonic elements, which are sequences that fall outside of the exons that encode protein structures. They looked outside not only protein-coding sequences but also outside of sequences known to encode regulatory RNAs–that is, outside of what are now often called noncoding genes. Their hypothesis was that if some of these nonexonic elements are found to be highly conserved–to recur more or less unchanged in the genomes of different species–we can assume they have some functional role and so are subjected to selective pressure which preserves them: they aren’t just random junk that would be expected quickly to degenerate and diverge between different species. Such conserved nonexonic elements (CNEEs) will probably have regulatory functions….
“They found that, rather than there being smooth and gradual changes in the frequencies of CNEEs, three distinct eras of change seem to have occurred over the past 650 million years. Until about 300 million years ago, when mammals split from birds and reptiles, changes in regulation seem to have happened mostly in parts of the genome close to transcription factors and the key developmental genes that they control. Then between 300 and 100 million years ago those changes tailed off, and instead there were changes near genes that code for the protein molecules serving as receptors of signals at the cell surface. In other words, what seemed to matter for these evolutionary changes was a shift in the way cells talk to one another. Finally, since 100 million years ago, as placental mammals developed, the regulatory changes seem to be associated with mechanisms for modifying protein structure after translation, especially for proteins that are associated with signal transduction within cells.
“Evolution, then, might be considered to have successively discovered ways to innovate and generate new organisms by first reshuffling how developmental genes are switched on and off, then how cells communicate, and then how information gets passed around inside cells. In all cases the action is taking place not at the genetic level but at higher levels of network organization.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 223-5; reference: Lowe, C.B. M. Kellis, A. Siepel, B.J. Raney, M. Clamp, S.R. Salama et al. 2011. “Three periods of regulatory innovation during vertebrate evolution.” Science. 333:1019-24.
“… one of the most useful pieces of advice I heard from Nature’s biology editor many years ago was that the answer in biology is always ‘yes.’ Could it be this or could it be that? Yes. The growth and maintenance of living things like us is a delicate (but also robust) dance of cause and effect, cascading up and down the hierarchy of scales in space and time. This leads to that, but then that creates a new this. It’s for this reason that life can only be understood as a dynamic process of becoming–from conception to the grave.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 248.
“The soil-dwelling nematode worm Caenorhabditis elegans, which has often been used as a very simple model for understanding animal development, possesses an unusual degree of predictability. It has two sexual forms: a hermaphrodite, the adult of which always has precisely 959 somatic cells, and a male form with exactly 1033 cells. That each cell is specified in terms of type and location certainly seems to encourage a ‘blueprint’ view of the genome. But nearly every other multicellular species has far less specificity, so C. elegans is in this respect a misleading and unrepresentative example.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 255 (note).
“In the mid-2000s Japanese biologists Shinya Yamanaka and Kazutoshi Takahashi showed that cell-fate commitments can be rescinded in a rather less dramatic intervention, involving relatively simple genetic manipulation. They demonstrated that mature, specialized mammalian cells can be restored to a pluripotent state, like the stem cells of the early embryo, by injecting them with genes that are active in such stem cells. There are many such genes, but Yamanaka and Takahashi found to their surprise that adding just four is sufficient to effect transformation…. …all encode transcription factors that reset the cell’s transcriptional networks….
“They have shown that oscillatory changes in the expression levels of the Yamanaka factors such as… [3 of the 4 found] are crucial for keeping cells in the pluripotent state and preventing the epigenetic changes that cause differentiation. Differentiated cells lose these oscillations–but reprogramming restores them. The researchers showed that the oscillating state is an attractor defined by this handful of genes, within a genome containing many thousands.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 259-260, 261; reference: Yamanaka, Y., K. Yoshioka-Kobayashi, S. Hamidi, S. Munira, K. Sunadome, Y. Zhang, et al. 2022. “Reconstituting human somitogenesis in vitro.” Preprint. https:// doi.org.10.1101/2022.06.03.49462.
“Because they [microRNAs] are small molecules, they [the genes for them] can be added into cells without the need for virus-based transfer techniques, which have the drawback that the genes get inserted rather randomly into the host genome. MicroRNAs have also been used for direct reprogramming of one cell type to another–fibroblasts to heart muscle cells, for example….
“The fates of our cells, and the nature of our tissues and bodies, are apparently far less inevitable and inexorable than was previously thought: living matter is plastic and (re)programmable.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 260-1.
“British computer scientist Richard Watson and coworkers have shown using a computer-simulation model that the process of cell differentiation, involving the reconfiguration of the cell’s interactome, is formally equivalent to the way a neural network performs a learning task, integrating information from multiple sources to come up with a decision.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 263. Reference not found.
“I don’t anticipate a consensus any time soon on the question of how to define life, but it seems to me that cognition provides a much better, more apt way to talk about it than invoking more passive capabilities such as metabolism and replication. Those latter two attributes might be necessary, but they are means to an end: they’re not really what life is about. And the fact that life has an aboutness at all is intrinsic to what it is.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 266.
“If you chop a planarian into more than a hundred tiny pieces, each fragment will grow into another worm.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 267.
“Levin thinks that bioelectric signaling can thus support a kind of non-neural information processing–which might even be involved in building the brain itself. He and coworkers have shown that the growth of the brain’s neural network seems to be governed by the voltage across the membrane of the cells that will become neurons.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 273; reference: Levin, Michael. 2020. “The biophysics of regenerative repair suggests new perspectives on biological causation.” BioEssays. 42:1900146.
“The potential for cells to find their way to specific attractors in morphospace is also dramatically illustrated by how certain sea slugs will, if they become heavily infected with parasites, separate their heads from their bodies through self-induced decapitation and then regrow entire new bodies within a few weeks.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 274.
“Most (perhaps 70-90 percent of) human zygotes never develop into a live birth, because things ‘go wrong’–either for genetic or environmental reasons, or by chance–along the way, leading to pregnancy termination…. Perhaps the high failure rate reflects early termination of any further resource investment in offspring that are already too compromised to warrant it.
“Developmental ‘abnormalities’ are, then, the norm; what matters is the degree. I believe that such a shift in perspective might not only be medically but also societally helpful.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 296.
“Once again, genes don’t encode the rules of how life unfolds, but merely supply the components that enact those rules.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 301.
“If cells are too far from the blood supply, they don’t get the oxygen they need for metabolism, and enter an ischemic state. This causes them to release proteins called angiogenic growth factors, including FGF1 and vascular endothelial growth factor (VEGF). These molecules diffuse through the tissue until they reach a blood vessel, which is triggered into sprouting a new bud. This grows in the direction of increasing concentration in the angiogenic factors–that is, toward the distressed ischemic cells that are in effect calling out for oxygenated blood. The rest is that, if all works well, no part of the developing tissue lacks an adequate blood supply, whatever shape it adopts–and at the same time, no blood vessel grows where it isn’t needed.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 324.
“Pathologist and systems biologist John Higgins and his colleagues have found that the numbers of white blood cells and platelets (which promote blood clotting) produced in an acute inflammatory response follow the same trajectory in time whether the person is recovering from COVID-19, heart attack, sepsis, surgical trauma, or several other conditions….
“In physics, ‘universal’ behavior of different systems is often a signature of a deep-seated equivalence in the underlying processes, transcending details of their specifics. Could that be the case here too? Indeed, Higgins suspects, such behavior reflects a shared basis of the physiological response to disease.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 392; reference: reference – personal communication to author.
“The immune system might then be regarded as analogous to the brain in that, while drawing on genetic resources, it needs autonomy to do its job. And like the brain, that job is inherently directed at a goal, to achieve which there can be no prescriptive strategy. Like a brain, the system must be able to learn, adapt, innovate, and improvise.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 398.
“It’s telling what kinds of genes oncogenes are. More than seventy of them are now known for humans, and typically they encode growth factors and their receptors, signal-transducing proteins, protein kinases, and transcription factors. In other words, they all tend to have regulatory functions–and moreover, ones that can’t be ascribed any characteristic phenotypic function….” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 403.
“The unpalatable truth is that tumor formation is something that our cells do: it is better regarded as a state that our cells can spontaneously adopt, much as ‘misfolded’ proteins are one of their inevitable attractor states. You might say that if cells are to exist at all as entities that can replicate and self-regulate in communal collectives–that is, in multicellular organisms like us–it may be inevitable that they have the potential to become cancerous. To develop into tumors is one of the particular hazards of pluripotent stem cells, precisely because they have such fecund versatility….
“It is not wholly inevitable in metazoans, however. Some, such as whales, elephants, and naked mole rats, experience little or no cancer. It’s not fully understood why this is so, but part of the reason seems to be not that their cells can’t turn cancerous but that they have better defenses against it. Whales, for example, have a higher incidence of tumor-suppressing genes than other mammals.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 406.
“Cancer isn’t really a consequence of the uncontrolled proliferation of a rogue cell, but might be best seen as the growth of a new kind of tissue or organ.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 409.
“In 2014 pathologist Brad Bernstein and his coworkers looked at brain tumors using single-cell RNA sequencing. What he found dismayed him: in any single tumor there is not one single type of cancer cell at work, but many…. Here it revealed cancerous tumors as mosaics of different cell types–including plenty of nonmalignant ‘healthy cells’ that have apparently been corralled into helping support the cancerous growth.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 409; no reference.
“Cancer cells are unusually plastic: they can transition back and forth between different states more readily than normal cells. The cells might differentiate a little bit and then revert, for example…. On the other hand, this fluidity of state suggests a new and dramatic approach to treating cancer. Instead of simply trying to kill the tumor cells, it might be possible to ‘cure’ them by guiding them gently back to a nonmalignant state–much as mature somatic cells can be reprogrammed to a stem-cell state. This is called differentiation therapy, and some researchers are now hunting for chemical agents that can cause the switch.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 410.
“Bodies aren’t arbitrary constructs.
“Neither, though, are they fully specified by a blueprint. As we have seen, they emerge as solutions to the rules that govern the production of tissues from cells. Guided by these rules, cells find solutions that work. An emerging discipline called synthetic morphology is now exploring how, and how far, those outcomes can be tailored and modified to alter the shapes and forms of living matter….
“Ultimately, we can imagine creating entirely new living beings shaped not by evolution but by our own designs. ‘By studying natural organisms, we are just exploring a tiny corner of the option space of all possible beings,’ says biologist Michael Levin. ‘Now we have the opportunity to really explore this space.’ For the plasticity of living matter, he adds, is ‘unbelievable.’” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 414-5; reference: personal communication with author.
“Yet as synthetic biology develops, it will be hard to anticipate all the possible problems, whether malevolent or inadvertent. ‘The repertoire over the coming decade is limitless,’ says bioterrorism expert George Poste. Fast-forward two decades and who knows what we might be able to make: ‘Biology is poised to lose its innocence.’” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 420; reference: Ball, P. 2004. “Starting from scratch.’ Nature. 431:624-26.
“The intrinsic capacity of cells to organize themselves into tissues is revealed when embryonic stem cells are cultured outside the body–‘in vitro,’ in a dish. If bathed in the nutrients they need, they will proliferate and begin to differentiate toward particular fates…. But cultured stem cells can be guided toward other fates too….
“By such means, embryonic stem cells can be transformed into heart, nerve, kidney, pancreatic, and other specialized cells. These targets can also be made from induced pluripotent stem cells (iPSCs), themselves produced by reprogramming mature, fully differentiated somatic cells into a stem-cell state with a cocktail of a genes that are highly active in embryonic stem cells….
“These organized, artificial conglomerates of cells are called organoids. They resemble the corresponding organs, but often somewhat sketchily, because the cells don’t receive the prompts from other cells and tissues surrounding them in an embryo that they need to fully develop their proper shape and function…. But researchers are starting to find ways of encouraging some of the stem cells to develop into blood vessels. That can happen automatically if the structures are grown in host organisms rather than in a dish: liver organoids transplanted into mice, for example, will become integrated into the animal’s blood supply.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 425, 426.
“But at the level of individual cells, the species barrier isn’t as important as we might think. All cells speak much the same language, and those of different species seem to get on fairly well together in the embryo. Many cross-species chimeric embryos have been created by artificial manipulation of stem cells in the early stages of development, and some will grow into perfectly viable and healthy creatures–for example, chimeras of mouse and rat, or of sheep and goats.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 432.
“The multi-tiered principles that generate complex animals like us do indeed seem to have some dramatically different possible outcomes. This was revealed in rather spectacular fashion by Levin, computer scientist Joshua Bongard, and their coworkers when they discovered that frog cells can assemble into multicellular structures that arguably qualify as full-fledged organisms–but which are nothing like frogs at all. The team called these entities ‘xenobots’….
“At a glance they might be mistaken for microscopic aquatic animals–larvae or plankton, say–swimming here and there with apparent agency. Some move in orbit around particles in the water, others patrol back and forth as though on the lookout for something. In a petri dish, many of them together act like a community, responding to one another’s presence and participating in collective activities….
“By ‘feeding’ them with the right nutrients, Levin’s team has been able to keep xenobots active for more than ninety days…..
“Xenobots apparently communicate with one another too. If three of them are set spaced apart in a row and one is activated by being pinched with fine tweezers, it will emit a pulse of calcium ions that, within seconds, shows up in the other two.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. pp. 433-434, 435-436; reference – personal communications with author.
“The search for trends and correlations in the use of words and phrases is called ‘culturomics,’ by explicit analogy with genomics, in which we look for correlations between genomic data and traits or diseases. Culturomics offers a new tool for analyzing culture and society.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 445.
“Perhaps more even than words like agency and purpose, meaning carries a lot of baggage in biology, and you’ll rarely see it used in an academic text on the topic. But it’s a crucial concept, because it conveys a large part of what distinguishes life from other states of matter. As we saw, agency requires a sifting of information in the agent’s environment to find that which has meaning–specifically, which is useful for achieving the agent’s goals…. The notion of meaning embeds and entangles life in its environment.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 448.
“The issues of causation and meaning sit at the core of biology, and yet they have been neglected. I believe that some of the discipline’s most contested arguments have arisen and persisted because of that neglect.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 448.
“Relying only on genetic hardwiring is inadequate to sustain the operation of robust multicellular systems, and I have argued the best way to think about the alternatives is as modes of cognition.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 450.
“I believe we are at the beginning of a profound rethinking of how life works. Far from being some new paradigm that threatens Darwinism, it is a rather glorious extension of it.” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 451.
“Consider Darwin’s famous Galapagos finches…. At face value it is not easy to evolve a beak shape and keep it functional: how, say, do you avoid the lower beak not becoming outsized with respect to the upper one? How are small, gradual changes to the beak kept proportionate to independent changes in the head and musculature? But developmental mechanisms smooth out such potential inconsistencies: a single signaling molecule influences the size of the whole beak…. The buffering provided by the higher levels of organization reduces the likely lethality of genetic change….” Ball, Philip. 2023. How Life Works: A User’s Guide to the New Biology. U. of Chicago Press. p. 457.
“Clearly, inasmuch as love is a pleasure almost everyone is looking for, the thing that gives meaning and intensity to almost everyone’s life, I am convinced that love cannot be a gift given on the basis of a complete lack of risk. The Meetic [online dating site in Paris] approach reminds me of the propaganda of the American army when promoting the idea of ‘smart bombs and ‘zero dead’ wars.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 7.
“The second threat love faces is to deny that it is at all important. The counterpoint to the safety threat [that one can use a lot of known criteria such as through online dating to filter out the perfect match as comparable to an arranged marriage] is the idea that love is only a variant of rampant hedonism and the wide range of possible enjoyment[s].” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 8.
“Love confronts two enemies, essentially: safety guaranteed by an insurance policy and the comfort zone limited by regulated pleasures…..
“Risk and adventure must be re-invented against safety and comfort.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. pp. 10, 11.
“In today’s world, it is generally thought that individuals only pursue their own self-interest. Love is an antidote to that. Provided it isn’t conceived only as an exchange of mutual favours, or isn’t calculated way in advance as a profitable investment, love really is a unique trust placed in chance. It takes us into key areas of the experience of what is difference and, essentially, leads to the idea that you can experience the world from the perspective of difference.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 17.
“Lacan doesn’t say that love is a disguise for sexual relationships; he says that sexual relationships don’t exist, that love is what comes to replace that non-relationship. That’s much more interesting. This idea leads him to say that in love the other tries to approach ‘the being of the other’. In love the individual goes beyond himself, beyond the narcissistic. In sex, you are really in a relationship with yourself via the mediation of the other. The other helps you to discover the reality of pleasure. In love, on the contrary, the mediation of the other is enough in itself.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. pp. 18-9.
“While desire focuses on the other, always in a somewhat fetishist manner, on particular objects, like breasts, buttocks and cock… love focuses on the very being of the other, on the other as it has erupted, fully armed with its being, into my life thus disrupted and re-fashioned.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 21.
“First, there is the romantic interpretation that focuses on the ecstasy of the encounter. Secondly, what we referred briefly to when discussing the Meetic dating agency, the interpretation based on a commercial or legalistic perspective, which argues that love must in the end by a contract…. Finally, there is the sceptical interpretation that turns love into an illusion. My own philosophical view is attempting to say that love cannot be reduced to any of these approximations and is a quest for truth.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. pp. 21-2.
“What is the world like when it is experienced, developed and lived from the point of view of difference and not identity? That is what I believe love to be.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 22.
“I really don’t like all these theological ruminations inspired by love, even though I know they have made a great impact on history. I can only see the ultimate revenge of One over Two. I believe there really is an encounter with the other, but an encounter is not an experience, it is an event that remains quite opaque and only finds reality in its multiple resonances within the real world.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 24.
“Love is always the possibility of being present at the birth of the world.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 26.
“We shouldn’t underestimate the power love possesses to slice diagonally through the most powerful oppositions and radical separations. The encounter between two differences is an event, is contingent and disconcerting, ‘love’s surprises’, theatre yet again. On the basis of this event, love can start and flourish. It is the first, absolutely essential point. This surprise unleashes a process that is basically an experience of getting to know the world. Love isn’t simply about two people meeting and their inward-looking relationship: it is a construction, a life that is being made, no longer from the perspective of One but from the perspective of Two.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 29.
“The enigma in thinking about love is the duration of time necessary for it to flourish. In fact, it isn’t the ecstasy of those beginnings that is remarkable. The latter are clearly ecstatic, but love is above all a construction that lasts. We could say that love is a tenacious adventure. The adventurous side is necessary, but equally so is the need for tenacity. To give up at the first hurdle, the first serious disagreement, the first quarrel, is only to distort love.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 32.
“Love, particularly over time, embraces all the positive aspects of friendship but love relates to the totality of the being of the other, and the surrender of the body becomes the material symbol of that totality.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 36.
“What is universal is that all love suggests a new experience of truth about what it is to be two and not one.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 39.
“Because, basically, that is what love is: a declaration of eternity to be fulfilled or unfurled as best it can be within time: eternity descending into time.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 47.
“There are points, tests, temptations and new appearances, and, each time, you must replay the ‘Two scene’, find the terms for a new declaration. After the initial declaration, love too must also be ‘re-stated’. And that is why love is also the source of violent existential crises. Like all processes involving the search for truth.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. pp. 51-2.
“… political action tests out the truth of what the collective is capable of achieving.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 53.
“What we must say, as love is our theme, is that love and political passion should never be confused. The problem politics confronts is the control of hatred, not of love.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 71.
“In all these instances [connections between romance and revolutionary movements or political passion], my intention isn’t to highlight the similarity between love and revolutionary commitment, but the kind of secret resonance that is created, in the most intimate individual experience, between the intensity life acquires when a hundred per cent committed to a particular Idea and the qualitatively distinct intensity generated by the struggle with difference in love. It is like two musical instruments that are completely different in tone and volume, but which mysteriously converge when unified by a great musician in the same work.” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 75.
“By ‘communist’ I understand that which makes the held-in-common prevail over selfishness, the collective achievement over private self-interest. While we’re about it, we can also say that love is communist in that sense, if one accepts, as I do, that the real subject of a love is the becoming of the couple and not the mere satisfaction of the individuals that are its components parts. Yet another possible definition of love: minimal communism!” Badiou, Alain with Nicolas Truong. 2009. In Praise of Love. Translated by Peter Bush. London: Serpent’s Tail. p. 90.
“The scientific name for body budgeting is allostasis. It means automatically predicting and preparing to meet the body’s needs before they arise….
“Your brain’s most important job is to control your body–to manage allostasis–by predicting energy needs before they arise so you can efficiently make worthwhile movements and survive.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. pp. 8, 10.
“Your human mind, wrote Plato, is a never-ending battle between three inner forces to control your behavior. One force consists of basic survival instincts, like hunger and sex drive. The second force consists of your emotions, such as joy, anger, and fear. Together, Plato wrote, your instincts and emotions are like animals that can pull your behavior in divergent, perhaps ill-advised directions. To counteract this chaos, you have the third inner force, rational thought, to rein in both beasts and guide you on a more civilized and righteous path….
“Perhaps it’s unsurprising, then, that scientists later mapped Plato’s battle onto the brain in an attempt to explain how the human brain evolved….
“According to this evolutionary story, the human brain ended up with three layers–one for surviving, one for feeling, and one for thinking–an arrangement known as the triune brain. The deepest layer, or lizard brain, which we allegedly inherited from ancient reptiles, is said to house our survival instincts. The middle layer, dubbed the limbic system, supposedly contains ancient parts for emotion that we inherited from prehistoric mammals. The outermost layer, part of the cerebral cortex, is said to be uniquely human and the source of rational thought; it’s known as the neocortex (‘new cortex’).” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. pp. 13, 14.
“If we think again of neurons as little trees, tuning means that the branch-like dendrites become bushier. It also means that the trunk-like axon develops a thicker coating of myelin, a fatty ‘bark’ that’s like the insulation around electrical wires, which makes signals travel faster. Well-tuned connections are more efficient at carrying and processing information than poorly tuned ones and are therefore more likely to be reused in the future….
“Meanwhile, less-used connections weaken and die off. Pruning is critical in a developing brain, because little humans are born with many more connections than they will ultimately use….
“Both processes also continue throughout life. Your bushy dendrites keep sprouting new buds, and your brain tunes and prunes them. Buds that aren’t tuned disappear within a couple of days.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. pp. 50, 51.
“In general, toddlers learn to tend their own body budgets better when their caregivers create learning opportunities for them instead of hovering and taking care of their every need.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 53.
“But you don’t sense with your sensory organs. You sense with your brain.
“What you see is some combination of what’s out there in the world and what’s constructed by your brain.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 70.
“Neuroscientists like to say that your day-to-day experience is a carefully controlled hallucination, constrained by the world and your body but ultimately constructed by your brain.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 71.
“His [Pavlov’s] dogs were not reacting to the sound by drooling. Their brains wee predicting the experience of eating food and preparing their bodies in advance to consume it.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 73.
“… social reality is a uniquely human ability. Scientists don’t know for sure how our brains developed this capacity, but we suspect it has something to do with a suite of abilities that I’ll call the Five Cs: creativity, communication, copying, cooperation, and compression.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 112.
“Each time one of your neurons compresses its inputs to make a summary, that multisensory summary is an abstraction of the inputs. At the front of your brain, the largest, most highly connected neurons produce your most abstract, multisensory summaries. That’s why you can view dissimilar objects like flowers and gold watches as similar [as gifts] and view an identical cup of wine as either celebratory or sacred.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 117.
“In short: The wiring of your cerebral cortex makes compression possible. Compression enables sensory integration. Sensory integration enables abstraction. Abstraction permits your highly complex brain to issue flexible predictions based on the functions of things rather than on their physical form. That is creativity. And you can share these predictions by way of communication, cooperation, and copying. That is how the Five Cs empower a human brain to create and share social reality.” Barrett, Lisa Feldman. 2020. Seven and a Half Lessons About the Brain. Boston: Mariner Books. p. 118.
“This book focuses on evolving masculinity and femininity as two energies within each individual, both striving toward an inner harmony. So long as these energies are projected onto others, we rob ourselves of our own maturity and our own freedom. Until we take responsibility for these projections, genuine relationship is impossible because we are entangled in our own images instead of relating to new possibilities that expand our boundaries.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 9.
“The Berlin Wall is down. The Wall of Mirrors through which men and women fail to see each other is still up. It stands invisible in the streets, in our institutions and in personal relationships…. Now as we try to plumb its illusive depths, we, both men and women, are facing our anguished femininity and her ravaged masculine partner, both victims of obsolete ideals. She will no longer be a silent victim, nor will he remain ostracized…. Yet if we could each take responsibility for our own inner victim and tyrant, we could truly depotentiate the old parental complexes. Released from their power, we would be free to love.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 10, 11.
“The first task that confronts us is to raise the feminine to a new level of consciousness so that matter (always associated with the feminine), instead of being experienced as dark and opaque, will be suffused with its own inner light, a radiant container strong enough to relate with vibrancy and creativity to the emerging masculine consciousness.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 14-5.
“Crucial to a discussion of the conscious feminine is the liberation of the word from its bondage to gender. While I am deeply concerned with forging a new relationship between the sexes, I am more immediately concerned with the inner basis of that new relationship through the coming together of masculine and feminine within the individual of either sex. The term ‘conscious feminine’ applies as much to men as to women, even as the term ‘conscious masculine’ applies to both sexes….
“Mature men and women of the new age will be bound together less by the attraction of opposites than by their shared humanity. This shared humanity does not neutralize sexual attraction. Differentiated masculinity in a woman attracts strong men; differentiated femininity in men attracts strong women.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 16.
“The old petrifying mother is like a great lizard lounging in the depths of the unconscious. She wants nothing to change. If the feisty ego attempts to accomplish anything, one flash of her tongue disposes of the childish rebel. Her consort, the rigid authoritarian father, passes the laws that maintain her inertia. Together they rule with an iron fist in a velvet glove. Mother becomes Mother Church, Mother Welfare State, Mother University, the beloved Alma Mater, defended by Father who becomes Father Hierarchy, Father Law, Father Status Quo….
“In my understanding of patriarchy, these outworn parental images wield the power that inhibits personal growth…. Men and women who are unconsciously trapped in power drives have no individual freedom, nor can they allow freedom to others. Women can be worse patriarchs than men….The sons and daughters of patriarchy are, in fact, mother-bound.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 17-8.
“Without the metaphor, the mind may be fed, but the imagination and heart go hungry. Without the pondering in the soul, the banquet table in dreams may be laden, but the food is not assimilated and so the soul starves.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 27.
“In the growing-up process in our culture, rational thinking supersedes imaginative perception to such a degree that imagination is stifled. Without it, spontaneity and creativity petrify. When eternal essence is no longer perceived in daily living, life becomes a repetitive treadmill. The feminine container, the receiver, is so shut down that nothing new registers. The contraries (spirit/matter, masculine/feminine) cease to be perceived as living paradox; without their tension, humor, wit, playfulness, the salt that gives life is savor is not there.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 28-9.
