Biology – our incomplete fundamental science

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Citations collected in 2022 (works listed above):

“Competition, cooperation, communication, and sexual reproduction provide the ecological context for powerful evolutionary forces. Social evolution is concerned with the evolution of phenotypes mediating these interactions and the impact they have on the fitness of individuals other than the actor. A distinguishing feature of social traits is that the ecological environment in which such traits operate includes the phenotypes of other individuals. Thus, the social part of the environment is underpinned by genes and can evolve in response to selection. Furthermore, the optimal phenotype for an individual depends in part on the genetic and phenotypic characteristics of the individuals with whom it interacts. This implies that social evolution creates a feedback between ecological and evolutionary processes, because the evolving phenotypes are also the ecological drivers of selection.” Araya-Ajoy, Yimen G., David F. Westneat & Jonathan Wright. 2020. “Pathways to social evolution and their evolutionary feedbacks.” Evolution. 74(9):1894-1907. doi: 10.1111.evo.14054. p. 1894.

“Different areas of evolutionary biology have used different approaches to study evolution in a social context. Behavioral ecology has explored the economics of social evolution using cost-benefit analyses…. In addition, game theory extended adaptive explanations to a broader array of social contexts, allowing predictions for evolutionary stable strategies in frequency-dependent scenarios where the fitness effects of a social trait depend on the traits of social partners. Models developed by quantitative geneticists have also greatly contributed to the study of social behavior, allowing the quantification of how social interactions generate variation in fitness in the form of social selection gradients, and how patterns of inheritance are affected by individuals plastically adjusting to their social environment in the form of indirect genetic effects.” Araya-Ajoy, Yimen G., David F. Westneat & Jonathan Wright. 2020. “Pathways to social evolution and their evolutionary feedbacks.” Evolution. 74(9):1894-1907. doi: 10.1111.evo.14054. pp. 1894-5.

“Once I understood how IMPs [integral membrane proteins] worked, I had to conclude that the cell’s operations are primarily molded by its interaction with the environment, not by its genetic code….

“The membrane’s function of interacting ‘intelligently’ with the environment to produce behavior makes it the true brain of the cell…. When you destroy its membrane, the cell dies just as you would if your brain were removed….

“To exhibit ‘intelligent’ behavior, cells need a functioning membrane with both receptor (awareness) and effector (action) proteins.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 68.

“Medical doctors are caught between an intellectual rock and a corporate hard place; they are pawns in the huge medical industrial complex. Their healing abilities are hobbled by an archaic medical education founded on a Newtonian, matter-only universe.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 96.

“The fact that most doctors are not trained to consider the impact of the placebo effect is ironic because some historians make a strong case that the history of medicine is largely the history of the placebo effect. For most of medical history, doctors did not have effective methods to fight disease. Some of the more notorious treatments once prescribed by mainstream medicine include blood-letting, treating wounds with arsenic, and the proverbial cure-all, rattlesnake oil. No doubt some patients, the conservatively estimated one third of the population who are particularly susceptible to the healing power of the placebo effect, got better with those treatments.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. pp. 132-3.

“When the mind, through positive suggestion, improves health, it is referred to as the placebo effect. Conversely, when the same mind is engaged in negative suggestions that can damage health the negative effects are referred to as the nocebo effect.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 136.

“These opposing movements [growth and protection] define the two basic cellular responses to environmental stimuli. Gravitating to a life-sustaining signal, such as nutrients, characterizes a growth response; moving away from threatening signals, such as toxins, characterizes a protection response….

“It turns out that the mechanisms that support growth and protection cannot operate optimally at the same time.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. pp. 149-150.

“Think back to the cell membrane’s stimulus-response mechanism, the receptor-effector proteins–the hypothalamus and pituitary gland are behavioral equivalents. Similar to the role of a receptor protein, the hypothalamus receives and recognizes environmental signals; the pituitary’s function resembles that of the effector protein in that it launches the body’s organs into action.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 152.

“According to the HPA [Hypothalamus-Pituitary-Adrenal axis as system that mobilizes protection against external threats] axis also interferes with our ability to think clearly. The processing of information in the forebrain, the center of executive reasoning and logic, is significantly slower than the reflex activity controlled by the hindbrain. In an emergency, the faster the information processing, the more likely the organism will survive. Adrenal stress hormones constrict the blood vessels in the forebrain, reducing its ability to engage in conscious volitional action.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 154.

“Almost every major illness that people acquire has been linked to chronic stress. Between 75 and 90 percent of primary-care physician visits have stress as a major contributing factor.” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 155.

“The cell engages in behavior when its brain, the membrane, responds to environmental signals, in fact, every functional protein in our body is made as a complementary ‘image’ of an environmental signal. If a protein did not have a complementary signal to couple with, it would not function. This means, as I concluded in that ‘aha!’ moment, that every protein in our bodies is a physical/electromagnetic complement to something in the environment. Because we are machines made out of protein, by definition we are made in the image of the environment….” Lipton, Bruce H. 2005. The Biology of Belief: Unleashing the Power of Consciousness, Matter & Miracles. Carlsbad, CA: Hay House. p. 207.

“Fungi produce around fifty megatons of spores each year–equivalent to the weight of five hundred thousand blue whales–making them the largest source of living particles in the air. Spores are found in clouds and influence the weather by triggering the formation of the water droplets that form rain and the ice crystals that form snow, sleet, and hail.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 6.

“… most fungi form networks of many cells known as hyphae: fine tubular structures that branch, fuse, and tangle into the anarchic filigree of mycelium. Mycelium describes the most common of fungal habits, better thought of not as a thing but as a process: an exploratory, irregular tendency.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 6.

“Some fungi have tens of thousands of mating types, approximately equivalent to our sexes. The mycelium of many fungi can fuse with other mycelial networks if they are genetically similar enough, even if they aren’t sexually compatible. Fungal self-identity matters, but is it not always a binary world. Self can shade off into otherness gradually.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 36-7.

“Receptive plant roots produce plumes of volatile compounds that drift through the soil and cause spores to sprout and hyphae to branch and grow faster. Fungi produce plant growth hormones that manipulate roots, causing them to proliferate into masses of feathery branches–with a greater surface area, the chances of an encounter between root tips and fungal hyphae become more likely. (Many fungi produce plant and animal hormones to alter the physiology of their associates.)” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 38.

“Among the most impressive sensory feats are those performed by predatory fungi that trap and consume nematode worms. Hundreds of species of worm-hunting fungi can be found all over the world. Most spend their lives decomposing plant matter and only start to hunt when there is insufficient material to eat. But they’re subtle predators: Unlike truffles, whose scent, once begun, is always on, nematode-eating fungi only produce worm-hunting organs and issue a chemical summons when they sense nematodes are close by. If there is plenty of material to rot, they don’t bother, even if worms abound….

“The methods fungi use to hunt nematodes are grisly and diverse. It is a habit that has evolved multiple times–many fungal lineages have reached a similar conclusion but in different ways. Some fungi grow adhesive nets, or branches to which nematodes stick. Some use mechanical means, producing hyphal nooses that inflate in a tenth of a second when touched, ensnaring their prey. Some–including the commonly cultivated oyster mushroom–produce hyphal stalks capped with a single toxic droplet that paralyzes nematodes, giving the hypha enough time to grow through their mouth and digest the worm from the inside. Others produce spores that can swim through the soil, chemically drawn toward nematodes, to which they bind. Once attached, the spores sprout and the fungus harpoons the worm with specialized hyphae known as ‘gun cells.’” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 39-40.

“Mycelium is ecological connective tissue, the living seam by which much of the world is stitched into relation…. If we made equivalent sets of diagrams to portray ecosystems, one of the layers would show the fungal mycelium that runs through them. We would see sprawling, interlaced webs strung through the soil, through sulfurous sediments hundreds of meters below the surface of the ocean, along coral reefs, through plant and animal bodies both alive and dead, in rubbish dumps, carpets, floorboards, old books in libraries, specks of house dust, and in canvases of old master paintings hanging in museums.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 46.

“… mycelial fungi are maze-dwellers, and solving spatial and geometrical problems is what they have evolved to do.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 48.

“Mycelium is a body without a body plan.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 49.

“Mycelial coordination is difficult to understand because there is no center of control. If we cut off our head or stop our heart, we’re finished. A mycelial network has no head and no brain. Fungi, like plants, are decentralized organisms.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 50.

“The difference between animals and fungi is simple: Animals put food in their bodies, whereas fungi put their bodies in the food….

“If food can be more easily found elsewhere, they [animals] move elsewhere. But to embed oneself in an irregular and unpredictable food supply as mycelium does, one must be able to shape-shift. Mycelium is a living, growing, opportunistic investigation–speculation in bodily form. This tendency is known as developmental ‘indeterminism’: No two mycelial networks are the same….

“Mycelium decants itself into its surroundings, but its growth pattern isn’t infinitely variable. Different fungal species form different kinds of mycelial networks. Some species have thin hyphae, some thick. Some are picky about their food, others less so. Some grow into ephemeral puffs that don’t range beyond their food source and could fit on a single speck of house dust. Other species form long-lived networks that roam over kilometers.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 51-2.

“A mycelial network is a map of a fungus’s recent history and is a helpful reminder that all life-forms are in fact processes not things.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 53.

“Nature is an event that never stops. As William Bateson, who coined the word genetics, observed, ‘We commonly think of animals and plants as matter, but they are really systems through which matter is continually passing.’ When we see an organism, from a fungus to a pine tree, we catch a single moment in its continual development.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 53; subquote: Bateson, William. 1928. William Bateson, Naturalist. Cambridge UP. p. 209.

“Mycelium usually grows from hyphal tips, but not always. When hyphae felt together to make mushrooms, they rapidly inflate with water, which they must absorb from their surroundings–the reason why mushrooms tend to appear after rain.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 53-4.

“Cut up a mushroom and you’ll see that it is made of the same type of cell as mycelium: hyphae.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 55.

“Hyphae grow into other structures besides mushrooms. Many species of fungus form hollow cables of hyphae known as ‘cords’ or ‘rhizomorphs.’ These range from slim filaments to strands several millimeters thick that can stretch for hundreds of meters. Given that individual hyphae are tubes, not threads–it is easy to forget about the fluid-filled space within the hyphae–cords and rhizomorphs are large pipes formed from many small tubes.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 55.

“Over short distances, substances can be transported through mycelial networks on a network of microtubules…. Transport using microtubule ‘motors’ is energetically costly, however, and over larger distances the contents of hyphae travel on a river of cellular fluid…. Efficient transport allows different parts of a mycelial network to engage in different activities.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 56.

“… Phycomyces is able to detect the presence of nearby objects, a phenomenon known as the ‘avoidance response.’ Despite decades of painstaking investigation, the avoidance response remains an enigma. Objects within a few millimeters cause the fruiting body of Phycomyces to bend away without ever making contact. Regardless of the object–opaque or transparent, smooth or rough–Phycomyces starts to bend away after about two minutes. Electrostatic fields, humidity, mechanical cues, and temperature have all been ruled out. Some hypothesize that Phycomyces uses a volatile chemical signal that deflects around the obstacle with tiny air currents, but this is far from proven.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 58.

“Hyphal tips are the parts of the mycelium that grow, change direction, branch, and fuse…. A given mycelial network might have anywhere between hundreds and billions of hyphal tips, all integrating and processing information on a massively parallel basis.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 59.

“For Adamatzky, the point of fungal computers is not to replace silicon chips. Fungal reactions are too slow for that. Rather, he thinks humans could use mycelium growing in an ecosystem as a ‘large-scale environmental sensor.’ Fungal networks, he reasons, are monitoring a large number of data streams as part of their everyday existence. If we could plug into mycelial networks and interpret the signals they use to process information, we could learn more about what was happening in an ecosystem.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 64; reference: Adamatzky, A. 2018. Towards fungal computer.” Journal of the Royal Society Interface Focus. 8:20180029.

“In 2017, researchers at the Swedish Royal Museum of Natural History published a report in which they describe fossilized mycelium preserved in the fractures of ancient lava flows. The fossils show branching filaments that ‘touch and entangle each other.’ The ‘tangled network’ they form, the dimensions of the hyphae, the dimensions of spore-like structures, and the pattern of its growth all closely resemble modern-day fungal mycelium. It is an extraordinary discovery because the fossils date from 2.4 billion years ago, more than a billion years before fungi were thought to have branched off the tree of life. There is no way to identify the organism with certainty, but whether or not it was a true fungus, it clearly had a mycelial habit.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 67; reference: Bengston, S. B. Rasmussen, M. Ivarsson, J. Muhling, C. Broman, F. Marone, M. Stampanoni & A. Bekker. 2017. “Fungus-like mycelial fossils in 2.4-billion-year-old vesicular basalt.” Nature Ecology & Evolution. 1:0141.

“Lichens encrust as much as eight percent of the planet’s surface, an area larger than that covered by tropical rainforests. They clad rocks, trees, roofs, fences, cliffs, and the surface of deserts.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 74.

“The capacity of lichens to survive in space has since been demonstrated in a number of studies, and the findings are broadly the same. The hardiest lichen species can recover their metabolic activity in full within twenty-four hours of being rehydrated and are able to repair much of the ‘space-induced’ damage they may have sustained…. Lichen samples exposed to six kilograys of gamma irradiation–six times the standard dose for food sterilization in the United States and twelve thousand times the lethal dose for humans–were entirely untroubled.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 79.

“Today, one in five of all known fungal species form lichens, or ‘lichenize’…. For some fungi, lichenization remains a life-style choice; they can live as lichens or not depending on their circumstances.

“It turns out that fungi and algae come together at the slightest provocation. Grow many types of free-living fungus and algae together, and they’ll develop into a mutually beneficial symbiosis in a matter of days. Different species of fungus, different species of algae–it doesn’t seem to matter. Completely new symbiotic relationships emerge in less time than it takes for a scab to heal….

“Not just any fungus could partner with any alga, however. One critical condition had to be fulfilled for a symbiotic relationship to arise: Each partner had to be able to do something that the other couldn’t achieve on its own.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 86, 87.

“… a study documenting a startling technique used by Entomophthora, a mind-manipulating fungus that infects flies…. When they extend their mouthparts to feed, a glue produced by the fungus sticks them to whatever surface they touch. When the fungus has consumed the fly’s body, starting with the fatty parts and finishing with the vital organs, it pushes a stalk out of the fly’s back and ejects spores into the air.

“The researchers were surprised to find that the Entomophthora fungus carries around a type of virus that infects insects, not fungi…. What’s whacky is the implication: that the fungus uses the virus to manipulate the mind of insects. It’s still a hypothesis, but it’s plausible. A number of related viruses specialize in modifying insect behavior. One such virus is injected by parasitic wasps into ladybirds, which tremble, remain rooted to the spot, and become guardians for the wasp’s eggs. Another similar virus makes honeybees more aggressive.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 103; reference: Coyle, M.C., C.N. Elya, M.J. Bronski & M.B. Eisen. 2018. “Entomophthovirus: An insect-derived iflavirus that infects a behavior manipulating fungal pathogen of dipterans.” bioRxiv: 371526.

“Today, more than ninety percent of all plant species depend on mycorrhizal fungi. They are the rule, not the exception: a more fundamental part of planthood than fruit, flowers, leaves, wood, or even roots.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 124.

“Mycorrhizal fungi are so prolific that their mycelium makes up between a third and a half of the living mass of soils. The numbers are astronomical. Globally, the total length of mycorrhizal hyphae in the top ten centimeters of soil is around half the width of our galaxy (4.5 X 1017 kilometers of hyphae, versus 9.5 X 1017 kilometers of space).” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 127.

“Mycorrhizal fungi can provide up to eighty percent of a plant’s nitrogen and as much as a hundred percent of its phosphorus. Fungi supply other crucial nutrients to plants, such as zinc and copper. They also provide plants with water, and help them to survive drought as they’ve done since the earliest days of life on land. In return, plants allocate up to thirty percent of the carbon they harvest to their mycorrhizal partners.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 132.

“If the same species of strawberry was grown with different species of fungus, would the flavor of the strawberries change? He [P. Orrell] conducted blind taste tests and found that different fungal communities did seem to change the flavor of the fruit….

“Bumblebees were more attracted to the flowers of strawberry plants grown with some fungal species and less attracted to others. Plants grown with some mycorrhizal species produced more berries than others. And the appearance of the berries changed depending on which fungi they partnered with.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 133; reference: Orrell, P. 2018. Linking Above and Below-Ground Interactions in Agro-Ecosystems: An Ecological Network Approach. PhD thesis, U of Newcastle.

“In one set of experiments, she [T.E. Kiers] found that plant roots were able to supply carbon preferentially to fungal strains that provided them with more phosphorus. In return, fungi that received more carbon from the plant supplied it with yet more phosphorus.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 136; reference: Kiers, T.E., M. Duhamel, Y. Beesetty, J.A. Mensah, O. Franken, E. Verbruggen, C. Fellbaum, C.R. Fellbaum, G.A. Kowalchuk, et al. 2011. “Reciprocal rewards stabilize cooperation in the mycorrhizal symbiosis.” Science. 333:88082.

“… different species of plant and fungus have different symbiotic manners. Some fungi make more cooperative partners; some are less cooperative and will ‘hoard’ phosphorus rather than exchange it with their plant partners. However, even a hoarder might not hoard all the time. Their behavior is flexible, a set of ongoing negotiations that depend on what is taking place around them and in other parts of themselves.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 136.

“The anthropologists Natasha Myers and Carla Hustak argue that the word evolution, which literally means ‘rolling outward,’ doesn’t capture the readiness of organisms to involve themselves in one another’s lives. Myers and Hustak suggest that the word involution–from the word involve–better describes this tendency: a ‘rolling, curling, turning inward.’ In their view, the concept of involution better captures the entangled pushing and pulling of ‘organisms constantly inventing new ways to live with and alongside one another.’” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 142; reference: Carla Hustak & Myers, Natasha. 2012. “Involutionary momentum: affective ecologies and the sciences of plant/insect encounters.” Differences. 23:74-118.

“Not only was the abundance of mycorrhizal fungi higher in organically managed fields but the fungal communities were also far more complex: Twenty-seven species of fungi were identified as highly connected, or ‘keystone species,’ compared with none in the conventionally managed fields.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 144.

“Mycorrhizal mycelium is a sticky living seam that holds soil together; remove the fungi, and the ground washes away. Mycorrhizal fungi increase the volume of water that the soil can absorb, reducing the quantity of nutrients leached out of the soil by rainfall by as much as fifty percent. Of the carbon that is found in soils–which, remarkably, amounts to twice the amount of carbon found in plants and the atmosphere combined–a substantial proportion is bound up in tough organic compounds produced by mycorrhizal fungi.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 145.

“Besides the hundreds or thousands of meters of fungal mycelium in a teaspoon of healthy soil, there are more bacteria, protists, insects, and arthropods than the number of humans who have ever lived on Earth.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 145.

“Monotropa are what’s known as ‘mycoheterotrophs’ [‘plants’ that survive only by tapping into mycelial networks] ‘Myco’ because they depend on a fungus for their nutrition; ‘heterotroph’ because they don’t make their own energy from the sun and have to get it from somewhere else….

“Monotropa and Voyria aren’t alone in living this way. About ten percent of plant species share the habit. Like lichens and mycorrhizal relationships, mycoheterotrophy is an evolutionary refrain and has arisen independently in at least forty-six separate plant lineages. Some mycohets, like Monotropa and Voyria, never photosynthesize. Others behave like mycohets when they’re young but become donors when they get older and start to photosynthesize, and approach what Katie Field calls ‘take now, pay later.’” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 156.

“In another study of birch and Douglas fir in Canadian forests, the direction of carbon transfer switched twice in the course of a single growing season. In the spring, when the fir–an evergreen–was photosynthesizing and the leafless birch was just bursting its buds, the birch behaved as a sink, and carbon flowed into it out of the fir [through fungal networks]. In the summer, when the birch was in full leaf, and the fir found itself in the shaded understory, the direction of carbon flow changed, moving downhill out of the birch and into the fir. In the autumn, when the birch started to drop its leaves, the trees switched roles again, and carbon moved downhill from the fir into the birch. Resources passed from areas of abundance to areas of scarcity.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 158-9.

“Plant-centric perspectives can distort. Paying more attention to animals than plants contributes to humans’ plant-blindness. Paying more attention to plants than fungi makes us fungus-blind….

“The language of the wood wide web doesn’t help. It is a metaphor that tugs us into plant-centrism by implying that plants are equivalent to the web pages, or nodes, in the network, and fungi are the hyperlinks joining the nodes to one another.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 160.

“Without the ability to regulate flow within their networks, much of fungal life–including the intricately choreographed growth of mushrooms–would be impossible.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 161.