“The virgin soul, if she is embraced, brings light (consciousness) into matter. She is matter in the continual process of becoming more light through the wisdom that is forever being revealed to her through her own matter. She is the personification of the redemption of matter. She becomes the ravished bride of the true bridegroom. Essential, therefore, to this understanding of the conscious feminine is a respect for the sacredness of its own creative unfolding. This is what the dragon-slaying myth rejects as an enveloping darkness even as the shadow of the unconscious feminine demonically parodies it as mystification and satanic allure.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 34.
“On the basis of his own experience, Keats was convinced that the creative process itself was the parent of those schemes of redemption which characterize the world’s religions, thus serving as the unifier of them all. Humanity was bound together in a religion of the soul, a global religion to which the word psychology would become attached, designating, as Keats himself insisted, that a knowledge of the soul is better than worship, for in worship lay the danger of deifying human powers in a manner that arrested them in some dogmatic form.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 34-5.
“We confuse it [love in the body] with sexuality and need. Genuine love, however, permeates every cell of the body. It is immediately recognized by animals, children and even some adults who were either born with it or have found it thorough suffering and surrender.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 43.
“The overwhelming sense of abandonment which terrorizes so many people is rooted not in the parents’ abandonment of the child, but in the abandonment of the child’s soul. By projecting their own image of their child, they obliterate the actual child who then goes underground, abandoned not only by the parents, but by the child itself. Out of this habitual abuse arises the sense of shame connected with some unknown crime for which the child feels guilty. Dreams of a murder being committed, or a corpse lying hidden, reveal the betrayal that is perpetuated into adulthood. When a relationship is endangered, for example, the adult again abandons the underground child, who is impossibly honest; then the personal takes over, trying to please, hoping to save the relationship at whatever cost. The guilt is two-fold: ‘I am guilty for being who I am,’ and, at a deeper level, ‘I have abandoned myself.’” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 43-4.
“The body-in-control is an unloved tyrant, resistant to light because it exists without love.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 48.
“As the veils of illusion are removed, and as the inner marriage becomes a possibility, the tension between masculinity and femininity intensifies, as it often does before an actual marriage. The problem is usually a discrepancy between masculine and feminine feeling. What is of value to one is either not valued or not perceived by the other.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 170.
“Many women who like to think of themselves as conscious, helplessly hand over their feeling function to intelligent but feelingless (not emotionless) men. Their own father complex colludes with their partner and rapes the very feelings they have worked so hard to experience. Life again becomes an empty ‘so what?’ Unless we have the feminine consciousness that values our feeling, we wallow in emotions that can run rampant, dragging us with them.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. pp. 171-2.
“Without the consciousness of Sophia’s wisdom illuminating not only our body, but the body of creation, we lack the crucial connection to our own feeling. We judge with our minds and forget we have hearts, lungs, spleens and bowels. Then we fail to temper our winged spirit with human limitations. Without embodied soul, spirit cannot manifest through human feeling. It flies like an angel with no place to land, archetypal energy that merely swoops through, leaving the body a burned-out shell demanding whatever perverted solace it can find.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 177.
“Allowing a mature Eros to permeate inner and outer masculinity is one of our biggest tasks. Repeatedly, men have wept in my office, saying, ‘I thought everything was fine. I don’t know what I did. I do not understand her.’ And women have wept, saying, ‘When I trusted him most, he left. I do not understand him.’
“The gap is in the feeling value. In the Chinese symbol of the inner marriage, the yang carries some yin, the yin some yang. Masculinity is tempered by the feminine, and vice versa. Disciplining masculinity that takes its superiority for granted demands as much strength and vigilance as training a wild horse that’s never known a harness. And we dare not use a whip that will ultimately break its spirit.” Woodman, Marion. 1990. The Ravaged Bridegroom: Masculinity in Women. Toronto: Inner City Books. p. 180.
“Democracies tend to lose so many great artists early because democracies believe that an artist needs only to be sincere.” Bly, Robert & Marion Woodman. [Robert Bly portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 77.
“The movement to demonize the father gods, and to create a sentimentalized version of the Goddess makes women and men more infantile. Moreover, it is a part of the shame of New Age culture that it confuses this infantile dependency upon the Goddess with mysticism or religious emotion.” Bly, Robert & Marion Woodman. [Robert Bly portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 88.
“Spirit without form is invisible; matter without spirit is dead. Matter and spirit love each other. They live through each other.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 122.
“Many women do point out that they seem to be doing more than their share in bringing consciousness to the relationship:’Why do I have to carry that responsibility?’ Well, my only answer is: ‘That’s the human story. Eve brought Adam to the Tree of Knowledge of Good and Evil, though little thanks she got, and now she may be bringing him to the other tree, the Tree of Life, for which she is likely, at least in the short run, to receive even less thanks.’
“The process we are discussing is a dialogue between consciousness and the unconscious as a divine mystery that reveals each of us to ourselves and to each other. The outer marriage depends for its human success upon the inner marriage forged out of the archetypal materials of the unconscious. It becomes the human expression of two individual inner marriages relating to each other. It’s the outer expression of an inner divine life. If there is in the relationship no awareness of this divine life to which in a crisis they can turn, the couple may settle for patchwork solutions. That is not a judgment. ‘The fullness of time’ is a fact in the unconscious. Nature has its own laws of maturing. If the time is not yet right, some temporary solution has to be found.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. pp. 128-9.
“The drive that is still hidden in our compulsive society could become a release into freedom, freedom from a shackling fusion with other people and things. We are being called to live our own identity.
“The feminine side of this identity is what I call the Conscious Virgin. As in the phrase virgin forest, the original meaning of the word virgin had to do with the natural state of an organic life form, a state that is always in touch with its own inherent resources without human interference. Psychologically, when I think of Conscious Virginity, I think of the natural state of an organic soul that has reached a consciousness of itself without that consciousness interfering with its natural evolution. What distinguishes our human state from other forms of life is the consciousness that illumines it to make it what it is. That illumination is inherent within the soul rather than imposed upon it. The Conscious Virgin is the conscious natural human state of Being.
“In this state, soul is not a prisoner waiting to be released from a body in which it is a stranger or a victim. Rather, body and soul are friends, maturing together, constantly interchanging messages….
“Conscious Virginity is Being, I am that reflects the eternal I am that I am. Like a lily of the field, the Conscious Virgin has no need to justify her existence, no need to fear aloneness.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. pp. 175-6.
“‘The Descent’ is a mythological term for the period during and after a powerful event in which the ego has been overwhelmed by a wave from the unconscious. Energy that is normally available to consciousness falls into the unconscious so the person is often disoriented, exhausted, perhaps in a trance state. This is known as journeying into the underworld, a state in which creative energies are going through transformations that the unaware ego may know nothing about until big changes begin to happen in the outer world….” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 177.
“Perfection polarizes the world, makes life impossible to live.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 187.
“As the newly released form of pent-up energy, the flaming bird [the Firebird of Russian fairy tale] is the transformation of ‘I desire’ as instinctual energy into ‘I desire’ as spiritual energy….
“The transformation of instinctual energy into spiritual energy does not involve the sacrifice of instinct, but rather a refinement of instinct.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. pp. 199-200.
“Thematically, the story deals with freedom and compulsion, the flight to freedom out of compulsion. The three horns are the instruments of the transition. The paradox still holds in the clutching of the feathers: freedom is not flight, if it remains, in part, bound to compulsion. The Baba Yaga does catch some feathers. Full flight without any compulsion would be pure spirit. As in life, the unconscious feminine is bound to nature, and nature is bound to the laws that govern it; the masculine as spirit would fly out of life. To fly off on the firebird would be to fly into death.
“The danger lies in hubris, ascending beyond the human limit by sacrificing instinct to pure spirit, like Icarus flying too close to the sun and falling into a bottomless ocean of unconsciousness. If we think of pure spirit, symbolized by the sun, as masculine, we can see that, released from the feminine, the masculine spirit is death. The feminine is what holds the masculine in life.
“This conflict/paradox becomes clearer with an illustration. We can speak of the healing of an addiction as the rescuing of the soul from the dark womb of the chthonic mother. The chthonic mother is the purely instinctual mother imprisoning her child in physical bonding. It is her energy that takes possession fo the ego in the addiction. The rescuer is an infusion of spirit, which, far from robbing the feminine of its chthonic ground, is bringing it to consciousness. The freeing of the soul from addiction is the birth of the Divine Child, the second birth. The soul free of addiction, inhabiting its own body, is matter living its own released energy, the partnership of conscious feminine and conscious masculine.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. pp. 201-2.
“‘Except for the point, the still point,
There would be no dance, and there is only the dance.” Eliot, T.S. from Four Quartets. From: Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 212.
“Love as the desire to be known is the state of being in love with love. It is a love that feeds on isolation, darkness, withdrawal. It is narcissistic because it is a state of being in love with one’s own projected image, one’s own fantasized image of oneself. This state of love is the unconscious form of the inner marriage….
“The withdrawal of the projection that is essential for the achievement of the inner marriage transforms the object of the projection, the Beloved, into a stranger. It is this confrontation with the stranger, with the otherness of the Beloved, that creates an ‘energy field’ of love. When that field of love is established within, the archetypal projections are taken off the outer partner. No need, then, for either partner to attempt to be god or goddess. An immense unnatural weight is removed from both. A freedom enters the relationship, which may be quite alarming at first. Gradually that freedom will be recognized as the freedom to love another human being as a human being without any hidden agenda and false expectations and needs. The inner marriage makes the outer marriage possible.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. pp. 218, 219.
“It is the Feminine–as matter–which makes the bridge between the divine and the human. The new feminine stands for a new kind of consciousness which can hold the divine and the human in one thought. Women feel angry about the distrust and rejection of matter by men in so many traditions and sciences. Women don’t want to be idealized when they are not recognized in their humanity. They want to be honored in their own sacred matter.” Bly, Robert & Marion Woodman. [Marion Woodman portion of book] 1998. The Maiden King: The Reunion of Masculine and Feminine. NY: Henry Holt & Co. p. 233.
“Conscious femininity is not bound to gender. It belongs to both men and women. Although in the history of the arts, men have articulated their femininity far more than women, women are now becoming custodians of their own feminine consciousness. For centuries, men have projected their inner image of femininity, raising it to a consciousness that left women who accepted the projection separated from their own reality. They became artifacts rather than people. The consciousness attributed to them was a consciousness projected onto them. That projection was sometimes an idealized image of beauty and truth, a sphinx, or a dragon. Whatever it was, it could not be an incarnated woman.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 1-2.
“One tragic loophole in our culture is our failure to tell the difference between identifying with an archetype and relating to it. When addicts talk about a high or a fix, what they mean psychologically is that they want to identify with an archetype. They want to forget the realities of being human beings and escape into godlike power. They want to give over their weak ego to unconscious drives….
“Identification is unconscious; relationship is conscious.
“Identification with archetypal energy breeds inflation that swings into deflation. False hope, false power, fake gods collapse in agony.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 13-14.
“As in many contemporary men and women, the feminine learns to trust the sun before daring to move toward the moon.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 23.
[7] “But paradoxically, the less I trusted my own inner masculine, the more I either credited or blamed the men about me for my successes or shortcomings. I was overvaluing the outer and devaluing the inner.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen] Kate speaking. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 76.
[7] “The critique I made early on of the patriarchal institutions I deplored, I now apply to my own being; not: I think, therefore I am; but rather: I am, therefore I think. All of me is being involved in the creative process, with Being stressed over Doing….
“On good days, I can experience feelings without being battered by them. Wary at all times, I am gradually surrendering to feelings of love without the inevitable suspicion that I will be somehow manipulated by them. I am learning to say yes, but only because I have begun to experience the power of no.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. Kate speaking. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 104-5.
[7] “Woman’s body has carried the man’s shadow of lust, greed, and sloth. If she colludes with that shadow, she becomes unconscious mother, allurement that once assured the propagation of the race. She decorates her body, exposes it, seduces, even allows her body to be penetrated by a total stranger. Consciousness is so absent that neither recognizes the rape of the bodysoul. Neither considers it a moral issue. Neither hears the voice crying out from the dis-eased genitals. Each goes to a doctor for pills or salve.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 111.
“Our major task is to bring to consciousness as much of the unconscious as possible without allowing our intellect to destroy the unconscious image-making process. The unconscious is the matrix (creative source) of all life-energy. The danger in bringing unconsciousness to the conscious level is that in recognizing that we have made choices out of our unconscious instincts, we may cut ourselves off from the numinous power of our animals. In recognizing, for example, that our partner is a father surrogate, we may experience the shutdown of all sexual desire. However, the sexual energy is still in our matter in some masked form….
“Jung recognized that ‘psychic processes seem to be balances of energy flowing between spirit and instinct.’ Having observed the dynamism that operates between these poles he concluded that ‘it is not only possible but fairly probable, even, that psyche and matter are two different aspects of one and the same thing.’” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 111-2.
“Jung understood religion as an instinct, and longing for eternal life as part of that instinct. He saw it as a need–the other pole of physical desire. If immortality is a need, then every instinctual act of a human being is a religious act.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 113.
[7] “Without that body wisdom, there is no presence between man and woman–no NOWS–where each can meet the other’s truth, no sacred spaces where both are stripped to their naked fear, anger, and love. Neither has a sanctuary in which their animals can be civilized and still want to live. The feminine is not related to her core, to that deepest survival chakra.
“This lack of dynamic is true intrapersonally as well so long as people are living a persona life without the heart connection that grounds them in their own body matrix. Individuals existing without that connection try to live by willpower. They try to make believe that life has meaning. Their neuroses (distorted instincts) cloak the vibrant life buried in their unconscious. They are cut off from their birthright to life.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 115.
[9] “Witch [character in writer Mary’s mind] holds me captive in my body; she is the ruling power complex (yet always so loving and caring!) controlling my every move. Witch is the essence of a woman’s unconscious identification with the instinctual power of the female body. Witch’s motto is, ‘Make them want you, but never let them have you.’ Through unconscious manipulation of the sexual energy of my own body, I unconsciously dress her up and act in whatever manner necessary to get what I believe I need in order to be successful. I can starve my body if thin means power in beauty; I can get degrees if intelligence means power in education. I can use my various physical appearances to seduce men mentally (they, who are always in the power position) to give me what I need–a job, prestige, attention. With Witch in control I can be a man’s ‘darling little princess,’ or his ‘bright little girl,’ or his ‘whore,’ or his ‘disembodied spiritual anima.’ In other words, I am an anima woman, reflecting whatever a man wants. Under the performing persona of my Good Mary dwells Witch who hates men. And ‘I,’ as conscious ego, am not there. No one is home and ‘i,’ as complexed ego, never knew it!” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. Mary speaking. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 144-5.
[9] “Eve [character in Mary’s mind] loves, is love. Eve knows that sexual energy is a sacred power of a divine nature. She lives a morality of the body that honors the interconnectedness of all forms of life. Through her eyes and her unconditional love my self-image is transformed from self-loathing to self-acceptance and eventually to self-love.
“‘I am Eve,’ she says to me in meditation. ‘I am beautiful, for my body is created by divine energy. The sacred snake coils around my body and penetrates my being with wisdom. I know how to say ‘Yes’ to life. When negative energy comes toward me, I know how to say ‘No’….
“‘When you release me from your frozen body, I am joyful. I am laughter, pleasure, and movement. I am a flower with the morning dew drop, but I need the sunlight to reflect my beauty. I am creative, for I am creation; creation happens through me. I am fully aware that whatever comes through me is the expression of the Great Goddess who gives form to the formless. I know that I am a vessel for her creativity; that is why creativity brings meaning to me. And whatever is created through me must be returned to the Goddess. All creations die. That is the cycle….
“‘It is women’s responsibility to become conscious of my sacred energy. When women are connected to me, their bodies become sacred temples. They do not abuse their bodies sexually, nor do they starve and exercise their bodies for beauty and power. Instead they care for their bodies in love of divine matter, and they express their divinity without shame and without guilt. Their radiating love of matter protects them from rape and abuse.
“‘I am the joy of planet Earth that simultaneously expresses death and life. But I am dying, my voice is getting weaker. You fight for security against death, instead of celebrating the birth of each day. You want to use my energy to satisfy your greed, but since you are severed from your serpent you no longer know what your real needs are. Connect to the serpent; connect to life and stop killing me with your power….
“‘My energy is the wisdom that knows that all things are in fact one, that the interrelatedness of all life is a delicate web of dependency, where all parts are equal and necessary. Each part of the planet is perfectly suited for its function in the web of life.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. Mary speaking. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 150, 151, 152.
“When I allow myself to experience my body as a sacred instrument capable of receiving and generating sensations, I start to notice that my attitude about my body becomes more impersonal. I am teaching myself to listen to the sensations resonating in my flesh and to differentiate between sensations originating without (‘I read the body receiving sensations’) and sensations originating from within (‘I read the body generating sensations’). As I allow others to affect me, I have to hold more firmly onto my own center of awareness. I know that if I lose my bearings and forget my own center, I will become possessed, possessed by the unconscious emotional life of others. (I realize that for most of my life I have lived this tragic condition.)” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. Mary speaking. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 155.
[8] “Most contemporary women are the daughters of patriarchy; their mothers and grandmothers were daughters of patriarchy. They know very well how to organize, how to set a goal in some transcendent perfection. They know, too, the shadow of that perfection that never ceases to judge, to blame, to find them guilty for the crime of being themselves. They know, too, the blind fury of the instincts that fight for recognition through addictions.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 352.
[8] “Contemporary men whose femininity is still locked in patriarchal parents are still pleasing mother or sullenly displeasing. In the marrow of their bones they yearn for women who will unabashedly adore them, sustain them, unconditionally love them. In handing over their power to such women, they choose to be boys, powerful so long as they are adored, broken when the adoration either flips into nagging criticism or realistic appraisal. Terror of abandonment can erupt if their woman moves toward consciousness.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 352.
“Crucial to the breaking of incestuous bonds to the parents is the recognition that we do not belong to them and they do not belong to us. Individuation begins with the painful recognition that we are all orphans. And the liberating recognition that the whole world is our orphanage.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 354.
“When the parents lack an ego structure that protects them from identification with the child’s unconscious archetypal projection, and/or where the egoless child accepts the parents’ unconscious archetypal projection (Daddy’s little princess or Mommy’s little man), the archetype may penetrate the human actuality in a completely destructive way. The result is psychic incest, which may become physical incest. Incest is natural in gods and goddesses; in human beings, it is a delusion of omnipotence.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 357.
“In Jung’s paradigm, the energy of the archetype has two poles. At one end, what he calls the infrared end, energy expresses itself in the dynamism of the instincts and body symptoms. At the ultraviolet end, energy expresses itself in the dynamism of the spirit through dreams, fantasies, active imagination. The shift in which the energy of raw instinct transforms into the energy of spirit is what Jung calls ‘the decisive transformation.’ In this shift, he suggests, all culture, all civilization is grounded….
“Until Jung’s time, this shift or transformation tended to be thought of as divine intervention from without, what Christians call grace. It was as if a supernatural energy penetrated an instinctual energy and redirected its flow, as for example, in the conversion of Saul on the road to Damascus. Jung, on the other hand, saw the taboo as being imposed from within, as a transforming agent, transforming raw instinct into spirit. In Symbols of Transformation, he wrote, ‘The symbolic truth …which puts water in place of the mother and spirit in place of the father, frees the libido from the channel of the incest tendency, offers it a new gradient, and canalizes it into a spiritual form.’” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 359-360.
[8] “The child, as feminine being [or both as tied to matter], was not reflected because centuries of patriarchal thinking have scorned matter. The hole is still jet black. It is not even despair. It is nothingness, oblivion without feeling, death without consciousness. It is shame so deep that it cannot be recognized until the ego container is strong enough to face the obliteration. It is matter so wounded, so betrayed that it is dissociated from consciousness. Women trapped in this incestuous bonding with the negative side of the mother archetype dream of doing battle with an ugly woman. They feel so betrayed by their body that they try to take up residence in their mind. As tiny children they learned not to breathe deeply because breath activated these feelings and sensations. Numbness makes life bearable. To obliterate matter, however, is also to obliterate soul. Soul killing in body is alienation from the positive mother; soul killing in spirit is alienation from the positive father.
“The black hole in many men is as black as it is in many women. Some even take a certain pride in being ‘shut down.’ The fact is their matter is dissociated from their spirit and their fundamental contempt for matter is in their cells. So long as they stay in their superficial persona, they may be caring, generous, even loving, but in the intimacy of sexuality they cannot feel their own passion connected to their own being. They may experience fear, emptiness, nothingness. Overcome by the back hole at the center, they cannot reflect themselves nor their partner, however much they try. If we are not bonded to the positive mother, we cannot trust our own cells; then full sexual surrender is impossible. Life cannot be fully lived without embodiment, nor can death be faced creatively. No wonder death is denied in a culture that rejects the beauty of its own humanity.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. pp. 362-3.
“While consciously holding the still point in Love, we can observe the opposites swinging through us without swinging with them. We can observe the power of the mother, who yearns to hold onto her child, letting go; we can observe the sexuality of the gypsy who wants life to serve her transforming into a love that is ready to serve life. We can remain invisible if necessary, feel ourselves being moved to a new conscious position, and sustained by Her, hold that new still point. Here mother and gypsy are one in the Bride. Gradually, we know that Her light in matter is Love. Like perfume, it permeates everything. Experiencing that Presence once changes our perception forever. Perhaps this is the real meaning of the coming to consciousness of the feminine. It must come slowly or our hearts would break. In our Mother’s house are many more mansions than we can yet dream of.” Woodman, Marion [w/ Kate Danson, Mary Hamilton, Rita Greer Allen]. 1993. Leaving My Father’s House: A Journey to Conscious Femininity. Boston: Shambhala. p. 364.
“To sum up, the right hemisphere is responsible for every type of attention except focused attention. Even where there is divided attention, and both hemispheres appear to be involved, it seems probable that the right hemisphere plays the primary role (possibly that of unifying the divided input….
“There have been suggestions that the basis for the right-hemisphere predominance for attention may lie in the more sophisticated visuospatial processing of the right hemisphere, but I would be inclined to see that as a consequence of the attentional difference rather than a cause of it.
“More specifically there is evidence of left-hemisphere dominance for local, narrowly focused attention and right -hemisphere dominance for broad, global, and flexible attention.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. pp. 39-40.
“If it is the right hemisphere that is vigilant for whatever it is that exists ‘out there’, it alone can bring us something other than what we already know. The left hemisphere deals with what it knows, and therefore prioritises the expected – its process is predictive. It positively prefers what it knows. This makes it more efficient in routine situations where things are predictable, but less efficient than the right wherever the initial assumptions have to be revised, or when there is a need to distinguish old information from new material that may be consistent with it. Because the left hemisphere is drawn by its expectations, the right hemisphere outperforms the left whenever prediction is difficult….
“The right hemisphere is, in other words, more capable of a frame shift; and not surprisingly the right frontal lobe is especially important for flexibility of thought, with damage in that area leading to perseveration, a pathological inability to respond flexibly to changing situations. For example, having found an approach that works for one problem, subjects seem to get stuck, and will inappropriately apply it to a second problem that requires a different approach – or even, having answered one question right, will give the same answer to the next and the next. It is the right frontal cortex that is responsible for inhibiting one’s immediate response and hence for flexibility and set-shifting; as well as the power of inhibiting immediate response to environmental stimuli.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. pp. 40-41.
“The more flexible style of the right hemisphere is evidenced not just in its own preferences, but also at the ‘meta’ level, in the fact that it can also use the left hemisphere’s preferred style, whereas the left hemisphere cannot use the right hemisphere’s. For example, although the left hemisphere gains more benefit from a single strong association than several weaker associations, only the right hemisphere can use either equally.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. p. 41.
“In general the left hemisphere is more closely interconnected within itself, and within regions of itself, than the right hemisphere. This is all part of the close focus style, but it is also a reflection at the neural level of the essentially self-referring nature of the world of the left hemisphere: it deals with what it already knows, the world it has made for itself.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. p. 42.
“In summary, the hierarchy of attention, for a number of reasons, implies a grounding role and an ultimately integrating role for the right hemisphere, with whatever the left hemisphere does at the detailed level needing to be founded on and then returned to, the picture generated by the right. This is an instance of the right –> left –> right progression which will be a theme of this book.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. p. 46.
“The right hemisphere sees the whole, before whatever it is gets broken up into parts in our attempt to ‘know’ it. Its holistic processing of visual form is not based on summation of parts. On the other hand, the left hemisphere sees part-objects. The best-known example of this process of Gestalt perception is the way in which the Dalmatian dog, sniffing the ground in the shade of a tree, suddenly emerges from this mass of dots and splashes. The process is not a gradual putting together of bits of information, but an ‘aha!’ phenomenon – it comes all at once.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. pp. 46-7.
“Neurocognitivists say that we can re-cognise, and therefore know, something only if we have already got the model of it in our brain. That does perfectly describe left-hemisphere processes: but it would mean that we were forever trapped in the re-presented, no longer alive, world of the left hemisphere’s knowledge, forever re-experiencing the familiar, the world forever going stale….
“The left hemisphere will never help us here. As one researcher has put it, the left hemisphere on its own, for example after a right-hemisphere stroke, just ‘sees what it expected to see’…. In other words we must learn to use a different kind of seeing: to be vigilant, not to allow the right hemisphere’s options to be too quickly foreclosed by the narrower focussing of the left hemisphere.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. pp. 163-4.
“Detachment has a deeply ambiguous nature. The cool, detached stance of the scientific or bureaucratic mind ultimately may lead where we do not wish to follow. And the relationship implied by the left-hemisphere attention brought to bear through the scientific method, with its implied materialism, is not no relationship – merely a disengaged relationship, implying, incorrectly, that the observer does not have an impact on the observed ( and is not altered by what he or she observes). The betweenness is not absent, just denied, and therefore of a particular – particulary ‘cold’ – kind.” McGilchrist, Iain. 2019. The Master and His Emissary: The Divided Brain and the Making of the Western World, New Expanded Edition. Yale UP. p. 166.
“Individual nerve cells, or neurons, are the basic signaling units of the brain. The human brain contains a huge number of these cells, on the order of 86 billion neurons, that can be classified into at least a thousand different types.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 56.
“The physiological signals that convey information about vision are identical to those that carry information about odors. Here we see a key principle of brain function: the type of information conveyed by an action potential is determined not by the form of the signal but by the pathway the signal travels in the brain. The brain thus analyzes and interprets patterns of incoming electrical signals carried over specific pathways, and in turn creates our sensations of sight, touch, taste, smell, and sound.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 58.
“Neurons are thus classified into three large groups: unipolar, bipolar, and multipolar.
“Unipolar neurons [cell body on one end] are the simplest because they have a single primary process, which usually gives rise to many branches. One branch serves as the axon; other branches function as receiving structures….
“Bipolar neurons [cell body in the middle] have an oval soma that gives rise to two distinct processes: a dendritic structure that receives signals from other neurons and an axon that caries information toward the central nervous system…
“Multipolar neurons [multiple extensions from the cell body] predominate in the nervous system of vertebrates. They typically have a single axon and many dendritic structures emerging from various points around the cell body. Multipolar cells vary greatly in shape, especially in the length of their axons and in the extent, dimensions, and intricacy of their dendritic branching.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 59.
“Nerve cells are also classified into three major functional categories: sensory neurons, motor neurons, and interneurons.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 59.
“A useful characterization of motor and sensory neurons alike is their temporal fidelity to matters outside the nervous system.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 61.
“Interneurons comprise the most numerous functional category and are subdivided into two classes: relay and local. Relay or projection interneurons have long axons and convey signals over considerable distances, from one brain region to another. Local interneurons have short axons because they form connections with nearby neurons in local circuits. Since almost every neuron can be regarded as an interneuron, the term is often used to distinguish between neurons that project to another neuron within a local circuit as opposed to neurons that project to a separate neural structure.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 61.
“Glial cells greatly outnumber neurons–thee are 2 to 10 times more glia than neurons in the vertebrate central nervous system.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 61.
“This pattern of connection, in which one neuron activates many target cells, is called divergence. It is especially common in the input stages of the nervous system; by distributing its signals to many target cells, a single neuron can exert wide and diverse influence. Conversely, a single motor cell in the knee-jerk circuit receives 200 to 450 input contacts from approximately 130 sensory cells. This pattern of connection is called convergence. It is common at the output stages of the nervous system; a target motor cell that receives information from many sensory neurons is able to integrate information from many sources.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 63.
“… almost all neurons can be described by a model neuron that has four functional components that generate the four types of signals: a receptive component for producing graded input signals, a summing or integrative component that produces a trigger signal, a conducting long-range signaling component that produces all-or-none conducting signals, and a synaptic component that produces output signals to the next neuron in line or to muscle or gland cells.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 64.
“Every cell, including a neuron, maintains a certain difference in the electrical potential on either side of the plasma membrane when the cell is at rest. This is called the resting membrane potential. In a typical resting neuron, the voltage of the inside of the cell is about 65 mV more negative than the voltage outside the cell.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 64.
“In many neurons, a 10-mV change in membrane potential (from -65 to -55 mV) makes the membrane much more permeable to Na+ than to K+. The resultant influx of Na+ further neutralizes the negative charge inside the cell, leading to even more permeability to Na+. The result is a brief and explosive change in membrane potential to +40 mV, the action potential.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 65.
“A reduction in membrane potential, called depolarization, enhances a cell’s ability to generate an action potential and is thus excitatory. In contrast, an increase in membrane potential, called hyperpolarization, makes a cell less likely to generate an action potential and is therefore inhibitory.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 65.
“… stretching of the muscle activates specific ion channels that open in response to stretch of the sensory neuron membrane…. The opening of these channels when the cell is stretched permits the rapid influx of Na+ ions into the sensory cell. This ionic current changes the membrane potential, producing a local signal called the receptor potential.
“The amplitude and duration of a receptor potential depend on the intensity of the muscle stretch: The larger or longer-lasting the stretch, the larger or longer-lasting is the resulting receptor potential. That is, receptor potentials are graded, unlike the all-or-none action potential.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 65.
“Sherrington first pointed out that the function of the nervous system is to weigh the consequences of different types of information and then decide on appropriate responses. This integrative function of the nervous system is clearly seen in events at the trigger zone of the neuron, the initial segment of the axon.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 67.
“Because the initial segment of the axon has the highest density of voltage-sensitive Na+ channels and therefore the lowest threshold for generating an action potential, an input signal spreading passively along the cell membrane is more likely to give rise to an action potential at the initial segment of the axon than at other sites in the cell. This part of the axon is therefore known as the trigger zone. It is here that the activity of all receptor (or synaptic) potentials is summed and where, if the sum of the input signals reaches threshold, the neuron generates an action potential.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 67.
“The action potentials carried into the nervous system by a sensory axon often are indistinguishable from those carried out of the nervous system to the muscles by a motor axon.
“Only two features of the conducting signal convey information: the number of action potentials and the time intervals between them….
“In addition to the frequency of the action potentials, the pattern of action potentials also conveys important information.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 67, 68.
“Inhibitory inputs have little information value in a silent cell. By contrast, in spontaneously active cells, inhibition can have a powerful sculpting role. By establishing periods of silence in otherwise ongoing activity, inhibition can produce a complex pattern of alternating firing and silence where none existed.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 68.
“Even cells that are similar morphologically can differ importantly in molecular details. For example, they can have different combinations of ion channels. … different ion channels provide neurons with various thresholds, excitability properties, and firing patterns.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 69.
“Indeed, because the nervous system has so many cell types and variations at the molecular level, it is susceptible to more diseases (psychiatric as well as neurological) than any other organ system of the body.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 70.
“… the basic neural structure of the simple reflex is often preserved. First, there is often an identifiable group of neurons whose firing rate changes in response to a particular type of environmental stimulus, such as a tone of certain frequency, or the juxtaposition of light and dark at a particular angle….
“Second, there is often an identifiable group of neurons whose firing rate changes before an animal performs a motor act.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 70.
“… the organization of the brain is simplified by three anatomical considerations. First, there are relatively few types of neurons. Each of the many thousands of spinal motor neurons or millions of neocortical pyramidal cells has a similar anatomical structure and serves a similar function. Second, neurons in the brain and spinal cord are clustered in functional groups called nuclei or discrete areas of the cerebral cortex, which form networks or functional systems. Third, the discrete areas of the cerebral cortex are specialized for sensory, motor, or associative functions such as memory.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 74.
“Like most motor behaviors, hitting a tennis ball is not hardwired into brain circuits but requires learning and memory. The memory for motor tasks, termed procedural or implicit memory, requires modifications to circuits in motor cortex, the basal ganglia, and the cerebellum. Finally, this entire act is accessible to consciousness and may elicit conscious recall of past similar experiences, termed explicit memory, and emotions.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 74.
“In the somatosensory system, a light touch and a painful pin prick to the same area of skin are mediated by different sensory receptors in the skin that connect to distinct pathways in the brain.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 74.
“However, the thalamus is not merely a relay. It acts as a gatekeeper for information to the cerebral cortex, preventing or enhancing the passage of specific information depending on the behavioral state of the organism….
“The thalamus is a good example of a brain region made up of several well-defined nuclei. As many as 50 thalamic nuclei have been identified.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 82.
“… the amount of surface area of cortex devoted to each body part is not proportional to its mass. Instead, it is proportional to the fineness of discrimination in the body, which in turn is related to the density of innervation of sensory fibers. Thus, the area of cortex devoted to the fingers is larger than that for the arms. Likewise, the representation of the lips and tongue occupies more cortical surface than that of the remainder of the face.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 84.
“The cerebral cortex is organized functionally into columns of cells that extend from the white matter to the surface of the cortex…. Each column is about one-third of a millimeter in diameter. The cells in each column form a computational module with a highly specialized function. Neurons within a column tend to have very similar response properties, presumably because they form a local processing network. The larger the area of cortex dedicated to a function, the greater the number of computational columns that are dedicated to that function.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 88.
“Beyond the dedication of the cortical column, a second major insight from the early electrophysiological studies was that the somatosensory cortex contains not one but several somatotopic maps of the body surface. The primary somatosensory cortex (anterior parietal cortex) has four complete maps of the skin….” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 88.
“The cortical areas involved in the early stages of sensory processing are concerned primarily with a single sensory modality. Such regions are called primary sensory or unimodal (sensory) association areas. Information from the unimodal association areas converges on multimodal association areas of the cortex concerned with combining sensory modalities.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [David G. Amaral, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 88.
“Studying such neural representations [of sensory information] and their relationship to external sensory cues, known collectively as neural coding, is a major area of neuroscience research. The process through which features of a stimulus are represented by neural activity is called encoding….
“Other brain areas, such as those that lead to decisions or generate motor actions, must correctly interpret the meaning of action potential sequences that they receive from sensory areas in order to respond appropriately. The process by which information is extracted from neural activity is called decoding.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 98, 99.
“O’Keefe discovered that individual cells in the rat hippocampus, termed place cells, fire only when the animal traverses a particular area of the environment, termed the cell’s place field. Subsequent research uncovered place cell-like activity in the hippocampus of several other mammalian species, including bats, monkeys, and humans. Distinct sets of place cells are activated by distinct locations in a given environment. Consequently, although individual place cells represent relatively small spatial areas, the full diverse population of place cells in the hippocampus tiles the entire environment, and any given location is encoded by a unique ensemble of cells.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 99-100.
“Critically, while single place cells encode only specific parts of the environment and are prone to occasional noisy firing outside of their place fields, entire populations of place cells provide more complete spatial coverage and the reliability of redundant place coding… In particular, it is possible to decode the activity of populations of place cells and estimate an animal’s location within an environment. This is accomplished by determining each cell’s spatial selectivity and using this selectivity as a template to decode ongoing activity. In practice, this decoding is often performed by weighting each cell’s contribution to the final estimate of the animal’s position by a factor proportional to that cell’s spatial coding reliability.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 100-101.
“Normally, excitatory connections lead to increased neural firing and inhibitory connections lead to decreased neural firing. Many neural circuits receive strong excitatory drive from hundreds or thousands of synapses. If not checked by inhibition, this synaptic excitation would lead to unstable neural activity. A near balance of excitation and inhibition is a common feature of neural circuits that may enhance their computational capacity.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 102.
“Moreover, the arrangement of the receptive fields in each visual brain area is topographically matched to the layout of the image of the external world on the retina, that is, the cortex forms a map of the visual field.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 104.
“Cerebellar granule cells provide an extreme example of divergent feedforward connectivity, with the information carried by approximately 200 million input fibers mixed and expanded onto the 50 billion granule cells….
“This analysis suggests that the role of the cerebellar granule cells is to combine a large number of input channels in many possible ways. Such a representation clearly would be useful for making inferences and generating actions that depend on the co-occurrence of combinations of stimuli and actions….
“In contrast to the highly divergent connectivity at the inputs to granule cells, connections between granule cells and Purkinje cells provide an extreme example of convergence. A single Purkinje cell receives input from over a hundred thousand granule cells.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 105.
“In 1949, Donald Hebb proposed that synapses should strengthen when a given presynaptic input to a neuron cooperates with a sufficient number of coactive inputs to cause that neuron to fire an action potential…. By itself, Hebbian plasticity would keep making synapses stronger and stronger, so some other form of plasticity must exist to prevent this from happening. Such compensatory forms of plasticity are called homeostatic, and experiments have revealed these forms of plasticity as well.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Larry F. Abbott, Attila Losonczy, Nathaniel B. Sawtell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 108.
“Neurons use four major classes of channels for signaling: (1) the passive electrical properties of neurons that determine the time course of synaptic potentials, their spread along dendrites, and the threshold for firing an action potential; (2) sensory receptor channels respond to certain sensory stimuli to generate local receptor potentials; (3) ligand-gated channels open in response to neurotransmitters, generating local synaptic potentials; and (4) voltage-gated channels produce the currents that generate self-propagating actions potentials.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 132.
“Nonetheless, glia in the vertebrate nervous system can be divided into two major classes: macroglia and microglia…. In the human brain, about 90% of all glial cells are macroglia. Of these, approximately half are myelin-producing cells (oligodendrocytes and Schwann cells) and half are astrocytes…. Astrocytes owe their name to their irregular, roughly star-shaped cell bodies and large numbers of processes; they support neurons and modulate neuronal signaling in several ways. Microglia are the brain’s resident immune cells and phagocytes, but also have homeostatic functions in the healthy brain.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Beth Stevens, Franck Polleux & Ben A. Barres, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 134.
“Astrocytes are found in all areas of the brain; indeed, they constitute nearly half the number of brain cells. They play important roles in nourishing neurons and in regulating the concentrations of ions and neurotransmitters in the extracellular space….
“Astrocytes have large numbers of thin processes that enfold all the blood vessels of the brain and ensheathe synapses or groups of synapses. By their intimate physical association with synapses, often closer than 1 μm, astrocytes are positioned to regulate extracellular concentrations of ions, neurotransmitters, and other molecules. In fact, astrocytes express many of the same voltage-gated ion channels and neurotransmitter receptors that neurons do and are thus well equipped to receive and transmit signals that could affect neuronal excitability and synaptic function.
“How do astrocytes regulate axonal conduction and synaptic activity? The first recognized physiological role was that of K+ buffering. When neurons fire action potentials, they release K+ ions into the extracellular space. Because astrocytes have high concentrations of K+ channels in their membranes, they can act as spatial buffers: They take up K+ at sites of neuronal activity, mainly synapses, and release it at distant contacts with blood vessels….
“Astrocytes also regulate neurotransmitter concentrations in the brain. For example, high-affinity transporters located in the astroctyte’s plasma membrane rapidly clear the neurotransmitter glutamate from the synaptic cleft. Once within the glial cell, glutamate is converted to glutamine by the enzyme glutamine synthetase. Glutamine is then transferred to neurons, where it serves as an immediate precursor of glutamate…. Astrocytes also degrade dopamine, norepinephrine, epinephrine and serotonin….
“The processes of one astrocyte connect to those of neighboring astroctytes through intercellular aqueous channels called gap junctions, allowing transfer of ions and small molecules between many cells. An increase in free Ca2+ within one astrocyte increases Ca2+ concentrations in adjacent astroctytes. This spread of Ca2+ through the astrocyte network occurs over hundreds micrometers….
“Astrocytes also are important for the development of synapses. Their appearance at synapses in the postnatal brain coincides with periods of synaptogenesis and synapse maturation. Astrocytes prepare the surface of the neuron for synapse formation and stabilize newly formed synapses.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Beth Stevens, Franck Polleux & Ben A. Barres, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 154, 159.
“The function of neurons and glia is tightly regulated by the extracellular environment of the CNS. Interstitial fluid (ISF) fills spaces between neurons and glia in the parenchyma. Cerebrospinal fluid (CSF) bathes the brain’s ventricles, the subarachnoid space of the brain and spinal cord, and the major cisterns of the CNS. The ISF and CSF deliver nutrients to cells in the CNS, maintain ion homeostasis, and serve as a removal system for metabolic waste products.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Beth Stevens, Franck Polleux & Ben A. Barres, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 160.
“Up to 100 million ions can pass through a single channel each second.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Bruce P. Bean, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 166.
“As a result [of conformational changes of each ion pump per movement of ion or group of ions], the rate of ion flow through pumps is 100 to 100,000 times slower than through channels.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Bruce P. Bean, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 166.
“Two types of ion channels–resting and gated–have distinctive roles in neuronal signaling. Resting channels are primarily important in maintaining the resting membrane potential, the electrical potential across the membrane in the absence of signaling. Some types of resting channels are constitutively open and are not gated by changes in membrane voltage; other types are gated by changes in voltage but are also open at the negative resting potential of neurons. Most voltage-gated channels, in contrast, are closed when the membrane is at rest and require membrane depolarization to open.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 190.
“A reduction or reversal of charge separation, leading to a less negative membrane potential, is called depolarization….
“However, when depolarization approaches a critical level, or threshold, the cell responds actively with the opening of voltage-gated ion channels, which produces an all-or-none action potential.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 191.
“Of the four most abundant ions found on either side of the cell membrane, Na+ and Cl- are concentrated outside the cell and K+ and A- (organic anions, primarily amino acids and proteins) inside.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 193.
“However, most resting channels in the membrane are permeable only to K+.
“Because K+ ions are present at a high concentration inside the cell, they tend to diffuse across the membrane from the inside to the outside of the cell down their chemical concentration gradient. As a result, the outside of the membrane accumulates a net positive charge (caused by the slight excess of K+) and the inside a net negative charge (because of the deficit of K+ and the resulting slight excess of anions).” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 193.
“Unlike glial cells, nerve cells at rest are permeable to Na+ and Cl- ions in addition to K+ ions. Of the abundant ion species in nerve cells, only the large organic anions (A-) are unable to permeate the cell membrane.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 194.
“Dissipation of ionic gradients is prevented by the sodium-potassium pump (Na+-K+ pump), which moves Na+ and K+ against their electrochemical gradients: It extrudes Na+ from the cell while taking in K+…. There is a continuous passive influx of Na+ and efflux of K+ through resting channels that is exactly counterbalanced by the Na+-K+ pump….
“Second, ion transport is much faster in channels: Ions typically flow through channels at a rate of 107 to 108 per second, whereas pumps operate at speeds more than 10,000 times slower.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 195.
“It [the membrane length constant] is a measure of the efficiency of electrotonic conduction–the passive spread of voltage changes along the neuron….
The efficiency of electrotonic conduction has two important effects on neuronal function. First, it influences spatial summation, the process by which synaptic potentials generated in different regions of the neuron are added together at the trigger zone of the axon. Second, electrotonic conduction is a factor in the propagation of the action potential. Once the membrane at any point along an axon has been depolarized beyond threshold, an action potential is generated in that region. This local depolarization spreads passively down the axon, causing successive adjacent regions of the membrane to reach the threshold for generating an action potential. Thus, the depolarization spreads along the length of the axon by local current driven by the difference in potential between the active and resting regions of the axon membrane. In axons with longer length constants, local current spreads a greater distance down the axon, and therefore, the action potential propagates more rapidly.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 205-6.
“For pathways in which rapid signaling is particularly important, conduction of the action potential is enhanced by myelination of the axon, an increase in axon diameter, or both. Conduction velocities can vary between or within axons in ways that optimize the timing of neuronal signals within a neuronal circuit.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [John D. Koester & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 209.
“Action potentials have four properties important for neuronal signaling. First, they can be initiated only when the cell membrane voltage reaches a threshold…. Second, the action potential is an all-or-none event. The size and shape of action potential initiated by a large depolarizing current is the same as that of an action potential evoked by a current that just surpasses the threshold. Third, the action potential is conducted without decrement. It has a self-regenerative feature that keeps the amplitude constant, even when it is conducted over great distances. Fourth, the action potential is followed by a refractory period. For a brief time after an action potential is generated, the neuron’s ability to fire a second action potential is suppressed. The refractory period limits the frequency at which a nerve can fire action potentials, and thus limits the information-carrying capacity of the axon.
“These four properties of the action potential–initiation threshold, all-or-none amplitude, conduction without decrement, and refractory period–are unusual for biological processes, which typically respond in a graded fashion to changes in the environment.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 211-2.
“However, we now know that the squid axon is unusually simple in expressing only two types of voltage-gated ion channels. In contrast, the genomes of both vertebrates and invertebrates include large families of voltage-gated Na+, K+, and Ca2+ channels encoded by sub-families of related genes that are widely expressed in different kinds of nerve and muscle cells.
“A neuron in the mammalian brain typically expresses a dozen or more different types of voltage-gated ion channels. The voltage dependence and kinetic properties of various Na+, Ca2+, and K+ channels can differ widely. Moreover, the distribution of these channels varies between different types of neurons and even between different regions of a single neuron. The great variety of voltage-gated channels in the membranes of most neurons enables a neuron to fire action potentials with a much greater range of frequencies and patterns than is possible in the squid axon, and thus allows much more complex information-processing abilities and modulatory control than is possible with just two types of channels.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 224-5.
“In a typical neuron, the opening and closing of certain ion channels can be modulated by various cytoplasmic factors, thus affording the neuron’s excitability properties greater flexibility….
“Intracellular Ca2+ concentration is one important factor that modulates ion channel activity….
“Intracellular Ca2+ concentration controls the gating of a number of channels. Several kinds of channels are activated by increases in intracellular Ca2+.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 228-9.
“Through the expression of a distinct complement of ion channels, the electrical properties of different neuronal types have evolved to match the dynamic demands of information processing. Thus, the function of a neuron is defined not only by its synaptic inputs and outputs but also by its intrinsic excitability properties.
“Different types of neurons in the mammalian nervous system generate action potentials that have different shapes and fire in different characteristic patterns, reflecting different expression of voltage-gated channels. For example, cerebellaer Purkinje neurons and GABAergic cortical interneurons are associated with high levels of expression of Kv3 channels. The rapid activation of these channels produces narrow action potentials. In dopaminergic and other monoaminergic neurons, there is a high level of expression of voltage-activated Ca2+ channels that open during the falling phase of the action potential. The inward Ca2+ current from these channels slows repolarization, resulting in broader action potentials.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 229.
“The pattern of action potential firing evoked by depolarization varies widely between neurons…. In the mammalian cerebral cortex, glutamaterigic pyramidal neurons typically fire rapidly at the beginning of the current pulse followed by progressive slowing of firing, a pattern known as adaptation. In contrast, many GABAergic interneurons fire with very little change in frequency. Other neurons have more complex firing patterns.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 229.
“A surprisingly large number of neurons in the mammalian brain fire spontaneously in the absence of any synaptic input. When such activity is regular and rhythmic, it is often referred to as ‘pacemaking’….
“Pacemaking in these cells [from the hypothalamus, which helps control the circadian rhythm and the sleep-wake cycle] is driven in part by sub-threshold persistent Na+ current, a small voltage-dependent current which flows through Na+ channels at voltages as negative as -70 mV. This current can slowly depolarize the neuron to the point where a fast action potential fires.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 231.
“Different regions of a neuron have different types of ion channels that support the specialized functions of each region. The axon, for example, functions as a relatively simple relay line. In contrast, the input, integrative, and output regions of a neuron typically perform more complex processing of the information they receive before passing it along.
“The trigger zone at the axon initial segment has the lowest threshold for action potential generation, in part because it has an exceptionally high density of voltage-gated Na+ channels. In addition, it typically has voltage-gated ion channels that are sensitive to relatively small deviations from the resting potential.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 231.
“Dendrites in many types of neurons have voltage-gated ion channels, including Ca2+, K+, HCN, and Na+ channels. When activated, these channels help shape the amplitude, time course, and propagation of the synaptic potentials to the cell body. In some neurons, the density of voltage-gated channels in the dendrites is sufficient to support local action potentials, typically with relatively high threshold voltages.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 231.
“Most neurons express multiple kinds of voltage-gated Na+, Ca2+, K+, HCN, and Cl- channels, with especially large diversity in the properties of K+ channels.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bruce P. Bean & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 233.
“… synapses are categorized into two major groups: electrical and chemical. At electrical synapses, the presynaptic terminal and the postsynaptic cell are in very close apposition at regions termed gap junctions. The current generated by an action potential in the presynaptic neuron directly enters the postsynaptic cell through specialized bridging channels called gap junction channels, which physically connect the cytoplasm of the presynaptic and postsynaptic cells. At chemical synapses, a cleft separates the two cells, and the cells do not communicate through bridging channels. Rather, an action potential in the presynaptic cell leads to the release of a chemical transmitter from the nerve terminal. The transmitter diffuses across the synaptic cleft and binds to receptor molecules on the postsynaptic membrane, which regulates the opening and closing of ion channels in the postsynaptic neuron that can either excite or inhibit the firing of an action potential.
“Receptors for transmitters can be classified into two major groups depending on how they control ion channels in the postsynaptic cell. One type, the ionotropic receptor, is an ion channel that opens when the transmitter binds. The second type, the metabotropic receptor, acts indirectly on ion channels by activating a bio-chemical second-messenger cascade within the postsynaptic cell. Both types of receptors can result in excitation or inhibition.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 239.
“Electrical synapses are employed primarily to send rapid and stereotyped depolarizing signals. In contrast, chemical synapses are capable of more variable signaling and thus can produce more complex interactions. They can produce either excitatory or inhibitory actions in postsynaptic cells and initiate changes in the postsynaptic cell that last from milliseconds to hours.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum & Gerald D. Fischbach, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 241.
“Another feature of electrical transmission is that the change in potential of the postsynaptic cell is directly related to the size and shape of the change in potential of the presynaptic cell. Even when a weak subthreshold depolarizing current is injected into the presynaptic neuron, some current enters the postsynaptic cell and depolarizes it….
“Most electrical synapses can transmit both depolarizing and hyperpolarizing currents.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum & Gerald D. Fischbach, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 244.
“At an electrical synapse, the pre- and postsynaptic components are apposed at the gap junction, where the separation between the two neurons (4nm) is much less than the normal nonsynaptic space between neurons (20nm). This narrow gap is bridged by gap-junction channels, specialized protein structures that conduct ionic current directly from the presynaptic to the postsynaptic cell.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum & Gerald D. Fischbach, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 244.
“Electrical transmision is also useful for orchestrating the actions of groups of neurons. Because current crosses the membranes of all electrically coupled cells at the same time, several small cells can act together as one large cell Moreover, because of the electrical coupling between the cells, the effective resistance of the network is smaller than the resistance of an individual cell. Thus, from Ohm’s law, the synaptic current required to fire electrically coupled cells is larger than that necessary to fire an individual cell. That is, electrically coupled cells have a higher firing threshold. Once this high threshold is surpassed, however, electrically coupled cells fire synchronously because voltage-activated Na+ currents generated in one cell are very rapidly conducted to other cells.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum & Gerald D. Fischbach, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 247.
“Although chemical transmission lacks the immediacy of electrical synapses, it has the important property of amplification. Just one synaptic vesicle releases several thousand molecules of transmitter that together can open thousands of ion channels in the target cell. In this way, a small presynaptic nerve terminal, which generates only a weak electrical current, can depolarize a large postsynaptic cell.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum & Gerald D. Fischbach, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 249.
“The threshold for generating an action potential in the muscle is particularly low at the end-plate, owing to a high density of voltage-gated Na+ channels in the bottom of the junctional folds. The combination of a very large EPSP [excitatory postsynaptic potential] and low threshold results in a high safety factor for triggering an action potential in the muscle fiber. In contrast, in the central nervous system, most presynaptic neurons produce postsynaptic potentials less than 1 mV in amplitude, such that inputs from many presynaptic neurons are needed to generate an action potential in most central neurons.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum & Gerald D. Fischbach, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 257.
“Nevertheless, synaptic transmission between central neurons is more complex [than for motor neurons] for several reasons.
“First, although most muscle fibers are typically innervated by only one motor neuron, a central nerve cell (such as pyramidal neurons in the neocortex) receives connections from thousands of neurons. Second, muscle fibers receive only excitatory inputs, whereas central neurons receive both excitatory and inhibitory inputs. Third, all synaptic actions on muscle fibers are mediated by one neurotransmitter, acetylcholine (ACh), which activates only one type of receptor (the ionotropic nicotinic ACh receptor). A single central neuron, however, can respond to many different types of inputs, each mediated by a distinct transmitter that activates a specific type of receptor….
“Finally, the nerve-muscle synapse is a model of efficiency–every action potential in the motor neuron produces an action potential in the muscle fiber. In comparison, connections made by a presynaptic neuron onto a central neuron are only modestly effective–in many cases at least 50 to 100 excitatory neurons must fire together to produce a synaptic potential large enough to trigger an action potential in postsynaptic neurons.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 273, 274.