“The decomposer fungi… range through ecosystems over large distances and link decaying leaves with fallen twigs, large rotting stumps with decomposing roots…. These fungi make up wood wide webs of a different sort: webs based around consuming plants rather than sustaining them.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 161.

“Fungal networks provide highways for bacteria to migrate around the obstacle course of the soil. In some cases, predatory bacteria use mycelial networks to pursue and hunt their prey. Some bacteria make their lives within fungal hyphae themselves, and enhance fungal growth, stimulate their metabolisms, produce key vitamins, and even influence fungal relationships with their plant partners. One species of mycorrhizal fungus, the thick-footed morel, actually farms the bacteria that live within its networks: The fungus ‘plants’ bacterial populations, then cultivates, harvests, and consumes them.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 164.

“Many of the researchers I have talked with share the view that plant communication through fungal networks is one of the most compelling aspects of mycorrhizal behavior.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 165.

“Today, the wood of some three trillion trees–more than fifteen billion of which are cut down every year–accounts for about sixty percent of the total mass of every living organism on Earth, some three hundred gigatons of carbon.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 176-7.

“Most enzymes–biological catalysts that living organisms use to conduct chemical reactions–lock onto specific molecular shapes. Faced with lignin, this approach is hopeless; its chemical structure is too irregular. White rot fungi work around the problem using nonspecific enzymes that don’t depend on shape. These ‘peroxidases’ release a torrent of highly reactive molecules, known as ‘free radicals,’ which crack open lignin’s tightly bonded structure in a process known as ‘enzymatic combustion’….

“Based on their ability to release free radicals, the peroxidases produced by white rot fungi perform what is technically known as ‘radical chemistry.’ ‘Radical’ has it right. These enzymes have forever changed the way that carbon journeys through its earthly cycles. Today, fungal decomposition–much of it of woody plant matter–is one of the largest sources of carbon emissions, emitting about eighty-five gigatons of carbon to the atmosphere every year. In 2018, the combustion of fossil fuels by humans emitted around ten gigatons.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 177.

“If given the chance, many types of fungi readily decompose coal, and a species known as the ‘kerosene fungus’ thrives in the fuel tanks of aircraft.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 178.

“Human life hinges on many forms of external digestion using fungi, from alcohol, to soy sauce, to vaccines, to penicillin, to the citric acid used in all fizzy drinks….

“Fungi can transform many common pollutants in soil and waterways that endanger lives, whether human or otherwise. They are able to degrade pesticides, synthetic dyes, the explosives TNT and RDX, crude oil, some plastics, and a range of human and veterinary drugs not removed by wastewater treatment plants, from antibiotics to synthetic hormones.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 184, 185.

“Heavy metals accumulate within fungal tissues, which can then be removed and disposed of safely.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 185.

“… Macrotermes build towering mounds that reach heights of nine meters, some of which are more than two thousand years old….

“Macrotermes mounds are giant, externalized guts–prosthetic metabolisms that allow the termites to decompose complex materials they can’t break down themselves. Like the fungi they cultivate, Macrotermes muddle the concept of individuality. An individual termite can’t survive apart from its society. A termite society can’t survive separate from the cultures of fungi and other microbes that feed them, and that they feed. The partnership is prolific: A substantial proportion of the wood decomposed in the African tropics passes through Macrotermes mounds.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 190.

“And whether it is bread or beer, yeasts were the primary beneficiaries of humans’ earliest agricultural efforts. In the preparation of either, humans feed yeast before they feed themselves.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 203.

“In 2013, in a paper called ‘Against the naming of fungi,’ the mycologist Nicholas Money went so far as to suggest that the concept of fungal species should be abandoned altogether.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 208; reference: Money, Nicholas. 2013. “Against the naming of fungi.” Fungal Biology. 117:463-65.

“The first international conference on symbiosis was held in London in 1963, six months after the Cuban Missile Crisis had brought the world to the brink of nuclear war. This was no accident. The editors of the conference proceedings commented that ‘the pressing problems of coexistence in world affairs may have influenced the Committee in their choice of subject for this year’s Symposium.’” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. p. 211.

“Today, the study of shared mycorrhizal networks is one of the fields most commonly beset with political baggage. Some portray these systems as a form of socialism by which the wealth of the forest can be redistributed. Others take inspiration from mammalian family structures and parental care, with young trees nourished by their fungal connections to older and larger ‘mother trees.’ Some describe networks in terms of ‘biological markets,’ in which plants and fungi are portrayed as rational economic individuals trading on the floor of an ecological stock exchange, engaging in ‘sanctions,’ ‘strategic trading investments,’ and ‘market gains.’” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 211-2.

“About ten million years ago, the enzyme our bodies use to detoxify alcohol, known as alcohol dehydrogenase, or ADH4, underwent a single mutation that left it forty times more efficient. The mutation occurred in the last common ancestor we shared with gorillas, chimpanzees, and bonobos. Without a modified ADH4, even small quantities of alcohol are poisonous….

“The ability to metabolize alcohol, they [Carrigan et al] speculate, played a crucial role in the ability of primates to make a living on the forest floor by opening up a new dietary niche: overripe, fermented fruit that had fallen from trees.

“The ADH4 mutation provides support for the ‘drunken monkey hypothesis,’ proposed by the biologist Robert Dudley to explain the origins of humans’ fondness for alcohol. In this view, humans are tempted by alcohol because our primate ancestors were. The scent of alcohol produced by yeasts was a reliable way to find ripe fruit as it rotted on the ground.” Sheldrake, Merlin. 2020. Entangled Life: How Fungi Make Our Worlds, Change Our Minds & Shape Our Futures. Random House. pp. 216, 217; references: Carrigan, M.A. O. Uryasev, C.B. Frye, B.I. Eckman, C.R. Myers, T.D. Hurley & S.A. Benner. 2015. “Hominids adapted to metabolize ethanol long before human-directed fermentation.” Proceedings of the National Academy of Sciences. 112:458-63; Dudley, R. 2014. The Drunken Monkey: Why We Drink and Abuse Alcohol. U. of California Press.

“There is no finish line, or heaven-like last act, no glorious arrival. There is only the glorious continuation of things living and dying, appearing and disappearing in staggered layers to keep each other alive in the continuation. However, the rental rate for this gift of being allowed to flourish and reside in this continuum with the rest of the world is that we do everything possible to be indigenously beautiful, promising that we make ourselves spiritually full and delicious so as to feed the next ones to appear in the ongoing river on the occasion of our passing.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 12.

“After all, a kiss between real lovers is not some type of contract, a neatly defined moment of pleasure, something obtained by greedy conquest, or any kind of clear saying of how it is. It is a grief-drenched hatching of two hearts into some ecstatic never-before-seen bird whose new uncategorizable form, unrecognized by the status quo, gives the slip to Death’s sure rational deal. For love is a delicious and always messy extension of life that unfrantically outgrows mortality’s rigid insistence on precise and efficient definition. Having all the answers means we haven’t really ecstatically kissed or lived, thereby declaring the world defined and already finished. Loving all the questions on the other hand is a vitality that makes any length of life worth living.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 76.

“Time, to speak colloquially, like all living things and people themselves, was known as an organic thing, a growing thing with a plantlike nature. To all Mayans everything in the world was understood according to the nature of plants. People, Time, and the Holy in Nature were all plantlike. The so-called Mayan day names were the officially designated names of what lived and died during each of those days, and were called flowerings. To keep the world flowering meant to keep the blossoms on the trunks and branches of Time flowering so the flowers could again make ‘seeds’ in hopes of replanting the continuing Eras of Time and the physical things that occurred during them.

“Time did not exist; it spoke. And when it spoke, it spoke in flowers. And when it sang its story, these flowers turned to fruit whose seeds sprouted the physical reality of our living world. It lived, grew, flowered like nodes on a grass, fruiting then dying back to seed again the next cycle back into view. Thus time had to be fed and fertilized for reality to grow.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. pp. 93-4.

“The Tzutujil [Mayan, near Lago Atitlan] word for Life and the word for spark is Kas. Any segment of Annual Time when coming alive made all the things that happened at the time come into tangible existence, i.e., the birth of all wild ungulates, the maturation of kinds of wild fruit, the beginnings of the spring heat and rain, the flowering of the red stone cactus, the wind of the season, etc. These things were Time become matter and tangible life. When the previous segment of Annual time, i.e., the previous twenty days, comes to ‘fruition,’ it does so 260 days after its previous ‘blossomings,’ a gestation of some nine months earlier. Therefore the blossoming of the next section of time immediately after is given life by the ‘universe-feeding death and decay’ of the ‘composting’ of the previous segment seen by the ceremonialists as ‘fat’ of the earth, which became the Fuel that makes the Fire (or Flower) burn and live; the past is burnt for a bright burning (flowering) present. This means the fat of our time must ceremonially fuel the next time. These fire-fueled rituals were called Flowerings.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 98.

“So not only did Time, like a tree, blossom, flower, fertilize fruit, feed, and reseed, but it also refueled or ‘caused to Flower’ the Flame of which this consuming-eating reality we live in consists. Flowers were what gave all things their food. Ask the Bees. Any plant that feeds an animal that feeds us or another animal depends on ‘seeds’ to regenerate and animals to pollinate them…. The Flowering of the Time in its annual tree cycles was caused by the burning into the humus of nutrition the previous cycle of time.

“Ritual of course was a human version of the same. A great culture-composting feast of human ornateness to keep Time from starving to death. And it was at these mountain shrines where these ‘Times’–as the earth, as matter, as God/Goddesses–were maintained by humans to account for the overconsumption we accrued to the surrounding Flowering of Time, above and beyond the original agreement we had with the Holy in the Seed.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. pp. 99-100.

“For while tzej means ‘to blossom’ and equally means ‘to ignite’ as far as Tzutujil thinking goes, you can cause a fire to ‘blossom’ in the morning to cook breakfast, as much as you can watch an orchard burst into a ‘flame’ of flowers. Fires are flowers and flowers are fires. As simple as this sounds, it really comes from something that needs to never be forgotten.

“When a ceremony is made to ‘feed’ a portion of Time Deified, a Goddess, or God whose body is the things that flower, harvest, or come to life during its reign, then that ritual is called a ‘blossoming.’ But the blossom that the tribe is making always begins and continues with the presence of fire, either in bonfires, candle fire, incense fire, fat fires, alcohol fires, with even more or all of the above.

“The procedures for making the fires were not arbitrary and always accompanied by ‘flowering’ words and handmade offerings. When the words have all been ‘consumed,’ the incense all burned, the alcohol burnt, the firewood gone, the fat candles all burned, the ritual dances, songs, and complex, expansive offering houses have disintegrated and returned back into the ground, the segment of Deified Time that lives in that place is said to have ‘eaten.’ For the Holy to eat, the ‘sustenance’ we feed them must disappear, consumed, taken by the Divine away from the present into the other world.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. pp. 103-4.

“The word ruach, for instance, while for the Tzutujil it means the fruit of any kind of plant, does also simultaneously and not as a homonym signify the ‘fruit’ or outcome of any action, direction of travel, idea, day, place, mood, etc. For all things and their functions are understood in a plant way. The phrase ‘Naqs ruach jaura”’ ‘What fruit does it carry”’ can also mean ‘What kind of plant is this’ or ‘What does this earth here grow?’ It can equally mean ‘This new idea: how will it turn out in the end?’ or ‘That person’s strange actions–what unseen possibility are they headed toward?’ and so on. Everything is about plants and plant natures, with trunks, branches, and Time flowers fruiting into what develops in time. This is why Time is understood as having a gradual plantlike nature: it grows and develops, plants, dies, and is reborn.

“With all of these meanings in the word ruach and none understood exclusively of the other, this word for fruit is the usual word meaning ‘a person’s face.’ The apparent natural form of anything in the world, any being, or any person is said to be called his or her face as a unique individual instead of a species or type; therefore all faces are ‘fruit.’ The Earth is even called Ruachuleu: the Face/Fruit of Soil! When saying hello to anyone you always politely enquire ‘L’utz a wach?’ ‘Your face is well?’ which is an abbreviation from the much more ceremonial, ‘Does your ‘fruit/face’ hang well on your ancestral trunk?’” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 105.

“But then after a silence, he [shamanic teacher Chiviliu] added as an afterthought in his rare whisper, ‘I know how you are, you are a purist, but watch out not to judge too narrowly the appearance of the fruit of the seed on its return, do not hate the seed for looking odd or different, or having a strange accent when it returns to you each time. Your only job is to figure out with the old-minded words and understandings how to keep the seeds alive. But don’t do it here in Atitlan, because that will have equally disintegrated. Do it in the USA, in the modern world, in the place you came from! You have to promise to plant the seeds in the land that sent us the trouble.’” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 147.

“At the core of the ritual obligations of Birth and Death there were particular women who knew what to do. During pregnancy and birth, of course, it was the midwives and their associates who administrated, coaching not only the mother and catching the newborn baby, but also directing a radiating tangle of the baby’s relations and honored villagers who always helped the mother and child by their positive presence, directing them in all the details of what the family’s ritual obligations should be before, during, and after a birth. The welfare of mother and baby depended on the ornate nature of the beauty of the diverse rituals known only by the midwife that Humans supplied and the Holy demanded that during birth needed doing by different age sets, kinship, and genders in the family.

“Likewise, ritual direction at the time of a death in a family was in the hands of a guild of mostly older women who after being properly ‘courted and called in’ by the relatives led the campaign for the beauty during the funeral. Functioning for all intents and purposes as nothing less than midwives for the dead, these women made sure the full weight and power of the deceased’s echo was fully received on the ‘other side.’

“Both types of midwives had to be women, one to bring the echo sprout in, the other to send its beauty echoing to feed the Holy. Both of their ritual careers depended largely on simple things: a special type of corn sed and a particular type of hand-spun native cotton thread, originally both very common and also very Holy….

“Though the valuable substance of a dead person’s body remained to feed and compost the welfare of the present, meeting with the divine digestion of the Lords and Ladies of Time–whose teeth of change are Holy Decay and whose eating gives life to the life-giving soil–the great beauty and energy of the soul released from the compost-bound body by Death was a power-filled echo, a responding death-freshened echo, that returned the audial shape of its innate worth and authority back to the cliffs of the Mind of the Holy in nature, who added to and returned that same echo as the living sound in the shape of a new life sprouting back into our world….

“And both [births and deaths] also had to possess an equal capacity of memory of mythological tribal history, in which roll calls of ancestral descendants bottomed out attached to the Sun, Moon, the Earth, the clouds, and all the trees. This capacity of recall had to be carried on in an equal capacity for both types of midwives to eloquently speak all of this ancient continuum in such a seamless water-like flow that it could merge into the spinning of the cotton thread of the past into the cotton of now so as to ritually draw from the ‘fluffy matrix of the present’ a thread that could ‘weave the cloth’ that hung on the shoulders of Time and gave form to creation. The sparkling birds chattering, green grass growing, lake rippling, and wooded hills are all the living embroidery of the clothing that hangs on the soul’s echo that gives Time a form. People at birth, during life, and especially at death had to become functional participants in all of this so as to ritually remake the world when anyone was born, or anyone died….

“And while there were experts who led them, the rituals were a thing of the people, made by regular people for regular people, and were in no way an esoteric function for the elite, not carried out by a trained hierarchy of priests or shamans.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. pp. 152, 153-4.

“This was the definition of the Tzutujil word for life: mutual indebtedness. The whole world was a ritual of a million component rituals in which every being kept alive another being by courting them by the beauty of their innate natures in order to be graced with the gift the other held of what each was missing.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 166.

“Real villages cannot really be created by people who will follow a single individual no matter how visionary. Such synthetic beginnings lack true origins and are bound to fail as they are well meaning. Real villages can only come from listening to the Holy in the ‘seeds,’ as the Tzutujil would say, not a person. Like people, ecosystems, cultures of interrelated animals, plants, winds, oceans, and people, villages must organically grow from the mind of the Holy in the Seed and ground.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 193.

“‘And above all,’ he’d said [shaman Chiviliu], ‘don’t be prejudiced against what the ‘seeds’ look like when they return to you. Don’t refuse them because you don’t recognize them. That’s not your job. Your job is to ‘keep the seeds alive.’ Your job is to welcome them and to give them a place. Just keep planting.’” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 297.

“Like victims of an ancient spiritual and cultural shipwreck, we have been adrift for four thousand years, floating on people-centered rafts of provisional civilizations that have convinced themselves they are the real thing and the cutting edge of human evolution, while designating our true magical origins of deep small cultures as some dirty, half-evolved, grunting, primitive past.

“But no matter how far we’ve drifted away from those real indigenous shores, the spirits of our last happy, intact, indigenous ancestors from before we began to drift are effortlessly coursing right along with us. Having merged with the vastness of the natural wild tossing sea we so fear to drown in, they follow each of us like a pod of giant sea turtles, their big sweet scaly heads thumping up under us, trying their best to get our attention and tow us home to our real selves, knocking on the hull of the lifeboat of today’s assumed culture….” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 310.

“What is in a seed that makes it sprout, grow, and flower and fruit is known as the Daughter of the Wild, and our presuming to take her–without asking her or obtaining her permission, as if the entire world were soulless and just lying there for our pleasure and exploitation–is at the base of all human incapacity for a life of relevance and happiness. Domestication was the beginning of the unconscious pervasive presence of human viciousness and cruelty in the world.

“People did not lose the ‘garden’ when Eve stole an apple from God’s plantation and gave it to Adam–the people lost themselves when Adam stole the garden from Eve, who was God!

“When we were hunting peoples or humans searching out and eating the abundance of seasonal cycles of wild tubers, inner barks, roots, wild fruit, vegetables, grains, and nuts, we were part of the natural landscape and never took the ‘daughter’ away from her ‘mother,’ the wild land, because there was no ‘other’ place to take her to: all land was wild….

“For this, for not asking, for not waiting for permission, and for not approaching the wild as befits the majesty of the wild as the sole source of all earthly sustenance, all farming and pastoralism of domesticated plants and animals on tamed land earned humans the endless stigma of Wild Nature’s hatred. This hatred showed itself in the lessened vitality of the ploughed land to ‘produce’ and in humans’ hatred of other humans.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. pp. 317-8.

“According to the Tzutujil Mayan version of this agreement, if the people continued to maintain their end of the original sworn agreement with the Wild, our ancient in-laws, the wild Holy in Nature, promised to continue contributing the densely rich nutrition and exuberant tenacity of life-grasping vigor and vitality that only wild untamed plants and animals have, to their now-domesticated grandchild.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 320.

“As a young man, I remember more than once catching a herd of scared, uncooperative, runaway horses by releasing horses that had remained in the corral and driving them to the vicinity of those that we couldn’t gather, and watching the scattered, scared ones falling in with that herd of confident ones as together we all headed home. Maybe if we run a few well–remembered old and loyal parts of other tribes’ indigenous agreements past your own scattered ancestral memories, the lost beauty of your own people’s very old past will follow us all home to a better time.” Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. p. 324.

“Here are a few of that old jar’s seeds [of indigenous agreements] sprouted into view.

“Sprout One: There has to be wild land, air, and sea. There has to be more wild land that is unmined, unhiked, unrafted, unphotographed, unclimbed, unlogged, and uninhabited than there is land under cultivation, filled with habitation, dedicated to recreation, or otherwise put to use by humans…. (324)

“Sprout Two: The Veld–sacred feral land. To keep our Agreement with the Wild there has to be a veld, a territory of uninhabited land neither wholly wild nor under cultivation, running along the edge of the Wild as a buffer zone between the activities of civilization and the sacred off-limits home of the Holy in the Wild…. (327)

“Sprout Three: All origins mut be known–where the seeds go, so the agreement must go…. (330)

“This vast education is what makes all things feel at home with all other things and to know where to tread and where to be cautious: how to lie still and when to move; how to eat, speak; and what things are biggest, and which are bigger still.

“The loss of this capacity, of detail in our modern lives descended from production-oriented imperial civilizations and may well be the driving force behind the need for science, as its penetrating need-to-know analytic capacity tries to fill the painful void of the civilization it serves to make up for the loss of the lyrical mythologic reality of the Indigenous Soul present at the deepest levels in all human beings.

“But the loss of this natural education has put our hearts into a zoo-like condition of unnatural confinement, causing the worldwide mass epidemic of depression, of lives lived at a spectator distance from the warm soil that births us…. (332-3)

“To have this awareness of spiritual agreement and conductivity we have to know everything about what we grow and what we eat, expanding in particular how we eat beyond the treatment of plants as faceless undivine ‘food’; simple carriers of chemically analyzed organic nutrients. This treatment of life and eating as if plants and animals were simply primitive forms of nutritional fuel capsules instead of embodying the great willingness of the Holy in Nature to feed us by their conscious acceptance of certain enslavement of their otherwise natural plants is anathema to the real human soul and a deterrent to happiness on this Earth. For it alienates us from the mythic, the mystery of the Holy in life, and our own feeling of worthiness in service to the grief of the enormity of sacrifice we cause the world to experience by just our eating, breathing, and pursuit of survival.