“… the effect of a synaptic potential–whether it is excitatory or inhibitory–is determined not by the type of transmitter released from the presynaptic neuron but by the type of ion channels in the postsynaptic cell activated by the transmitter. Although some transmitters can produce both EPSPs and IPSPs, by acting on distinct classes of ionotropic receptors at different synapses, most transmitters produce a single predominant type of synaptic response; that is, a transmitter is usually inhibitory or excitatory.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 274.
“Although dendrites are normally postsynaptic and axon terminals presynaptic, all four regions of the nerve cell–axon, presynaptic terminals, cell body, and dendrites–can be presynaptic or postsynaptic sites of chemical synapses. The most common types of contact… are axodendritic, axosomatic, and axo-axonic (by convention, the presynaptic element is identified first).” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 276.
“As a general rule, the proximity of a synapse to the axon initial segment is thought to determine its effectiveness. A given postsynaptic current generated at a site near the cell body will produce a greater change in membrane potential at the trigger zone of the axon initial segment, and therefore have a greater influence on action potential output than an equal current generated at more remote sites in the dendrites.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 276.
“In addition, the NMDA [N-methyl-D-aspartate] receptor is unique among ligand-gated channels thus far characterized because its opening depends on membrane voltage as well as transmitter binding….
“Thus, the NMDA receptor-channel conducts current maximally when two conditions are met: Glutamate is present, and the cell is depolarized. That is, the NMDA receptor acts as a molecular ‘coincidence detector,’ opening during the concurrent activation of the presynaptic and postsynaptic cells….
“At first glance, the function of these receptors is even more puzzling because their intrinsic channel is normally blocked by Mg2+ at the resting potential. However, the high permeability of the NMDA receptor-channels to Ca2+ endows them with the special ability to produce a marked rise in intracellular [Ca2+] that can activate various calcium-dependent signaling cascades, including several different protein kinases. Thus, NMDA receptor activation can translate electrical signals into biochemical ones.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 283, 284.
“The different biophysical properties of synaptic conductances can be understood as distinct mathematical operations carried out by the postsynaptic neuron. Thus, inhibitory inputs that hyperpolarize the cell perform a subtraction on the excitatory inputs, whereas the shunting effect [consequence of synaptic inhibition is called the short-circuiting or shunting effect] of the conductance increase performs a division. Adding excitatory inputs (or removing nonshunting inhibitory inputs) results in summation. Finally, the combination of an excitatory input with the removal of an inhibitory shunt produces a multiplication. These arithmetic effects, however, are often mixed and can vary with time as the membrane potential of neurons constantly varies….” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 290.
“Each neuron in the central nervous system is constantly bombarded by an array of synaptic inputs from many other neurons. A single motor neuron, for example, may be the target of as many as 10,000 different presynaptic terminals. Some are excitatory, others inhibitory; some are strong, others weak. Some inputs contact the motor cell on the tips of its apical dendrites, others on proximal dendrites, some on the dendritic shaft, others on the soma. The different inputs can reinforce or cancel one another.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 291.
“The net effect of the inputs at any individual excitatory or inhibitory synapse will therefore depend on several factors: the location, size, and shape of the synapse; the proximity and relative strength of other synergistic or antagonistic synapses; and the resting potential of the cell. And, in addition, all of this is exquisitely dependent on the timing of the excitatory and inhibitory input. Inputs are coordinated in the postsynaptic neuron by a process called neuronal integration. This cellular process reflects the task that confronts the nervous system as a whole. A cell at any given moment has two options: to fire or not to fire an action potential.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 291.
“At the initial segment, the depolarization increment required to reach the threshold for an action potential (-55 mV) is only 10 mV from the resting level of -65 mV. In contrast, the membrane of the cell body must be depolarized by 30 mV before reaching its threshold (-35mV). Therefore synaptic excitation first discharges the region of membrane at the initial segment, also called the trigger zone.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 292.
“… the mammalian central nervous system has a large variety of GABAergic inhibitory interneurons that differ in developmental origin, molecular composition, morphology, and connectivity…. The different types of GABAergic interneurons form extensive synaptic connections with their neighboring excitatory and inhibitory neurons. Thus, even though only 20% of all neurons are inhibitory, the overall levels of inhibition and excitation tend to be nearly balanced in most brain regions. This results in the tuning of neural circuits to respond to only the most salient excitatory information.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 294.
“Indeed, we now know that the dendrites of most neurons contain voltage-gated Na+, K+, and Ca2+ channels in addition to ligand-gated channels and resting channels. In fact, the rich diversity of dendritic conductances suggests that central neurons rely on a sophisticated repertory of electrophysiological properties to integrate synaptic inputs.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 295.
“When a cell has several dendritic trigger zones, each one sums the local excitation and inhibition produced by nearby synaptic inputs; if the net input is above threshold, a dendritic action potential may be generated, usually by voltage-gated Na+ or Ca2+ channels. Nevertheless, the number of voltage-gated Na+ or Ca2+ channels in the dendrites is usually not sufficient to support all-or-none regenerative propagation of an action potential to the cell body. Rather, action potentials generated in the dendrites are usually local events that spread electrotonically to the cell body and axon initial segment, producing a subthreshold somatic depolarization that is integrated with other input signals in the cell.
“Dendritic voltage-gated channels also permit action potentials generated at the axon initial segment to propagate backward into the dendritic tree. These backpropagating action potentials are largely generated by dendritic voltage-gated Na+ channels.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 295-6.
“Because the thin spine neck [of a dendrite] restricts, at least partly, the rise in Ca2+ and, thus, long-term plasticity to the spine that receives the synaptic input, spines also ensure that activity-dependent changes in synaptic function, and thus memory storage, are restricted to the synapses that are activated. The ability of spines to implement such synapse-specific local learning rules may be of fundamental importance for the ability of neural networks to store meaningful information.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Rafael Yuste & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 297.
“Metabotropic receptors modulate behaviors; they modify reflex strength, activate motor patterns, focus attention, set emotional states, and contribute to long-lasting changes in neural circuits that underlie learning and memory. Metabotropic receptors are responsible for many of the actions of transmitters, hormones, and growth factors.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, David E. Clapham & Eve Marder, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 302.
“The number of substances that act as second messengers in synaptic transmission is much fewer than the number of transmitters. More than 100 substances serve as transmitters; each can activate several types of receptors present in different cells. The few second messengers that have been well characterized fall into two categories, intracellular and transcellular. Intracellular messengers are molecules whose actions are confined to the cell in which they are produced.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, David E. Clapham & Eve Marder, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 305.
“Compared with other organs of the body, the brain contains an exceptionally large variety of G proteins. Even so, because of the limited number of classes of G proteins compared to the much larger number of receptors, one type of G protein can often be activated by different classes of receptors.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, David E. Clapham & Eve Marder, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 305.
“Ionotropic receptors are channels that function as simple on-off switches; their main job is either to excite a neuron to bring it closer to the threshold for firing or inhibit the neuron to decrease its likelihood to fire. Because these channels are normally confined to the postsynaptic region of the membrane, the action of ionotropic receptors is local. Metabotropic receptors, on the other hand, because they activate diffusible second messengers, can act on channels some distance from the receptor. Moreover, metabotropic receptors regulate a variety of channel types, including resting channels, ligand-gated channels, and voltage-gated channels that generate action potentials, underlie pacemaker potentials, and provide Ca2+ influx for neurotransmitter release.
“Finally, whereas transmitter binding leads to an increase in the opening of ionotropic receptor-channels, the activation of metabotropic receptors can lead to an increase or decrease in channel opening.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, David E. Clapham & Eve Marder, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 312.
“Modulatory projection neurons or neurohormones can coordinately influence the properties of large numbers of neurons to change the state of a neural circuit or of the entire animal. For example, modulators released from a relatively small number of neurons are important in the control of the transitions between sleep and wakefulness.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, David E. Clapham & Eve Marder, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 319.
“… transmitter is released in discrete amounts they called quanta. Each quantum of transmitter produces a postsynaptic potential of fixed size, called the quantal synaptic potential. The total postsynaptic potential is made up of a large number of quantal potentials. EPSPs seem smoothly graded in amplitude only because each quantal potential is small relative to the total potential….
“Quantal transmission has been demonstrated at all chemical synapses so far examined. Nevertheless, the efficacy of transmitter release from a single presynaptic cell onto a single postsynaptic cell varies widely in the nervous system and depends on several factors: (1) the number of individual synapses between a pair of presynaptic and postsynaptic cells (that is, the number of presynaptic boutons that contact the postsynaptic cell); (2) the number of active zones in an individual synaptic terminal; and (3) the probability that a presynaptic action potential will trigger release of one or more quanta of transmitter at an active zone.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, Thomas C. Suedhof & Richard W. Tsien, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 332, 335.
“When firing at high frequency, a typical presynaptic neuron is able to maintain a high rate of transmitter release. This can result in the exocytosis of a large number of vesicles over time, more than the number morphologically evident within the presynaptic terminal. To prevent the supply of vesicles from being rapidly depleted during fast synaptic transmission, used vesicles are rapidly retrieved and recycled.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, Thomas C. Suedhof & Richard W. Tsien, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 341.
“Synaptic strength can be modified presynaptically, by altering the release of neurotransmitter, postsynaptically, by modulating the response to transmitter, or both.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Steven A. Siegelbaum, Thomas C. Suedhof & Richard W. Tsien, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 350.
“… all sensory systems perform two fundamental functions: detection and discrimination.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 385.
“Today neurobiologists recognize intuition as inferences derived from previous experience and thus the result of cognitive as well as sensory processes.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 385.
“Our senses include the classic five senses plus a variety of modalities not recognized by the ancients but essential to bodily function: the somatic sensations of pain, itch, temperature, and proprioception (posture and movement of our own body; visceral sensations (both conscious and unconscious) necessary for homeostasis; and the vestibular senses of balance (the position of the body in the gravitational field) and head movement.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 385-6.
“The richness of sensory experience begins with millions of highly specific sensory receptors. Sensory receptors are found in specialized epithelial structures called sense organs, principally the eye, ear, nose, tongue, and skin. Each receptor responds to a specific kind of energy at specific locations in the sense organ and sometimes only to energy with a particular temporal or spatial pattern. The receptor transforms the stimulus energy into electrical energy; thus, all sensory systems use a common signaling mechanism. The amplitude and duration of the electrical signal produced by the receptor, termed the receptor potential, are related to the intensity and time course of stimulation of the receptor. The process by which a specific stimulus energy is converted into an electrical signal is called stimulus transduction.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 391.
“Most receptors are optimally selective for a single type of stimulus energy, a property termed receptor specificity.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 391.
“… blue cone cells in the retina are most sensitive to light of 430 to 440 nm, green cone cells respond best to 530 to 540 nm, and red cone cells respond most vigorously to light of 560 to 570 nm. Responses of the three cone cells to other wavelengths of light are weaker as the incident wavelengths differ from these optimal ranges.
“Each rod and cone cell thus responds to a wide spectrum of colors. The graded sensitivity of photoreceptors encodes specific wavelengths by the amplitude of the evoked receptor potential. However, this amplitude also depends upon the intensity of brightness of the light, so a green cone responds similarly to bright orange or dimmer green light. How are these distinguished? Stronger stimuli activate more photoreceptors than do weaker ones, and the resulting population code of multiple receptors, combined with receptors of different wavelength preferences, distinguishes intensity from hue.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 393.
“The analog signal of stimulus magnitude in the receptor potential is transformed into a digital pulse code in which the frequency of action potentials is proportional to the intensity of the stimulus. This is spike train encoding.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 395.
“… the intensity of a stimulus is represented in the brain by all active neurons in the receptor population. This type of population code depends on the fact that individual receptors in a sensory system differ in their sensory thresholds or in their affinity for particular molecules.
“Most sensory systems have low- and high-threshold receptors. When stimulus intensity changes from weak to strong, low-threshold receptors are first recruited, followed by high-threshold receptors.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 395-6.
“Distributed patterning of firing in neural ensembles allows the use of vector algebra to quantify how stimulus properties are distributed across populations of active neurons. For example, although humans possess only three types of cone cells in the retina, we can clearly identify colors across the entire spectrum of visible light.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 396.
“Humans can report changes in sensory experience that correspond to alternations within a few milliseconds in the firing patterns of sensory neurons.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 396.
“Sensory systems detect contrasts, changes in the temporal and spatial patterns of stimulation. If a stimulus persists unchanged for several minutes without a change in position or amplitude, the neural response and corresponding sensation diminishes, a condition called receptor adaptation.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 396.
“Receptors that respond to prolonged and constant stimulation–known as slowly adapting receptors–encode stimulus duration by generating action potentials throughout the period of stimulation. In contrast, rapidly adapting receptors respond only at the beginning and end of a stimulus; they cease firing in response to constant amplitude stimulation and are active only when the stimulus intensity increases or decreases.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 396.
“The skin area, location in the body, retinal area, or tonal domain in which stimuli can activate a sensory neuron is called its receptive field. The region from which a sensation is perceived to arise is called the neuron’s perceptive field. The two usually coincide.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 397.
“That is, each sensory modality is represented by an ensemble of central neurons connected to a specific class of receptors. Such ensembles are referred to as sensory systems, and include the somatosensory, visual, auditory, vestibular, olfactory, and gustatory systems.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 398.
“They [Mortimer Mishkin & Leslie Ungerleider] discovered that sensory information arriving in the primary visual areas is divided in two parallel pathways.
“One pathway carries information needed for classification of images, while the other conveys information needed for immediate action.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 402.
“Ventral and dorsal streams of sensory information also contribute to two major forms of memory: semantic (also called explicit) memory, which we use to talk about objects or persons, and procedural (also called implicit) memory, which we use to interact with objects, persons, or the immediate environment.
“Ventral stream information generates nouns that we use to identify and classify persons, places, and objects, such as spheres, bricks, and cars. Dorsal stream information motivates verbs enabling the actions performed based on sensory inputs and subjective intentions, such as grasping, lifting, or driving.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 403.
“What we perceive is always some combination of the sensory stimulus itself and the memories it both evokes and builds upon… Their [W. James and John Stuart Mill] idea was that sensory and perceptual experiences that occur together or in close succession, particularly those that do so repeatedly, become associated so that thereafter the one triggers the other. Association is a powerful mechanism, and much of learning consists of forging associations through repetition.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 404.
“How can a network of neurons ‘recognize’ a specific pattern of inputs from a population of presynaptic neurons? One potential mechanism is called template matching. Each neuron in the target population has a pattern of excitatory and inhibitory presynaptic connections. If the pattern of arriving action potentials fits the postsynaptic neuron’s pattern of synaptic connections even approximately–activating many of its excitatory synapses but mostly avoiding activating its inhibitory synapses–the target neuron fires.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 404.
“The neural activity in a set of thousands or millions of neurons should be thought of as coordinated activity that conveys a ‘neural image’ of specific properties of the external world.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Esther P. Gardner & Daniel Gardner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 406.
“The existence of parallel pathways in the visual system raises one of the central questions of cognition, the binding problem: How are different types of information carried by discrete pathways brought together into a coherent visual image?” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 496.
“The central idea of the Gestalt psychologists is that what we see about a stimulus–the perceptual interpretation we make of any visual object–depends not just on the properties of the stimulus but also on its context, on other features in the visual field.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 497.
“The principle of good continuation is an important basis for linking line elements into unified shapes.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 497.
“Statistical studies of natural scenes show that object boundaries are likely to contain visual elements that lie in close proximity, are continuous across intersections, or form smooth contours.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 497.
“The brain analyzes a visual scene at three levels: low, intermediate, and high. At the lowest level, … visual attributes such as local contrast, orientation, color, and movement are discriminated. The intermediate level involves analysis of the layout of scenes and of surface properties, parsing the visual image into surfaces and global contours, and distinguishing foreground from background. The highest level involves object recognition.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 497.
“The pixel-like bits of visual input falling on individual photoreceptors–rods and cones–are analyzed by retinal circuits to extract some 20 local features, such as the local contrasts of dark versus light, red versus green, and blue versus yellow. These features are computed by different populations of specialized neural circuits forming independent processing modules that separately cover the visual field. Thus, each point in the visual field is processed in multiple channels that extract distinct aspects of the visual input simultaneously and in parallel.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 499.
“Simple attributes of the visual environment are analyzed (low-level processing), and these low-level features are then used to parse the visual scene (intermediate-level processing): Local visual features are assembled into surfaces, objects are segregated from background (surface segmentation), local orientation is integrated into global contours (contour integration), and surface shape is identified from shading and kinematic cues. Finally, surfaces and contours are used to identify the object (high-level processing).” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 500.
“The preservation of the spatial arrangement of inputs from the retina is called retinotopy, and a neural map of the visual field is described as retinotopic or having a retinotopic frame of reference.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 501.
“All connections between cortical areas are reciprocal–each area sends information back to the areas from which it receives input. These feedback connections provide information about cognitive functions including spatial attention, stimulus expectation, and emotional content, to earlier levels of visual processing.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 505.
“The on-enter cells fire when a spot of light is turned on within a circular central region. Off-center cells fire when a spot of light in the center of their receptive field is turned off. The surrounding annular region has the opposite sign.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 506.
“The size on the retina of a receptive field varies both according to the field’s eccentricity–its position relative to the fovea, the central part of the retina where visual acuity is highest–and the position of neurons along the visual pathway. Receptive fields with the same eccentricity are relatively small at early levels in visual processing and become progressively larger at later levels.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 506.
“The characterization of parallel pathways [of groups of neurons in columns] is only an approximation, as there is considerable interaction between the pathways. This interaction is the means by which various visual features–color, form, depth, and movement–are linked, leading to a unified visual percept. One way this linkage, or binding, may be accomplished is through cells that are tuned to more than one attribute.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 513.
“A neuron’s response peaks at a particular value and tails off on either side of that value, forming a bell-shaped tuning curve with a particular bandwidth. Thus, a neuron with a peak response at 650 nm and a bandwidth of 100 nm might give identical responses at 600 and 700 nm.
“To be able to determine the wavelength from neuronal signals, one needs at least two neurons representing filters centered at different wavelengths. Each neuron can be thought of as a labeled line in which activity signals a stimulus with a given value. When more than one such neuron fires, the convergent signals at the postsynaptic relay represent a stimulus with a wavelength that is the weighted average of the values represented by all the inputs.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 517.
“A single visual percept is the product of the activity of a number of neurons operating in a specific combinatorial and interactive fashion called a population code. Population coding has been modeled in various ways. The most prevalent model is called vector averaging.
“We can illustrate population coding with a population of orientation-selective cells, each of which responds optimally to a line with a specific orientation. Each neuron responds not just to the preferred stimulus but rather to any line that falls within a range of orientations described by a Gaussian tuning curve with a particular bandwidth. A stimulus of a particular orientation most strongly activates cells with tuning curves centered at that orientation; cells with tuning curves centered away from but overlapping that orientation are excited less strongly.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 517.
“The nervous system does not, however, represent entire objects by the activity of single neurons. Instead, some cells represent parts of an object, and an ensemble of neurons represents an entire object. Each member of the ensemble may participate in different ensembles that are activated by different objects. This arrangement is known as a distributed code. Distributed codes can involve a few neurons or many. In any case, a distributed code requires complex connectivity between the cells representing a face and those representing the name and experiences associated with that person.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 518.
“The foregoing discussion assumes that neurons signal information by their firing rate and their line labels. An alternative hypothesis is that the timing of action potentials itself carries information, analogous to Morse code. The code might be read from the synchronous firing of different sets of neurons over time. At one instant, one group of cells might fire together followed by the synchronous firing of another group. Over a single train of action potentials, a single cell could participate in many such ensembles. Whether sensory information is represented this way and whether the nervous system carries more information than that represented by firing rate alone are not known.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert & Aniruddha Das, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 518.
“The retina’s output is conveyed to the brain by just one million optic nerve fibers, and yet almost half of the cerebral cortex is used to process these signals.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 521.
“Cones are much less sensitive to light [than rods]; they make no contribution to night vision but are solely responsible for vision in daylight.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 525.
“Because the optic nerve has only about 1% as many axons as there are receptor cells, the retinal circuit must edit the information in the photoreceptors before it is conveyed to the brain.
“This step constitutes low-level visual processing, the first stage in deriving visual percepts from the pattern of light falling on the retina.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 530.
“A typical ganglion cell is sensitive to light in a compact region of the retina near the cell body called the cell’s receptive field. Within that area, one can often distinguish a center region and surround region where light produces opposite responses in the cell. An ON cell, for example, fires faster when a bright spot is focused in the cell’s receptive field center but decreases its firing when the spot is focused on the surround. If light covers both the center and the surround, the response is much weaker than for center-only illumination. A bright spot on the center combined with a dark annulus covering the surround elicits very strong firing. For an OFF cell, these relationships are reversed; the cell is strongly excited by a dark spot and a bright annulus.
“The output produced by a population of retinal ganglion cells thus enhances regions of spatial contrast in the input, such as an edge between two areas of different intensity, and gives less emphasis to regions of homogeneous illumination.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 531.
“The outline of an object is particularly useful for inferring its shape and identity. Similarly, objects that move or change suddenly are more worthy of immediate attention than those that do not. Retinal processing thus extracts low-level features of the scene that are useful for guiding behavior and selectively transmits those to the brain. In fact, the rejection of features that are constant either in space or in time accounts for the spatiotemporal sensitivity of human perception.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 531.
“In total, more than 20 types of ganglion cells have been described. The population of each type covers the retina in a tiled fashion, such that any point on the retina lies within the receptive field center of at least one ganglion cell. One can envision that the signals from each population together send a distinct neural representation of the visual field to the brain. In this view, the optic nerve conveys 20 or more neural representations that differ in polarity (ON or OFF), spatial resolution (fine or coarse), temporal responsiveness (sustained or transient), spectral filtering, (broadband or dominated by red, green, or blue), and selectivity for other image features such as motion.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 531…536.
“For many ganglion cells, a step change in light intensity produces a transient response, an initial peak in firing that declines to a smaller steady rate. Part of this sensitivity originates in the negative-feedback circuits involving horizontal and amacrine cells….
“In both cases, the delayed-inhibition circuit favors rapidly changing inputs over slowly changing inputs. The effects of this filtering, which can be observed in visual perception, are most pronounced for large stimuli that drive the horizontal and amacrine cell networks most effectively. For example, a large spot can be seen easily when it flickers at a rate of 10 Hz but not at a low rate.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 537.
“Retinal circuits seem to go to great lengths to speed up their responses and emphasize temporal changes. One likely reason is that the very first cell in the retinal circuit, the photoreceptor, is exceptionally slow.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 537.
“The intensity of the light coming from an object depends on the intensity of the ambient illumination and the fraction of this light reflected by the object’s surface, called the reflectance. The range of intensities encountered in a day is enormous, with variation spanning 10 orders of magnitude, but most of this variation is useless for the purpose of guiding behavior.
“The illumination intensity varies by about nine orders of magnitude, mostly because our planet turns about its axis once a day, while the object reflectance varies much less, by about one order of magnitude in a typical scene. But this reflectance is the interesting quantity for vision, for it characterizes objects and distinguishes them from the background. In fact, our visual system is remarkably good at calculating surface reflectances independently of ambient illumination.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 540.
“In conclusion, light adaptation has two important roles. One is to discard information about the intensity of ambient light while retaining information about object reflectances. The other is to match the small dynamic range of firing in retinal ganglion cells to the large range of light intensities in the environment. These large gain changes must be accomplished with graded neuronal signals before action potentials are produced in optic nerve fibers, because the firing rates of these fibers can vary effectively over only two orders of magnitude. In fact, the crucial need for light adaptation may be why this neural circuitry resides in the eye and not in the brain at the other end of the optic nerve.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Markus Meister & Marc Tessier-Lavigne, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 543.
“We have seen … that the eye is not a mere camera, but instead contains sophisticated retinal circuitry that decomposes the retinal image into signals representing contrast and movement. These data are conveyed through the optic nerve to the primary visual cortex, which uses this information to analyze the shape of objects. It first identifies the boundaries of objects, represented by numerous short line segments, each with a specific orientation. The cortex then integrates this information into a representation of specific objects, a process referred to as contour integration.
“These two steps, local analysis of orientation and contour integration, exemplify two distinct stages of visual processing. Computation of local orientation is an example of low-level visual processing, which is concerned with identifying local elements of the light structure of the visual field. Contour integration is an example of intermediate-level visual processing, the first step in generating a representation of the unified visual field. At the earliest stages of analysis in the cerebral cortex, these two levels of processing are accomplished together.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 545.
“Intermediate-level visual processing thus involves assembling local elements of an image into a unified percept of objects and background. Although determining which elements belong together in a single object is a highly complex problem with an astronomical number of potential solutions, each relay in the visual circuitry of the brain has built-in logic that allows assumptions to be made about the likely spatial relationships between elements.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 545-6.
“Three features of visual processing help overcome ambiguity in the signals from the retina. First, the way in which a visual feature is perceived depends on everything that surrounds it. The perception of a point, line, or surface, for example, depends on the relationship between that feature and what else is present in the scene. That is, the response of a neuron in the visual cortex is context-dependent: It depends as much on the presence of contours and surfaces outside the cell’s receptive field as on the attributes within it. Second, the functional properties of neurons in the visual cortex can be altered by visual experience or perceptual learning. Finally, visual processing in the cortex is subject to the influence of cognitive functions, specifically attention, expectation, and ‘perceptual task’ (the active engagement in visual discrimination or detection). The interaction between these three factors–the context or entire set of signals representing a scene, experience-dependent changes in cortical circuitry, and expectation–is vital to the visual system’s analysis of complex scenes.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 546-7.
“Visual primitives include contrast, line orientation, brightness, color, movement, and depth.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 547.
“As we scan the visual environment, the boundaries of stationary objects move across the retina. In fact, visual perception requires eye movement. Visual cortex neurons do not respond to an image that is stabilized on the retina.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 549.
“To define the shape of the object as a whole, the visual system must integrate the information on local orientation and curvature into object contours. The way in which the visual system integrates contours reflects the geometrical relationships present in the natural world. As originally pointed out by Gestalt psychologists early in the 20th century, contours that are immediately recognizable tend to follow the rule of good continuation (curved lines maintain a constant radius of curvature and straight lines stay straight).” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 549.
“Depth is another key feature in determining the perceived shape of an object. An important cue for the perception of depth is the difference between the two eyes’ views of the world, which must be computed and reconciled by the brain.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 550.
“As we move about or as the ambient illumination changes, the retinal image of an object–its size, shape, and brightness–also changes. Yet under most conditions, we do not perceive the object itself to be changing. As we move from a brightly lit garden into a dimly lit room, the intensity of light reaching the retina may vary a thousandfold. Both in the room’s dim illumination and in the sun’s glare, we nevertheless see a white shirt as white and a red tie as red. Likewise, as a friend walks toward you, she is seen as coming closer; you do not perceive her to be growing larger even though the image on your retina does expand. Our ability to perceive an object’s size and color as constant illustrates again a fundamental principle of the visual system: It does not record images passively, like a camera, but instead uses transient and variable stimulation of the retina to construct representations of a stable, three-dimensional world.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 556.
“However, a small percentage of neurons do respond to the interiors of surfaces, signaling local brightness, texture, or color, and the responses of these neurons are influenced by context. The cell’s response changes as the brightness of surfaces outside a cell’s receptive field change, even when the brightness of the surface within the receptive field remains fixed.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 558.
“To identify an object, we must know the properties of its surface rather than those of the reflected light, which are constantly changing. Computation of an object’s color is therefore more complex than analyzing the spectrum of reflected light.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 558.
“A more useful distinction [in trying to define the receptive field by functional connections from other receptors] contrasts the response of a neuron to a simple stimulus, such as a short line segment, with its response to a stimulus with multiple components. Even in the primary visual cortex, neurons are highly nonlinear; their response to a complex stimulus cannot be predicted from their responses to a simple stimulus placed in different positions around the visual field. Their responses to local features are instead dependent on the global context within which the features are embedded. Contextual influences are pervasive in intermediate-level visual processing, including contour integration, scene segmentation, and the determination of object shape, object motion and surface properties.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 558.
“Horizontal connections exist in every area of the cerebral cortex, but their function varies from one area to the next depending on the functional architecture of each area.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 558.
“The plasticity of cortical maps and connections did not evolve as a response to lesions but as a neural mechanism for improving our perceptual skills. Many of the attributes analyzed by the visual cortex, including stereoscopic acuity, direction of movement, and orientation, become sharper with practice….
“Perceptual learning involves repeating a discrimination task many times and does not require error feedback to improve performance. Improvement manifests itself, for example, as a decrease in the threshold for discriminating small differences in the attributes of a target stimulus or in the ability to detect a target in a complex environment. Several areas of visual cortex, including the primary visual cortex, participate in perceptual learning.
“An important aspect of perceptual learning is its specificity: Training on one task does not transfer to other tasks.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 559.
“The pop-out of complex shapes such as numerals supports the idea that early in visual processing neurons can represent, and be selective for, shapes more complex than line segments with a particular orientation.
“Scene segmentation–the parsing of a scene into different objects–involves a combination of bottom-up processes that follow the Gestalt rule of good continuation and top-down processes that create object expectation.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 560.
“Neurons in visual cortical areas have properties consonant with Gestalt grouping rules. They perform a local and global analysis of scene properties in parallel. The local properties are the visual primitives, which include orientation selectivity, direction selectivity, contrast sensitivity, disparity selectivity, and color selectivity. The corresponding global properties include contour integration, object movement, border ownership, disparity capture, and color constancy.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 562.
“Evidence is emerging that rather than having fixed functions, neurons are adaptive processors, taking on different functional roles under different behavioral contexts. Neurons may mediate this functional diversity by input selection, expressing task-relevant inputs and suppressing task-irrelevant inputs.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Charles D. Gilbert, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 563.
“High-level visual processing is concerned with identifying behaviorally meaningful features of the environment and thus depends on descending signals that convey information from short-term working memory, long-term memory, and executive areas of cerebral cortex.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 564.
“It is the behavioral significance of objects that guides our action based on visual information.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 564.
“In humans, there are two basic categories of visual agnosia, apperceptive and associative, the description of which led to a two-stage model of object recognition in the visual system. With apperceptive agnosia, the ability to match or copy complex visual shapes or objects is impaired. This impairment results from disruption of the first stage of object recognition: integration of visual features into sensory representations of entire objects. With associative agnosia, the ability to match or copy complex objects remains intact, but the ability to identify objects is impaired. This impairment results from disruption of the second stage of object recognition: association of the sensory representation of an object with knowledge of the object’s meaning or function.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 567.
“Neurons of the inferior temporal cortex are organized in functionally specialized columns that extend from the surface of the cortex. According to this model, each column includes neurons that respond to a specific visually complex object. Columns of neurons that represent variations of an object, such as different faces or different fire extinguishers, constitute a hypercolumn.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 569.
“For object recognition to take place, these invariant attributes must be represented independently of other image properties. The visual system does this with proficiency, and its behavioral manifestation is termed perceptual constancy. Perceptual constancy has many forms ranging from invariance across simple transformations of an object, such as changes of size or position, to more difficult ones, such as rotation in depth or changes in lighting, and even to the sameness of objects within a category: All zebras look alike.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 571.
“Form-cue invariance refers to the constancy of a form when the cues that define the form change. The silhouette of Abraham Lincoln’s head, for example, is readily recognizable whether it is black on white, white on black, or red on green. The responses of many inferior temporal neurons do not change with changes in contrast polarity, color, or texture.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 571.
“Viewpoint invariance refers to the perceptual constancy of three-dimensional objects observed from different angles. Because most objects we see are three-dimensional and opaque, when looked at from different viewpoints, some parts become invisible, while others are revealed, and all others change in appearance. Yet despite the limitless range of retinal images that might be cast by a familiar object, an observer can readily recognize and object independently of the angle at which it is viewed.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 571.
“All forms of perceptual constancy are the product of the visual system’s attempts to generalize across different retinal images generated by a single object. A still more general type of constancy is the perception of individual objects as belonging to the same semantic category. The apples in a basket or the many appearances of the letter A in different fonts, for example, are physically distinct but are effortlessly perceived as categorically identical.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 572.
“Studies of the role of experience in visual perception have focused on two distinct types of experience-dependent plasticity. One stems from repeated exposure or practice, which leads to improvements in visual discrimination and object recognition ability. These experience-dependent changes constitute a form of implicit learning known as perceptual learning. The other occurs in connection with the storage of explicit learning, the learning of facts or events that can be recalled consciously.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 573.
“One of the most intriguing features of high-level visual processing is the fact that the detection of an image in one’s visual field and the recall of the same image are subjectively similar. The former depends on the bottom-up flow of visual information and is what we traditionally regard as vision. The latter, by contrast, is a product of top-down information flow. This distinction is anatomically accurate but obscures the fact that under normal conditions afferent and descending signals collaborate to yield visual experience.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 578.
“As we have seen, visual associative memories are stored in the visual cortex through changes in the functional connectivity between neurons that independently represent the associated stimuli. The practical consequence of this change is that a neuron that responded only to stimulus A prior to learning will respond to both A and B after these stimuli have been associated.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 578.
“Objects are perceived as members of a category. This simplifies the selection of appropriate behaviors, which often do not depend on stimulus details.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Thomas D. Albright & Winrich A. Freiwald, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 580.
“At the lowest level, muscles themselves have properties that can contribute to control even without any change in the motor command. Unlike the electric motors of a robot, muscles have substantial passive properties that depend on both the motor command acting on the muscle as well as the muscle’s length and rate of change of length.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 715.
“… sensory inputs can cause motor output directly without the intervention of higher brain centers. Sensorimotor responses, such as spinal reflexes, control for local disturbance or noxious stimuli. Reflexes are stereotyped responses to specific stimuli that are generated by simple neural circuits in the spinal cord or brain stem. For example, a spinal flexor withdrawal reflex can remove your hand from a hot stove without any descending input from the brain…. The fastest is the monosynaptic stretch reflex, which drives contraction of a stretched muscle. In this reflex circuit, sensory neurons that are activated by stretch receptors in the muscle (the muscle spindle) directly synapse onto motor neurons that cause the same muscle to contract. The time from the stimulus to the response is around 25 ms….
“While this monosynaptic stretch reflex is not adaptable on short timescales, multisynaptic reflexes, which involve higher level structures such as motor cortex, can produce responses at around 70 ms. Unlike the monosynaptic reflex, multisynaptic reflexes are adaptable to changes in behavioral goals because the circuit connecting sensory and motor neurons can be modified by task-dependent properties.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 716.
“Increasing the response time permits additional neural circuitry to be involved in the sensorimotor loop and tends to increase the sophistication and adaptability of the response, leading to a trade-off between the speed of the response and the sophistication of processing as one ascends the motor hierarchy.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 716.
“The central nervous system must exercise both control and prediction to achieve skilled motor performance. Prediction and control are two sides of the same coin, and the two processes map exactly onto forward and inverse models. Prediction turns motor commands into expected sensory consequences, whereas control turns desired sensory consequences into motor commands.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 718.
“A better system [than a house thermostat which releases a quantity of heat regardless of the error of current temperature to desired temperature] is one in which the control signal is proportional to the error.
“Such proportional control of movement involves sensing the error between the actual and desired position of, for example, the hand. The size of the corrective motor command is in proportion to the size of the error and in a direction to reduce the error. The amount by which the corrective motor command is increased or decreased per unit of positional error is called the gain.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 719.
“The brain is particularly sensitive to the occurrence of unexpected events or the nonoccurrence of expected events (ie, to sensory prediction errors).” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 723.
“Sensory feedback can arise as a consequence of both external events and our own movements. In the sensory receptors, these two sources are not distinguishable, as sensory signals do not carry a label of ‘external stimulus’ or ‘internal stimulus.’” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 723.
“A growing body of research supports the idea that the sensory information used to control actions is processed in neural pathways that are distinct from the afferent pathways that contribute to perception. It has been proposed that visual information flows in two streams in the brain.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 724.
“In general, effort and accuracy are in conflict. Accuracy requires energy because corrections require muscular activity and thus comes at some cost. The trade-off between accuracy and energy varies for different movements. When walking, we could choose to step gingerly to ensure we never trip, but this would require substantial energy use. Therefore, we are willing to save energy by allowing ourselves the risk of occasionally tripping. In contrast, while eating with a knife and fork, we prioritize accuracy over energy to ensure the fork does not end up in our cheek.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 727.
“The aim of optimal feedback control is not to eliminate all variability, but to allow it to accumulate in dimensions that do not interfere with the task while minimizing it in the dimensions relevant for the task completion. The minimal intervention principle is supported by studies….” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 728.
“For some skills, there can be a complex relation between the actions performed and success or failure at the task. For example, when children first sit on a swing, they have to learn the complex sequence of leg and body movements required to make the swing go higher…. Learning in such complex scenarios can be achieved using reinforcement learning in which the sensorimotor system adjusts its commands in an effort to maximize reward, that is, task success….
“Reinforcement learning is more general than error-based learning in that the training signal is success or failure, rather than an error at each point in time.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 734.
“Skill learning for real-world tasks typically involves a sequence of decision-making processes at different spatiotemporal scales. The skill of a tennis player, for example, is not only determined by the precision with which she can strike the ball but also by the speed with which she can make the correct decision on where to aim it and how well she uses her senses to extract task-relevant information.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 734.
“Motor primitives can be thought of as neural control modules that can be flexibly combined to generate a large repertory of behaviors. A primitive might represent the temporal profile of a particular muscle activity or a set of muscles that are activated together, termed a synergy.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 734.
“There is a trade-off in the speed versus sophistication of the different levels of sensorimotor response from rapid reflexes to slower voluntary control.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daniel M. Wolpert & Amy J. Bastian, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 735.
“Emotional and homeostatic behaviors all involve the coordination of one or more somatic, autonomic, hormonal, or cognitive processes. Subcortical brain regions concerned with a range of functions–including feeding, drinking, heart rate, breathing, temperature regulation, sleep, sex, and facial expressions–play a critical role in this coordination.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [C. Daniel Salzman & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 977.
“Six neurochemical modulatory systems in the brain stem modulate sensory, motor, and arousal systems. The dopaminergic pathways that connect the midbrain to the limbic system and cortex are particularly important, because they are involved in processing stimuli and events in relation to reinforcement expectation, and therefore contribute to motivational state and learning.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [C. Daniel Salzman & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 977.
“Rostral to the brain stem lies the hypothalamus, which functions to maintain the stability of the internal environment by keeping physiological variables within the limits favorable to vital bodily processes.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [C. Daniel Salzman & John D. Koester, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 978.
“The brain stem automatically generates breathing movements beginning in utero at 11 to 13 weeks of gestation in humans, and continues nonstop from birth until death.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Clifford B. Saper & Joel K. Elmquist, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 994.
“As noted earlier, dopaminergic inputs to the striatum adjust the likelihood that a specific motor pattern or even a cognitive pattern will be expressed. Low dopamine levels reduce output from the direct pathway striatal neurons (which release behaviors) and increase activity of indirect pathway striatal neurons (which inhibit behavior). Dopamine also has been linked to reward-based learning.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Clifford B. Saper & Joel K. Elmquist, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1004.
“Building on the basic plan of the spinal cord, motor and sensory neurons concerned with the face, head, neck, and internal viscera form into discrete nuclei with specific functions and territories of innervation.
“Neurons in the reticular formation surrounding these cranial nerve nuclei develop into ensembles of neurons that can generate patterns of autonomic and motor responses that subserve simple, stereotyped, coordinated functions, ranging from facial expression to feeding and breathing. These behavior patterns are sufficiently complex and flexible to represent the entire behavioral repertory of a new born baby.
“As the forebrain develops and exerts its control over these brain stem pattern generators, a variety of more complex responses and ultimately volitonal control of behavior evolve.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Clifford B. Saper & Joel K. Elmquist, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1007.
“The autonomic motor system is distinct from the somatic motor system, which controls skeletal muscle. Whereas somatic motor neurons regulate contractions of striated muscles, autonomic motor neurons regulate blood vessels, the heart, the skin, and visceral organs through synapses upon smooth and cardiac muscle cells, upon glands cells that serve endocrine and exocrine functions, and upon metabolic targets such as adipocytes.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Bradford B. Lowell, Larry W. Swanson & John P. Horn, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1011.
“A second epoch [after the first which is the generation and differentiation of neurons and glia] encompasses the steps by which neurons wire up: the migration of their somata to appropriate places, the guidance of axons to their targets, and the formation of synaptic connections. The complexity of the wiring problem is staggering–axons of many neuronal types must navigate, often over long distances, and then choose among a hundred or more potential synaptic partners….
“In the third epoch, the genetically determined patterns of connectivity (the hardware) are molded by activity and experience (the software). Unfortunately for investigators, these steps in mammals are shared to a very limited degree with invertebrates and lower vertebrates. A newly hatched bird or fly is not remarkably different in its behavioral repertoire from its adult self, but no one could say that about a person. This is largely because our nervous system is something of a rough draft at birth.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1104.
“At present, the true number of neuronal types in the mammalian central nervous system remains unknown, but it is surely more than a thousand. The number of glial types is even less clear….” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1107.
“Thus, brain pathways and neocortical regions are established through genetic programs during early development but later depend on afferent inputs for their specialized anatomical, physiological, and behavioral functions.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1126.
“At early stages of embryonic development, most progenitor cells in the ventricular zone of the neural tube proliferate rapidly. Many of these early neural progenitors have the properties of stem cells: They can generate additional copies of themselves, a process called self-renewal, and also give rise to differentiated neurons and glial cells.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1131.
“Neural stem cells divide to produce two stem cells, and in this way expand the population of proliferative progenitor cells…. A second mode is asymmetric: The progenitor produces one differentiated daughter and another daughter that retains its stem cell-like properties…. A third mode leads to production of two differentiated daughters. In this symmetric mode, the stem cell population is depleted.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1131.
“The amino acid L-glutamate is the major excitatory transmitter, whereas γ-aminobutryric acid (GABA) is the major inhibitory transmitter. Some spinal cord neurons use another amino acid, glycine, as their inhibitory transmitter. In the peripheral nervous system, sensory neurons use glutamate, motor neurons use acetylcholine, and autonomic neurons use acetylcholine or norepinephrine. Smaller numbers of neurons use other transmitters, such as serotonin and dopamine. The choice of neurotramsitter determines which postsynaptic cells a neuron can talk to and what it can say.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1143.
“More recently, evidence has accumulated that the transmitter phenotype of central neurons can also be influenced by signals including hormones and electrical activity. When the spontaneous activity of embryonic amphibian neurons is increased, some motor neurons can be respecified to synthesize and use the inhibitory neurotransmitter GABA instead of or in addition to acetylcholine. Conversely, when activity is decreased, some inhibitory neurons switch to using the excitatory neurotransmitter glutamate along with or instead of GABA. Postsynaptic partners typically express new receptors that correspond to the transmitter being released onto them. These switches occur without overall respecification of the neuron and are best viewed as homeostatic responses aimed at keeping the overall activity of the system in a narrow range.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1147.
“We now know that the phenomenon of neuronal overproduction, followed by a phase of neuronal death, occurs in most regions of the vertebrate nervous system.
“The early discoveries of Levi-Montalcini and Hamburger laid the foundations for the neurotrophic factor hypothesis. The core of this hypothesis is that cells at or near the target of a neuron secrete small amounts of an essential nutrient or trophic factor and that the uptake of this factor by nerve terminals is needed for the survival of the neuron.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1147.
“The choice between neuronal and glial fate is determined by signals from ligands of the Delta family to receptors of the Notch family on neighboring cells. Initially, cells express both Notch and Delta. Activation of Notch leads to a glial fate, downregulating Delta, which in turn attenuates Notch activity on the neighbors, promoting their differentiation into neurons.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes & Thomas M. Jessell, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1153.
“Interactions among dendrites are critical for dendritic patterning. Repellent interactions among the dendrites of a single cell, a process called self-avoidance, leads to even coverage of an area, with minimal gaps or clumps. Repellent actions between dendrites of neighboring cells, a process called tiling, minimizes overlap of dendritic fields. In some cases, dendrites avoid other dendrites from their own neuron but interact with dendrites of nominally identical neighboring cells. This process is called self-/ non-self-discrimination.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1179.
“Receptors on the growth cone recognize and bind ligands in the environment through which the axon is extending, guiding the growth. These interactions lead to generation of their second messengers that mediate growth, turning and stopping of the growth cone, and branching of the axon….
“The growth of an axon to a distant target is broken into discrete shorter steps. At each step, molecules on the surface of or secreted by neighboring structures guide the axon. They can also lead to alterations in the growth cone’s complement of receptors, allowing it to respond to different sets of cues at the subsequent stage.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1179.
“Three key processes drive synapse formation. First, axons make choices among many potential post-synaptic partners. By forming synaptic connections only on particular target cells, neurons assemble functional circuits that can process information. In many cases, synapses are even formed at specific sites on the postsynaptic cell; some types of axons form synapses on dendrites, others on cell bodies, and yet others on axons or nerve terminals….
“Second, after cell-cell contacts have formed, the portion of the axon that contacts the target cell differentiates into a presynaptic nerve terminal, and the domain of the target cell contacted by the axon differentiates into a specialized postsynaptic apparatus. Precise coordination of pre- and postsynaptic differentiation depends on interactions between the axon and its target cell….
“Finally, once formed, synapses mature, often undergoing major rearrangements. One striking aspect of the rearrangement is that as some synapses grow and strengthen, many others are eliminated. Like neuronal cell death, synapse elimination at first glance is a puzzling and seemingly wasteful step in neural development. It is increasingly clear, however, that it plays a key role in refining initial patterns of connectivity.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1181, 1182.
“Synapse formation stands at an interesting crossroads in the sequence of events that assemble the nervous system. The initial steps in this process appear to be largely ‘hardwired’ by molecular programs. However, as soon as synapses form, the nervous system begins to function, and the activity of neural circuits plays a critical role in subsequent development. Indeed, the information-processing capacity of the nervous system is refined through its use, most dramatically in early postnatal life but also into adulthood. In this sense, the nervous system continues to develop throughout life.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1182.
“One important contributor to synaptic matchmaking in the inner plexiform layer is its division into sublayers. The processes of each amacrine and bipolar cell type, as well as the dendrites of each functionally distinct ganglion cell type, branch and synapse in just one or a few of approximately 10 sublayers.
“This layer-specific arborization of pre- and postsynaptic processes restricts the choice of synaptic partners to which they have ready access. Similar lamina-specific connections are found in many other regions of the brain and spinal cord. For example, in the cerebral cortex, distinct populations of axons confine their dendritic arbors and synapses to just one or two of the six main layers.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1182, 1183.
“Each olfactory sensory neuron in the nasal epithelium expresses just one of approximately 1,000 types of odorant receptors.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1184.
“Nerve terminals not only discriminate among candidate targets but also terminate on a specific portion of the target neuron. In the cerebral cortex and hippocampus, for example, axons arriving in layered structures often confine their terminals to one layer, even if the dendritic tree of the postsynaptic cell traverses numerous layers.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1186-7.
“Once synapses form, however, neural activity within the circuit plays a critical role in refining synaptic patterns.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1187.
“A third key feature of neuromuscular junction development is that new synaptic components are added in several distinct steps. The newly formed synapse is not simply a prototype of a fully developed synapse. Although nerve and muscle membrane form close contacts at early stages of synaptogenesis, only later does the synaptic cleft widen and the basal lamina appear….
“This elaborate sequence is not orchestrated by the simple act of contact between nerve and muscle. Instead, multiple signals pass between the cells–the nerve sends a signal to the muscle that triggers the first steps in postsynaptic differentiation, at which point the muscle sends a signal that triggers the initial steps of nerve terminal differentiation. The nerve then sends further signals to the muscle, and this interaction continues.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1190.
“In adult mammals, each muscle fiber bears only a single synapse. However, this is not the case in the embryo. At intermediate stages of development, several axons converge on each myotube and form synapses at a common site. Soon after birth, all inputs but one are eliminated….
“Each motor axon withdraws branches from some muscle fibers but strengthens its connections with others, thus focusing its increasing capacity for transmitter release on a decreasing number of targets.
“Like synapse formation, synapse elimination results from intercellular interactions. Every muscle fiber ends up with exactly one input: None have zero, and very few have more than one.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1204.
“Classical studies of synapse formation and maturation focused, logically enough, on the pre- and postsynaptic partners. More recently, however, there has been a growing appreciation of the role played by a third type of cell: the glial cells that cap nerve terminals. Schwann cells are the glia at neuromuscular junctions, and astrocytes are the glia at central synapses. Both have been implicated in synapse formation and maturation.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1205.
“Matching cell-surface recognition molecules on pre- and postsynaptic partners provide one prevalent mechanism for synaptic specificity. They include members of the cadherin, immunoglobulin, and leucine-rich repeat protein superfamilies. Individual members are selectively expressed by subsets of neurons and exhibit selective binding. Often, the binding is homophilic, biasing connectivity in favor of partners expressing the same molecule.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1207.
“Motor neurons and muscle fibers can express genes encoding pre- and postsynaptic components, respectively, in each other’s absence, but they exert profound influences on the levels and distribution of these components in their partners. Thus, signals between synaptic partners are best viewed as organizers rather than inducers.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1208.
“Many of the synapses that form initially in both the peripheral and cental nervous systems are subsequently eliminated, generally by competitive, activity-dependent mechanisms. The consequence is that as circuits mature, the number of inputs a neuron receives may decrease dramatically, but the size and strength of the remaining inputs increase even more dramatically.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1208.
“This two-part sequence–genetically determined connectivity followed by experience-dependent reorganization–is a common feature of mammalian neural development, but in humans, the second phase is especially prolonged.
“At first glance, this delay in human neural development might seem dysfunctional. It does exact a toll, but it also provides an advantage. Because our mental abilities are shaped largely by experience, we gain the ability to custom fit our nervous systems to our individual bodies and unique environments. It has been argued that it is not just the large size of the human brain but also its experience-dependent maturation that makes our mental capabilities superior to those of other species.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1210-1211.
“Computation of the temporal difference in the arrival of sounds at the two ears [such as for owls in distinguishing location of prey by sound] is particularly crucial. The difference is only a few tens of microseconds, as expected from calculations based upon the speed of sound and the width of the head. Remarkably, the auditory system is sensitive to these extremely short interaural time differences (ITDs) and can calculate prey position from them.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Joshua R. Sanes, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1227.
“Motor and sensory functions take up less than one-half of the cerebral cortex in humans. The rest of the cortex is occupied by the association areas, which coordinate events arising in the motor and sensory centers.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Eric R. Kandel & Steven A. Siegelbaum, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1287.
“These studies [of memory] have yielded three major insights.
“First, there are several forms of learning and memory. Each form of learning and memory has distinctive cognitive and computational properties and is supported by different brain systems. Second, memory involves encoding, storage, retrieval, and consolidation. Finally, imperfections and errors in remembering can provide clues about the nature and function of learning and memory and the fundamental role that memory plays in guiding behavior and planning for the future.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1292.
“Memory can be classified along two dimensions: (1) the time course of storage and (2) the nature of the information stored. In this chapter, we consider the time course of storage. In the next two chapters, we focus on the cellular, molecular, and circuit-based mechanisms of different forms of learning and memory, based largely on studies of animal models.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1292.
“Not all forms of memory, however, constitute ‘former states of mind.’ In fact, the ability to store information depends on a form of short-term memory, called working memory, which maintains current, albeit transient, representations of goal-relevant knowledge. In humans, working memory consists of at least two subsystems–one for verbal information and another for visuospatial information. The functioning of these two subsystems is coordinated by a third system called the executive control processes. Executive control processes are thought to allocate attentional resources to the verbal and visuospatial subsystems and to monitor, manipulate, and update stored representations.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1292.
“We now know that the brain does not have a single long-term store of episodic memories. Instead, the storage of any item of knowledge is widely distributed among many brain regions that process different aspects of the content of the memory and can be accessed independently (by visual, verbal, or other sensory clues). Second, episodic memory is mediated by at least four related but distinct types of processing: encoding, storage, consolidation, and retrieval.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1297.
“Consolidation is the process that transforms temporarily stored and still labile information into a more stable form…. … consolidation involves expression of genes and protein synthesis that give rise to structural changes at synapses.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1297.
“Retrieval of memory is much like perception; it is a constructive process and therefore subject to distortion much as perception is subject to illusions. When a memory is retrieved, it becomes active again, providing an opportunity for an old memory to be encoded again. Because retrieval is constructive, re-encoding of a retrieved memory can differ from the original memory.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1297.
“Some forms of implicit memory have also been studied in nonhuman animals, and these animal studies have distinguished two types of implicit memory: nonassociative and associative. With nonassociative learning, an animal learns about the properties of a single stimulus. With associative learning, the animal learns about the relationship between two stimuli or between a stimulus and a behavior….
“Nonassociative learning results when a subject is exposed once or repeatedly to a single type of stimulus. Two forms of nonassociative learning are common in everyday life: habituation and sensitization…. Sensitization (or pseudo-conditioning) is an enhanced response to a wide variety of stimuli after the presentation of an intense or noxious stimulus. For example, an animal will respond more vigorously to a mild tactile stimulus after receiving a painful pinch.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1304, 1305.
“With sensitization and dishabituation, the timing of stimuli is not important because no association between stimuli must be learned. In contrast, with two forms of associative learning, the timing of the stimuli to be associated is critical. Classical conditioning involves learning a relationship between two stimuli, whereas operant conditioning involves learning a relationship between the organism’s behavior and the consequences of that behavior.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1306.