“Therefore all farming, gardening should not be felt as some small, inoffensive, off-the-grid, relaxing hobby but a large, powerful, deeply emotional working necessity without which we can never fully develop into a worthy human presence of initiatory possibility…. (333)

“Sprout Four: When the people marry, the seeds marry…. (341)

“Among all the world’s ancient gardening and stock-raising people, when any food seed finally was conceded as a gift to an outside people to use for their own cultivation, it came on the tail of long, serious discussions, divinations, and finally only after a reluctant decision…. (345)

“Sprout Five: Kneel at the feet of the mother of the food you eat and ask her to adopt you…. (348)

“If you live in the modern world and aren’t growing food somehow, then someone or something is starving on account of you while you take up space and nutrients. Stop living in coffee shops, and get out under the leaf litter. The Holy is certainly not being fed by your sitting around thinking about it. Better to grow food and feed somebody beautiful food than whine, get pale, and rot…. (349)

“When you consider what just one citified human this day and age takes out of the Holy earth to support them for five minutes, a thinking person could despair. But that kind of despair is just laziness with a college education, for if you carry well just even a small chunk of that weight, it will be more help than you can estimate, especially when it comes to what in the modern world is called an ‘energy crisis,’ your physical health and a general open pollination of a well-proportioned mental vision of yourself and all those you touch.

“Turn that worthless lawn into a beautiful garden of food whose seeds are stores sown, whose foods are living origins. Grow a garden on the flat roof of your apartment building, raise bees on the roof of your garage, grow onions in the iris bed, plant fruit and nut trees that bear, don’t plant ‘ornamentals,’ and for God’s sake don’t complain about the ripe fruit staining your carpet and your driveway: rip out the carpet, trade food to someone who raises sheep for wool, learning to weave carpets that can be washed, tear out your driveway, plant the nine kinds of sacred berries of your ancestors, raise chickens and feed them from your garden, use your fruit in the grandest of ways, grow grapevines, make dolmas, wine, invite your fascist neighbors over to feast, get to know their ancestral grief that made them prefer a narrow mind, start gardening together, turn both your griefs into food; instead of converting them, convert their garage into a wine, root, honey, and cheese cellar–who knows, peace might break out…. (349-350)

“To indigenous people worldwide, plants are the most sentient beings of all and should be respected as much as any animal should. They just have a larger, more temporally spread-out nervous system than most humans can sense, which can be better measured geologically in eons instead of minutes, millennia instead of days, by synaptic wave patterns like the rippled growth of stalactites in a cave.

“The old Tzutujil, for example, held animals as ‘organs’ of plants. Plants extended beyond their roots, stalks, leaves, and flowers, and had four basic parts. One was a smaller plant or fungi that grew at its root, the next was a land mammal that lived in, on, around the plant, or in the shade of its trunk, the next was a flying animal, bird, or insect that resided in its branches, and then there was the plant itself.

“The fungi were the kidneys, intestines, and memory of the plants. The animal was its moving part, the bird its ‘calling’ voice and lungs for the plant’s body, which was the ‘seeded’ largesse of providence for all the other three and the skeleton upon which all life was dressed as its flesh…. (351)

“For in every case [of eating] it is an instance of a ‘mother’ plant or animal giving up her children for you to eat at your dinner table, or a ‘mother’ giving up her own children’s sustenance, plant or animal, to feed your children.

“Better than sitting around feeling superior for adherence to any kind of food habit, it would be better for you to physically kneel in front of your mother fruit tree, and at the knees of your milk cow, or at the woolly face of your ewe, and ask permission to speak to them, and then ask that they adopt you as the hungry orphan that you really are without them; ask to be her calf, or her lamb, or her shoot in the leaf litter of the mother tree’s shade, for you are none other than the one who has already eaten her children and drunk her children’s milk; tell her you want to be accepted as her lamb because, indeed, you are fed by no other…. (352)

“It is really arrogant to think you should be above and outside this constant reality that all things live only because another has died to give them life through food; wanting to transcend this unavoidable core of all existence can only mean you want to have your cake and eat it too…. (353)

“Sprout Six: Beautiful farming.

“Indigenous agriculturalists worldwide have always spent a lot of time making and adorning all their tools, making meaningfully ornate the walls and floors of their homes, adorning their own bodies and farm animals, making beautiful their graves, and more so the sacred architecture of their fields… (354)

“While endless examples of how the world’s peoples have done this [farmed with beauty] or the few that still do could be laid out in front of us–and indeed it would be good to see what such a thing really looks like–but what I’m really inspired toward is the possibility of how a truly ugly world-killing-corporately-extorted culture of abstract money, suits, camouflage, acrylic carpets, fake food, and business-serving petro-dependent technology could voluntarily break down into small, not simple, but excellent, symbiotic, beautiful, ornate, new, remnant micro cultures of peoples of differing speech and beauty who, learning to revere nature, develop ways to grow and live with their food, that leaves nature whole, and use their last money to underwrite spiritual, small, nonviolent, courteous, elegant, courageous, happy humans with hearts that house a love for the Holy Wild, instead of dreams of isolationist fortresses of intimidation and fake power…. (357)

“Sprout seven: A temple called a field…. (360)

“Now build a beautiful precinct in your garden, a special ‘palace’ for all the plants you designate as weeds, for the animals you call intruders, and the birds you fear will finish it all off. Here you cultivate a couple of all the plants you grow out in the rest of your plant temple city and promise you will not harvest any of it, leaving them for the wild things…. (362)

“Sprout eight: The majesty of decay …. (364)

“Sprout nine: The body of the Plants City…. (369)

“The Husband of the Holy in the Wild is Holy Decomposition…. (371)

“Sprout Ten: Offerings–farmers as the jewelers of vitality…. (375)

“For the most part it is only civilizations who ‘worship’ deities that have everything and don’t need the people. Indigenous people on the other hand don’t worship, but feed and maintain God, like they do their children, like the Holies do for us. Neither do intact indigenous people resort much to sacrifice; they are more of an offering-gift type of people…. (375-6)

“First of all, an offering should be small and beautiful: something that nature cannot make, but something the Divine, the diversity in wild nature wants or even needs but cannot themselves create. It cannot be something perfunctory, convenient, easy, lazily made, or purchased…. (376)

“Sprout eleven: Kiss your pumpkins–sacred pantry temples …. (381)

“But when your Big Food harvest does return, and the seeds return back from the sacred architecture of the fields back to your pantries, granaries, cellars, fridges, and into the hands of the cooks, then the returning Seeds, the Harvest, must be welcomed with as much wonder, genuine awe, and admiration as one would have for one’s lost half who miraculously returned unexpectedly alive and well from the impossible struggle of regenerating themselves…. (384)

“Sprout Twelve: Learning to live beyond our time–the dead must feed the living …. (391)

“But the majesty of indigenous spiritual thinking is that the maintenance of the present life by the dead of the past is what life as a dead person is all about. The well-known adage ‘that was then, this is now’ for the old Priest Farmer mind runs more like ‘that was then, and this now is fed by then.’” (393) Prechtel, Martin. 2012. The Unlikely Peace at Cuchumaquic: The Parallel Lives of People as Plants: Keeping the Seeds Alive. Berkeley: North Atlantic Books. pp. 324-393 as noted.

“The air [coming into human lungs] passes through these steadily narrowing passages to culminate in grapelike sacs called alveoli. An average lung has 300 million alveoli, with a total cellular surface area the size of a tennis court!…

“… the alveoli are lined with a three-layered film that is fifty times thinner than a sheet of airmail stationery. Called a surfactant, the film reduces the surface tension at the boundary of the air and the blood cells, thus encouraging diffusion of gases across it. The surfactant also adheres to inhaled particles until macrophages, our cellular garbage collectors, can come to cart them away. The air is literally fused to the surfactant, blurring the line where air leaves off and our cells begin as categories merge–gaseous and liquid, outside and inside–as the planet’s atmosphere enters our bloodstream.” Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 57.

“A forest is an intricate device for catching, holding, using, and recycling water. You might liken it to a large sponge, except that it is far more complex… In essence, forests rain upwards, into the heavens.

“Forests also harvest moisture from the sky. Particularly in coastal areas, where there is a high incidence of fog and mist, trees comb the air. Water droplets condense on needles and leaves and fall to the forest floor, drip by precious drip contributing to the forest’s stores of water.” Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 86.

“But metabolic production of water [breakdown of carbohydrates and fats] only accounts for 11.5 per cent of the normal requirement of 2.5 litres a day. The rest usually comes from the fluids we drink (52.2 per cent of our daily needs) and from solid food (36.3 per cent). This intake is balanced with our daily losses–about 1.5 litres in urine, 0.9 litre in expired air and sweat, and 0.1 litre in feces.” Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 92; reference: Despopoulus, A. & S. Silbernagl. 1991. Color Atlas of Physiology, 4th edition. NY: Theime Medical Publishers.

“Ambient humidity and air temperature, together with your level of physical activity, determine how much water moves through your skin into the surrounding air. In the same way, external and internal conditions regulate the water you imbibe and the water you eliminate. The same is true of all other creatures: this lifelong balancing act is part of a global circus, a performance stage-managed by the planet and its inhabitants together.” Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 94.

“Because of this property [the high specific heat of water], large bodies of water, such as lakes and oceans, absorb a great deal of heat in summer, release it in winter and thus modulate surface temperatures. Ocean currents absorb large amounts of heat in the tropics and transport it to temperate regions, where it warms the surround air. When the water reaches the polar areas, it is cooled and then moves back towards the equator, where it will lower air temperatures as it absorbs more heat. The planet’s water supplies have other effects on climate as well: the whiteness of snow and clouds reflects sunlight away from the Earth, whereas water vapour behaves as a greenhouse gas and reflects heat back onto the surface.” Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 97.

“On everything that has formed you you may depend. Do not balk at this apparent slavery… a debtor to many, you pay for your advantages by the same number of dependencies. Understand that independence is a form of poverty; that many things claim you, that many also claim kinship with you.” Gide, Andre. 1947. The Journals of Andre Gide, V. 1. Alfred A. Knopf. Quoted in: Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 239.

“The more we know of other forms of life, the more we enjoy and respect ourselves… Humanity is exalted not because we are so far above other living creatures but because knowing them well elevates the very concept of life.” Kellert, S.R. & E.O. Wilson (eds). 1993. “Studies supporting biophilia hypothesis.” The Biophilia Hypothesis. Washington, D.C.: Island Press. Quoted in: Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 259.

“For perhaps the first time the landscape of meaning is supplanted by the landscape of fact. Before the Renaissance human beings, like other creatures, occupied a qualitatively heterogenous world, riddled with significant places. Only the offspring of the Renaissance have ever imagined it to be all the same, neutral matter for transformation and exploitation. This they accomplished by scraping all traces of value from the environment and vesting it solely within the boundaries of the ego. The result is an aggrandizement of the individual human being and the creation of a bare and bleached environment.” Evernden, Neil. 1993. The Natural Alien: Humankind and Environment. Toronto: U of Toronto Press. Quoted in: Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 278.

“A tree, we might say, is not so much a thing as a rhythm of exchange, or perhaps a centre of organizational forces. Transpiration induces the upward flow of water and dissolved materials, facilitating an inflow from the soil. If we were aware of this rather than the appearance of a tree-form, we might regard the tree as a centre of a force-field to which water is drawn… The object to which we attach significance is the configuration of the forces necessary to being a tree… rigid attention to boundaries can obscure the act of being itself.” Evernden, Neil. 1993. The Natural Alien: Humankind and Environment. Toronto: U of Toronto Press. Quoted in: Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 284.

“O chestnut-tree, great-rooted blossomer,
Are you the leaf, the blossom or the bole?
O body swayed to music, O brightening glance,
How can we know the dancer from the dance?” Yeats, W.B. “Among School Children.” Quoted in: Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. p. 285.

“Critical of the shortsighted view of his profession [architecture], McDonough [William] likes to cite a story related by the eco-philosopher Gregory Bateson. At New College in Oxford, England, the huge oak beams of the university’s main hall are some 12 metres long and 0.5 metres thick. In 1985, dry rot had finally weakened them so much that they needed to be replaced. If oak trees of such size could have been found in England, they would have cost about US$250,000 per log for a total replacement cost of around US$50 million. Then the university forester informed the administrators that when the main hall had been built 350 years earlier, the architects had instructed that a grove of oak trees be planted and maintained so that when dry rot set in about three and a half centuries later, the beams could be replaced. Now that is long-term planning, and McDonough believes this has to become standard in architectural thinking.” Suzuki, David. 2007. The Sacred Balance: Rediscovering Our Place in Nature. Vancouver: Greystone Books. pp. 314-5. Reference: McDonough, William & M. Braungart. 2002. Cradle to Cradle: Remaking the Way We Make Things. NY: North Point Press.

“Suppose that the incoming energy is of higher ‘quality’ than the outgoing energy and hence represents a net flow of order into the Earth. Then we can imagine some enterprising middleman inserting itself in the middle of this process and skimming off some of the incoming flow of order, using it to create more and better middlemen. Looking only at the middle layer, it would seem as though order were magically increasing. That is,

“The flow of energy through a system can leave behind increased order.

“This is life’s big trick. The middle zone is our biosphere; we are the middlemen. (Note: A second, largely independent, biosphere exists in hot ocean vents, fueled not by the Sun but by high-energy chemicals escaping from inside the Earth.)” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 9.

“Plants consume order, not energy….

“Again, life doesn’t really create order from nowhere. Life captures order, ultimately from the Sun. This order then trickles through the biosphere in an intricate set of processes that we will refer to generically as free energy transductions.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 10.

“Again, the directed motion of the original molecule has been degraded to a tiny increase in the average random motion of its peers. But, average random velocity is just temperature…. In other words, mechanical energy has been converted to thermal energy in the process of reaching equilibrium. Friction is the name for this conversion.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 83.

“… a typical chemical bond energy is Ebond ~ 2.4 x 10-19 J, about 60 times bigger than the typical thermal energy Ethermal .” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 91.

“We can crudely classify polymers as ‘compact’ or ‘extended’ by comparing the volume occupied by the polymer with the minimal volume it would occupy if all its monomers were tightly packed together. Most large proteins and nonbiological polymers then fall unambiguously into one or the other category….” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 115.

“To make progress [in understanding mixing versus nonmixing flows], we need some physical criterion that explains why corn syrup (and other fluids like glycerine and crude oil) generally undergo laminar flow, whereas water (and other fluids like air and alcohol) commonly exhibit turbulent flow. The surprise will be that the criterion depends not only on the nature of the fluid but also on the scale of the process under consideration. In the nanoworld, water will prove to be effectively much thicker than the corn syrup in your experiment; thus, essentially all flows in the nanoworld are laminar.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 154.

“Biological question: If energy is always conserved, how can some devices be more efficient than others?
Physical idea: Order controls when energy can do useful work, and it’s not conserved.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 184.

“Heat flows to maximize disorder.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 190.

“… we define temperature abstractly as the quantity that comes to equal values when two subsystems exchanging energy come to equilibrium.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 192.

“In fact, a sufficiently simple system, like the Moon orbiting earth, has no useful concept of T; at any moment, it’s in one particular state, so we don’t need a statistical description. In a complex system, in contrast, the entropy S, and hence T, involve all allowed microstates. Temperature is a qualitatively new property of a complex system not obviously contained in the microscopic laws of collisions. Such properties are called emergent.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. pp. 193-4.

“Entropy is not conserved.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 194.

“The one-way increase in entropy implies a fundamental irreversibility to physical processes…. The origin of the irreversibility is not in the microscopic equations of collisions, but in the choice of a highly specialized initial state.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 197.

“The cost of recreating order is that we must degrade some organized energy into thermal form….

“The cost of upgrading energy from thermal to mechanical form is that we must give up order.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. pp. 195, 201.

“The cells in your body contain a variety of macromolecules…. It wouldn’t be nice if they just acquiesced, clumping into a ball of sludge at the bottom of the cell, with the water on top…. One way Nature, and we its imitators, avoid this ‘clumping catastrophe’ is to arrange for the colloidal particles to have the same sign of net charge. Indeed, most of the macromolecules in a cell are negatively charged and hence repel one another.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 246.

“The chemical potential goes up when the concentration increases (more molecules are available), but it’s also greater for molecules with more internal energy (they’re more eager to dump that energy into the world as heat, thereby increasing the world’s disorder). In short,

“A molecular species will be highly available for chemical reactions if its concentration c is big or its internal energy ε is big.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 281.

“In other words, many monomers must cooperate to create a micelle, and this cooperativity sharpens the transition [from single molecules to the number of bunched molecules to reduce hydrophobic effects], mitigating the effects of random thermal motion.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 302.

“A two state transition can be sharp either because its ΔE is large or because of cooperativity between many similar units. A modest amount of cooperativity can give as much sharpness as a very large ΔE….” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 349.

“Biological question: How does a molecular motor convert chemical energy, a scalar quantity, into directed motion, a vector?
“Physical idea: Mechanochemical coupling arises from a free energy landscape with a direction set by the geometry of the motor and its track. Like any chemical reaction out of equilibrium, the motor executes a biased random walk on this landscape.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. p. 378.

“… a chemical reaction, despite having a favorable free energy change, may proceed very slowly because of a large activation energy barrier… … this circumstance gives cells a convenient way to store energy, for example, in glucose or ATP, until it is needed.” Nelson, Philip. 2020. Biological Physics: Energy, Information, Life. Philadelphia: Chiliagon Science. pp. 378-9.

“The product here [at Amazon-like warehouse] is not so much books as that goal of ten thousand years of history, the thing the human brain craves above all else and nature will die refusing to give: convenience. Ease is the disease and Nick [employee in warehouse] is its vector. His employers are a virus that will one day live symbiotically inside everyone. Once you’ve bought a novel in your pajamas, there’s no turning back….

“Nick squanders a full five precious seconds of his time-motion gazing down the gorge of books. The sight fills him with a horror inseparable from hope. Somewhere in all these boundless, compounding, swelling canyons of imprinted paper, encoded in the millions of tons of loblolly pine fiber, there must be a few words of truth, a page, a paragraph that could break the spell of fulfillment and bring back danger, need, and death.” Powers, Richard. 2018. The Overstory. NY: W.W. Norton. pp. 379, 380.

“Every one imagines that fear and anger, violence and desire, rage laced with the surprise capacity to forgive–character–is all that matters in the end [of books]. It’s a child’s creed, of course, just one small step up from the belief that the Creator of the Universe would care to dole out sentences like a judge in federal court. To be human is to confuse a satisfying story with a meaningful one, and to mistake life for something huge with two legs. No: life is mobilized on a vastly larger scale, and the world is failing precisely because no novel can make the contest for the world seem as compelling as the struggles between a few lost people.” Powers, Richard. 2018. The Overstory. NY: W.W. Norton. p. 383.

“Full-out, four-alarm, symphonic narrative mayhem plays out all around them [in nature as in backyards]…. Civilized yards are all alike. Every wild yard is wild in its own way.” Powers, Richard. 2018. The Overstory. NY: W.W. Norton. p. 384.

“The problem begins with the word world. It means two such opposite things. The real one we cannot see. The invented one we can’t escape.” Powers, Richard. 2018. The Overstory. NY: W.W. Norton. p. 466.

“Behaviorism was an exciting adventure for experimental psychology but by the mid-1950s it had become apparent that it could not succeed…. If scientific psychology were to succeed, mentalistic concepts would have to integrate and explain the behavioral data. We were still reluctant to use such terms as ‘mentalism’ to describe what was needed, so we talked about cognition instead.” Miller, George A. 2003. “The cognitive revolution: a historical perspective.” TRENDS in Cognitive Sciences. 7(3):141-4. p. 142.

“I argued [in 1977] that at least six disciplines were involved: psychology, linguistics, neuroscience, computer science, anthropology and philosophy…. These fields represented, and still represent, an institutionally convenient but intellectually awkward division. Each, by historical accident, had inherited a particular way of looking at cognition and each had progressed far enough to recognize that the solution to some of its problems depended crucially on the solution of problems traditionally allocated to other disciplines.” Miller, George A. 2003. “The cognitive revolution: a historical perspective.” TRENDS in Cognitive Sciences. 7(3):141-4. p. 143.

“For myself, I prefer to speak of the cognitive sciences, in the plural. But the original dream of a unified science that would discover the representational and computational capacities of the human mind and their structural and functional realization in the human brain still has an appeal that I cannot resist.” Miller, George A. 2003. “The cognitive revolution: a historical perspective.” TRENDS in Cognitive Sciences. 7(3):141-4. p. 144.

“Viruses are one of the most impressive and beautiful examples of macromolecular assembly. These assemblies are a collection of proteins and nucleic acids (though many viruses have lipid envelopes as well) that form highly ordered and symmetrical objects with characteristic sizes of 10s to 100s of nanometers. The architecture of viruses is usually a protein shell where the so-called capsid is made up of a repetitive packing of the same protein subunits over and over to form an icosahredron.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. p. 53.

“… we show how the time scale of certain biological processes is dictated by how long it takes some particular procedure (such as replication) to occur. We will refer to this as procedural time… … we consider a broad class of biological processes whose timing is of the ‘socks before shoes’ variety. That is, processes are linked in a sequential string and in order for one process to begin, another must have finished. We will refer to this kind of time keeping as relative time… Finally,… reveals a third way of viewing time in biological processes, as a commodity to be manipulated. In a process we will call manipulated time, we show how cells and organisms find ways to either speed up or slow down key processes such as replication and metabolism.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. pp. 76-7.

“Genetic networks are collections of genes whose expression is interrelated.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. p. 100.

“In considering energy minimization calculations, we will often make an explicit or implicit assumption that the system is operating close to equilibrium, such that any small excursion of the system will typically result in it returning to its original state. How do we reconcile the mathematically convenient equilibrium assumption with the real-world observation that biological systems are constantly dynamic and changing? The key insight is that different processes occur at different time scales, and so we can frequently isolate some small part of a biological process occurring at a relatively rapid time scale and pretend that it is at equilibrium with respect to its effects on processes that occur more slowly.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. p. 168.

“ATP is a useful energy currency because this amount of energy is comparable in the energy consumed in many kinds of biochemical transformations and is intermediate between thermal energy (kBT) and the energy of a typical covalent bond (150 kBT). ATP can be considered as the 20 dollar bill of the cell because of its intermediate value in the overall energy economy of the cell.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. p. 173.

“However, the case of greatest interest for biological model building is associated with a variational middle ground between the strictly mechanical ambition of minimizing energy and the statistical ambition of maximizing entropy…. The variational injunction in these cases is to minimize the free energy, which can be thought of intuitively as teasing out the competition between maximizing multiplicity and minimizing energy….

“Free energy minimization can be thought of as an alternative formulation of entropy maximization.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. pp. 206, 207.

“What statistical mechanics tells us precisely is that the probability of finding a given microstate with energy Ei is
p(Ei) = e-Ei/kBT/Z
where 1/Z is a constant set by the requirement that when we sum over all probabilities the result is 1. The quantity Z has legendary status in statistical mechanics and is known as the partition function. The probability distribution … is know as the Boltzmann distribution and has the same central role in statistical mechanics as does the equation F = ma in mechanics…. The normalization constant 1/Z can be determined by requiring that Σp(Ei) = 1 [summing from i= 1 to N], which implies
Z = Σe-Ei/kBT [summed from i = 1 to N]
Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. p. 218.

“Regulation of protein activity by covalent attachment of phosphate groups is one of the most important regulatory modes in all of biology. It is estimated that the human genome encodes more than 500 kinase enzymes that attach phosphate groups to specific substrates…. The kinase enzymes catalyze the transfer of the terminal phosphate group from ATP to an appropriate nucleophilic chemical group on the protein…. Furthermore, this dramatic alteration is readily reversible through the action of a separate set of enzymes called phosphatases. Phosphatases use water to hydrolyze the bonds connecting the phosphate to the proteins’s amino acid side chain releasing free inorganic phosphate and the original unmodified protein as products….

“For enzymes encountered in cells the increase in activity upon phosphorylation spans a wide range, from factors of 2 or so, to 1000.” Phillips, Rob, Jane Kondev & Julie Theriot. 2009. Physical Biology of the Cell. NY: Garland Science. pp. 268, 269.

“Recently we presented a simple yet thermodynamically reasonable artificial chemistry. When held out of equilibrium, this chemistry formed moderately large and complex autocatalytic cycles (that is, moderately large sets of species that are collectively capable of exponential growth). Unlike many previous studies, this chemistry did not include an a priori notion of catalysis. Instead, catalytic effects emerged as dynamical properties of the reaction network. The system was allowed to dynamically ‘choose’ the direction of its reactions according to thermodynamic principles, and it was this property that allowed it to self-organize into autocatalytic cycles.” Virgo, Nathaniel, Takashi Ikegami & Simon McGregor. 2016. “Complex Autocatalysis in Simple Chemistries.” Artificial Life. 22:138-152. doi: 10.1162/ARTL_a_00195. pp. 138-9.

“Without a direct pathway from initial conditions to equilibrium [in authors’ artificial chemistry system], autocatalytic pathways tend to be observed. Blocking the simplest type of autocatalytic cycle results in the formation of more complex cycles, giving rise to nonlinear phenomena such as bistability and oscillations.” Virgo, Nathaniel, Takashi Ikegami & Simon McGregor. 2016. “Complex Autocatalysis in Simple Chemistries.” Artificial Life. 22:138-152. doi: 10.1162/ARTL_a_00195. p. 139.

“That is [in their artificial chemistry where Ai polymers of monomers a of length i are formed by synthesis and decomposition or splitting randomly but with fixed probabilities], two monomers (A1) are not allowed to directly join to form a dimer (A2), and, vice versa, a dimer cannot directly split into monomers. All other reactions are permitted. There are multi-step reactions that can convert monomers into dimers in this system, such as the autocatalytic cycle
A1 + A2 –> A3,
A1 + A3 –> A4,
A4 –> 2 A2,
which has the net reaction 2 A1 +A2 –> 2 A2. This is called a first-order autocatalytic cycle, because there is only one A2 on the left-hand side. First-order autocatalysis leads to exponential growth….” Virgo, Nathaniel, Takashi Ikegami & Simon McGregor. 2016. “Complex Autocatalysis in Simple Chemistries.” Artificial Life. 22:138-152. doi: 10.1162/ARTL_a_00195. p. 143.

“It is interesting to note that we found complex behavior in this system by removing reactions [simply forbidding certain reactions [assuming that these could be present in prebiotic chemistry as low probability reactions] rather than by adding them. If we consider the full A-polymerization chemistry, including both forward and reverse reactions, all of these autocatalytic cycles–both first- and higher-order–are already present as its subnetworks. Whether the more complex networks become manifested or not is a matter of whether the right constraints exist to prevent simpler networks from being manifested instead.

“Many authors in the origins of life have worried about the problem of side reactions that can prevent autocatalysis from occurring. Our results suggest that under the right energetic conditions, such issues might not arise. Our reaction networks contain many possible reactions besides the ones that eventually form the autocatalytic cycles, yet these do not seem to disrupt the autocatalysis to any meaningful extent. The reason is that any molecules produced by side reactions eventually end up participating in autocatalytic cycles of their own. We therefore make the prediction that when one complex autocatalytic cycle is observed experimentally, it will tend to be accompanied by many others.” Virgo, Nathaniel, Takashi Ikegami & Simon McGregor. 2016. “Complex Autocatalysis in Simple Chemistries.” Artificial Life. 22:138-152. doi: 10.1162/ARTL_a_00195. p. 151.

“A closely related issue in the origins of life is the combinatorial explosion that can arise from several small molecular components combining in different ways. Our model is incomplete in regard to this issue–we have monomers of only one type, and they combine only linearly–but nevertheless our results suggest that the combinatorial explosion might not be as serious as might at first seem. One can imagine a class of molecules that can grow in multiple ways, leading to a combinatorial explosion, but that can also undergo reactions that decompose them into smaller molecules. With such a chemistry, at low concentrations one should still expect exponential growth through the mechanism that arises in the first of our models. We therefore suggest that the future of origins-of-life models might be not in taming the combinatorial explosion but in embracing it. If every molecule forms part of an autocatalytic cycle, then the combinatorial explosion represents an efficient way to explore the space of possible replicators, and it may be that it was through such a process that the first high-fidelity replicators arose.” Virgo, Nathaniel, Takashi Ikegami & Simon McGregor. 2016. “Complex Autocatalysis in Simple Chemistries.” Artificial Life. 22:138-152. doi: 10.1162/ARTL_a_00195. p. 151.

“… the biosphere, which we define as the sum of all the live and dead materials on Earth….

“Some workers use the term biosphere to refer to the regions or volume of Earth that harbor life. We prefer the definition used here, so that the oceans, atmosphere, and surface crust can be recognized separately. Our definition of the biosphere recognizes that it has mass, but also functional properties derived from the species that are present.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 5.

“The origin of the Earth’s atmosphere is closely tied to the appearance and evolution of its crust, which differentiated from the mantle by melting and by density separation under the heat generated by large impacts and internal radioactive decay. During melting, elements such as H, O, C, and N would have been released from the mantle as volcanic gases. Several lines of evidence point to the existence of a continental crust as early as 4.4 bya, and its volume appears to have grown through Earth’s history. Thus, the accumulation of a secondary atmosphere began early in Earth’s history [very little gas in Earth’s primary atmosphere at planetary formation].” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 26.

“In fact, even today the presence of water vapor and CO2 in the atmosphere creates a significant greenhouse effect on Earth–about 75% due to water vapor and 25% from CO2. Without these gases, Earth’s temperature would be about 33̊C cooler, and the planet would be covered with ice.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 29.

“Indeed, many elements that are rare in seawater are familiar poisons to living systems (e.g., Be, As, Hg, Pb, and Cd)….

“Those elements that were abundant in seawater are important biochemical constituents. Phosphorus appears as an important exception–an important biochemical constituent that has been in short supply for much of the Earth’s biosphere through geologic time.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 33.

“The release of O2 by photosynthesis is perhaps the single most significant effect of life on the geochemistry of the Earth’s surface…. However, of all the oxygen ever evolved from photosynthesis, only about 2% resides in the atmosphere today; the remainder is buried in various oxidized sediments, including Banded Iron Formations and Red Beds.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 41.

“Although there is some fossil evidence for the occurrence of extensive microbial communities on land during the Precambrian, it is unlikely that higher organisms were able to colonize land abundantly until the ozone shield developed.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 43-4.

“The size of Earth and its gravitational field ensure that photolysis of N2 does not result in the loss of N from the planet…. Thus, the main effect of life has been to dilute the initial nitrogen-rich atmosphere on Earth with a large quantity of O2.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 50.

“The tropospheric air [atmosphere up to about 10km] in each hemisphere mixes on a time scale of a few months…. Each year, there is also complete mixing of tropospheric air between the Northern and the Southern Hemispheres across the intertropical convergence zone.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 55-6.

“From a biogeochemical perspective, N2 is practically inert; reactive N is found only in molecules such as NH3 and NO. Collectively the reactive nitrogen gases are sometimes called ‘odd’ nitrogen, because the molecules have an odd number of N atoms (versus N2 or N2O).” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 67.

“The instantaneous combustion of all the organic matter now stored on land would reduce the atmospheric oxygen content by only 0.45%.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 68.

“The dissolved constituents in rainfall are often separated into two fractions. The rainout component consists of constituents derived from cloud processes, such as the nucleation of raindrops. The washout component is derived from below cloud level, by scavenging of aerosol particles and the dissolution of gases in raindrops as they fall.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 78.

“The dryfall received in many areas contains a significant fraction [of elements necessary for plant growth] that is easily dissolved by soil waters and immediately available for plant uptake. Despite the high rainfall found in the southeastern United States, Swank and Henderson reported that 19-64% of the total annual atmospheric deposition of ions such as Ca, Na, K, and Mg, and up to 89% of the deposition of P, was derived from dryfall.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 80; reference: Swank, W.T. & G.S. Henderson. 1976. “Atmospheric input of some cations and anions to forest ecosystems in North Carolina and Tennessee.” Water Resour. Res. 12:541-546.

“In addition to the uptake of CO2 in photosynthesis, vegetation also absorbs N- and S-containing gases directly from the atmosphere. Uptake of pollutant O3, SO2, and NO2 by vegetation is particularly important in humid regions, where plant stomata remain open for long periods.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 80.

“Since early geologic time, the atmosphere has interacted with the exposed crust of the Earth, causing rock weathering. Many of the volcanic gases in the Earth’s earliest atmosphere dissolved in water to form acids that could react with surface minerals. Later, as oxygen accumulated in the atmosphere, rock weathering occurred as a result of the oxidation of reduced minerals, such as pyrite, that were exposed at the earth’s surface. At least since the advent of land plants, rock minerals have also been exposed to high concentrations of carbon dioxide in the soil as a result of the metabolic activities of soil microbes and plant roots. Today, carbonic acid (H2CO3), derived by reactions of CO2 with soil water, is the major cause of rock weathering in most ecosystems. Higher levels of CO2 in Earth’s atmosphere can be expected to increase the rate of rock weathering globally. In recent years, humans have added large quantities of NOx and SO2 to the atmosphere, causing acid rain and increasing the rate of rock weathering in many areas.

“Siever proposed a basic equation to summarize the close linkage between the Earth atmosphere and its crust:
Igneous Rocks + Acid Volatiles = Sedimentary Rocks + Salty Oceans

“This formula recognizes that through geologic time the primary minerals of the Earth’s crust have been exposed to reactive, acid-forming C, N, and S gases of the atmosphere….

“Rock weathering is especially important to the bioavailability of elements that have no gaseous forms (e.g., Ca, K, Fe, and P).” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 99-100; reference: Siever, R. 1974. “The steady state of the Earth’s crust, atmosphere, and oceans. Sci. Am. 230:72-79.

“Quartz is a relatively simple silicate mineral consisting only of silicon and oxygen in tetrahedral crystals that are linked in three dimensions. In many cases, the sand fraction of soils is largely composed of quartz crystals that remain following the chemical weathering and loss of other constituents during soil development.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 103.

“Because plant roots and soil microbes release CO2 to the soil, the concentration of H2CO3 in soil waters is often much greater than that in equilibrium with atmospheric CO2 at 400 ppm. Buyanovsky and Wagner report seasonal CO2 concentrations of greater than 7% in the soil beneath wheat fields in Missouri….

By maintaining high concentrations of CO2 in the soil, plants and soil microbes control the process of rock weathering–a good example of biogeochemistry at the Earth’s surface.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 104, 105; reference: Buyanovsky, G.A. & C.H. Wagner. 1983. “Annual cycles of carbon dioxide levels in soil air.” Soil Sci. Soc. Am. J. 47:1139-1145.

“Soil microbes and plant roots appear to preferentially colonize and weather the surface of minerals that contain elements, such as phosphorus, that are otherwise in short supply for their growth and reproduction.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 106.

“This view [weathering by plants] holds that the process of photosynthesis acts to speed the transfer of an acid volatile, CO2, from the atmosphere to the soil profile. Even before the advent of vascular land plants, the Earth’s surface may have been covered with algae and lichens, producing relatively high levels of CO2 in the soil.

“Other workers disagree, suggesting that tectonic uplift and erosion–processes that stimulate mechanical weathering–are the most important determinants of the rate of chemical weathering. Still others argue that temperature and precipitation are the dominant factors controlling chemical weathering, with plants playing a lesser role. In sum, a variety of factors–tectonics, mineralogy, climate, plants, and soil microbes–play important roles in determining the rate of rock weathering, and it is likely fruitless to attribute a predominant role to any one of them.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 106-7.

“Indeed, Jenny suggested that soil profile development could only be understood as a multivariate function:
Soils = (f) climate + biota + topography + parent material + time
Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 118; reference: Jenny, H. 1980. The Soil Resource. Springer.

“In contrast to soil development in forests, where precipitation greatly exceeds evapotranspiration and excess water is available for soil leaching and runoff, soil development in grasslands proceeds under conditions of relative drought…. Overall, the intensity of chemical weathering and podzolization in grassland soils is much less than in forests….

“Nevertheless, grassland soils contain large stores of organic matter because the limited availability of water also results in slower rates of decomposition.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 122, 123.

“Because chemical weathering involves the reaction between atmospheric constituents and rock minerals, weathering of 100kg of igneous rock results in 113 kg of sediments that are deposited in the ocean and about 2.5 kg of salts that are added to seawater. Thus, a significant fraction of the transport of total dissolved substances in rivers is derived from the atmosphere and does not represent true chemical denudation of the continents.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 133.

“While the presence of vegetation appears to increase the rate of chemical weathering in soils, it retards the removal of materials by mechanical weathering. In a world without plants, most hillslopes would be barren.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 136.

“Worldwide, human activities have simultaneously nearly doubled the transport of suspended materials in rivers, but reduced the amount of the mobilized material reaching the oceans owing to the construction of dams and reservoirs.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 136-7.

“The total denudation of land is dominated by the products of mechanical weathering, which exceeds chemical weathering by three to four times, worldwide. The mean rate of total continental denudation is about 1000 kg/ ha / yr, with approximately 75% carried in the suspended sediments in rivers.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 137-8.

“… the global rate of sediment transport, an overall measure of mechanical weathering, may have been about four times greater before the land surface was colonized by plants. Indeed, today, especially high concentrations of suspended sediment are seen in rivers draining arid and semi-arid regions where vegetation is sparse.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 138.

“Indeed, the presence of organic carbon in soils and sediments and O2 in our atmosphere provides the striking contrast between biogeochemistry on Earth and the simple geochemistry that characterizes our neighboring planets.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 142.

“There is a trade-off in photosynthesis; when plant stomates are open, allowing CO2 to diffuse inward, O2 and H2O diffuse outward to the atmosphere. The loss of water through stomates, transpiration, is a major mechanism by which soil moisture is returned to the atmosphere…. Globally about 39% of the precipitation that falls on land is returned to the atmosphere by plants….

“As atmospheric concentrations of CO2 rise, plants are able to acquire more CO2 at lower stomatal conductance, thus increasing WUE [water-use efficiency].” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 144.

“Gross primary production – plant respiration = net primary production [GPP – Rp = NPP]

“NPP is, however, not directly eqivalent to plant growth as measured by foresters, ranchers, and farmers. Some fraction of NPP is lost to herbivores, fires, and in the death and loss of tissues, known collectively as litterfall. Foresters frequently call the NPP that remains the true increment, which adds to the accumulation of live biomass over many years.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 149.

“Root biomass ranges between 20% and 40% of total biomass in forest ecosystems, and the annual growth of root tissues accounts for a significant fraction of the total NPP in most communities–averaging about 15-25% across a broad range of plant size.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 150.

“We define net ecosystem production (NEP) as:

“NEP = NPP – (Rh + Rd) … where Rp, Rh, and Rd represent the respiration of plants, herbivores, and decomposers, respectively.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 153, 154.

“Agricultural lands account for up to 10% of global NPP, but only about 1% of the NPP from croplands is fed to humans or livestock, and the rest is left in the field as crop residues or lost to spoilage during shipping and marketing.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 161.

“Fires return carbon to the atmosphere, largely as CO2, analogous to a large, generalist herbivore.

“Fires are a normal part of the Earth’s terrestrial ecosystems, especially in areas of tropical savanna….. Global estimates of CO2 emissions from fires range average about 2.5 X 1015 g C/yr–about 4% of terrestrial NPP.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 164.

“Globally, herbivores consume about 5% of terrestrial NPP. Respiration by decomposers consumes most of the rest.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 165.

“… global forest cover in 2005 was 38.81 +/- 1.38 X 106 km2, with annual deforestation of 0.73 X 106 km2 and gains of 0.28 X 106 km2 due to regrowth.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 165.

“Accounting for the CO2 emissions associated with the production of fertilizer and pesticides, pumping of irrigation water, and cultivation itself, agricultural lands are a net source of CO2 to the atmosphere (i.e., negative NEP).” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 166.

“Among forests, accumulations in the forest floor increase from tropical to boreal climates. Net primary productivity shows the opposite trend, so the accumulation of soil organic matter is largely due to differences in decomposition.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 175.

“… NPP typically captures less than 1% of the available sunlight energy. Most of the remaining energy evaporates water and heats the air, resulting in the global circulation of the atmosphere. Thus, the terrestrial biosphere is fueled by a relatively inefficient initial process.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 181.

“… the availability of some elements, such as N and P, is often limited, and the supply of these elements determines the rate of net primary production in many terrestrial ecosystems….

“Conversely, for elements that are typically available in greater quantities in soil relative to plant demand (e.g., Ca and S), the rate of net primary production often determines the rate of cycling in the ecosystem and losses to stream waters.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 184.

“Only in isolated instances, for example, in animals at natural salt licks, do we find a direct transfer of elements from inorganic form to animal biochemistry–geophagy. There are few vitamin pills in the natural biosphere!” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 185.