“In a typical laboratory example of operant conditioning, a hungry rat or pigeon is placed in a test chamber in which the animal is rewarded for a specific action. For example, the chamber may have a lever protruding from one wall. Because of previous learning, or through play and random activity, the animal will occasionally press the lever. If the animal promptly receives a positive reinforcer (eg, food) after pressing the lever, it will begin to press the lever more often than the spontaneous rate.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1307.
“If we think of classical conditioning as the formation of a predictive relationship between two stimuli (the CS and the US [conditioned stimulus and unconditioned stimulus]), operant conditioning can be considered as the formation of a predictive relationship between an action and an outcome…. Thus, operant behaviors are said to be emitted rather than elicited. In general, actions that are rewarded tend to be repeated, whereas actions followed by aversive, although not necessarily painful, consequences tend not to be repeated. May experimental psychologists think that this simple idea, called the law of effect, governs much voluntary behavior.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1307.
“Memory’s imperfections have been classified into seven basic categories, dubbed the ‘seven sins of memory’: transience, absent-mindedness, blocking, misattribution, suggestibility, bias, and persistence.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1308.
“Absent-mindedness and blocking are sins of omission: At a moment when we need to remember information, it is inaccessible. However, memory is also characterized by sins of commission, situations in which some form of memory is present but wrong.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1308.
“Persistence refers to obsessive memory, constant remembering of information or events that we might want to forget.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1308.
“Indeed, many memory imperfections may have adaptive value. False memories and suggestibility may both be related to one of the most basic adaptive functions of memory: the integration of experiences separated in time into a network of learned associations. For memory to play an important role in guiding future behavior, it must be flexible so that we can leverage past experiences to make inferences about future events even when the circumstances have changed. Similarly, although the various forms of forgetting (transience, absent-mindedness, and blocking) can be annoying, a memory system that automatically retains every detail of every experience could result in an overwhelming clutter of useless trivia.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Daphna Shohamy, Daniel L. Schacter & Anthony D. Wagner, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1309.
“Well before children produce their first words, they learn the sound patterns underlying the phonetic units, words, and phrase structure of the language they hear.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Patricia K. Kuhl, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1371.
“Regardless of the age at which learning begins, second-language learning is improved by a training regimen that mimics critical components of early learning–long periods of listening in a social context (immersion), the user of both auditory and visual information, and exposure to simplified and exaggerated speech resembling ‘parentese.’” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Patricia K. Kuhl, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1377.
“But Broca’s aphasics have difficulty comprehending sentences with meanings that depend mostly on grammar. Broca’s aphasics can understand The apple that the girl ate was green, but have trouble understanding The girl that the boy is chasing is tall. This is because they can understand the first sentence without recourse to grammatical rules–girls eat apples but apples do not eat girls; apples can be green but girls cannot. However, they have difficulty with the second sentence because both girls and boys can be tall, and either can chase the other.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Patricia K. Kuhl, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1383.
“By 12 months, discrimination for native-language sounds has dramatically increased, whereas discrimination of foreign-language sounds decreases…. By the age of 3, infants know 1,000 words. Mastery of grammatical structure in complex sentences continues until the age of 10.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Patricia K. Kuhl, section author] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1388.
“… as we shall see, neuroscience recognizes the rudiments of cognition in simple behaviors that display two types of flexibility–contingency and freedom from immediacy. Contingency means that a stimulus does not command or initiate an action in the way it does for a reflex. A stimulus might motivate a particular behavior, but the action may be delayed, pending additional information, or it may never occur.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1392.
“Both types of flexibility–contingency and time–are on display when we make decisions. Of course, not all decisions invoke cognition. Many behavioral routines–swimming, walking, feeding, and grooming–have branch points that may be called decisions, but they proceed in an orderly manner without much flexibility or control of tempo….
“A decision is a commitment to a proposition, action, or plan based on evidence (sensory input), prior knowledge (memory), and expected outcomes. The commitment is provisional. It does not necessitate behavior, and it can be modified. We can change our mind. The critical component is that some consideration of evidence leads to a change in the state of the organism that we liken to a provisional implementation of an action, strategy, or new mental process.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1392-3.
“The concept of a plan emphasizes freedom from immediacy. Moreover, not all plans come to fruition. Not all thought leads to action, but it is useful to conceive of thought as a type of plan of action. This view invites us to consider knowing as the result of directed–mostly nonconscious–interrogation, rather than an emergent property of neural representations.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1393.
“A simple rule is the application of a threshold to a representation of the evidence.
“The criterion instantiates the decision-maker’s policy or strategy. If the criterion is lax–that is, the threshold is low–the decision-maker will rarely fail to detect the stimulus, but they will often respond ‘yes’ on the trials when there was no stimulus because the background noise exceeds the threshold. This type of error is called a false alarm. If the criterion is more conservative–that is, the threshold is high–the decision-maker will rarely say ‘yes’ when the stimulus is absent but will often say ‘no’ when the stimulus is present. This type of error is called a miss. The appropriate criterion depends on the relative cost of the two types of errors and also on the design of the experiment….
“The important point is that the criterion represents a decision rule, which instantiates knowledge about the problem and an attitude about the positive value associated with making correct choices (hits and correct rejections) and the negative value of making errors (misses and false alarms).” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1393-1395.
“The challenge for neuroscience is to relate the terms signal, noise, and criterion to neural representations of sensory information and operations upon those representations that result in a choice.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1395.
“However, decision-making normally takes some time, so that when the viewing duration is longer, decisions tend to be more accurate [for a random dot motion discrimination task where the percentage of dots moving in a coherent direction, left or right, varies from 0% to 100%]. In fact, the strength of motion that is required to support 75% accuracy, termed the sensory threshold, decreases as a function of viewing duration…. The suggestion then is that the difference in firing rates of left- and right-preferring direction-selective neurons supplies the momentary evidence to another process that accumulates this noisy evidence as a function of time–in this case, two processes that accumulate evidence for left and right, respectively.
“The accumulation of noisy evidence follows a path comprising random steps in both the positive and negative direction on top of a constant bias determined by the coherence and direction of the moving dots. This is termed a biased random walk or drift plus diffusion process…. The accumulations evolve with time and continue to do so until the stimulus is turned off or until one of the accumulations reaches an upper stopping bound, which determines the answer, left or right. Even the 0% coherence (pure noise) stimulus will reach a stopping bound eventually, but it is equally likely that the left or right accumulation will do so….
“This simple idea thus explains the observed trade-off between the speed and accuracy of a decision.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1401.
“Neurons that represent the evolving decision increase their firing rates gradually as the evidence mounts for one of the choices, and they decrease gradually when the evidence favors the other option.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1403.
“Many, if not most, decisions made by humans and animals are expressions of preference, based on an assignment of value. In some instances, the value is innate…. In the vast majority of instances, however, value is learned through experience, or it is derived from reasoning based on other preferences.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1408.
“States of knowledge have persistence. Even if they concern information derived from the senses, the knowledge of sensation generally outlasts the sensory activity itself. In this way, the state of knowledge resembles a perceptual decision–a commitment to a proposition about the object, based on sensory evidence.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1409.
“Naturally, sensory neurons must change their response when the environment changes or the observer moves in the environment, whereas knowledge states persist through sensory changes and without a continuous stream of input. Indeed, persistent activity is apparent in areas of the brain that associate sources of information–from the senses and from memory–with circuits that organize behavior.
“In the prefrontal cortex, persistent states represent plans of action, abstract rules, and strategies. In the parietal and temporal lobes, neural representations have the dual character of knowledge and the behavior that knowledge bears upon, such as making an eye movement or reaching, eating, or avoiding.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1409.
“Let us defer for the moment the aspect of the knowledge state that includes conscious awareness and consider the simpler sense of knowledge as a state of possible utilization. Such preconscious ideation is probably the dominant state in which an animal interacts with the environment…. Two important insights emerge from this perspective. The first is that the correspondence between knowledge and neuronal activity lies at a level of brain organization between sensation and behavior….
“The second insight is that the computation leading to a knowledge state has the structure of a decision–a provisional commitment to something approximating a possible selection from a submenu of the behavioral repertory. We might say that the parietal association neurons interrogate the sensory areas for evidence bearing on the possibility of a behavior: look there, reach there, posture the hand this way to grasp. Of course, neurons do not ask questions. Nevertheless, we can think of the circuits as if they scan the world looking for evidence bearing on a possible behavior.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1409.
“Sir Arthur Conan Doyle endowed Sherlock Holmes with the insight that the key to discovery was knowing where to look and what to look for. We acquire knowledge by controlling the brain’s interrogation system.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1409.
“From the perspective of decision-making, perceiving, believing, and thinking have the character of a provisional commitment to a proposition. Brain states that correspond to a sense of knowing, be it perceiving or believing, share two important aspects with decision-making: an extended temporal profile that withstands changes in the sensory and motor streams (ie, a freedom from immediacy) and a propositional character captured by the term ‘affordance.’ Knowing is not solely about the information but is like the outcome of a decision to embrace a proposition: Might I do something, enact something, approach someone, or retain the possibility of trying the option I am not choosing now?
“Two caveats deserve mention. This framework does not replace a computational account of information processing, nor does it explain the neural mechanisms that support these computations. It mainly tells us about the level of brain organization that carries out these operations. For example, consider the search for the neurons that achieve knowledge about the color red, despite changes in the spectral content of the morning and evening light–a phenomenon known as color constancy. Instead of searching in sensory areas for neurons that respond selectively to red in this invariant way, one might look for neurons that guide the choice of ripe fruit…. In animals that lack language, the knowledge state may not be dissociable from ‘ripe vegetation.’
“The second caveat is that we have not distinguished knowledge states that we are consciously aware of from those that we experience unconsciously.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1411-1412.
“Imagine a mother and father sleeping comfortably in their bedroom as a storm ensues outdoors. There are also traffic sounds and even the occasional thunder. This scene goes on for some time, until the cry of a baby awakens the parents. This common occurrence tells us that the nonconscious brain is capable of processing sounds and deciding to become conscious. It decides, nonconsciously, that some sounds afford an opportunity for more sleep while others sound a call to nurture. This decision is similar to the perceptual decisions considered earlier in this chapter. Both involve nonconscious processing of evidence. However, the commitment to awaken and parent is a decision to engage the environment consciously. This may be a touchstone between neurology-consciousness and the more intriguing consciousness that you are experiencing as you read these words.
“When neuroscientists, psychologists, and philosophers ponder the mysteries of consciousness, they are referring to loftier themes than wakefulness. This loftier set of phenomena comprises awareness, imagery, volition, and agency. There is a subjective component to all conscious experience.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1412-3.
“We used the term deliberation earlier in this chapter to describe the thought process leading to a decision. Our use of the term was metaphorical. It describes a computation and a biological mechanism, but it does not require awareness. Actual deliberation implies conscious intention. We are aware of the steps of reasoning along the way. We could report, were we asked, about the evidence we relied upon–that is, the evidence we were consciously aware of during the decision and possibly some of the evidence we used nonconsciously were it accessible from memory to include in our report. Could the difference between conscious awareness of an item and nonconscious processing of that item be a mere matter of whether the brain has decided on the possibility of reporting? Could it be this simple?
“Consider the following scenario. A psychologist concludes that a study participant has seen something nonconsciously because the item affected a subsequent behavior and the participant denies having seen it. Suppose the subsequent behavior involved reaching in the direction of the object. Based on what we know about decision-making, we would conclude that brain circuits like the ones discussed earlier received sufficient evidence to commit to the possibility of looking, reaching, and approaching, but there was insufficient evidence to commit to the possibility of reporting. Just as the brain entertains the possibility of looking, reaching, or grasping, it may also entertain the possibility of reporting. That is, reporting is also a provisional affordance.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1413.
“Just as we attach states of spatial knowledge to configurations of the hand for reaching and grasping, we must consider the knowledge state that accompanies the affordance of reporting. Whether by language or gesture (eg, pointing), the report is a provisional communication with another agent or oneself (eg, in the future). It presumes knowledge about the mind of the receiver.
“Cognitive scientists use the term theory of mind to refer to this type of knowledge or mental capacity….
“Theory of mind–in concert with narrative–has profound consequences for the knowledge state associated with the reporting affordance. Imagine a woman looking at a power drill resting on a table. She experiences the location of the drill, relative to her eyes and hand, as well as its texture and shape…. The drill brings to mind other affordances associated with its utility as a tool, its potential to make noise, and the potential danger posed by the sharp bit at one end. This is an elaborate, potentially rich collection of knowledge, but it could all be experienced nonconsciusly. For example, if the woman were pre-occupied with some other task, such as a phone conversation with her friend, she might nonetheless make use of these knowledge states.
“But suppose there is a man on the other side of the table and suppose the woman–her brain, that is–has also reached a provisional commitment to report to the man about the drill between them. Consider the change to her knowledge state. The drill now has a presence not only in her visual field, relative to her gaze, her hand, and her repertory of actions, but also in the man’s field of vision and his possible actions. The parts of the drill that are not in plain sight to her are known to be in the line of sight of the man. Indeed, her capacity for ‘theory of mind’ also supplies knowledge that other parts of the drill are seen only by her and that the man could be experiencing those parts just as she experiences the parts that are not in her direct line of sight–that is, both preconsciously as occluded parts of the object and consciously as part of an object that could be seen directly from another vantage point. There is something about the drill that is at once private, public, and in the world–independent of either mind. The drill is there for the next person who enters the room, or an imagined person. The transformation of knowledge of the drill is from a collection of first-person experiences (eg, qualities and affordances) to a thing in the world that possesses an existence unto itself. It is conceivable that this state of knowledge is our conscious awareness of the world, or at least a part of it, for the knowledge state associated with a decision to report is further enriched by content of the report itself.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. pp. 1413-4.
“To summarize, the conscious awareness of an item might arise when the nonconscious brain reaches a decision to report the item to another mind…. … the possibility of reporting to another agent (or self), about whom we have theory of mind, corresponds to the knowledge of an item in a way that satisfies most aspects of conscious awareness.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1414.
“Decision-making provides a window on the neuroscience of cognition. It models contingent behavior and mental operations that are free from the immediate demands of sensory processing and control of the body’s musculature.” Kandel, Eric R., John D. Koester, Sarah H. Mack & Steven A. Siegelbaum (eds.) [Michael N. Shadlen & Eric R. Kandel, section authors] 2021. Principles of Neural Science, 6th Edition. NY: McGraw Hill. p. 1415.
“The philosopher Immanuel Kant already saw the problems a mechanistic view of organisms would run into and formulated specific properties of living entities. He formulated the evident inability of mechanistic thinking to explain regularities of organismal function and development and expressed the idea that organisms are self-organizing, self-synthesizing entities. He considered Newton’s laws of motion to have described the very nature of matter. However, Newton’s laws claim that matter is inert, not self-moving. When it changes, it does so through the influence of external forces. Matter does not organize and replicate itself. Yet organisms do all these things. If Newton’s laws lay down the rules by which matter conducts itself, organisms flout them flagrantly.” Rosslenbroich, Bernd. 2023. Properties of Life: Toward a Theory of Organism Biology. Springer. pp. 81-2.
“In brief, information, program and signal in biology are not proper theoretical entities, but just metaphors linking the current use of these terms with the theoretical ones enunciated in rigorous mathematical theories. Moreover, these mathematical theories are purely abstract, and do not pertain to physical or biological entities.” Soto, Ana M. & Carlos Sonnenschein. 2020. “Information, programme, signal: dead metaphors that negate the agency of organisms.” Interdiscip Sci Rev. 45(3):331-343. doi: 10.1080/03080188.2020.1794389. p. 333.
“After all, life is based on the distinct materials organisms are made from, namely, particular DNA, RNAs, proteins and membranes. Unlike hammers that can be made of diverse suitable materials, there is no way to dissociate the specific materials that make a living organism from the functions this organism accomplishes. Giuseppe Longo felicitously calls this ‘the radical materiality of life’ which rules out the software-hardware dualism in biology.” Soto, Ana M. & Carlos Sonnenschein. 2020. “Information, programme, signal: dead metaphors that negate the agency of organisms.” Interdiscip Sci Rev. 45(3):331-343. doi: 10.1080/ 03080188.2020.1794389. p. 335; reference: Longo, G. & A.M. Soto. 2016. “Why do we need theories?” Prog Biophys Mol Biol 122(1):4-10.
“Far-from-equilibrium physical systems like flames and micelles are ahistorical because they appear spontaneously. In contrast, organisms are a consequence of the reproductive activity of a pre-existing organism. Thus, understanding biological organization requires a historical analysis.” Soto, Ana M. & Carlos Sonnenschein. 2020. “Information, programme, signal: dead metaphors that negate the agency of organisms.” Interdiscip Sci Rev. 45(3):331-343. doi: 10.1080/03080188.2020.1794389. p. 337.
“The objects of physics are generic and thus interchangeable, like rocks and planets. Instead, biological objects are specific, i.e., they are individuals permanently undergoing individuation…. … variation is intrinsic to the properties of organisms.” Soto, Ana M. & Carlos Sonnenschein. 2020. “Information, programme, signal: dead metaphors that negate the agency of organisms.” Interdiscip Sci Rev. 45(3):331-343. doi: 10.1080/03080188.2020.1794389. p. 337.
“… our primary aim here was to understand how regulation, as a second-order control mechanism, could contribute to the dynamic robustness of metabolizing protocells when ‘the possible’ becomes much larger than ‘the actual’…. In that context, regulatory mechanisms come to rescue, channelling system responses according to the patterns of change – or the challenges – that the protocells get from the environment.” Shirt-Ediss, Ben, Arian Ferrero-Fernandez, Daniele De Martino, Leonardo Bich, Alvaro Moreno & Kepa Ruiz-Mirazo. 2024. “Modelling the prebiotic origins of regulation and agency in evolving protocell ecologies.” Preprint, in review. doi: 10.1101/ 2024.11.20.624505. p. 2.
“Indeed, regulatory mechanisms that modulate, specifically, the outward behaviour of single protocells (including the interactive dynamics they engage into with their peers) must have constituted a basic requirement for the first adaptive forms of agency to, ever, unfold in nature.” Shirt-Ediss, Ben, Arian Ferrero-Fernandez, Daniele De Martino, Leonardo Bich, Alvaro Moreno & Kepa Ruiz-Mirazo. 2024. “Modelling the prebiotic origins of regulation and agency in evolving protocell ecologies.” Preprint, in review. doi: 10.1101/ 2024.11.20.624505. p. 3.
“Harboring components capable of playing different functional tasks is a fundamental requirement for division of labor. However, a cohesive integration between these different tasks is only achieved when those different activities are orchestrated so that they collectively contribute to the maintenance of the system. To so do and carry out the activities required to maintain itself while avoiding internal conflicts, a biological system needs to control its parts and coordinate them. Control is therefore fundamental to establish mutual dependence between parts and achieve integration.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 3.
“A constraint is not part of the process it modifies, and it is stable during the time scale in which the process takes place. Through its activity, it canalizes a process toward outcomes that otherwise would be extremely improbable or practically impossible.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 5.
“As pointed out by Pattee, control requires a special type of constraint. It requires the presence of dynamic constraints that actively select between the degrees of freedom available in a process or a component…. By operating in this way, control constraints do not reduce degrees of freedom once and for all. Instead, they are sensitive to the state of the system or the environment, and they dynamically modulate the controlled process or the behavior of other constraints accordingly.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 5.
“According to most recent characterizations by the organizational account, biological agency can be defined as the set of activities of a living system, modulated by regulatory control, that modify the environment of the system and are performed in such a way as to contribute to the maintenance of the system itself.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 6 (note).
“The cohesion of a biofilm as an integrated functional unit capable of collectively maintaining itself results from the action of several types of control constraints operating at different ranges…. It includes bacterial conjugation—an interaction through which one bacterium transfers genetic material to another through direct contact. In case of nutritional stress, it might also include the direct exchange of enzymes responsible for the control of some physiological processes….
“Medium-range control is performed by a combination of quorum sensing processes (QS) and the EPS [extracellular polymeric matrix]. These control processes are responsible for the formation of the biofilm and its overall functioning as an organized whole. QS is a process in which individual bacteria, in the presence of some specific boundary conditions or perturbations, release molecules into their environment and in turn sense and respond to the concentration of these molecules in their environment. Responses are thus calibrated to the number of bacteria present. It is a collective control process. The individual bacteria are both the dynamic constraints synthesizing and releasing an autoinducer molecule into the environment, and the controlled systems, because their own gene expression is modified in response to the concentration of autoinducer interacting with their receptors. The result is the generation of gradients of collective activation through the diffusion of signaling molecules.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 8.
“During biofilm aggregation and formation, the rotation of bacterial flagella is mechanically blocked by the presence of EPS. This event triggers internal signal cascades that differentiate bacterial cells into persisters, characterized by an increased deposition of matrix molecules. This, in turn, inhibits the flagellar rotation in other cells and stimulates their matrix production, thus favoring the overall growth of the biofilm through a cascade effect.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 9.
“Long-range control is realized in animals mainly by means of vascularization and by the nervous system. Vascularization is the simplest way to exert control at larger scales by making components mobile, and thus allowing control molecules and cells to diffuse in a fluid medium in a constrained manner.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 11.
“The two major hypotheses on the origin of the nervous system, i.e., the contractile network hypothesis and the secretory network hypothesis, both characterize the emergence of the early nervous system as a response to the need to establish forms of thorough control upon tissues and organs (movement and integration of signals) in organisms with increasingly larger bodies. They emphasize the importance of the integrating function of early nervous systems at long ranges over the cognitive function, and the continuity of physiological control functions across different types of biological subsystems.
“In cnidaria, the nervous system operates, and it is thought to have originated according to the contractile network hypothesis, as a means to coordinate muscle contraction for movement and for the transport of food in the guts. In jellyfish individual muscles can communicate directly with adjacent ones, but a synchronized propulsion movement requires a fast long-range coordination of their contractions. This is achieved by neurons, which control the contractions of muscle cells across whole sheets of muscles. The contractions of the muscles responsible for the movement of food in the guts are similarly controlled. The enteric nervous system of mammals controls a wide range of movements of the gut muscles, including peristaltic movement, segmentation or nonpropulsive mixing, slow orthograde propulsion, and retropulsion of noxious substances….
“The secretory network hypothesis on the origin of the nervous system focuses on chemical wiring instead, and it identifies the early function of the nervous system in maintaining and enhancing signaling efficiency to reduce the inefficiency of chemical signaling taking place through diffusion in the larger bodies of animals. According to this hypothesis, ancestors of neural cells were ciliated cells that started secreting neuropeptides. They specialized in cells capable of sensory perception and neuropeptide release. Scattered among other cells, these specialized sensory-effector cells enabled synchronized activity (pulses or waves of activities of ensembles of cells) and the integration of signals by linking up into a chemical network capable to ensure the release of peptides across entire fields of cells with a more coherent effect.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 13.
“In vertebrates, the bridge between these two systems, vascular and nervous, is constituted by the hypothalamus, by means of which the nervous system extends and coordinates endocrine controls and the release and distribution of hormones in the circulatory system.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 14.
“This [the importance of integration for understanding biological individuality] is particularly relevant for an account of individuality such as the physiological one, which has not received enough theoretical treatment and, unlike evolutionary individuality, it has not given rise to precise and detailed analyses.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 17.
“An important implication of this framework, which bases individuality in integration through control, is that by distinguishing degrees of physiological integration, it supports the thesis that there are different ways to achieve individuality and that individuality comes in degrees.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 17.
“According to the framework developed in this paper the degree of individuality of a biological system is determined by the ranges of control performed within it.” Bich, Leonardo. 2024. “Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.” Acta Biotheoretica. 72(1):1-22. doi: 10.1007/ s10441-023-09476-4. p. 18.
“Our aim to broaden the problem agenda of biological individuality stems from our work within the DFG-funded Collaborative Research Centre “A Novel Synthesis of Individualisation across Behaviour, Ecology and Evolution: Niche Choice, Niche Conformance, Niche Construction” (in the following ‘CRC’). The CRC is a large interdisciplinary research group involving ecologists, behavioral biologists, evolutionary biologists, and theoretical biologists, in which we participate as resident philosophers. The biologists in the CRC address the task of identifying, studying, and explaining individual differences, such as differences in personalities of individual animals (e.g., boldness, optimism/pessimism), and individualized niches (individuals having different ecological niches).” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 2.
“Identifying biological individuals is closely linked to other tasks, such as demarcating a biological individual from its environment (including from other individuals), decomposing the biological individual into parts, and specifying the kind of unity that holds an individual’s parts together. This is why discussions about biological individuality are often interwoven with discussions about part-whole relations, demarcation, decomposition, constitution, levels, integration, and unity.” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 5.
“The many and contrary biological individuality concepts present problems for both monists and pluralists. Monists aim to find a single consistent, unified and universal concept of biological individuality, which typically prioritizes one kind of identification criterion, such as evolutionary criteria. Hence, monists debate which of the multiplicity of concepts of biological individuality is the right one. As Clarke puts it, “there is a choice to be made about which definition […] to accept.” Pluralists, in contrast, endorse the adequacy of many different individuality concepts in different contexts and for different purposes. A common pluralistic view is that there are different kinds of biological individuality—evolutionary, developmental, metabolic, ecological, immunological, and so on. Pluralists face the problem of determining which of the many individuality concepts operate in which contexts, how they relate to each other and which are appropriate for which purposes.” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 6; reference: Clarke, Ellen. 2010. “The problem of biological individuality.” Biological Theory. 5:312-325. doi: 10.1162/BIOT_a_00068. p. 315.
“The CRC is a large research center with seventeen projects bringing together ecology, behavioral biology, evolutionary biology, theoretical biology, statistics, and philosophy of biology. What unites these projects is their joint interest in identifying, studying, and explaining individual differences, that is, differences between individual organisms in a population. Especially important are individual differences that are temporally stable and contextually consistent, and that are not attributable to broad categories like age, sex, or morphological type. Different fields study individual differences in their own way, including polymorphism in evolutionary biology, individual specialization in ecology, and animal personality in behavioural biology.” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 7.
“The first two of these abstract questions [causes and consequences of individual differences] are related to the CRC’s new framework of so-called NC3 mechanisms (i.e., mechanisms of Niche Construction, Niche Choice, and Niche Conformance).” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 8.
“Since there are many biological individuals with nonunique genomes, genetic uniqueness is usually rejected as a criterion of biological individuality. Other kinds of uniqueness that have been discussed or mentioned include immunological uniqueness, historical uniqueness, epigenetic uniqueness and phenotypic uniqueness.” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 13.