“Mass flow of water to the root, driven by transpiration from leaf surfaces, aids in the delivery of N, P, and K to the plant, but the concentrations of these elements in the soil solution are often so low, that plant uptake must be enhanced by enzymes–transporters–that carry ions through channels in the root membrane using active transport.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 186.

“Normally, the uptake of N and P is so rapid and the concentrations in the soil solution are so low that these elements are effectively absent in the soil solution surrounding roots, and the rate of uptake is determined by diffusion to the root from other areas. Phosphate is particularly immobile in most soils, and the rate of diffusion strongly limits P supply to plant roots.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 187.

“Plant uptake of nutrients from the soil is allocated to the growth of new tissues. Although short-lived tissues (leaves and fine roots) compose a small fraction of total plant biomass, they receive the largest proportion of the annual nutrient uptake. Growth of leaves and roots received 87% of the N and 79% of the P allocated to new tissues in a deciduous forest in England.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 199.

“Decomposition of dead organic matter completes the intrasystem cycle. Decomposition is a general term that refers to the breakdown of organic matter. Mineralization is a more specific term that refers to processes that release carbon as CO2 and nutrients in inorganic form.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 208.

“Only a small fraction of the measured soil microbial biomass is active at any given time; however, total microbial biomass is often measured as an index of its activity.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 209.

“Microbial biomass (living bacteria + fungi) typically comprises < 3% of the mass of organic carbon found in soils.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 210.

“Nitrate (NO3-)may be taken up by plants and microbes or lost from the ecosystem in runoff waters or in emissions of N-containing gases during denitrification. An intermediate product in the nitrification reaction, NO2- appears to bind to soil organic matter by abiotic processes. Nitrate taken up by soil microbes (immobilization) is reduced to NH4+ by nitrate reductase and used in microbial growth. This process is known as assimilatory reduction. Nitrate can also be utilized by dissimilatory nitrate-reducing bacteria to produce NH4+, which can cycle back through these pathways. Dissimilatory nitrate reduction to ammonium is best known from its occurrence in wet tropical soils, where it can exceed denitrification–the conversion of NO3- to N2.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 214-5.

“The ratio of N2O to N2 produced in denitrification varies widely. On average, N2O represents about 50% of the total gas loss by denitrification.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 221.

“When leaves and twigs are burned under laboratory conditions, up to 90% of their N content can be lost, presumably as N2 or as one or more forms of nitrogen oxide gases….

Expressed as a percentage of the amount present in aboveground vegetation and litter before fire, the total loss of plant nutrients in gases and particulates often follows the order N > K > Mg > Ca > P > 0%…. Phosphorus aerosols derived from forest fires in Africa fertilize the Amazon Basin and the southern oceans.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 228, 229.

“Outside of the highly weathered soils of the humid tropics, where net primary production is limited by P, the growth of most [terrestrial] vegetation worldwide is controlled by the availability of N.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 233.

“Generally, ecosystems shift from N limitation to P-limitation with age and soil development, and the long-term productivity of terrestrial vegetation may depend on periodic renewal of weatherable minerals.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 235.

“… because oxygen diffuses 104 more slowly in water than it does in air, water indirectly limits biogeochemical activity in wetlands by constraining oxygen supply.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 250.

“… aquatic ecosystems receive substantial inputs of organic materials and minerals from the surrounding terrestrial catchments.

“The importance of these subsidies from terrestrial ecosystems depends to a great extent on the ratio of shoreline to the volume of the ecosystem. In many aquatic ecosystems these allochthonous (i.e., externally derived) inputs of energy and elements can exceed autochthonous (in situ) inputs by photosynthesis, such that many (perhaps most) aquatic ecosystems are net heterotrophic, or reliant on surrounding terrestrial ecosystems to provide the majority of their annual supply of organic matter and essential elements.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 250.

“Only a few species of herbaceous vegetation have successfully adapted to life in full-strength seawater, since the high ionic strength of saltwater makes it difficult for plants to maintain osmotic balance.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 254.

“If the plant remains are still recognizable [in wetlands], these organic materials are called peat. As decomposition removes carbon and the relative mineral fraction increases, the peat forms a darker muck without recognizable plant tissues.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 260.

“Soils and sediments that resist change in their redox potential are said to be highly poised. Conceptually, poise is to redox as buffering capacity is to pH. As long as soils are exposed to the atmosphere, they will appear to be highly poised, since O2 will maintain a high redox potential under nearly all conditions.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 276.

“On an annual basis, most freshwater ecosystems respire more CO2 than is fixed by photosynthesis and are classified as net heterotrophic (NEP < 1)…. Generally, we expect the P:R ratio [production to respiration] to increase as the size of lakes or rivers increases, because the receipt of solar energy in an aquatic ecosystem is a function of its surface area and because the relative importance of terrestrial inputs declines with decreasing edge-to-volume ratios.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 306.

“The most recent satellite imagery based global inventory estimates that Earth has ~117 million lakes of >0.002 km2 in size, that collectively comprise 5 X 106 km2 (or 3.7%) of the planet’s nonglaciated land area. The vast majority of natural lakes are located in the northern temperate zone in formerly glaciated landscapes. This areal estimate is surprisingly dynamic due to both the creation of new impoundments and reservoirs and the reductions in water inputs to many lakes due to extractive water use in their watersheds.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. pp. 307-8.

“Thus lake phytoplankton have a mechanism for acquiring additional inputs of nitrogen [growth of nitrogen-fixing algae], but there is no equivalent biogeochemical process that can increase the supply of phosphorus in lakes when it is in short supply.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 317.

“Globally rivers transport ~21 X 1012 g of phosphorus to the oceans each year, with nearly all of this phosphorus in particulate form. Only about 10% of the particulate phosphorus is biologically available; the rest is strongly bound to soil minerals. For rivers without significant wastewater or fertilizer inputs, very little inorganic phosphorus is found in the water column. Phosphorus mineralized from organic matter is rapidly adsorbed or assimilated, keeping P out of solution.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 341.

“Intensive land use by humans, whether for agriculture or for settlement tends to dramatically reduce water residence time in upland soils while increasing water residence time in impoundments. Collectively, water control structures have tripled the average residence time of water in the world’s rivers.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 350.

“In contrast to the major ions, the concentrations of macronutrients (N, P) and micronutrients (Fe, Mo, Cu, Zn) in seawater are variable in both space and time…. … the nutrient supply along coastal margins can be quite high…. In the open (pelagic) ocean, the supply of most nutrients is quite low, depending on atmospheric inputs or, in the case of N, biological fixation. Compounding these low inputs, nutrients are lost via the sinking of organic matter out of the photic zone. Although much of the nutrient content of this sinking organic matter is mineralized during downward transport to ocean sediments, vertical stratification prevents these nutrients from returning to the photic zone except in areas of upwelling. As a result, most nutrients share a similar depth profile throughout the world’s oceans, with concentrations depleted throughout the photic zone, and increasing with depth.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 376.

“In average surface seawater all three forms of DIC [dissolved inorganic carbon] are in chemical equilibrium with 90% of the DIC as HCO3-, 9% as CO32- and only 1% as CO2. The marine carbonate buffer system allows the ocean to absorb far more atmospheric CO2 that [=than?] would occur based on solubility alone.

“The carbonate buffering system has several important implications for ocean carbon cycling. First, most of the CO2 absorbed at the ocean’s surface is converted to forms of DIC that are not subject to gas exchange with the atmosphere. The carbonate buffering system thus greatly increases the residence time of CO2 in seawater. Second, the addition of CO2 to the world’s oceans increases the concentration of H+ which leads to the conversion of CO32- to HCO3- and reduces the acid buffering potential of the ocean.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 380.

“The highest rates of NPP are measured in coastal regions, where nutrient-rich estuarine waters mix with seawater, and regions of upwelling, where nutrient-rich deep waters are mixed into the photic zone. In contrast, among open-water environments, even the most productive areas show NPP of <300gCm-2yr-1, roughly similar to the NPP of an arid woodland. Much of the open ocean has rates of NPP more akin to a desert. Nevertheless, as a result of their large area, the open oceans account for about 80% of total marine NPP, with continental shelf areas accounting for the remainder.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 386.

“However, the total nutrient supply from rivers, atmospheric inputs, and vertical movements (upwelling + diffusion + eddy convection) provides only a small fraction (11% for N and 9% for P) of the total nutrient requirement in the surface ocean, so nutrient recycling in the surface waters must supply the rest. Rapid turnover of nutrients is consistent with the rapid turnover of 80 to 90% of the organic carbon in the surface ocean.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 388.

“In the oceans, nitrogen fixation, the process that alleviates N limitation for most freshwater ecosystems, is often highly constrained by the limited supply of micronutrients, particulary Fe and Mo, that are necessary for building nitrogenase enzymes.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 388.

“Phosphorus limitation: Given its relative global rarity and its key role in limiting freshwater NPP, it is curious that phosphorus rarely appears to be the primary limiting nutrient in the oceans…. The freshwater ‘iron trap’ for P is effectively replaced with a highly efficient sulfur trap for Fe, reducing the abiotic sink for P and maintaining higher P availability in saltwater.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 390.

“In much of the open ocean, dissolved organic phosphorus (DOP) is the dominant pool of phosphorus, often an order of magnitude higher in concentration that DIP…. To access the P contained in these molecules, algae and microbes produce alkaline phosphatase enzymes to liberate PO43- ions. [There are] Two dominant bacterial alkaline phosphatase enzymes produced in the oceans, PhoX and PhoZ, and both require Fe as cofactors. Thus, access to P may be limited by the very low availability of iron in the open ocean.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 390.

“Whereas zooplankton represent the first step in a trophic chain that eventually leads to large animals such as fish, bacteria are consumed by a large population of bacteriovores that mineralize nutrients and release CO2 to the surface waters. Thus, when bacteria are abundant, a large fraction of the carbon fixed by NPP in the sea is not passed to higher trophic levels. In areas where bacterial growth is inhibited, such as in cold waters, more NPP is available to pass to higher trophic levels, including commercial fisheries.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 395.

“Viable bacteria collected from 1626m below the seafloor near Newfoundland, Canada, where ambient temperatures range from 60̊ C to 100̊ C, currently represent the maximum known extent of the biosphere into the Earth’s crust…. Genomic analyses of the ‘deep biosphere’ document the presence of all three domains of life, with active bacteria, fungi and archaea, and suggest that sulfate reduction, methanogenesis and anaerobic methane oxidation are primary forms of metabolism in the deep biosphere. Although their activity is slow, the vast quantity of deep ocean sediments is estimated to contain 2.9 X 1029 microbial cells, an estimated 4.1 X 1015 g of C and 0.6% of Earth’s total living biomass–equivalent to our estimates of soil microbial biomass. Note that this living biomass represents only a small fraction of the total organic carbon contained in sedimentary environments.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 403.

“The ocean contains nearly 12 times as much carbon as the atmosphere, terrestrial biosphere, and soils combined, has taken up 93% of the excess heat generated by global warming increase since 1971….” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 427.

“Global mean sea level has risen by 16-21 cm since 1900 and is expected to continue to rise by 30-130 cm by 2100. While the mechanisms apply to the entire ocean, the actual rates of sea level rise along continental margins varies widely due to local geomorphology and differences in the rates of uplift and subsidence of continental plates.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 428.

“Biogeochemistry in the oceans offers striking contrasts to that on land. The environment on land is spatially heterogeneous; within short distances there are great variations in soil characteristics, including redox potential and nutrient turnover. In contrast, the sea is relatively well mixed. Large, long-lived plants dominate the primary production on land, versus small, ephemeral phytoplankton in the sea. A fraction of the organic matter in the sea escapes decomposition and accumulates in sediments, whereas soils contain little permanent storage of organic matter.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 429.

“Soils contain 121,800 km3 of water, of which about 58,100 km3 is within the rooting zone of plants.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 435.

“Globally plants appear to be responsible for about 60% of total terrestrial evapotranspiration to the atmosphere.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 435.

“Nevertheless, a large volume of water, perhaps equivalent to the current volume of the oceans, is found in Earth’s mantle.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 443.

“The recent, rapid changes in sea level are largely derived from changes in the height of coastal land, changes in the temperature of seawater, and changes in the volume of ice held on land.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 445.

“The Earth contains about 32 X 1023 g of carbon, mostly held in the lower mantle and core. About 7 X 1022 g C is found in the upper mantle, and a similar amount is contained in the atmosphere, oceans, land plants, and sedimentary rocks at Earth’s surface…. Live biomass contains a relatively small pool of carbon–about 713 X 1015 g C, distributed between the land and ocean.

“The sum of the active pools of carbon at the Earth’s surface is about 40 X 1018 g C…. At equilibrium, the sea contains about 50 times as much carbon as the atmosphere. On land, the largest pool of carbon is contained in soils, followed by vegetation. Surprisingly, the atmosphere contains more carbon than all of the Earth’s living vegetation.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 454.

“At the current estimated rates of subduction and volcanic emissions, the entire mass of carbon in the upper mantle, 7 X 1022 g, would recycle in less than a billion years; thus, it is likely that much of the carbon in the mantle has spent some time in the biosphere in the geological past. If this cycle were not complete, rock weathering would deplete CO2 in the atmosphere and oceans in < 500,000 years, and all carbon would be stored in sedimentary rocks.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 464.

“It is perhaps entertaining to speculate whether the carbon cycle on Earth drives the oxygen cycle, or vice versa.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 481.

“A large number of biochemical transformations of nitrogen are possible, since nitrogen is found at valence states ranging from -3 (in NH3) to +5 (in NO3-). A variety of microbes capitalize on the potential for transformations of N among these states and use the energy released by the changes in redox potential to maintain their life processes. Collectively, these microbial reactions drive the cycle of nitrogen. In contrast, whether it occurs in soils or in biochemistry, phosphorus is almost always found in combinations with oxygen (i.e., as PO43-). Most metabolic activity is associated with the synthesis or destruction of high-energy bonds between a phosphate ion and various organic molecules, but in nearly all cases the phosphorus atom remains at a valence of +5 in these reactions. Potassium is nearly always found in ionic form, K+, and is involved in osmotic balance and electrochemical reactions in biochemistry.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 484.

“Thus, nitrogen fixation supplies only about 9-15% of the nitrogen that is assimilated by land plants each year. The remaining nitrogen must be derived from internal recycling and the decomposition of dead materials in the soil.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 488.

“Fossil fuel combustion produces about 25 X 1012 g of fixed N (viz., NOx) annually. Some of this is derived from the organic nitrogen contained in fuels, but is best regarded as a source of new, fixed N for the biosphere because in the absence of human activities, this N would remain inaccessible in the Earth’s crust.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 489.

“Each molecule of N2O has the potential to contribute about 300 times more to the greenhouse effect relative to each molecule of CO2, so the current increase in the atmosphere has the potential to impact global climate over the next century. Also, as a result of reductions in the emissions of chlorofluorocarbons, nitrous oxide is now the dominant reactant that causes ozone depletion in Earth’s stratosphere.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 498.

“Current global reserves [of phosphorus rock reserves] are estimated at about 9 X 1015 g P. At current rates of use, the global estimate of phosphorus reserves will last about 300 years.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 504.

“Movements of potassium are the major determinant of stomatal function in plants. In humans potassium controls the electrolyte balance of blood, and a cellular sodium/ potassium pump controls the contraction of muscles…. Together with N and P, potassium should be expected to exert a major control on terrestrial plant productivity.” Schlesinger, William H. & Emily S. Bernhardt. 2020. Biogeochemistry: An Analysis of Global Change, Fourth Edition. London: Academic Press. p. 505.

“Institutions are probably an ancient feature of human social life….” Richerson, Peter, Ryan Baldini, Adrian V. Bell, Kathryn Demps, Karl Frost, Vicken Hillis, Sarah Mathew, Emily K. Newton, Nicole Naar, Lesley Newson, Cody Ross, Paul E. Smaldino, Timothy M. Waring & Matthew Zefferman. 2016. “Cultural group selection plays an essential role in explaining human cooperation: A sketch of the evidence.” Behavioral and Brain Sciences. doi: 10.1017/S0140525X1400106X, e30. p. 2.

“The institutions of another society are often hard to observe because outsiders can seldom see the entire system of rules working together. Institutions are hard to try out, because for an institution to be effective, some critical mass of group members has to adopt its rules. Considerable collective decision-making and learning effort must be expended to integrate a novel institution with the other institutions of the adopting society.” Richerson, Peter, Ryan Baldini, Adrian V. Bell, Kathryn Demps, Karl Frost, Vicken Hillis, Sarah Mathew, Emily K. Newton, Nicole Naar, Lesley Newson, Cody Ross, Paul E. Smaldino, Timothy M. Waring & Matthew Zefferman. 2016. “Cultural group selection plays an essential role in explaining human cooperation: A sketch of the evidence.” Behavioral and Brain Sciences. doi: 10.1017/S0140525X1400106X, e30. p. 2.

“The integrated cultural nature of human behavior is strikingly expressed in emblematic feats of cooperation and coordination–such as when hunting like ‘a highly competitive group-level predator’–but it also permeates the human way of life entirely and into its most minute details. For example, resources obtained using cultural hunting and foraging strategies go on to enter an intricate cultural ‘metabolic system’ where they are processed, stored, distributed, disposed, and turned into a wide variety of products. These products themselves are part of the operation of this cultural system, which is much wider and older than its individual human stewards, who depend on it for their survival. This uniquely human ‘cultural community’ embodies an emergent ecological strategy that cannot be reduced either to its learned or its genetic components.

“In many ways, this sounds more like the description of an organism than of an animal social community…. In human cultural communities, however, these integrated qualities cannot be understood genetically. While clearly underpinned by genetic adaptations, the exceptional variation of behavior seen in human communities is not explained by genetic variation. Our genetic adaptation in this regard is indirect–it permits cultural adaptation to happen.” Davison, Dinah R., Claes Andersson, Richard E. Michod & Steven L. Kuhn. 2021. “Did Human Culture Emerge in a Cultural Evolutionary Transition in Individuality?” Biological Theory. 16:213-236. doi: 10.1007/s13752-021-00382-x. pp. 213-4.

“A variety of criteria have been proposed by researchers to define and test whether candidate entities qualify as evolutionary individuals. In the following sections we will use the most commonly applied criteria as reviewed by Hanschen et al.: spatial boundaries, informational uniqueness, informational homogeneity, indivisibility, group-level adaptations, division-of-labor, and the applicability of a specific kind of multilevel selection termed multilevel selection 2. These criteria identify features that are generated by and/or enabling of group-level selection, and that are thereby likely to arise during an ETI, but unlikely to be seen otherwise (in particular together and in a highly developed state).” Davison, Dinah R., Claes Andersson, Richard E. Michod & Steven L. Kuhn. 2021. “Did Human Culture Emerge in a Cultural Evolutionary Transition in Individuality?” Biological Theory. 16:213-236. doi: 10.1007/s13752-021-00382-x. p. 217; reference: Hanschen, E.R., D.R. Davison, Z.I. Grochau-Wright & R.I. Michod. 2017. “Evolution of individuality: a case study in the volvocine green algae.” Philosophy, Theor. Pract. Biol. 9:20170801.

“We argue that hominin communities were preadapted to act (under the right set of ecological circumstances) as ‘social protocells’ with regard to heritable cultural traditions and hominins.

“The social protocell model paints a ‘culture first’ scenario where the hallmark deep cooperativity and cumulative culture of Homo originated from mutualistic cooperation between simple atomistic cultural traditions (similar to those observed in Pan today). Homo here emerges as the outcome of mutualistic evolution, as a component of the increasingly organismal organization of the novel type of macroscopic and bio-socio-technical evolutionary individual (EI) that coalesced within the social protocell. We refer to this emergent EI as a ‘sociont.’” Andersson, Claes & Petter Toernberg. 2019. “Toward a Macroevolutionary Theory of Human Evolution: The Social Protocell.” Biological Theory. 14:86-102. doi: 10.1007/s13752-018-0313-y. pp. 86-7.

“The proposed hominin ETI [evolutionary transition in individuality] would have begun in early Homo communities ca 2.6 mya, with large game carnivory, we argue, as the kernel around which the initial mutualistic system of traditions coalesced. The dramatic range expansion across the Old World that took place ca. 1.8 mya signals that the ETI had settled into a functioning new evolutionary machinery capable of macroscopic adaptation in previously unseen ways. The equally dramatic and unusual physiological change that followed in Homo, as well as the increasing organizational complexity of Homo societies, we see as evidence of a shift from micro- to macrolevel (community) selection, and to a mutualistic evolutionary trajectory between the hominin organism and the exotic sociont host organism that coalesced around it.” Andersson, Claes & Petter Toernberg. 2019. “Toward a Macroevolutionary Theory of Human Evolution: The Social Protocell.” Biological Theory. 14:86-102. doi: 10.1007/s13752-018-0313-y. p. 87.

“The outcome, we argue, was a macroscopic evolutionary population of group-selected communities–socionts–that seamlessly combined and integrated biological, social, and technical components. The socionts were evolutionary individuals exhibiting phenotypic variation, differential fitness, and heritable fitness.” Andersson, Claes & Petter Toernberg. 2019. “Toward a Macroevolutionary Theory of Human Evolution: The Social Protocell.” Biological Theory. 14:86-102. doi: 10.1007/s13752-018-0313-y. p. 87.

“I feel grief has been colonized by the clinical world, taken hostage by diagnoses and pharmaceutical regimes. For the most part, grief is not a problem to be solved, not a condition to be medicated, but a deep encounter with an essential experience of being human.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. xviii.

“Sorrow is a sustained note in the song of being alive. To be human is to know loss in its many forms. This should not be seen as a depressing truth. Acknowledging this reality enables us to find our way into the grace that lies hidden in sorrow. We are most alive at the threshold between loss and revelation; every loss ultimately opens the way for a new encounter.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. xix.

“The first gate: everything we love, we will lose….

“The second gate: the places that have not known love….

“These neglected pieces of soul live in utter despair. What we perceive as defective about ourselves, we also experience as loss. Whenever any portion of who we are is denied, we live in a condition of loss. The proper response to any loss is grief, but we cannot grieve for something that we feel is outside the circle of worth. That is our predicament….

“The third gate of grief opens when we register the losses of the world around us….

“This is the gate where we most directly experience the soul of the world, the anima mundi. Here the alchemical observation that ‘the greater part of the soul lies outside the body’ becomes evident. As Jung noted, we live in psyche, psyche does not live in us….

“The fourth gate: what we expected and did not receive….

“When we are born, and as we pass through childhood, adolescence, and the stages of adulthood, we are designed to anticipate a certain quality of welcome, engagement, touch, and reflection. In short, we expect what our deep-time ancestors experienced as their birthright, namely, the container of the village….

“At the core of this grief is our longing to belong….

“The fifth gate of grief is what I call ‘ancestral grief.’ This is the grief we carry in our bodies from sorrows experienced by our ancestors.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. pp. 24, 31, 46, 54, 63.

“[It is] ‘a holy thing to love what death can touch.’” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 25; quotation of poem “For Those Who Have Died” by Judah Halevi or Emanuel of Rome.

“The neglected pieces of soul live in utter despair. What we perceive as defective about ourselves, we also experience as loss. Whenever any portion of who we are is denied, we live in a condition of loss. The proper response to any loss is grief, but we cannot grieve for something that we feel is outside the circle of worth. That is our predicament–we chronically sense the presence of sorrow….” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 31.

“… it is clear to me that finding a target to blame is effortless. Nothing is asked of us when we simply assign fault to someone else for the suffering we are experiencing. Psychology has colluded in the blame game, pointing an accusing finger at our parents.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 41.

“Regrets are another part of the second gate, those choices we made that hindered or harmed others or ourselves: the unlived life of abandoned dreams, friendships that withered and died, or the decision to withdraw our hearts from the world and neither receive nor offer love.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 43.

“It is important to remember that grief does not appear solely through tears; it is also expressed through our anger and outrage.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 44.

“Grieving, by its very nature, confirms worth. I am worth crying over; my losses matter.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 45.

“Thomas Berry said that we have become autistic to the world and have ceased to register the songs and moods of the singing planet. Human biologist Paul Shepard said, ‘The grief and sense of loss, that we often interpret as a failure in our personality, is actually a feeling of emptiness where a beautiful and strange otherness should have been encountered.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 50; reference: Shepard, Paul. 1994. Interview by Jonathan White in White’s book Talking on the Water: Conversations about Nature and Creativity. SF: Sierra Club Books. p. 214.

“We are suffering from what ecophilosopher Richard Louv calls nature deficit disorder.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 52.

“There is a ritual that my community does annually called Renewing the World in which we communally address the earth’s need to be fed and replenished. The ritual lasts three days, and we begin with a funeral to acknowledge all that is leaving the world. We build a pyre, and then together we name and place onto the fire what we have lost.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 53.

“‘How do you earn a living?’ I find that question obscene. We have gone from being seen as valuable to the community, a carrier of gifts, to having to earn a living. No one asks, ‘What is the gift you carry in your soul? What have you brought with you into the heart of the village?’ We long to feel cosmically significant, that it matters that we are here and that we make a difference…. We have become spiritually unemployed.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 58.

“Grief is our common bond. Opening to our sorrow connects us with everyone, everywhere.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 70.

“Ritual is the original art form, weaving the personal and the communal in ways that help us relate directly with the larger, unseen world.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 77.

“We suffer from what I call premature revelation, sharing too much, too soon, and with little regard for the shyness of the soul.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 92.

“Perhaps the most salient obstacle to grieving is the lack of collective practices for the releasing of grief.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 109.

“… too many of us suffer from premature death, never fully embracing our lives and being open to the beauty and terror of existence. This is a result, in great part, of our refusal to accept life on life’s terms. Instead, we try to avoid pain and suffering. We don’t turn our face into the world, into the full experience of life, but instead we slowly back into the grave, stubbornly trying to avoid our losses, ignoring the truth that these sorrows can be our greatest teachers, our greatest gifts.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 124.

“If we are in the throes of our own species disappearance, then what it really comes down to is good manners.

“If we are leaving, then we owe it, as an act of respect and manners, to try to do whatever we can to mitigate against further damage. If our species is leaving, there will be others that remain. And if the salmon are returning, we should do whatever we can to make their waters clean and take down the obstacles that interfere with their ability to spawn.” Weller, Francis. 2015. The Wild Edge of Sorrow: Rituals of Renewal and the Sacred Work of Grief. Berkeley: North Atlantic Books. p. 143.

“Most archaeologists agree that sedentism had little if any evolutionary precedent for the human species and that sedentism facilitated the evolution of highly distinct microhabitats on the landscape from the end of the Pleistocene through the Holocene.” Stiner, Mary C., Mihriban Oezbasaran & Guenes Duru. 2021. “Asikli Hoeyuek: The Generative Evolution of a Central Anatolian PPN [Pre-Pottery Neolithic] Settlement in Regional Context.” Journal of Archaeological Research. doi: 10.1007/s10814-021-09167-z. p. 3.

“Asikh Hoeyuek (AH) is the earliest known PPN settlement in central Anatolia…. The site was founded around 10,400 years ago and was occupied continuously for about one millennium.” Stiner, Mary C., Mihriban Oezbasaran & Guenes Duru. 2021. “Asikli Hoeyuek: The Generative Evolution of a Central Anatolian PPN [Pre-Pottery Neolithic] Settlement in Regional Context.” Journal of Archaeological Research. doi: 10.1007/s10814-021-09167-z. p. 5.

“The PPN communities of central Anatolia were on their own developmental trajectory, not entirely out of contact with far-flung communities but evolving largely within their own bounds. Gradual change was the rule at Asikh, yet the cumulative transformations in architecture, settlement layout, and caprine management were great. None of these major trends can be explained by innovations coming from outside of the community. Rather, strong motors worked via feedback (especially positive feedback) processes from the inside out. Relationships between humans and animals, and between humans and crop and weed plants, grew increasingly symbiotic. New efficiencies developed for recycling nutrients and raw materials, which in turn enhanced crop and livestock productivity. The strategies of caprine management went through a succession of apparently viable systems, from raising a few young lambs or kids to a true herding system that utilized distant and nearby grazing lands. The symbioses within the Asikh system expanded with time, funneling more energy into producing food, protecting it, and making it last.” Stiner, Mary C., Mihriban Oezbasaran & Guenes Duru. 2021. “Asikli Hoeyuek: The Generative Evolution of a Central Anatolian PPN [Pre-Pottery Neolithic] Settlement in Regional Context.” Journal of Archaeological Research. doi: 10.1007/s10814-021-09167-z. pp. 32-3.

“… it seems that many of the trends that we observe at Asikh Hoeyuek over a full millennium were propelled by feedback relationships between humans, the human-altered environment, and the mix of animal and plant species that they sought to manage. As such, Asikh represents a compelling case of co-evolution via a niche constructing process, driven largely from within and continuously stimulated by offsets in social, economic, and physical constraints. The impressive outcomes of this process did not require human prescience at evolutionary time scales. People’s day-to-day and longer-term decisions were intentional, but the collective consequences of their actions were not. It seems that many grand human ‘designs’ were not really designed at all.” Stiner, Mary C., Mihriban Oezbasaran & Guenes Duru. 2021. “Asikli Hoeyuek: The Generative Evolution of a Central Anatolian PPN [Pre-Pottery Neolithic] Settlement in Regional Context.” Journal of Archaeological Research. doi: 10.1007/s10814-021-09167-z. p. 34.

“… I direct our attention to four concepts or motifs that arise repeatedly in biophysical explorations.

“The first is self-assembly, the idea that the instructions for building with biological components–whether molecules, cells, or tissues–are encoded in the physical characteristics of the components themselves….

“The second recurring motif is that of a regulatory circuit….

“Our third concept is that of predictable randomness. The physical processes underlying the machinery of life are fundamentally random but, paradoxically, their average outcomes are reliably predictable….

“Our final recurring biophysical motif is that of scaling, the idea that physical forces depend on size and shape in ways that determine the forms accessible to living, growing, and evolving organisms.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. pp. 5, 7, 8.

“All phase transitions reflect a conflict between order and disorder. Order is typically driven by the energy associated with attraction or alignment, while disorder is often driven by geometry, the ways in which constituents can arrange themselves in space. Temperature amplifies the impact of disorder. At low temperatures, the tendency to be ordered wins; at high temperatures, disorder is dominant.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. p. 23.

“Returning to the overwhelming majority of proteins that do have a unique three-dimensional form, it remains surprisingly difficult to predict what that form will be given the protein’s amino acid sequence….

“All these strategies [elaborate computer programs, parallel processing of many computers, crowd sourcing of computer time to many users, etc.] and more have proved useful, though a quick and general method for computing the structure an amino acid chain will adopt remains elusive.

“It is humbling to consider that the proteins themselves have solved the protein folding problem, shaping their structures within fractions of a second in every cell of every creature on earth. Self-assembly is awe-inspiring; it allows form to emerge from the pieces and forces intrinsic to nature’s substances themselves.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. pp. 41, 42-3.

“A tool kit of proteins adds and subtracts particular sets of atoms from histone proteins [used to hold DNA in loops for storage], influencing their further assembly or disassembly as dense DNA-histone fibers. This modification of histones is particularly important during the early development of an embryo, as descendants of a handful of cells permanently adopt distinct cellular identities, and in cancer, as cells change into rapidly growing and migrating forms. Genes that aren’t needed by particular cell types remain packed away, as if in storage in an attic–available, but not readily accessible.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. p. 73.

“These membrane-associated proteins account for over a third of the human genome and form the majority of pharmaceutical targets….” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. p. 76.

“As we’ve seen, proteins fold themselves into particular three-dimensional shapes, driven by physical interactions between the amino acids that make them up. Logo bricks, however, also have particular interactions between them, but a pile of bricks doesn’t spontaneously assemble itself into some form. Brownian motion explains the difference. Being small, the amino acid chain is in constant, vigorous motion. The molecule is always jiggling about, placing some amino acids in close proximity to others, then others, then others still, until it settles into a configuration in which sufficiently strong interactions lock it into place. Similarly, thermal energy drives the random motion of lipids; they find each other and assemble into a membrane. The recipe for self-assembly, therefore, is not merely physical interactions, but physical interactions together with Brownian motion.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. pp. 95-6.

“In bone, minerals are incorporated into the protein network, but even prior to mineralization the material is hard, about 10 times as stiff as muscle, which in turn is about 10 times as stiff as brain tissue….

“In an elegant and influential experiment reported in 2006, Dennis Discher and colleagues at the University of Pennsylvania grew stem cells of a type that can form neurons, muscle progenitors, or bone progenitors on gels of different stiffnesses, with the liquid broth around them kept the same in every case. They found that the stem cells grown on the softest gels, similar in stiffness to brain tissue, transformed into neurons; those on intermediate-stiffness gels into muscle-progenitor cells; and those on the most rigid gels, similar in stiffness to premineralized bone, into bone-progenitor cells.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. p. 125; reference: Engler, J., S. Sen, H.L. Sweeney & D.E. Discher. 2006. “Matrix elasticity directs stem cell lineage specification.” Cell. 126:677-89.

“Membrane-spanning proteins can adhere, often via various intermediaries, to the external meshwork [of other cells or from intercellular matrix] as well as the internal filamentous scaffolding. Tugging on the cell or the surroundings applies tension to the proteins, which can alter their conformations. This restructuring may, for example, expose sites that were previously hidden, triggering changes in the binding or chemical reactivity of proteins, leading ultimately to the activation or deactivation of transcription factors that orchestrate the activity of genes.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. pp. 126-7.

“Disorders as varied as diabetes, inflammatory bowel disease, gastrointestinal cancers, and even neurological ailments, such as multiple sclerosis and Parkinson’s disease, all seem to be associated with altered makeup of the microbial communities of their sufferer’s guts, compared to healthy people. These differences aren’t characterized by the presence or absence of just one or two species. Unlike ‘classic’ diseases like tuberculosis (caused by the bacterium …) or bubonic plague (caused by the bacterium …), it seems that a broad shift in the abundance of tens or hundreds of species somehow takes place in the course of these more mysterious diseases.

“Of course, correlation isn’t causation.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. p. 138.

“Such studies [of animals raised germ free and sometimes with single bacterium species added later] have revealed that germ-free animals exhibit a wide range of abnormalities; resident microbes seem crucial to the training and stimulation of immune cells, the proliferation of cells that line the gut, and more.” Parthasarathy, Raghuveer. 2022. So Simple a Beginning: How Four Physical Principles Shape Our Living World. Princeton UP. p. 141.

“[Quote from a San Bushman as told by another to author:] ‘If one day I see a small bird and recognize it, a thin thread will form between me and that bird. If I just see it but don’t really recognize it, there is no thin thread. If I go out tomorrow and see and really recognize that same individual small bird again, the thread will thicken and strengthen just a little. Every time I see and recognize that bird, the thread strengthens. Eventually it will grow into a string, then a cord, and finally a rope. This is what it means to be a Bushman. We make ropes with all aspects of the creation in this way.’” Young, Jon. 2012. What the Robin Knows: How Birds Reveal the Secrets of the Natural World. Boston: Houghton Mifflin Harcourt. p. xxv.

“Observers of bird language listen to, identify, and interpret five vocalizations:

“• Songs
“• Companion calls
“• Territorial aggression (often male to male)
“• Adolescent begging
“• Alarms….

“The finer filter would include certain migratory flight calls, whisper songs, and copulation calls….

“The first four vocalizations–all but the alarms–are what ornithologists call ‘maintenance behavior.’ I prefer the term ‘baseline.’ Quite simply, baseline is the backdrop against which everything else plays out…. To identify the disturbances, we first have to understand the patterns. Baseline is the environmental condition collaboratively created by all the animals and birds–all their creeping, crawling, hopping, grazing, prowling, and flying; all their barking, howling, chattering, grunting, whinnying, and singing. It is the intricately woven tapestry of the preferred status quo….” Young, Jon. 2012. What the Robin Knows: How Birds Reveal the Secrets of the Natural World. Boston: Houghton Mifflin Harcourt. pp. 1-2.

“Broadly defined, wake hunting [hunting that follows another hunter, a member of another species, or anything or one moving to disturb the environment or hide the real hunter] is ubiquitous throughout the natural world, but my all-time favorite observation of it in any species was from my office in Redmond, Washington: a Cooper’s hawk that cruised right above the cars on the city streets of the old downtown, matching the vehicles speed for speed, just above their antennas and just below the canopy of overhanging trees, poised to pick off starlings by sharply swooping up and into the branches in a sudden arc of death. The cars provided the hawk perfect cover, and the starlings were too busy chattering and maybe ignoring the cars to notice the very sudden winged danger.” Young, Jon. 2012. What the Robin Knows: How Birds Reveal the Secrets of the Natural World. Boston: Houghton Mifflin Harcourt. p. 15.

“Ultimately, tracking an animal makes us sensitive to it–a bond is formed, an intimacy develops. We begin to realize that what is happening to the animals and to the planet is actually happening to us. We all are one. Tracking and reading sign help us to learn not only about the animals that walk in the forest–what they are doing and where they are going–but also about ourselves. For me, this interconnection is survival knowledge and the true value of tracking an animal.” Rezendes, Paul. 1999. Tracking and the Art of Seeing: How to Read Animal Tracks and Sign, Second Edition. NY: HarperCollins. p. 16.

“RAF [reflexively autocatalytic and food-generated] theory has also been applied in other fields, including ecology and cognition, and the ideas may have application in other contexts. In economics, for instance, the production of consumer items can be viewed as a catalyzed reaction; for example, the production of a wooden table involves nails and wood (reactants) and a hammer (a catalyst, as it is not used up in the reaction but makes the reaction happen much more efficiently), and the output (reaction product) is the table. On a larger scale, a factory is a catalyst for the production of the items produced in it from reactants brought into the factory. In both these examples, notice that each reactant may be either a new material (i.e., the elements of a ‘food set’) or a product of other (catalyzed) reactions, whereas the products may, in turn, be reactants, or catalysts, for other catalyzed reactions. Products can sometimes also inhibit reactions; for example, the production of internal combustion engines resulted in processes for building steam engines being abandoned.” Kauffman, Stuart & Mike Steel. 2021. “The Expected Number of Viable Autocatalytic Sets in Chemical Reaction Systems.” Artificial Life. 27:1-14. doi: 10.1162/artl_a_00333. p. 2.

“The history of research into our own origins began at the end of the 1980s in Westerwald while processing the 20 million year old volcanoes in this region in the Rhenish Massif in Germany. In the course of investigations, structures became apparent that could only be explainable through special supra-regional tectonic processes and fracture structures in the crust, but this could not be clarified. It was only later on, after the turn of the millennium, that the opportunity came about to investigate the formation of fracture structures further in the neighboring region of the Eifel. The mapping of tectonic fault zones, which provide a vertical gas-permeable connection to the earth’s mantle, delivered a surprise. Every time fracture zones and the escape of gas–mainly of carbon dioxide–were identified, the presence of hill-building forest ants was identified locally at the same time. The correlations were so obvious that, based on personal experience, predictions about forest ant sites could be made based on geological knowledge alone, an absurdity in biology!” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 8.

“The formation of the earth’s core is key to the origin of life. Its creation from a mixture of liquid iron and nickel laid the foundation for the development of the earth’s magnetic field….

“At that time [around the time a planetary crash caused the formation of the moon], the earth’s gravitational pull was actually sufficiently large enough to stop water vapor, carbon dioxide, and nitrogen escaping into space. Nevertheless, an atmosphere that had existed for longer has to be questioned, since presumably a sufficiently strong magnetic field capable of offering protection from the solar wind had not developed inside the earth.

“The planetary magnetic field is the reason why the stream of particles continuously released from the sun (solar wind) fails to reach the earth’s surface…. It has to be assumed that parts of the young atmosphere were eroded again and again by such events. During the initial phase, the sun emitted a solar wind that was a hundred times stronger than today.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. pp. 18, 19.

“In any case, the models that assume that life developed on the face of the earth also need to answer the question of it being completely iced over during the first hundreds of millions of years of its life.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 25.

“A high concentration with constant replenishment is just as important as the removal of superfluous components. This final aspect has only become clear in recent years. It has been shown that the reactivity gradually comes to a standstill with the constant supply of organic chemical compounds in a suitable space in which the molecules can react. The unusable part needs to be disposed of constantly; otherwise the porridge becomes too thick, and formation processes suffocate.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 39.

“An indiscriminate combination of left-handed and right-handed amino acids leads to a disordered chain with different properties than chains with only one handedness of the amino acids. If the chains consist exclusively of the D [dexter, right] or L version, folding will occur faster. This is turn leads to more stable structures and thus to a longer lifespan for the molecule. The determination of only one handedness in all cells that originate from LUCA is an indication of the special importance of longer amino acid chains.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 45.

“Large enzymes, the tRNA synthetases, which take on this task [matching specific amino acids to specific tRNAs] have been developed for this purpose in the course of evolution. These take the form of special molecular tools that ensure that only one amino acid is linked to the corresponding tRNA. Each amino acid species has its own synthetase which only merges it and one of the matching tRNAs.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 61.

“Tectonic faults are caused by fracture zones in the earth’s crust where slices of rock rub against one another….