“When asking about individual differences biologists look for a certain kind of temporal stability in phenotypic traits. Two subtypes of temporal stability can be distinguished: continuity and repeatability. Continuous individual differences are those that are constantly exhibited over an extended period of time, such as a whole developmental period or a whole lifetime. For instance, color pattern is an important continuous individual difference in adult fire salamanders. Project A04 [part of CRC] seeks to determine how larval experience affects this continuous individual difference in adulthood. Repeatability, by contrast, refers to traits that are exhibited consistently by an individual at many distinct time points. Animal personalities, for instance, are individual differences in behavioral phenotypes that are stable across times and contexts. For example, an individual beetle is characterized as bold only if it shows the same bold behavior in repeated behavioral tests. In general, biologists discuss whether relevant individual differences should extend across developmental periods, at what timescales they exist and can be studied, and how continuous or repeatable a phenotypic trait must be in order to count as a relevant individual difference .” Kaiser, M.I. & Trappes, R. 2021. “Broadening the problem agenda of biological individuality: individual differences, uniqueness and temporality.” Biol Philos 36(15). doi: 10.1007/s10539-021-09791-5. p. 21.
“Therefore, three different elements, namely the metabolic features of life requiring the maintenance of an energized non-equilibrium situtation, an evolutionary capability, and a dissipative process, turn out to be intimately linked to each other in constituting a living entity. All depend on the continual presence of disequilibrium of the system with respect to the environment.
“At this stage, two main conclusions can be drawn. The first, that no single molecular entity can bear all of these features, so a process involving different components, and therefore a systems chemistry approach, is required. The second, that chemical processes devised to reproduce features of life should therefore simultaneously possess the three essential capabilities specified above.” Pross, Addy & Robert Pascal. 2023. “On the Emergence of Autonomous Chemical Systems through Dissipation Kinetics.” Life. 13:2171. doi: 10.3390/life13112171. pp. 4-5.
“An autocatalytic set is a self-sustaining chemical reaction network in which all the molecules mutually catalyze each other’s formation from a basic food source.” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 224.
“… the authors [Hordijk et al 2015] define a chemical reaction system (CRS) as a tuple Q = {X, R, C, F}, where:
“– X = {x1, x2, …, xn } is a set of molecule types.
“– R = {r1, r2, …, rn } is a set of reactions. A reaction r is an ordered pair r = (a, B) where A, B ⊂ X. The (multi-Set A = {a1,…, as,} are the reactants and the (multi) set B ={b1, …, bt} are the products.
“– C ⊆ X x R is a set of catalysis assignments. A catalysis assignment is a pair (x, r) with x ∈ X and r ∈ R, denoting that molecule type x can catalyze reaction r.
“– F ⊂ X is a food set, i.e., molecule types that can be assumed to be available from the environment.” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 233; reference: Hordijk, W. JI Smith & M. Steel. 2015. “Algorithms for detecting and analysing autocatalytic sets.” Algorithms for Molecular Biology. 10:15.
“In other words, a subset of reactions R’ is a RAF set [reflexively autocatalytic and food-generated set] if for each of its reactions at least one catalyst and all reactants are in the closure of the food set relative to R’. A RAF set thus formalizes Kauffman’s original notion of an autocatalytic set….
“Thus, the RAF formalism, algorithm, and results not only put the notion of autocatalytic sets on a firm theoretical basis, but also put to rest the earlier criticism….” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. pp. 233, 234.
“First the authors [Vasas et al., 2012] make a distinction between the ‘core’ of an autocatalytic set (i.e., a closed catalytic loop), and its ‘periphery’ (i.e., catalyzed reactions branching out from the core)…. … they also allow spontaneous (uncatalyzed) reactions to happen with low probability, which occasionally generates a new catalyst that could even give rise to an entirely new core coming into existence. Finally, they assume that the autocatalytic sets are contained within compartments (e.g., lipid membranes) that grow and divide, distributing the internal molecules between the offspring compartments randomly. In other words, ‘‘Mutation’ happens either when uncatalyzed reactions result in the emergence of a novel core, or when molecular components of a viable core are stochastically lost after compartment splitting’ (p. 10).
“Their investigations then lead them to state: ‘We conclude that only when a chemical reaction network consists of many such viable cores, can it be evolvable. When many cores are enclosed in a compartment there is competition between cores within the same compartment, and when there are many compartments, there is between-compartment competition due to the phenotypic effects of cores and their periphery at the compartment level. Acquisition of cores by rare chemical events, and loss of cores at division, allows macromutation, limited heredity and selectability, thus explaining how a poor man’s natural selection could have operated prior to genetic templates’ (p. 1).
“Such compositional inheritance may only allow for a limited form of evolution, but could very well have been a necessary step towards true open-ended evolution. As the authors state: ‘However, a viable core constitutes one bit of heritable information and therefore the number of possible selectable attractors is relatively small, meaning that autocatalytic networks may not be able to sustain open-ended evolution. While we think this to be the case, the potential role of these autocatalytic networks as a route to nucleotide-based template self-replicating systems should not be underestimated’ (p. 10).” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 236; reference: Vasas, V., C. Fernando, M. Santos, S. Kauffman & E. Szathmary. 2012. “Evolution before genes.” Biology Direct. 7:1.
“In other words, in a hypercycle each member is an autocatalytic self-replicator and, in addition, also catalyzes the self-replication of the next member in the cycle. In contrast, as Kauffman had already stated from the beginning, in an autocatalytic set ‘no molecule need catalyze its own formation’….
“In fact, such confusion also exists between the concepts of autocatalytic sets and autocatalytic cycles. Suffice it to say here that hypercycles are actually a special subclass of autocatalytic sets. However, each member also needing to catalyze its own formation seems a rather strong requirement, which is perhaps why there are (so far) no known experimental chemical examples of hypercycles.” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 238.
“Most enzymes contain one or more small molecules (often referred to as cofactors), such as various metals like iron, zinc, or magnesium, or organically produced molecules like ATP, flavin, or CoA, which actually perform the catalysis. The complicated three-dimensional structure of the protein largely serves to hold everything (the reactants and the cofactor catalyst in the right place. The protein thus makes the cofactor a more specific and more efficient catalyst….
“Indeed, the RAFs found in the metabolic network of E. coli only have a small number of (cofactor) catalysts, just over 40, that together catalyze the close to 1800 reactions in the network.” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 239.
“What Hordijk et al (2018) show is that there is a close mathematical correspondence between chemical organizations [COT theory] and so-called closed RAFs.” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 241.
“Instead of life starting with single self-replicating RNA molecules (for which there still is no experimental evidence), perhaps it started with simple autocatalytic sets that form quite easily, and that initially used molecules like metals and small self-produced organics (modern-day cofactors) as their catalysts. However, these initial autocatalytic sets were able to produce the basic building blocks for RNA and proteins. Once these polymers came into existence, they could have started taking over the role of the initial catalysts, or incorporated them as their cofactors, making them more efficient. This, in turn, would allow for the formation of yet other molecules, in an upward spiral of complexity and diversity, all the way to the first real metabolic networks.” Hordijk, Wim. 2019. “A History of Autocatalytic Sets.” [possibly not final version] Biological Theory. 14:224-246. 10.1007/s13752-019-00330-w. p. 244.
“Despite this history [autocatalysis from dynamical behaviors in so-called dissipative structures, such as bistable reactions, oscillating reactions, and chemical waves … to prebiotic systems], a unified theory of autocatalysis is still lacking…. Here, we present a framework that unifies the different descriptions of autocatalysis and is based on reaction network stoichiometry.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25230.
“[basic definitions of catalysis and autocatalysis from the International Union of Pure and Applied Chemistry] A substance that increases the rate of a reaction without modifying the overall standard Gibbs energy change (▵G̊) in the reaction; the process is called catalysis. The catalyst is both a reactant and product of the reaction. Catalysis brought about by one of the products of a (net) reaction is called autocatalysis.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25230.
“… we derive conditions to determine whether a subnetwork embedded in a larger chemical network can be catalytic or autocatalytic. These conditions provide a mathematical basis to identify minimal motifs, called autocatalytic cores. We found that cores have five fundamental categories of motifs. They allow classification of all previously described forms of autocatalysis, and also reveal hitherto unidentified autocatalytic schemes. We then study the kinetic conditions, which we call viability conditions, under which autocatalytic networks can appear and be maintained on long timescales. We find that networks have different viabilities depending on their core structure, and, notably, that viability is increased by internal catalytic cycles. Finally, we expand the repertoire of autocatalytic systems, by demonstrating a general mechanism for their emergence in multicompartment systems (e.g., porous media, vesicles, multiphasic systems). This mechanism strongly relaxes chemical requirements for autocatalysis, making the phenomenon much more diverse than previously thought.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25230.
“The following reactions have the same net mass balance but a different status regarding catalysis:
“I [:] A ⇆ B,
“II [:] A + E ⇆ B + E,
“III [:] A + B ⇆ 2B,
“Since no species is both a reactant and product in reaction I, it should be regarded as uncatalyzed. Reactions II and III instead contain species which are both a reactant and a product, species E in reaction II and species B in reaction III, and, following the definition above, these species can be considered as catalysts. In reaction II, the amount of species E remains unchanged, in contrast to the case of reaction III, where the species B experiences a net production. For this reason, reaction III represents genuine autocatalysis. Although reaction II is usually referred to as simply catalyzed in the chemistry literature, we propose to call it an example of allocatalysis to contrast it with the case of autocatalysis, catalysis being common to both.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. pp. 25230-1.
“An autocatalytic core is an autocatalytic motif which is minimal because it does not contain any smaller autocatalytic motif. Consequently, an autocatalytic system is either a core or it contains one or several cores.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25232.
“Autocatalytic cores are found to belong to five categories, denoted as type I to type V…. As can be seen in these graphs, all minimal motifs contain a fork, which is a reaction with a single reactant and two products. The presence of at least one fork is consistent with the intuition that autocatalysis requires reaction steps that amplify the amount of autocatalysts. In type I cores, the fork ends with two copies of the same compound, whereas , in types II to V, forks end with different compounds.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25232.
“Stoichiometric conditions do not guarantee that autocatalysts within motifs amplify. Whether an initial autocatalyst amplifies or degrades depends on kinetic considerations.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25233.
“Autocatalytic motifs provide different degrees of robustness, which we evaluated using the notion of viability. Viability can be computed as a survival probability in an appropriately defined branching process. This approach is generally applicable to autocatalytic models upon identification of their cores, highlighting the interest of a unified framework. Viability results from a competition between reactions that produce autocatalysts and side reactions such as degradation…. Autocatalytic motifs are more likely to be found in large networks with many different chemical components engaging in many different reactions, but putting many components together favors side reactions, leading to extinction.
“Multicompartment autocatalysis introduced here offers a way around this problem: Coupled compartments [permitting diffusion of some members of ACS and not for others] effectively enlarge the number of species without requiring new reactions. In multicompartment autocatalysis, cycles rely on the environmental coupling of reaction networks, which allows access to conditions unattainable in a single compartment. In this way, autocatalysis can emerge from reaction schemes as simple as a bimolecular reaction, provided certain semipermeability conditions are met for the exchange of compounds between compartments.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25235.
“Overall, our framework shows that autocatalysis comes in a diversity of forms and can emerge in unexpected ways, indicating that autocatalysis in chemistry must be more widespread than previously thought. This invites a search for further extensions of autocatalysis, which provides new vistas for understanding how chemistry may complexify toward life.” Blokhuis, Alex, David Lacoste & Philippe Nghe. 2020. “Universal motifs and the diversity of autocatalytic systems.” PNAS. 117(41):25230-36. 10.1073/ pnas.2013527117. p. 25235.
“Using this model [that the paper develops of autocatalytic chemical reaction networks], we show that a single autocatalytic cycle exhibits dynamics similar to the population dynamics of a single biological species. Furthermore, the interactions between multiple autocatalytic cycles can be described in the framework of community ecology, including competitive, predator-prey, and mutualistic interactions.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 3.
“Although autocatalysis was originally ascribed to single reactions, it has long been appreciated that a set of reactions can be viewed as autocatalytic insofar as there are some chemicals that (a) raise the rate of the reaction set, and (b) are present in the products of the reaction set. Thus, if for every catalyzed reaction the catalyst is treated as both a reactant and a product, we can define autocatalysis as a process consisting of one or multiple elementary chemical reactions, where at least one chemical is present in both the reactants and products but with a smaller stoichiometric coefficient on the reactant side than that on the product side. Any chemical showing this stoichiometric asymmetry will be referred to here as a member chemical (or briefly, as a member) of the autocatalytic process. Among other chemicals, those with larger stoichiometric coefficients on the reactant side will be referred to as food, and those only present in the products will be referred to as waste. Thus, autocatalytic systems consume food to produce more members (and, perhaps, waste). Under this stoichiometry-based definition of autocatalysis, any autocatalytic process will have some cyclical organization within its reaction network, because there must be at least one chemical that is present in both the reactants and products of the system as a whole.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 3.
“We show that simple autocatalytic cycles exhibit logistic growth in a flow reactor when the reactor is seeded with a small quantity of a member and the ratio of the food concentration to the dilution rate is above a threshold. In such cases, the growth rate and carrying capacity can be connected back to flow parameters and reaction kinetics. This result demonstrates that individual autocatalytic cycles have conceptual equivalence to populations of individual species and implies that chemical reaction networks composed of multiple autocatalytic cycles that are actualized in a specific environment can be equated with a chemical ecosystem.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 14.
“Diverse interactions among autocatalytic cycles, combined with the potential for rare seeding of previously inactive cycles, allows chemical ecosystem to show complex, long-term dynamics. Among other patterns, it is possible for a chemical ecosystem to transition between a series of transiently steady states, each characterized by a different set of active and viable cycles (together with their peripheral reactions). We would argue that this phenomenon, which is driven by both stochastic and deterministic forces, can validly be equated with ecological succession and exhibits some evolutionary features.
“Using a series of numerical simulations, we have demonstrated that autocatalytic cycles can negatively affect one another, via predation on member chemicals, production of cross-inhibitors, or competition for food or waste. Likewise, autocatalytic cycles can form reciprocal mutualisms, for example by cross-feeding or removal of waste. Indeed, sets of cooperating autocatalytic cycles can be seen to show autocatalysis at a higher hierarchical level in much the same way that biological ecosystems can show autocatalysis among multiple individual species.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 14.
“An emerging view [Walker & Davies, 2013] is that heritability in early life was encoded by chemical concentrations, or analog inheritance, with a later transition to sequence-based encoding in linear polymers, or digital inheritance.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 15.
“Although we were able to show that a sufficient flux of food can drive a system out of equilibrium regardless of the standard Gibbs energy change of the chemical reactions, we also observed that autocatalytic systems that are thermodynamically favored, having higher rate constants in the autocatalytic direction, tend to grow faster and achieve higher carrying capacity, resulting in a competitive advantage. This implies that, if competing cycles were seeded over time, and those cycles could exploit different food and/or generate different waste chemicals, the cycles that persist will tend to be those that are most thermodynamically favored, using food that is further from thermodynamic equilibrium and producing lower-energy waste. We would go so far as to speculate that the irreversibility of modern life is not an indication that the life state requires truly irreversible chemistry but that there has been a persistent tendency for less and less reversible cycles to have become enriched in metabolic systems over the eons due to adaptive evolution.
“We also show that, regardless of thermodynamics, autocatalytic cycles with overall higher rate constants are favored. Since catalysts, by definition, raise reaction rate constants, this implies that catalyzed cycles will also tend to predominate.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 17.
“Generally, we would expect polymers to behave like predators or parasites of monomer-producing cycle(s) since they would siphon off member chemicals and reduce growth. However, if some polymers provided a benefit to the monomer-producing cycle through catalysis, the polymers and the monomer-producing cycle could both increase in abundance, making them collectively more competitive and more extinction-resistant.” Peng, Zhen, Alex M. Plum, Praful Gagrani & David A. Baum. 2020. “An ecological framework for the analysis of prebiotic chemical reaction networks.” J. Theor. Biol. 507:110451. 10.1016/ j.jtbi.2020.110451. [page numbering uncertain] p. 17.
“Recently, it was shown that orotidine containing RNA has severely compromised base pairing properties, which would detrimentally affect the functions of an informational/catalytic RNA. Nevertheless, it could be argued that weaker-base pairing could have helped overcome inhibitions of strong base-pairing systems in a primordial system or orotic acid could have acted as site-specific catalyst in a ribozyme. Moreover, a detrimental functioning capability of orotidine vis-a-vis uridine or cytidine would be easily understood and argued in an evolutionary sense: orotidine is functionally inferior and would be outcompeted by uridine and cytidine. However, appealing, it should be noted that the base-pairing function or catalysis argument can be applied only at the level of an RNA oligomer and not at the level of the RNA monomer (nucleoside or nucleotide). Thus, the ‘uselessness’ of orotic acid/orotidine versus the ‘usefulness’ of uracil/uridine or cytosine/cytidine cannot be determined at the point of prebiotic origination of the monomers but only at the much higher level of a functional RNA polymer – which is not available by the type of prebiotic reactions that give rise to the various nucleobases. One cannot impose teleology on the nuclobases or nucleotides anticipating their usefulness ‘up the evolutionary road’. Therefore, the mere formation (or presence) of the uracil and cytosine (or for that matter, any other canonical or non-canonical nucleobase) and their respective nucleosides and nuclotides, under potential prebiotic conditions (in meteorites), cannot be used to justify their presence or absence in life’s processes. While their prebiotic formation is a necessary condition, it is not the only condition that needs to be fulfilled. It is merely a first step in a long process towards assessing whether they are useful in a functional context – a selection that is based on an emergent property manifested at the supramolecular level.” Krishnamurthy, Ramanarayanan. 2018. “Life’s Biological Chemistry: A Destiny or Destination Starting from Prebiotic Chemistry?” Chemistry: A European Journal. 24(63):16708-16715. 10.1002/chem.201801847. [page numbering uncertain] pp. 4-5.
“Autocatalytic reactions, however, were never popular in conventional chemistry and chemical technology mainly for two reasons: (1) autocatalysis gives rise to positive feedback, which is difficult to control and to handle in large reactors, and (2) autocatalytic systems may show complex dynamical phenomena such as bistability, oscillations, deterministic chaos, and spontaneous formation of spatial patterns or waves, which are not desirable in chemical production. The whole collection of these phenomena has been called nonlinear chemical dynamics by Irving Epstein and others.” Schuster, Peter. 2019. “What is special about autocatalysis?” Monatshefte fuer Chemie. 150:763-775. 10.1007/s00706-019-02437-z. p. 763; reference: Epstein, I.R. & J.A. Pojman. 1998. “An introduction to nonlinear chemical dynamics: oscillations, waves, patterns, and chaos. Oxford UP.
“We develop the concept of seed-dependent autocatalytic systems (SDASs)–subnetworks whose components can self-propagate once activated by ‘seed’ molecules, which might result from rare reactions or import from other environments.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 2.
“Whatever the nature of the first evolver, it must have been able to self-propagate because a system that lacks a way to make more of itself has no way to generate descendants that can manifest heritable differences, as is required for evolution. Moreover, self-propagation ability is needed for a system to maintain status quo in any open environment, since dilution and other disturbances are inevitable in the long run. As a result, for the first evolver to exhibit two core attributes of life, namely self-maintenance and the capacity to evolve, it must have been autocatalytic.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 2.
“… Chemical Organization Theory (COT), which is an otherwise promising candidate for explaining abiogenesis, does not necessarily require autocatalysis because it does not enforce environmental openness. Therefore, COT, in its current form, is not optimal for elucidating abiogenesis.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 2.
“The theories of collectively autocatalytic sets (CASs), and reflexively autocatalytic, food-generated sets (RAFs), have been used extensively to explore autocatalysis in relation to abiogenesis. Both models assign a central role to explicit catalysis: for a chemical reaction network represented by connected nodes of species and reactions, explicit catalysis applies when a reaction node is directly catalyzed by one or multiple species nodes within the network. Although explicit catalysis is highly enriched in modern metabolism, primarily due to the activity of enzymes and ribozymes, we believe that it is improbable that most reactions in the first evolver were explicitly catalyzed by internally synthesized catalysts. Considering the relative simplicity of the prebiotic Earth, it was more likely that most reactions in the first evolver occurred without explicit catalysis or depended on simple environmental catalysts. Moreover, an emphasis on explicit catalysis can distract attention from a key feature of autocatalytic systems, namely the potential for stoichiometric increase of the system’s internal components. An autocatalytic cycle can show stoichiometric autocatalysis even if it does not include any explicit catalysts. For example, with A provided as food, A + B ⇄ C, C + A ⇄ 2B is an autocatalytic cycle but not a RAF.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 3.
“Our results support the idea that sequential activation of SDASs, combined with occasional deactivation of previously active SDASs, may be a primordial mechanism of evolution before the origin of genetic polymers.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 3.
“In an open environment where F constantly flows in but A cannot spontaneously emerge, A + F –> 2A is a simple SDAS because a seed comprising the member species, A, is able to trigger the sustainable conversion of F into A. Here, A is a supported seed. Alternatively, this SDAS could be seeded by a species that can be converted into A; for example, given another reaction B ⇄ A + C, B is an unsupported seed, because sustained production of B also requires C, which is not provided as environmental food. However the SDAS is triggered, it is not guaranteed to be able to self maintain in practice, because the reaction(s) may not be fast enough to overcome ongoing dilution. This illustrates that SDASs are topological not kinetic features of chemical reaction networks.”
“A seed, supported or unsupported, could comprise a single chemical species (e.g., A or B in the preceding), being a singleton seed, or it could comprise a set of chemicals that need to be seeded together to trigger a SDAS, being a composite seed.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 4.
“An activated SDAS increases the diversity and perhaps complexity of the chemical species that can be sustained in an open environment.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 5.
“Some species of an initial SDAS could be essential for another SDAS to be sustained. In this case, it may be possible to seed the latter, higher-tier SDAS only after the lower-tier SDAS has been activated. This resembles a biological ecosystem where a higher-trophic-tier consumer can only invade an ecosystem that already contains suitable lower-trophic-tier organisms. Because higher-tier-SDAS members likely require more reactions to be synthesized from environmental food, on average we might expect higher chemical complexity in higher-tier SDASs than in lower-tier SDASs.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 6.
“An interesting potential effect of SDAS-organized networks is scaffolding. This applies when a lower-tier structure, a scaffold, helps build a higher-tier structure but, once built, the higher-tier structure is robust to the removal of the scaffold.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 6.
“To summarize this conceptual framework, sequential activation of hierarchically organized SDASs provides a potential mechanism for reaction networks to complexify in an open environment. Such a network architecture would mean that rare reactions or occasional influx of chemicals could induce stepwise complexification in an environment receiving simple species as food, as commonly assumed in abiogenesis scenarios. Moreover, some higher-tier SDASs could alter emergent properties, for example conferring resilience to environmental perturbations, potentially mediating primordial adaptation.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 6.
“We formalized the concept of SDASs, developed methods to detect and analyze them, and used the methods to explore the potential for self-maintenance and complexification in two real chemical reaction networks. We found that the abiotic and biochemical networks share multiple properties, including hierarchically organized SDASs converting simple materials and energy to more complex species.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 15.
“For anyone who knows Louis Pasteur’s gooseneck flask experiment and accepts that a bacterium is an autocatalyst, the idea of seeding should be straightforward – an autocatalytic system can, once seeded, propagate itself in the presence of food but cannot spontaneously emerge from food alone. Multiple researchers have stressed this feature of autocatalytic systems, although with different terminology and framing, for example ‘obligate autocatalyst’, ‘exclusive autocatalysis’, and ‘reactions that are part of autocatalytic cycles’ but are not accessible by ‘direct synthesis reactions’.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 16.
“As we have pointed out previously, the seeding of autocatalytic motifs provides a basis for heritable change and, thus, evolution. When a new, viable SDAS is activated by a seed or an existing SDAS is deactivated due to environmental changes (as in the case of scaffolding), a new heritable state may arise. This makes activation and deactivation of SDASs the pre-genetic analog of mutations. Indeed, insofar as a genetic mutation entails a rare chemical reaction creating or deleting a nucleic acid sequence that is capable of autocatalytic maintenance due to the replication machinery, a genetic mutation is a special case of a chemical seed. This suggests that the concept of seed-dependent autocatalysis provides a conceptual bridge between the evolution-like dynamics of food-driven, small-molecule reaction systems and the more familiar Darwinian evolution of genetic-based systems.” Peng, Zhen, Jeff Linderoth & David A. Baum. 2022. “The hierarchical organization of autocatalytic reaction networks and its relevance to the origin of life.” PLOS Computational Biology. 10.1371/ journal.pcbi.1010498. p. 16.
“The circularity of process and structure shapes the development of the living being over time.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 2.
“Thus, living [object body, Koerper] and lived body [subject body, Leib] are in a relation of mutual concealment, because they bring forth or constitute each other, and this is what defines our embodiment. A well-known manifestation of this reciprocal relation is the phenomenon of double touch as highlighted by Husserl: if one’s right hand touches the left, the latter appears as a palpable object offering resistance to the right hand’s touch (i.e. as Koerper); however, through a change of attention, it can also become a feeling hand, sensing the touch, that is, a part of the bodily subject (Leib).
“This example shows that lived body and living body correspond to two different perspectives or attitudes between which we shift in everyday life, usually without being aware of it. Nevertheless, both perspectives are related to one and the same living being, a living being that displays two different aspects…. Instead of such a gap between two radically different ontologies (the mental and the physical), we are now faced with a duality of aspects within embodiment. The question, then, is about the relation between one’s body as a living organism and one’s body as subjectively lived. And the answer must be that processes of living and processes of experiencing (in German: Leben and Erleben) are both aspects of the organism’s life process seen from different but complementary points of view.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 2.
“In sum, taking an embodied and enactive approach implies extending one’s view, both with regard to space and time: looking at the wider system and how it develops over time. Then we can see both experiential and physiological processes, the lived body and the physical body as belonging to a more encompassing system, namely, the system of the living being and its environment, or of the person and her world – an ecological system that is in continuous development.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 3.
“To begin with, there are two interactive or feedback cycles that form the basis of the embodied mind:
“(a) Cycles of organismic self-regulation, engendering a basic bodily sense of self; and
“(b) Cycles of sensorimotor coupling between organism and environment, implying an ‘ecological self.’” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 3.
“Affective neuroscience, represented by authors like Damasio and Panksepp, has emphasized the dependence of a background consciousness on the homeodynamic regulation of the entire body: various centers in the brain stem, hypothalamus, and insular and medial parietal cortices process the proprioceptive, visceral, vasomotor, endocrine, and other afferences from the internal body and integrate them into a ‘body landscape’ that is constantly changing.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 4.
“The foundation of subjectivity thus lies in the visceral or ‘deep body’ and its vital self-regulation. This may be considered as an organismic basis for the life-mind continuity thesis supported by enactivism.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 4.