“Faults always occur in a complex network, are interconnected, cross one another, and exchange materials. They also carry water if they are open. Rising gases cause components and water to be transported from a great depth. Water that seeps down into the high mountains can penetrate deep into the crust and rise artesically [sic] through other fault paths. From the very beginning, a substantial proportion of atmospheric gases were emitted from the mantle through fault zones of this type, which also occur in a similar form in the ocean crust. The starting substances for organic chemistry can be derived from them. This means that the raw materials for biological development were available in unlimited quantities if we go by the tectonic fault model. These include carbon dioxide, carbon monoxide, nitrogen, hydrogen, ammonia, and even sulfur compounds. A phosphate is also included that acidic water could extract from the mineral apatite which is a calcium phosphate.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. pp. 92, 93.

“Gases assume a special phase state from a specific temperature and pressure. They become supercritical. The density of supercritical gases is about half that of the same substance in liquid form. With CO2, the transition from gas to the supercritical phase takes place at around 31̊ C and 74 bar.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 97.

“In its supercritical state, CO2 behaves like an organic solvent which also has a very low surface tension. It can dissolve nonpolar organic substances which are not soluble in water.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 99.

“We are already familiar with the many small reaction chambers, our micro-autoclaves, in which the most diverse range of organic molecules can be formed over the crust’s entire vertical extension. And with supercritical CO2, we have a non-polar solvent that absorbs all substances that do not dissolve in water. These therefore represent ideal conditions for the supercritical gas droplets. The droplets move through the entire crust and collect specific molecules on the way. At the same time, they create a gentle flow of water through which other molecules, which are dissolved in the water, are transported. If on their journey upward, the CO2 droplets collect in cavities and protrusions in the fault zone, small reaction chambers are formed, which are separated into two different phases. Supercritical CO2 remains suspended in the head space while underneath still or lightly flowing water can be found. Besides water-soluble organic molecules, the water contains different concentrations of dissolved salts, which cannot be dissolved in the supercritical CO2.

“And now one of the most important potentials of the system becomes clear: in the supercritical CO2 and especially at the interface to the water, reactions are possible that would not take place in the water alone. There, water-soluble substances can react with water-insoluble substances, thus forming amphiphilic soap-like components that can create membranes. These conditions also favor reactions in which a water molecule is released during the linking (condensation reactions), e.g., in the reaction of amino acids with each other to form peptides, the amino acid chains.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 100.

“But not only masses of water are attracted to the moon. The solid crust of the earth cannot resist its attraction either. Even today regions exist where locations can be raised and lowered twice a day by up to 40 cm. As with the water masses, the force of attraction on the crust was much stronger at the beginning. This resulted in cyclical pressure fluctuations, which caused cyclic phase transitions between the supercritical and the sub-critical state in the boundary zone [where not all CO2 was supercritical or a gas].” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 101.

“If all the factors in favor of biogenesis are collected and weighted, our enthusiasm for the continental crust fault zone model can be understood. Through contact with the earth’s mantle, the fault zones offer ideal conditions for organic chemical reactions. Due to the continuous outgassing of the earth and the decomposition of minerals, all the raw materials required are available in large quantities and over very long periods of time. They can react at different depths with different pressure and temperature conditions and pH values to form larger molecules, be transported along with rising fluids, and also be concentrated in a narrow zone…. Another advantage is that the conditions remain stable over very long periods of time, i.e., many millions of years, that destructive UV radiation or plasma particles from the solar wind do not strike, and that the impact of meteorites has little influence–conditions that we can search for in vain on the face of the earth. Rising supercritical gases and cyclical pressure fluctuations can also generate energy and entropy gains that are the driving force behind the early development of life.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 103.

“… it is my irrefutable conviction that a joint development must in principle have taken place that allowed the ‘software’ (RNA) and the ‘hardware’ (enzymes) to be mutually built up.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 118.

“In summary [for phase 2 of 6 towards LUCA in the continental crust fault zone model], it can be stated that:

“* Vesicles and peptides form in the crust at a depth of approx. 1000 m [at the lowest depth where some carbon dioxide comes out of supercritical state].
“* Certain peptides interact with the vesicles: the peptides that are protected by the membrane accumulate.
“* Different vesicle membranes lead to differently structured peptides, which are highly variable in the order of the amino acids but can be assigned to groups. Peptide groups also exist that do not interact with vesicles.
“* Mixed peptides with L- and D-amino acids are normally formed. However, differences exist that depend on the pH. While the mixed peptides with both orientations are formed in the neutral range at pH 7, enantiomerically pure one[s] can only occur from one species at low pH values.
“* If longer chains form in this environment, three-dimensional structures develop quickly that are more stable and survive longer than unfolded peptides.
“* The hydrothermal environment leads to the preferred formation of the simplest amino acids glycine and alanine. Glycine is achiral and alanine is chiral. Under acidic conditions, this combination can easily form enantiomericallly pure peptides from only two amino acids.
“* A tRNA develops from the ribosomal RNA, which through mutations forms numerous variations. The different formations have different preferences in contact with the enzymes from the different groups.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 127.

BEGINNING OF SERIES OF QUOTES BELOW THAT CONJECTURE HOW MUTUAL EVOLUTION OF PROTEINS AND RNA ARE BUILT IN TANDEM BY FOCUSING ON tRNAs AND SYNTHETASES WITH RNA AND PROTEINS IN SUPPORTING ROLES OF RECORDING AND FUNCTIONALITY (their phase 5 of 6)

“In the event that a P-ribosome [precursor ribosome] assisted in the random link [where tRNAs lined up to allow their amino acids to form a chain also offered the chance for a chain of complementary RNA could form so that a random peptide had a saved sequence in case it was functional], it means that the attachment of the nucleotides to the anticodons of the randomly arranged tRNAs was not left completely free. The link was made accordingly more or less specifically by the catalytic function of the simple P-ribosome. This may mean that there might have been at least two different P-ribosomes. One catalyzed the formation of the synthetases by selecting the information from one of the early RNAs, and the other catalyzed the formation of random amino acid chains without any information. The random formation of the amino acid chains means that the documentation of the random sequence in an RNA would have been possible at the same time. Or maybe only one ribosome molecule existed that was capable of performing both functions.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 136.

“Each time a peptide with a random amino acid sequence is formed, a representative for an enormously large number of variations is created, almost 100% of which have no functions. They get lost again if they are not stored with their sequence in an RNA in rare cases as described. Proteins that fold and develop into catalytically active enzymes can exist among these. A functional enzyme would, for example, be a third specific synthetase which allows a further tRNA to be loaded specific. The third tRNA may have resulted from mutations in which a base was exchanged in the anticodon. Together with the new synthetase, this would result in a third amino acid, which brings about a further increase in the possible variations when the tRNAs are randomly combined. The interesting thing about this process is that the new synthetase still consists of only two amino acid species (glycine and alanine) but that a third species links precisely to a tRNA. If the information about the sequence of the amino acids for the new synthetase is stored in an RNA formed in parallel, this can, like the third tRNA, be attached to already existing RNAs. The grown RNA is now available for copies of all building blocks, including the third synthetase.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. pp. 136-7.

END OF QUOTES ON MUTUAL EVOLUTION OF tRNAs AND SYNTHETASES

“In summary, it can be stated that [for their phase 3 of 6]:

“* The hydrothermal chemistry in the fault zones provides the starting materials for the formation of nucleotides that lead to RNA strands being able to be linked in the scCO2/gCO2 [supercritical/gaseous respectively] transition zone.
“* The pH values for the aqueous environment and magnesium and boron ions offer optimal conditions for the stability of the RNA.
“* A double-strand formation of the RNA, which prevents the formation of copies, is resolved by cyclical increases in temperature following geyser eruptions. Subsequently, the addition of complementary nucleotides and therefore the copying process become possible. These processes take place particularly effectively in the vicinity of mist droplets in the gas phase for CO2.
“* High levels of radionuclides lead to a multitude of mutations due to ionizing radiation, which creates new RNA variants.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. p. 149.

CORE OF PHASE 4 OF 6 FOR ORIGIN OF LIFE PER HYPOTHESIS:
“Under the starting conditions described, the possible conditions available in a micro-autoclave in the continental crust are as follows: under the special conditions in the cavities, amino acid chains formed which belonged to certain groups of peptides/proteins despite their large variation in the sequence. With the help of their membranes, the vesicles sorted out certain groups that interacted with the vesicle shells. In addition, other groups emerged separate to the vesicle contact. From a certain length, enzymes from all groups were folded, which gave them greater stability. They consisted of the amino acids available in the hydrothermal environment (about 10 species), but with a significant accumulation of glycine and alanine. Among them were enzymes that had catalytic functions and contributed to the tRNAs being loaded with amino acids (synthetases). This represented the first functional contact between the RNA world and the protein world.

“Some enzymes always existed within the groups that preferred to have a pocket for the amino acid glycine and a docking place for a suitable tRNA, and some provided the same for the amino acid alanine….

“The combination of amino acids, tRNAs, and certain groups of enzymes resulted in loaded tRNAs that flowed through the fluids in the cavities in high concentration. They arrived at RNA strands that were able to act as catalysts (P-ribosomes [precursor ribosomes]). The loaded tRNAs collect on them time and time again, briefly form layers together, and link the amino acids they have brought with them. These separated from the tRNAs and gradually formed a chain. Glycine and alanine must have made up most of the supply in these processes. It was only a question of time before the many variations in chain formations included some that, because of the oversupply, only consisted of glycine and alanine, which were then folded and able to form an enzyme….

“While the amino acids on the P-ribosome provided assistance are linked after the tRNA has been attached, the respective three bases of the tRNA (anticodon) are so favorable that complementary RNA building blocks can attach themselves. If they are linked, they form a codon that is the counterpart to the anticodon of the respective tRNA. If this process occurs for each subsequent tRNA molecule that docks onto the P-ribosome and the codons are also linked, a new RNA is gradually created….

“The conclusion is that the most important molecule in the overall process for life, the tRNA molecule, connects the protein world with the RNA world for the first time over a logical link.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. pp. 153, 154, 155.

“In our considerations, we have now linked a large number of amino acids in cavities in the earth’s crust to form peptides and subjected some of them to a relatively broad sorting process by continuously forming and decaying vesicles. The processes here contributed to a concentration of mixed amino acids in peptides (Phase I). Low pH values led to selected amino acids with only one orientation linking to form chains. As soon as longer peptides were formed, more complex structures could also be formed by folding. The next step involved a selection, which led to the formation of a peptide with few species (in the case under consideration two species) ( Phase II). In parallel, a ribosomal RNA was formed that was capable of copying itself and from which tRNAs emerged. The tRNAs interacted with the continuously emerging peptides from Phase I, with the result being that they were each linked to certain amino acids (Phase III). A natural oversupply led to the preferred selection of the two simplest amino acid species, which were transported by different tRNAs and linked to new peptides with their own amino acid sequence (Phase IV). Here, the anticodons from the tRNAs could be used as the first template for a simultaneously forming RNA. After an indefinite period of time, one (or a little later two) enzyme was present, which retained the property of a tRNA synthetase and whose sequences were stored in an RNA. These must have been the type that could each catalytically bind one of the two own amino acid species built into them and connect them to one of the tRNAs. The advantage from now on was that the sequence of the amino acid species from the two chains was stored in an RNA, so that the synthetases could be reproduced continuously. The free attachment of loaded tRNAs was also possible in parallel, which led to a large number of nonfunctional peptides. In some cases, their sequences were also stored in an RNA formed in parallel. There were occasionally enzymes that were synthetase-like and able to load a third, fourth, fifth, etc. tRNA with its own amino acid. If information was stored for them in an RNA in parallel, this made it part of the equipment for the entire system.

“Following the development of the minimum building blocks required for a dividing cell, the opportunity for the start had arrived. All that was required was to place the right selection of components in one of the protocells into one of the countless vesicle formation cycles. An important prerequisite for this was for the number of building blocks entering the vesicle to be significantly higher than required. Membrane proteins, which allowed the passage of ‘nutrients’ and protons, as well as the entire machinery for enzyme formation and transfer of the information, were also important. The supply form the outside through the cell membrane meant that both the complex molecules of the inner life and the lipids of the cell envelope could be continuously reproduced. The latter led to the growth of the cell membrane, which, when reaching a critical size, was divided by simple physical shearing. The high number of all preformed molecules ensured that in both sub-cells emerging from the mother cell, more building blocks for a ‘basic equipment’ were available than was minimally necessary, meaning that division process could be repeated in the same way a short time later for both cells. LUCA had started to multiply (Phase VI).

“This makes it clear that the parallel development of peptides, vesicles, and RNA molecules outside of a cell compartment delivers a great advantage. The most important components are in an open system and are supplied by it. The complicated molecules required for the functions and processes within a cell only play a role later.” Schreiber, Ulrich C. & Christian Mayer. 2020. The First Cell: The Mystery Surrounding the Beginning of Life. Springer. pp. 156-7.

“Transcription networks are designed with a strong separation of timescales; the input signals usually change transcription factor activities on a sub-second timescale. Binding of the active transcription factor to its DNA sites often reaches equilibrium in seconds. Transcription and translation of the target gene takes minutes, and the accumulation of the protein product can take hours. Thus, the different steps between the input signal and the accumulation of the output protein have very different timescales.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 7.

“In contrast [the number of autoregulating circuits in E. coli as compared to random networks], the real network has 40 self-arrows, which exceeds the random networks by 35 standard deviations, which means they occur far more often than at random. Note that 35 standard deviations mark a very high statistical significance.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 24.

“The production rate of a given gene, β, fluctuates over time due to variations in the metabolic capacity of the cell and its regulatory systems. These cell-cell differences in β are typically on the order of tens of percents, and last over the entire generation time of the cells. Thus, a snapshot of genetically identical cells grown under identical conditions will show cell-cell differences in the expression of every protein. Noise is an unavoidable property of biological material.

“Simple gene regulation is affected quite strongly by fluctuations in production rate β…. In contrast, negative autoregulation buffers fluctuations in the production rate [giving robustness to production rates].” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 29.

“The main point is that out of the many possible patterns that could appear in the network, only a few are found significantly – the network motifs. Network motifs have defined information processing functions. The benefit of these functions may explain why the same network motifs are rediscovered by evolution again and again in diverse systems.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 37.

“We see that the feedforward loop is a strong network motif. It occurs much more often than at random. Its frequency exceeds its frequency in the ensemble of randomized networks by more than 30 standard deviations [for E. coli]. In contrast, the three-node feedback loop is not a network motif (it is actually an anti-motif in many biological networks)….

“In fact, in sensory transcription networks such as those of E. coli and yeast, the feedforward loop is the only significant network motif of the 13 possible three-node patterns.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 38.

“The eight FFL [feedforward loops] types can be classified into two groups: coherent and incoherent. In coherent FFLs, the indirect path has the same overall sign [considering activation as positive and repression as negative] as the direct path. The overall sign of a path is given by multiplying the signs of the arrows on the path, so that two minus signs give an overall plus sign.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 40.

“The three ways to speed response times are:

“1. Increased degradation rate…. However, there is a cost to this strategy: to maintain a given steady state, Xst = β/α [production rate/ degradation rate], one needs to increase the production rate β to balance the effects of increased degradation α. This creates a futile cycle, where the protein is rapidly produced and rapidly degraded. This cycle can be selected by evolution in some systems, despite the costs of increased production, due to the benefit of faster response.

“2. Negative autoregulation…. This speedup is due to the ability to use a strong promoter (large production rate β) to give rapid initial production, and then to turn production off by self-repression when the desired steady state is reached. The negative autoregulation strategy works only for proteins that can repress themselves, namely, only for transcription factor proteins.

“3. Incoherent FFL [feedforward loops]: The incoherent type-1 FFL can speed up ON-responses…. This is due to initially rapid production that is later turned off by a delayed repressor, to achieve a desired steady state.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 49.

“Such analysis shows that all four types of coherent FFLs can act as sign sensitive delays, with delays after ON or OFF steps of input. All four types of incoherent FFLs can generate pulses and biphasic responses….

“Because all FFLs can have potentially useful functions, it is an open question why two types, C1-FFL and I1-FFL, appear much more often than the other six.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 51.

“Of the 13 three-gene patterns, only the FFL is a network motif in the transcription networks of E. coli and yeast as well as in the sensory transcription networks of higher organisms. Of the eight possible sign combinations of the FFL, two are most commonly found, the C1-FFL in which all interactions are positive, and the I1-FFL, in which an activator activates both a gene and its repressor. The C1-FFL acts as persistence detector, filtering out brief pulses of input. The incoherent type-1 FFL (I1-FFL) can act as a pulse generator in time and in input dose, and a response accelerator. This acceleration can be used in conjunction with the other mechanisms of acceleration, such as increased degradation and negative autoregulation. Evolution converged again and again on the FFLs in different gene systems and in different organisms. Thus, this recurring network motif is an example of a pattern that may have been selected for its specific dynamical functions.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 52.

“Each of these larger motifs [larger than three nodes] corresponds to a family of patterns that share a common architectural theme. The first such motif family found in transcription networks is called the single-input module, or SIM for short.

“In the SIM network motif, a master transcription factor X controls a group of target genes, Z1, Z2, … Zn. Each of the target genes in the SIM has only one input; No other transcription factor regulates any of the genes. In addition, the regulation signs (activation/repression) are the same for all genes in the SIM. The last feature of the SIM is that the master transcription factor X is usually autoregulatory.

“The most important role of SIMs is to control a group of genes according to the signal sensed by the master transcription factor. The genes in a SIM always have a common biological function….

“The SIM can generate temporal programs of expression in which genes are activated in a defined order.

“The temporal order is based on different thresholds of X for each of the target genes, Zi.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 61-2.

“SIMs evolved by convergent evolution, just as we saw for the FFL motif. SIMs regulate homologous genes in different organisms, but the master regulators in these SIMs are very different. This means that rather than duplication of an ancestral SIM together with the regulator, evolution converged on the same regulation pattern in the different organisms.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 64.

“There are 199 possible four-node patterns [theoretically possible]. Of these, only two, are significant motifs in the known sensory transcription networks.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 64.

“The multi-output FFL can generate FIFO [first-in-first-out] temporal programs.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 66.

“This family of patterns is our last network motif in sensory transcription networks, called dense-overlapping regulons (a regulon is the set of genes regulated by a given transcription factor), or DORs for short.

“The DOR is a row of input transcription factors that regulate a row of output genes in a densely overlapping way. The DORs are usually not fully wired, that is, not every input regulates every output. However, the wiring is much denser than in the patterns found in randomized networks.

“The DOR can be thought of as a combinatorial decision-making device. It functions as an array of gates (input functions) that integrate multiple inputs to compute the regulation of each output gene.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 69.

“Transcription networks, such as those of E. coli and yeast, show several large DORs, each controlling tens to hundreds of genes. The genes in each DOR have a shared global function, such as stress response, nutrient metabolism or biosynthesis of key classes of cellular components.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 69.

“In summary, sensory transcription networks across organisms are built of four motif families: autoregulation, FFLs, SIMs and DORs. Almost all of the genes participate in these motifs. Each network motif carries out a defined dynamical function, such as speeding responses, generating temporal programs, persistence detection or combinatorial decision-making.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 72-3.

“Multi-cellular organisms also have another type of transcription network, called developmental transcription networks. These networks govern the nearly irreversible changes that occur when a cell transforms itself into another type of cell [in contrast to sensory transcription networks that respond to external stimuli and are found in almost all cells].” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 77.

“Developmental networks have many more positive autoregulation (PAR) loops than sensory networks do. In PAR, a protein activates its own transcription.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 78.

“The double-positive feedback loop can have two stable steady states. In one stable state, genes X and Y are both ON, and the two transcription factors enhance each other’s production. In the other stable state, X and Y are both OFF. A signal that causes protein X or Y to be produced can lock the system into the ON state. This type of bistable switch is called a lock-on mechanism because X and Y are both ON or both OFF. The double-positive feedback loop is most useful when genes regulated by X and genes regulated by Y encode proteins that belong to the same tissue….

“The double-negative loop can also have two stable steady states. In one stable state, X is ON and Y is OFF, because protein X represses Y. The other stable state is the reverse: X is OFF and Y is ON. Thus, unlike the double-positive feedback loop that can express both X and Y (or neither), the double-negative loop expresses either X or Y. For this reason, this circuit is also called a toggle switch. A toggle switch is useful when genes regulated by X belong to different cell fates than the genes regulated by Y.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 80-1.

“An additional important family of network motifs in developmental networks (that is rare in sensory networks) is long transcriptional cascades. Transcriptional cascades are chains of interactions in which transcription factor X regulates Y, which in turn regulates Z, and so on….

“Long cascades are too slow for sensory transcription networks that need to respond quickly to environmental stresses and nutrients.

“Developmental networks, in contrast, work on precisely the scale of one or a few cell generations.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 84.