“In phenomenological terms, each bodily action implies anticipations or protentions (being prepared for the response of the environment) that may or may be not fulfilled in subsequent perceptions. Thus, protention and response form a temporal circle that extends into the future. Similarly, objects are always perceived as enabling possible actions, or in Heidegger’s terms, as objects ‘ready to hand’. This is captured, in ecological psychology, by Gibson’s term affordances, which are objective structures of usefulness or viability provided by the environment. ‘The uses of things are directly perceived’, but this perception is at the same time a perception of future possibilities that correspond to the body’s capacities and protentions. An object such as a knife can only be perceived by an embodied agent capable of somehow interacting with it, for example, by having suitable limbs to walk toward the knife, grasp it, and so forth, thus perceiving the knife as an affordance structure. In a way, the knife is a unity of present and future. Indeed the entire body (and by no means only the brain) may be regarded as a system of expectations and ‘predictions,’ which make sense of the environment as a space of potentialities or affordances and their possible fulfillment.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 5.
“Homeostasis is now achieved not just by simple set point regulation but also through external sensorimotor loops by which the organism actively establishes and ensures the conditions of its self-sustainment. The circular structure of internal self-regulation is thus extended spatially as well as temporally: through anticipating possible satisfaction or danger, living beings are able to seek preferable situations and to avoid precarious ones – a crucial mark of their adaptivity. As this goes beyond internal homeostasis, Sterling and Vernon et al. have introduced the suitable model of allostasis to describe a mode of self-regulation by anticipating needs and preparing to satisfy them before they arise…. For these extended loops, drives and emotions play a crucial role: distant goals require a striving (or aversive) anticipation.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 5; references: Sterling, P. 2012. “Allostasis: a model of predictive regulation.” Physiol Behav. 106:5-15. 10.1016/j.physbeh.2011.06.004; Vernon, D., R. Lowe., S. Thill & T. Ziemke. 2015. “Embodied cognition and circular causality: on the role of constitutive autonomy in the reciprocal coupling of perception and action.” Front. Psychol. 6:1660. 10.3389/ fpsyg.2014.001660.
“The account of sense-making given so far also allows us to see affordances as having a dual aspect, as Gibson has suggested:
“‘[A]n affordance is neither an objective property nor a subjective property; or it is both if you like’.
“The concept of circularity can be applied to this dual aspect of affordances, which are neither purely physical properties nor subjective mental projections:…
“– On the other hand, the environment objectively offers precisely these possibilities of interaction [affordances], thus providing a suitable ‘niche of affordances’ for the living or object body. In the course of a concrete action, these affordances and their sensory flow continually define the body’s further sense-making activity.
“In other words, there is a circular interrelation between the needs of animals and the corresponding affordances in the environment, which are disclosed by these needs. This relation itself is an objective feature of the ecological system. Affordances are real, regardless of whether they are currently perceived or used. Thus, the structural coupling of organism and environment renders affordances objective relational properties in the world.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 5; subquote: Gibson, J.J. 1979. The Ecological Approach to Visual Perception. Houghton Mifflin. p. 129.
“The brain functions rather as an organ of suitable dispositions: Through its networks, it provides open loops of possibility that are closed by suitable complements in the environment and thus become functional cycles of interaction.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 5.
“Therefore, neural processes should be described neither as internal representations nor as models or predictions but rather as dispositional patterns that participate in dynamic sensorimotor cycles involving the whole organism-environment system….
“Hence, consciousness may not be localized in any one place; it is the ‘integral’ of the ongoing interaction and resonance between the brain, body, and environment.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 6.
“As we can see, from an enactive approach, the phenomenology of bodily being in the world corresponds to the ecology of the organism in relation to its environment.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 6.
“… the basic self-awareness arising from the deep body forms the core of the body-as-subject. This core is extended as bodily ‘being toward the world,’ where the body functions as medium of our sensorimotor interactions with the environment. Both the basic bodily self-awareness and the extended lived body may be regarded as the integral of the brain-body and the brain-body-environment cycles, respectively.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 6.
“In other words, my embodied intentions and protentions are able to organize their physical implementation with the potential to even achieve a future state that does not yet exist. On a more basic level, such temporal loops also enable the allostasis mentioned above, by which conscious organisms regulate their needs in advance. The coupling of an organism’s protentions and the corresponding environmental affordances act as a higher-order cause of the respective interaction. As overarching and future-directed enactments of life, conscious processes may thus be effective in the behavior of a living being without ‘acting on brain processes’ in an external way.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 7.
“Development, learning, and memory formation may thus be conceived as a circularity of living process and solidified structure, continuously modifying each other….
“All this may be expressed by the principle ‘form follows function’: consciously interacting with the environment induces the development of the neuronal structures necessary for ever smoother interaction and experience.
“This is the basis of learning, memory, and development from birth on: a downward effect of the superordinate body-environment system, corresponding to the subjective experience, induces adaptive changes in the neural substrate, which in turn enable improved functioning. It may also be described as a continuous circularity between experiential process and organic structure, or in other words, between lived body and physical body. Over time, repeated experiences are sedimented or incorporated in what may be termed body memory, namely, the totality of dispositions, habits, skills, and interactive schemes acquired by an individual in the course of his or her development.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. pp. 8, 8-9.
“Switching between both aspects in the diachronic sequence [the wider system of organism and environment and physiological processes], we can also speak of a spiral-shaped development: lived body and organic body, each considered as aspects of the life process, mutually influence and modify each other….
“In the diachronic dimension [considering the above spiral over time], then, the two-dimensional circle of body-environment interaction actually becomes a three-dimensional spiral. Experience turns into the organism’s altered dispositions, which change the perceived environment and its selected affordances, thus in turn enabling new experiences, and so on.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 9.
“In this paper, I have studied the interrelation of lived or subject body (Leib) on the one hand and living or object body (Koerper) on the other. Both were considered as complementary, irreducible, mutually constituting, and also mutually concealing aspects of the living being. They correspond to two different attitudes that we may adopt: in the personalistic attitude, we experience our own lived body from a first-person perspective or the other’s lived body from a second-person perspective. In the naturalistic attitude, we observe or investigate the physical body from a third-person perspective. Whereas the personalistic attitude and its corresponding aspect require a holistic view of the living being or the person, the naturalistic attitude allows for focusing on increasingly narrow sections and details of the physical body, albeit at the price of losing the phenomena of life and mind.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. pp. 10-11.
“In order to further investigate the relation of both aspects and the ‘body-body problem,’ I have interpreted the intertwinement of subject body and object body on the basis of the concept of circularity. First, embodiment shows a circular structure, because it is based (a) on the cycles of homeostatic self-regulation between the brain and body and (b) on the sensorimotor cycles between the brain, body, and environment. The first cycle is the foundation of the feeling of being alive, or the pre-reflective background feeling of the body itself. The second cycle is the basis of bodily ‘being toward the world’ (Merleau-Ponty), or of situated, enactive subjectivity. Here, in terms of ecological psychology, living beings and their surroundings constitute an interactive system, with each constituent being reciprocal to the other: what we perceive are not objects as such but objects to deal with, or the functional relations between self and world.” Fuchs, Thomas. 2020. “The Circularity of the Embodied Mind.” Frontiers in Psychology. 11(1707). 10.3389/ fpsyg.2020.01707. p. 11.
“The ability to selectively perceive specific stimuli, the discrimination between favourable and unfavourable, the assessment of the overall valence of a situation, the retention of memory, and the integration of information for decision-making–all of this was in place in one form or another in unicellular organisms and early metazoans that did not (yet) possess a nervous system. In consequence, what did the nervous system enable? A first answer can be easily framed: nervous system evolution is about information exchange and integration between cells. It is about shifting cognition from the unicellular to the multicellular level; it is about the evolution of circuits.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 1.
“As advocated by the twentieth-century comparative neurobiologists, the new functionality that came with the nervous system may indeed have been most apparent at the tissue level–with a nerve net as a whole-body integrative system. Nascent nerve nets may have coordinated body movements–involving contractions of tissue sheets for rapid shape changes, or ciliary beating across tissues for feeding and locomotion. Either option finds support in recent single-cell transcriptomics-based, whole-body cell type and tissue comparisons; and both inventions would have been especially relevant in animals of increasing body size. This suggests that the non-neural-to-neural transition may have occurred more than once, in different tissues and, possibly, distinct evolutionary lineages.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 2.
“Parker and followers emphasized the sensory nature of the first neuron, and regarded it the sister cell type of sensory epithelial cells. Implicit to this view, these sensory cells would have started secondarily to emit signals to the neighbouring effector cells via secretion. Other authors turned this view around and instead assumed that the secretory nature of the neuronal precursors was first and the sensory nature secondary. They thus considered the sister cell type of the first evolving neuron a secretory cell. Consequentially, neurons would have first appeared as neurosecretory cells.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 4; reference: Parker, G.H. 1919. The Elementary Nervous System. Philadelphia: Lippincott; Jekely, G. 2011. “Origin and early evolution of neural circuits for the control of ciliary locomotion.” Proc. R. Soc B. 278:914-922. 10.1098/rspb.2010.2027.
“In search of the first evolutionary manifestation of the nervous system, some authors in the mid twentieth century no longer envisaged local, vertical circuits. Instead, they postulated the primacy of the elementary nerve net: i.e. neurons forming large horizontal networks spanning entire tissues from the very beginning…. A primordial nature of the nerve net would require that some kind of tissue- or body-wide system predated the nervous system, which then evolved into the nerve net. If so, what was the nature of this system and what was its function?” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 5.
“Just like tissue contraction, ciliary beating patterns that may have enabled such swimming movements [for Ediacaran “multicellulars”] would have required increasing degrees of coordination with increasing body size.
“A concurrent scenario for nerve net evolution at the tissue level thus gains momentum: namely that ciliated tissue with coordinated beating was centre stage in nerve net evolution.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 7.
“Here [the neurosecretory network hypothesis], nervous system evolution starts from a sheet of ciliated cells. Initially, cilia are both sensory and motile and respond to environmental cues autonomically with changes in their beating pattern. Enhanced synchronization between cells is then achieved via the basal release of neuropeptides that trigger autocrine and paracrine amplification. Via division of labour, some of these cells specialize in sensory perception and neuropeptide release and become sensory-secretory cells interspersed among ciliary effector cells…. In this arrangement, all tissue cells would be linked up into a chemical network made up of diffusible neuropeptides. Yet, signalling via diffusion of peptides becomes inefficient in larger bodies. This prompts the gradual horizontal elongation of basal secretory processes until they overlap between distant neurosecretory cells. Finally, synapses would evolve between these processes, thus interconnecting sensory-neurosecretory cells of the same type into coherent nerve nets … This way, the now physically interconnected network cells would be able to display rapid synchronized activity with pulsatile peptide release for the tissue-wide control of ciliary beating or contractions.
“The neurosecretory network hypothesis finds support by the omnipresence of complex peptidergic signalling in all animals except sponges….” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. pp. 7-8.
“All of the above views [list below in text] on nervous system origins assume specific sister cell type relationships between neurons and other body cells. The contractile network hypothesis considers some kind of myocytes to be most closely related to neurons. In contrast, the neurosecretory network hypothesis would see secretory cells in this position. Alternatively, immune cells might be the most closely related to neurons. These hypotheses can nowadays be tested on molecular grounds.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 9.
“Recent progress in sequencing the transcriptomes of single cells from entire bodies allows the testing of these hypotheses [for genetic clues to origin of neuron] via comparison of cell type-specific transcriptional profiles within and across species…. …first observations indicate support for both the contractile network hypothesis and the neurosecretory network hypothesis.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 11.
“According to all prevailing hypotheses the incipient nerve nets enabled some complex feeding or locomotor behaviour, and can thus be seen as an adaptation towards enabling such whole-body movements under the constraint of increasing body sizes.” Arendt, Detlev. 2020. “Elementary nervous systems.” Philosophical Transactions of the Royal Society: B. 376:20200347. 10.1098/ rstb.2020.0347. p. 11.
“In this paper, we propose that Darwinian evolution is not a discretely delimited mechanism of change but one member of a broader class of autocatalytic chemical ecosystem (ACE) processes. ACE processes are characterized by self-amplifying subsystems called autocatalytic cycles (ACs) that include not only the life cycles of genes and organisms but also motifs that are abundant within abiotic chemical reaction networks. Importantly, because ACs tend to persist once activated (given sufficient flux of food/energy), they serve as a basic unit of memory or inheritance. It can be shown that superficially different ACEs, for example cells, ecosystems and certain localized chemical reaction systems, can all be described using the same formalism.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. pp. 1-2.
“A biological ecosystem comprises a location where food and energy flux allow the persistence of a community of one or more species. Each species in the community is composed of organisms whose life cycles are canonical examples of ACs. An AC can be defined as a series of reactions that consumes [sic] inputs, which we will call food, and includes reactions among a set of internal components, which we will call members, where there is at least one ‘branching reaction’ that confers stoichiometric growth.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. pp. 2-3.
“When ecosystems contain more than one species, these species may be linked by diverse ecological interactions, including competition, predation and mutualism. These interspecific interactions can link autocatalytic life cycles together into higher-level ACs. A simple example would be a pair of obligately mutualistic species that exchange key resources. In that case, the exchanged resources are members of a combined AC, which contains at least two branching reactions (one in each life cycle). As a result, when we track all the chemical and physical resources, any real ecosystem forms a complicated chemical network with multiple inter-connected and nested ACs. Thus, a biological ecosystem is a special case of an ACE: a localized environment that receives a flux of food and energy and sustains ACs.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 3.
“One important set of ACs inside a cell are those that result in gene replication. Strand separation of a DNA duplex following second-strand synthesis is a branching reaction where each product can be converted back to a new duplex by complementary base pairing and new strand synthesis.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 3.
“Seed-dependent autocatalytic systems have the property that, once seeded into a supportive ecosystem, they have the potential to persist indefinitely. In this sense, succession can, indeed, be seen as intrinsic change, because the set of species present at a moment in time is highly correlated with the set present at an earlier time, even if the physical environment changed greatly in between. Thus, seeding of species into an ecosystem represents a kind of ecological memory, which is analogous to the heritable changes that underlie evolution.
“As ACE processes, succession via species seeding and evolution via genetic mutation have many deep similarities. In succession, seeding of a new AC occurs via stochastic dispersal of a viable seed from a regional species pool. In evolution, mutation occurs when a rare chemical reaction yields a different DNA sequence (usually destroying an ancestral molecular sequence in the process) that is a member of a new gene replication AC. In either case, if the new AC is viable in that physical environment, it will become established. This will transition the ACE to the vicinity of a new dynamical attractor, resulting in a novel quasi-stable state where the new AC is active.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. pp. 4-5.
“If a single cell is equated with a localized chemical ecosystem, then a population of cells is equivalent to an auto-catalytic chemical meta-ecosystem or ACME. The ecological analogue of evolution applies when the frequency of different ecosystem compositions (where an ecosystem’s composition is its set of active ACs) changes in an ACME….
“Based on this analysis, changes in biological meta-ecosystems and genetic populations are deeply homologous: in both cases, changes in the abundance of different ACs in an ACME provide the basis of intrinsic (thus heritable) change.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 5.
“Taken together, it seems inevitable that chemical ecosystems on the prebiotic Earth would have complexified by a process resembling biological succession with chemical ACs providing the units of heritable change. Combined with the insight that ecological change and Darwinian evolution are both examples of ACE processes, it is likely that the first prebiotic systems showed succession-like dynamics but became more and more paradigmatically Darwinian in character over time.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 6.
“If the first evolving systems resembled canonical meta-ecosystems with independent AC dispersal, then explaining the origin of autopoietic cells requires that we provide a mechanism by which co-dispersal dynamics could arise–ideally a mechanism that predicts a selective advantage to those ACs whose members promote co-dispersal.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 6.
“Others have argued that such autopoietic entities are too complicated to arise spontaneously, a position we are inclined towards. In that case, a growth-division life cycle must be an evolved feature regardless of whether the first evolving entities were bounded by discontinuities in the physical environment or lacked boundaries entirely, for example ACEs confined to a continuous mineral surface.
“Under the view that autopoiesis is an evolved characteristic, the origin of the first autopoietic system was the first major transition in evolution.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 6.
“Thus, ACs whose members promote co-dispersal, for example by chemical tethering or entrapping multiple chemical seeds, could be favoured by ecosystem-level selection. Combined with the capacity for amphiphilic compounds to self-assemble into vesicles, it is not hard to imagine how a protocell-like compound seed (i.e. a unit seeding many ACs at once) could arise and eventually give rise to a protocell.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 7.
“In contrast, nucleic acid molecules have a generic ability to undergo template-mediated replication, independent of the cellular functions of those sequences: almost any DNA sequence is a member of an AC (along with its reverse-complementary sequence’s AC). Moreover, the seeding of a new gene replication AC happens via mutation, where a rare chemical reaction replaces a pre-existing sequence with a new, but very similar mutant sequence. Genetic mutation is, thus, a seeding process where the resulting seed is highly correlated to the prior state. This increases the changes that a new AC will be viable and explains the ability of genetic populations to constantly tinker with already-functional phenotypes, permitting the systematic exploration of adaptive landscapes by hill-climbing.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 7.
“Moreover, paradigmatic Darwinian evolution also entails genetic variation introduced by migration or lateral gene transfer. In this way, the distinction between genetic mutations and ecological seeding becomes blurred. Moreover, there are mechanisms available that could result in a system becoming progressively more genetic (and less ecological) over time.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 7.
“Mathematical models have demonstrated that given a protocell with analogue inheritance involving many RNA molecules, a single master genome can gradually evolve.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 8.
“In this section, we have shown that two key features of modern cells, template-replicating heteropolymers and covalent genomes enhance cellular adaptation…. We have also provided logical arguments to support the claim that both features could gradually evolve in populations of compositional protocells. Combined with our prior discussions, this insight implies that paradigmatic Darwinian evolution is a derived rather than ancestral feature of life–a claim that has profound implications for the study of life’s origin on Earth and (presumably) elsewhere in the Universe.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 8.
“In this paper, we have argued that cells and organisms are ecosystems with a formal equivalence to local patches in a biological or strictly chemical meta-ecosystem. While modern cells are self-bounding and contain many ACs that include genetic polymers, these are differences in degree rather than kind. This observation means that autocatalytic ecology not only defines formal identity of very different kinds of ACEs, but also provides a framework for exploring the gradual evolution of genetic cells from non-genetic, non-autopoietic ancestors.
“The position staked out here is that ecological and evolutionary changes are not inherently different but represent ends of a continuum. This implies that it ought to be possible to articulate a general theory of change that applies to phenomena as diverse as succession, development, Darwinian evolution and chemical reaction dynamics.” Baum, David A., Zhen Peng, Emily Dolson, Eric Smith, Alex M. Plum & Praful Gagrani. 2023. “The ecology-evolution continuum and the origin of life.” Journal of the Royal Society Interface. 20:20230346. p. 8.
“Recent findings suggest that the CNS simplifies motor control by constraining muscles to be activated in fixed groups, or synergies, where each synergy is defined as a set of muscles recruited by a single neural command signal. Complex muscle activation patterns in a wide range of motor tasks including locomotion, finger spelling, and postural tasks, can be decomposed into the summed activation of just a few muscle synergies. A muscle synergy control structure provides an attractive simplifying strategy for the control of complex movements because it reduces the number of output patterns that the nervous system must specify for a large number of muscles yet allows flexibility in the final expression of muscle activation.” Torres-Oviedo, Gelsy, Jane M. Macpherson & Lena H. Ting. 2006. “Muscle Synergy Organization Is Robust Across a Variety of Postural Perturbations.” J. Neurophysiol. 96:1530-1546. 10.1152/jn.00810.2005. p. 1530.
“In conclusion, we identified a set of five functional muscle synergies that was robust across a range of dynamic postural tasks [for cats] as well as quiet stance and generalized across subjects. This finding suggests that a synergy organization forms part of the neural control structure for the motor system. This type of neural mechanism effectively reduces the musculoskeletal redundancy inherent in the multisegmented limb and allows for rapid activation of functionally appropriate responses for automatic postural adjustments. It is likely that such a control structure underlies other types of automatic as well as voluntary movements.” Torres-Oviedo, Gelsy, Jane M. Macpherson & Lena H. Ting. 2006. “Muscle Synergy Organization Is Robust Across a Variety of Postural Perturbations.” J. Neurophysiol. 96:1530-1546. 10.1152/jn.00810.2005. p. 1545.
“Our analysis extends the literature on bodily regulation by suggesting that allostasis is a whole-brain phenomenon, rather than attempting to localize it to a small set of brain regions.” Katsumi, Yuta, Jordan E. Theriault, Karen S. Quigley & Lis Feldman Barrett. 2022. “Allostasis as a core feature of hierarchical gradients in the human brain.” Network Neuroscience. 6(4):1010-1031. 10.1162/netn_a_00240. p. 1011.
“Evolutionary, developmental, and anatomical studies of the vertebrate brain all suggest that its fundamental job is to efficiently regulate the body’s internal systems as an animal navigates its environmental niche. Predictive regulation is an improvement over reaction because reactive systems adapt only in the face of error, but any mistake is potentially fatal. Prediction also limits the extent to which incoming signals need to be encoded, which may save the metabolic costs of learning predictable information.” Katsumi, Yuta, Jordan E. Theriault, Karen S. Quigley & Lis Feldman Barrett. 2022. “Allostasis as a core feature of hierarchical gradients in the human brain.” Network Neuroscience. 6(4):1010-1031. 10.1162/netn_a_00240. p. 1011.
“That allostasis is one of the brain’s core tasks is further supported b converging evidence for predictive processing models about bodily regulation and/or interoception. A variety of specific proposals abound, but they are united by three components that are thought to be implemented in a hierarchical arrangement in the brain’s architecture: (a) prediction signals that the brain generatively constructs using memory–or alternatively, an ‘internal model’, ‘top-down’ processing, a ‘forward model’, or ‘feedback’ signals; (b) prediction errors (or ‘bottom-up’ processing, or ‘feedforward’ signals) that encode the differences between predicted sensory inputs and incoming sense data from the body’s sensory surfaces; and (c) precision signals (or attention signals or executive control) that modulate the strength and durability of predictions and prediction errors, and their ability to access motor control and influence behavior.” Katsumi, Yuta, Jordan E. Theriault, Karen S. Quigley & Lis Feldman Barrett. 2022. “Allostasis as a core feature of hierarchical gradients in the human brain.” Network Neuroscience. 6(4):1010-1031. 10.1162/netn_a_00240. p. 1015.
“Although speculative, one final intriguing hypothesis emerging form this view is that all psychological phenomena (e.g., cognition, emotion, and perception) may be whole-brain phenomena with allostatic features, rather than separate states arising from unique computations that are localized to specific regions. This idea is consistent with a growing body of anatomical and functional evidence. For example, as mentioned above, exteroceptive sensory processing is statistically associated with processing of bodily signals. Primary motor cortex contains visceromotor maps, suggesting intimate integration of skeletomotor and visceromotor functions. The anterior cingulate cortex (visceromotor cortex) sends direct projections to neurons in V1, which may carry top-down prediction signals. Indeed, a substantial fraction of activity in the visual cortex does not depend on incoming visual input, and the majority of synapses in V1 originate from top-down sources. Such evidence runs counter to traditional assumptions that psychological functions can be uniquely localized to specific brain regions or networks and is consistent with the hypothesis of a domain-general computational architecture of the brain. This ‘whole-brain’ view is increasingly gaining empirical support in human neuroimaging studies that are designed to be sensitive to such observations and in nonhuman animal research. An allostatically oriented whole-brain framework has the potential to unify our understanding of brain, mind, and body.” Katsumi, Yuta, Jordan E. Theriault, Karen S. Quigley & Lis Feldman Barrett. 2022. “Allostasis as a core feature of hierarchical gradients in the human brain.” Network Neuroscience. 6(4):1010-1031. 10.1162/netn_a_00240. p. 1023.
“Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: Cells keep track of time, communicate, move, adapt, evolve and replicate continuously.” Merindol, Remi & Andreas Walther. 2017. “Materials Learning from Life: Concepts for Active, Adaptive and Autonmomous Molecular Systems.” Chem. Soc. Rev. 46:5588-5619. 10.1039/C6CS00738D. p. 5588.
“Overall, temporal control in living organisms relies on combinations of positive and negative feedback loops, as well as delay mechanisms.” Merindol, Remi & Andreas Walther. 2017. “Materials Learning from Life: Concepts for Active, Adaptive and Autonmomous Molecular Systems.” Chem. Soc. Rev. 46:5588-5619. 10.1039/C6CS00738D. p. 5590.
“Cells can rapidly contract, generate protrusions, divide, move and organize internal organelles according to internal (or external) signals…. The cytoskeleton, a network of dynamic structures, takes care of generating the appropriate response to these signals. The cytoskeleton contains three main out-of-equilibrium supramolecular assemblies, constantly polymerizing and depolymerizing: Microtubules, actin filaments and the intermediate filaments. The microtubules, the largest of these structures, are mechanically stiff, highly dynamic, and alternate between stable growth and fast depolymerization. They are the prototype chemically fueled, energy-dissipating self-assembly with dynamic and adaptive properties. Microtubules consist of a tubular assembly of a hetero-dimeric protein (tubulin) bound to a guanosine di- or triphosphate. The binding of GTP is the energy uptake step and renders the GTP-tubulin building blocks metastable. Those metastable GTP-tubulins add to the end of the microtubule and hydrolyze into GDP-tubulin soon after their incorporation (energy dissipation step)…. Once hydrolysis reaches the tips and overcomes growth by addition of (activated) GTP-tubulin, the microtubules turn fully unstable and depolymerize rapidly. These dynamic instabilities allow for a quick reorientation and a fast search of the cellular space. Target organelles emit signals that stabilize microtubules that have found their targets…..
“An important feature of this dissipative self-assembly is the fact that structures only form as long as there is energy (GTP) in the system. Hence, the overall lifetime of the steady-state microtubule self-assembly (e.g. in vitro) is bound to the GTP fuel present in the system. Once all GTP is consumed, the structures decay entirely.” Merindol, Remi & Andreas Walther. 2017. “Materials Learning from Life: Concepts for Active, Adaptive and Autonmomous Molecular Systems.” Chem. Soc. Rev. 46:5588-5619. 10.1039/C6CS00738D. p. 5593.
“In out-of-equilibrium chemical system where diffusion and mixing are slower than the reactive process, the local chemical state may change across the material. We encountered such systems already for self-oscillating hydrogels…. Each infinitesimal sub-element of the material therefore exchanges chemical information with its neighbor by diffusion (communication) while local, feedback-controlled reactions take place.
“New properties emerge from such continuous reaction-diffusion systems, in which the material adapts to its environment both spatially and temporarily. They can support long-range signal transport, spatial sensing or lead to the spontaneous appearances of patterns.” Merindol, Remi & Andreas Walther. 2017. “Materials Learning from Life: Concepts for Active, Adaptive and Autonmomous Molecular Systems.” Chem. Soc. Rev. 46:5588-5619. 10.1039/C6CS00738D. p. 5610.