“To elicit rapid responses, the cell also contains much faster information processing networks, called protein-protein interaction networks or PPI for short.

“PPI networks are fast because they work by interactions between existing proteins. No new proteins need to be made. In PPI, proteins activate and inhibit each other by various means: proteins can bind each other, chemically modify each other or even degrade each other. Their typical timescale is seconds to minutes, compared to hours for transcription networks.

“PPI circuits have their own network motifs, with delightfully intricate design….

“For now, it is useful to note that PPI networks and transcription networks [hybrid network motifs] operate in an integrated fashion. Many PPI circuits have transcription factors as their output, and proteins in a PPI network are regulated by transcription networks.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 85.

“One finds that:

“1. Most real-world networks [across many fields of research] are built of a small set of network motifs.
“2. Networks from a given field share the same network motifs.
“3. Different fields show different network motifs.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 88.

“p53 [name of a protein] is called the guardian of the genome because it governs cell decisions when DNA is damaged. The cell must decide to repair the DNA, or, if it is too damaged, to avoid becoming cancerous by committing programmed cell death or becoming a zombie-like senescent cell that stops dividing. p53 is a transcription factor that regulates genes for repair and for cell death/senescence. That is why p53 is mutated in most cancers, bypassing cell death and allowing cancer cells to proliferate despite damage.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 100.

“Biochemical circuits have the saving grace that concentrations cannot diverge and cannot go negative.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 104.

“This principle [of robustness] states that biological systems have special designs that make their essential function work precisely despite naturally occurring noise. Thus, to define robustness, we will ask for any given system which of it’s functions are robust with respect to which source of noise or errors.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 117.

“We will see that diverse molecular recognition systems in the cell employ the same principle to achieve high precision. This principle is called kinetic proofreading.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 117.

“It is the off-rate kw’ [wrong tRNA to codon on messenger RNA after kinetic proofreading because on- and off-rates are roughly similar and limited by diffusion] which distinguishes the correct codon from the incorrect one: the wrong tRNA unbinds more rapidly than the correct tRNA, kw’ >> kc’ [correct rate of binding], because of the weaker chemical bonds that hold it in the bound complex….

“The affinity of codons to correct and incorrect tRNAs was experimentally measured to find an affinity ratio of about Kc/Kw [dissociation constants] ~ 1/100. Hence, there is a large discrepancy between the predicted equilibrium recognition error, F0 ~ Kc/Kw ~ 1/100, and the actual translation error rate, F = 1/10,000. It therefore seems that equilibrium recognition cannot explain the high fidelity found in this system….

“In this reaction [case of kinetic proofreading where new molecule is added to tRNA while bonded to codon], the tRNA, after binding the codon, undergoes a chemical modification. That is, c [a particular tRNA] binds to C [another molecule] and is then converted to c*. This reaction is virtually irreversible, because it is coupled to the hydrolysis of a GTP molecule….

“This cost [energy from GTP for many tRNAs] adds up to a large part of the cell’s energy balance. However, it is precisely this design that generates high fidelity. The secret is that c offers a second discrimination step: the wrong tRNA, once modified, can fall off the codon, but it cannot mount back on.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 120, 121.

“The precision of the recognition of non-self-proteins [for immune responses where T-cells attack foreign cells with antigen proteins on their surface] by T-cells is remarkable. T-cells can recognize minute amounts of a foreign protein antigen in a background of self-proteins, even though the self-proteins have only a slightly lower affinity to the T-cell receptor than the foreign target. The error rate of recognition is less that 10-6, although the affinity of the antigen is often only 10-fold higher than the affinities of the self-proteins.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 124.

“Kinetic proofreading is a general mechanism that provides specificity due to a delay step, which gives the incorrect ligands a chance to dissociate before recognition is complete….

“Kinetic proofreading uses modification of the T-cell receptor after ligand binding to create a delay. This process is not unique to T-cell receptors. In fact, these types of modifications occur in practically every receptor in mammalian cells, including receptors that sense hormones, growth factors and other ligands. This raises the possibility that delays and kinetic proofreading are widely employed by receptors to provide robustness against misrecognition of the background of diverse molecules in the organism.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 126, 127.

“In the 1970s, Michael Savageau provided evidence for a rule, called the demand rule. The demand of a gene is the probability that the gene is expressed at the high end of its range in the environment in which the organism evolved. Thus, high demand genes are usually ON, and low demand genes are usually OFF.

“Savageau found that in E. coli, high demand genes tend to be regulated by activators, and low demand genes by repressors….

“In both cases, the regulator binds its site most of the time. Binding of the regulator to its site protects it from nonspecific binding by the other regulators in the cell, a phenomenon known as crosstalk. Therefore, the demand rule minimizes crosstalk errors. For example, if a high demand gene went against the rule and was regulated by a repressor, its site would be unbound most of the time and more exposed to errors.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 128-9.

“Let’s define the robustness we seek. Suppose that a signal-transduction circuit has an input signal S, sensed by the receptor. The output of the circuit is the concentration of activated transcription factor. The output as a function of input, f(S), is the circuit’s input-output curve….

“If the input-output curve depends on the concentrations of the proteins that make up the circuit, we say that it is non-robust. Since variations in protein concentration are an unavoidable property of biological matter, a non-robust f(S) means that different individual cells will show a different response to the same input signal. The input is inaccurately read by most cells.

“In contrast, a robust input-output curve is insensitive to variations in the concentrations of the proteins that make up the circuit.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 137, 138.

“Remarkably, such robustness occurs in bacterial two-component systems – a class of thousands of systems. Each two-component system is made of a receptor X that senses specific inputs, and its dedicated messenger Y.

“At the heart of the design of two-component systems is a bifunctional component. The receptor X catalyzes two opposing reactions both phosphorylating and dephosphorylating Y.

“Thus, the opposing kinase and phosphatase activities are rolled up into the same protein, instead of being separated on two different proteins. The receptor has another seemingly arbitrary biochemical detail that will turn out to be crucial: X is an autokinase and a phosphotransferase: it first uses ATP to phosphorylate itself and only then transfers the phosphoryl group to Y.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 140.

“There are a total of several thousand receptor proteins in each cell. They are localized in a cluster on the membrane, such that ligand binding to one receptor affects the state of neighboring receptors. Thus, a single ligand binding event is amplified, because it can affect more than one receptor, increasing the sensitivity of this molecular detection device.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 156.

“Sensory systems have certain universal features that make them good measurement devices. One such feature is exact adaptation, found in the bacterial chemotaxis system of the previous chapter, and animal vision, olfaction and hearing. Exact adaptation is the ability to perfectly adjust to the background signal. When we go from sunlight into a dark room lit by a candle, at first we don’t see very well but after a while our pupils dilate to let in more light and our eyes adjust.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 175.

“Indeed, the way that the body compensates for decreased insulin sensitivity is by increasing the number of beta cells in order to increase insulin levels, to exactly match the decrease in s [insulin sensitivity, the effect of a unit of insulin on the removal rate of glucose]. For example, people with obesity that are insulin resistant have more beta cells than lean individuals. They thus secrete more insulin, compensating for their insulin resistance.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 194.

“Cell dynamics are quite unlike the dynamics we studied so far for the concentrations of proteins inside cells. For proteins we used equations that, at their core, have production and removal terms, dx/dt = β – αx [β = production; α = decay rate per concentration], and safely converge to a stable fixed point, x = β/α.

“Cells, however, live on a knife’s edge. Their basic equations contain an inherent instability. The equations describe cell proliferation and removal. Since all cells are made by cells, the proliferation rate is intrinsically autocatalytic, a rate constant times the concentration of cells; proliferation = pB. As a result, the balance between proliferation rate pB and death rate dB leads to exponential growth of cells at rate μ = p – d
dB/dt = pB – dB = (p – d)B = μB

“If proliferation exceeds death, growth rate μ is positive and cell numbers rise exponentially, B ~ eμt. If death exceeds proliferation, μ is negative, and cell numbers exponentially decay to zero. Such an explosion in cells numbers occurs in cancer, and a decay in cell numbers occurs in degenerative diseases. This is the problem of tissue size control.

“To keep cell numbers constant, we need additional feedback control, because we need to balance proliferation and death in order to reach zero growth rate, μ = 0. Moreover, the feedback loop must keep the tissue at a good functional size. Hence, the feedback mechanism must somehow register the biological activity of the cells and accordingly control their growth rate….

The feedback signal is blood glucose: glucose controls the cells’ proliferation and death rates, so that μ = μ(G). The death rate of beta cells is high at low glucose, and falls sharply around 5 mM glucose. Death rate rises again at high glucose, a phenomenon called glucotoxicity….” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 195-6.

“The glucotoxicity strategy eliminates mutants that strongly misread glucose. However, this strategy is still vulnerable to certain mutants of smaller effect: for example, mutants that misread 5 mM glucose as a slightly higher level that lies between the two fixed points. Such mutants have a growth advantage, because they are too weak to be killed by glucotoxicity, but still have higher proliferation rate than removal rate.

“Luckily, such intermediate-effect mutants are rarer than mutants that strongly activate or deactivate signaling. Designs that can help against intermediate mutants are found in beta cells: beta cells are arranged in the pancreas in isolated clusters of ~1000 cells called islets of Langerhans, so that a mutant can take over just one islet and not the entire tissue. Slow growth rates for beta-cells also help keep such mutants in check. Karin and Alon estimate that a small fraction of the islets are taken over by mutants in a lifetime.

“This mutant-resistance mechanism can be generalized: to resist mutant takeover of a tissue-level feedback loop, the feedback signal must be toxic at both low and high levels. Such U-shaped phenomena are known as biphasic responses, and occur across physiology. Examples include neurotoxicity, in which both under-excited and over-excited neurons die, and immune-cell toxicity at very low and very high antigen levels. These toxicity phenomena are linked with diseases, for example Alzheimer’s and Parkinson’s in the case of neurons.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 203; reference: Karin, O. & U. Alon. 2017. “Biphasic response as a mechanism against mutant takeover in tissue homeostasis circuits.” Molecular Systems Biology. 13. doi: 10.15252/msb.20177599.

“Tissues have robustness constraints beyond those of protein circuits inside cells. First, tissues have a fundamental instability due to exponential cell growth dynamics. They require feedback to maintain steady state and a proper size. Such feedback loops use a signal related to the tissue function, to make both organ size and function stay at a proper stable fixed point. This fixed point is maintained as the cells constantly turn over on the scale of days to months.

“Tissue-level circuits, such as hormone circuits, are also challenged by the fact that they need to operate on distant target tissues. These target tissues have variation in their interaction parameters, such as insulin resistance. Hormone circuits can show robustness to such parameters by means of dynamical compensation (DC), which arises due to an invariance built into the structure of the equations. In dynamical compensation, tissue size grows and shrinks in order to precisely buffer the variation in parameters.

“Tissue-level feedback loops need to be protected from another consequence of cell growth – the unavoidable production of mutants that misread the signal and can take over the tissue. This constraint leads to a third principle: biphasic responses found across physiological systems, in which the signal is toxic at both high and low levels. Biphasic responses can protect against mutants by giving them a growth disadvantage. This comes at the cost of fragility to dynamic instability and disease.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 203.

“Additional processes, including cell movement, contact, mechanical forces and adhesion, further shape tissues in animals.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 210.

“Robustness can help distinguish between different mechanisms and point to unexpected designs. Only a small fraction of the designs that generate a given function can do so robustly. Therefore, the principle of robustness can help us arrive at biologically plausible mechanisms. Furthermore, the robust circuits often show a pleasing elegance.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 220.

“Optimality theory is based on the ability of natural selection to maximize fitness, and hence to converge on particular circuit designs and parameter values in a given environment. Thus, optimality theory aims to predict and understand which circuit and parameters will arise in each situation.

“There is extensive evidence that biological circuits are optimized, at least to a certain extent. For example, most mutations and other changes to the cells’ networks cause a decrease in performance. Furthermore, we’ve seen that evolution converges again and again to the same network motifs, presumably due to their functional benefits.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 227.

“Optimality theory predicts that the protein expression level that is selected maximizes the fitness function. The fitness function in this case is growth rate F as a function of the number of copies of the protein expressed in the cell F(Z).” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 228.

“… the Pareto front … is the set of designs that cannot be simultaneously improved at both tasks [for engineers interested in optimal solutions for two tasks simultaneously].” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 251.

“This standard use of Pareto optimality requires us to define in advance what the tasks are: however, in many cases in biology we don’t know what the tasks are in advance…. Thus, we can not directly use performance space to do Pareto optimality….

“Remarkably, we can still make progress, using an approach called Pareto task inference, or ParTI. We simply plot the data in trait space, using all the traits that we can measure. The axes are the traits, and each phenotype is a point in this space. For example, each beak is a point in a space of traits such as beak width, depth, curvature, and so on.

“We will now see that evolution under several tasks makes the data show particular geometric shapes. These shapes can help us discern the number of tasks, and even what the tasks might be. Thus, we solve the inverse problem of Pareto optimality, by inferring the tasks from the data. For example, when there are two tasks at play, the data will fall on a line segment. The two ends of the segment give us clues about what the tasks are.

“To see where this line-segment geometry comes from, let’s imagine that each of the two tasks has a performance function, P1(T) and P2(T). The contours of these performance functions are plotted in trait space…. The peak of each performance function is a special phenotype, called the archetype. The archetype is the phenotype (trait combination) that is best at the task. If there was only that one task, evolution would converge to the archetype….

“We want to find the beak shape that maximizes fitness, F(P1, P2), where F can be any increasing function. The surprise is that, no matter what F is, one can prove that, under certain assumptions, the optimal solution must fall on the line segment that connects the two archetypes….

“This is the set of phenotypes that cannot be improved at both tasks at once – the Pareto front (plotted in trait space, not in performance space).” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 252-3.

“Ammonite shells [nautilus like] can be described in an elegant trait space with two parameters…. In this trait space, the outer shell is a logarithmic spiral, whose radius grows with each whorl by a factor W, the whorl expansion rate. The inner shell is also a logarithmic spiral, with a constant ratio between the inner and outer shell radii, denoted D.

“In this W-D trait space, ammonite shapes fill out a triangle. There is empty trait space, without ammonites, at large D and W. This empty trait space includes shells shaped like French horns, which are found in other clades, but not ammonites. The three archetypes at the corners of the triangle match the shell shapes that are optimal for three tasks: economy (maximal internal volume per shell material), swimming (lowest drag) and predator avoidance (rapid growth of shell diameter.

“There were three mass extinctions in which ammonites were wiped out except for a few surviving genera…. Remarkably, in about 10 million years after each extinction, ammonites diversified to refill essentially the same triangle. This suggests that tasks and archetypes did not move much in this case.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 256.

“A modular system is a system that can be decomposed, at least to a first approximation, into structurally independent parts. Each part also has a specific function. Modules have input and output ports to interface with other modules. Inside the module are internal connections that are shielded from the rest of the system….

“The vast majority of random networks are non-modular. But biological systems on all scales show modularity.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 274.

“Proteins themselves are made of modular domains: for example, a typical transcription factor such as the lac repressor LacI has a domain that binds to its input signal, a domain that binds DNA and a protein-binding domain to form LacI tetramers.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 275.

“It is important to realize that not all evolved networks are modular. The opposite is true: non-modular solutions are the norm in simple computer simulations of evolution….

“Modules are useful in engineering when the design goals change over time.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. pp. 275, 278.

“Switching between two such modular goals is called modularly varying goals or MVG….

“A perfect solution in MVG means that when the goal is G1, the circuits perfectly solve G1. When the goal switches to G2, fitness drops (because the circuits solve G1 and not G2) but within about a few generations, a perfect solution to G2 evolves and takes over the population. Then when the goal switches back to G1, fitness drops and within a few generations a perfect solution to G1 is again found.

“Strikingly, the solutions found in MVG evolution are modular in structure. Each of the modules also has a specific function.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 279.

“The modular solution found by MVG uses more gates than the non-modular solutions found when the goal is constant. Thus, in terms of the cost of components, modularity is suboptimal. Indeed, if we start with a modular solution and stop switching the goals, modularity decays within tens of generations and evolution converges on a non-modular solution. Thus, the need to adapt to a changing environment creates selection pressure to maintain modularity against forces that would wash it out.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 280.

“The speedup by MVG is also found when evolving circuits that are more complex. For example, one can evolve toward goals with six inputs, such as G1 = (X XOR Y) AND (Z XOR W) OR (U XOR V). Here, constant-goal evolution takes much longer than the four-input goal G1 above, rising to millions of generations. As always, it gives rise to non-modular circuits. Using MVG that periodically switches between several goals G1, G2, G3 and G4 that each change only one of the sub-goals (e.g., an AND to an OR) leads to evolution of modular circuits. And it does so faster than when the goal is constant.

“It turns out that the speedup provided by MVG is larger the more complex the goal.” Alon, Uri. 2020. An Introduction to Systems Biology: Design Principles of Biological Circuits, Second Edition. Boca Raton: CRC Press. p. 280.

“True adulthood, or psychological maturity, has become an uncommon achievement in Western and Westernized societies, and genuine elderhood nearly nonexistent. Interwoven with arrested personal development, and perhaps inseparable from it, our everyday lives have drifted vast distances from our species’ original intimacy with the natural world and from our own uniquely individual natures, our souls.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 2.

“My beginning premise is that a more mature human society requires more mature human individuals….

“My second premise is that nature (including our own deeper nature, soul) has always provided and still provides the best template for human maturation….

“A third premise is that every human being has a unique and mystical relationship to the wild world, and that the conscious discovery and cultivation of that relationship is at the core of true adulthood.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. pp. 2, 3.

“In addition to creating new cultural establishments, we must enable our very mode of being human to evolve.

“But I do not mean something implausible or fanciful. I mean what simply amounts to growing up. Rather than become something other-than-human or superhuman, we are summoned to become fully human. We must mature into people who are, first and foremost, citizens of Earth and residents of the universe, and our identity and core values must be recast accordingly. This kind of maturation entails a quantum leap beyond the stage of development in which the majority of people live today. And yet we must begin now to engender the future human.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 7.

“… our cultural resources have been so degraded over the centuries that the majority of humans in ‘developed’ societies now never reach true adulthood. An adolescent world, being unnatural and unbalanced, inevitably spawns a variety of cultural pathologies, resulting in contemporary societies that are materialistic, greed-based, hostilely competitive, violent, racist, sexist, ageist, and ultimately self-destructive.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 7.

“Stand still. The trees ahead and the bushes beside you
Are not lost. Wherever you are is called Here,
And you must treat it as a powerful stranger,
Must ask it permission to know it and be known.
The forest breathes. Listen. It answers,
I have made this place around you.
If you leave it, you may come back again, saying Here.
No two trees are the same to Raven.
No two branches are the same to Wren.
If what a tree or bush does is lost on you,
You are surely lost. Stand still. The forest knows
Where you are. You must let it find you.” Poem by David Wagoner. “Lost.” In: Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 29.

“By soul, I mean a thing’s ultimate place in the world. I use the word thing to embrace the fact that every thing has a particular place in the world and therefore has a soul – all creatures, objects, events, and relationships….

“By place, I mean not a geographical location but the role, function, station, or status a thing has in relation to other things. A thing’s place tells you how it fits in the world.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 30.

“To speak of soul as an ultimate place, we need a means of characterizing identity that is transcultural and independent of human creations. And we in fact have such a means: the natural world–its images, roles, patterns, processes, events, and animate beings. The language of nature is how soul identifies itself to us.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 35.

“The first time you consciously inhabit your ultimate place and act from your soul is the first time you can say, ‘Here’ and really know what it means. You’ve arrived, at last, at your own center. As long as you stay Here, everywhere you go, geographically or socially, feels like home. Every place becomes Here.

“This is the power of place, the power of Here.

“Before soul initiation, wherever you go, there you are. After soul initiation, wherever you go, Here you are.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 40.

“An adult is someone who has encountered her soul, retrieved some knowledge of her ultimate place in the world, acquired some practical means for occupying this place among her people, made a commitment to doing so, and is doing it.

“An elder is someone who, after many years of adulthood, consistently occupies his ultimate place without any further effort to do so. This frees him for something with yet greater scope and depth and fulfillment, namely, caring for the soul of the world. He does this by assisting others to prepare for, discover, and embody their souls, and by supporting the human-Earth system in the evolution of its soul.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 41.

“By upperworld, middleworld, and underworld, … three realms of consciousness, or three domains of human life or identity, roughly corresponding to spirit, ego, and soul, respectively.

“Upperworld denotes transpersonal states of consciousness identified with spirit and characterized by unity (or nonduality), grace, bliss, transcendence, emptiness, light, enlightenment….

“Middlwworld refers to our everyday, waking identity and state of consciousness – the ‘dayworld,’ the personal and interpersonal world of ego….

“A healthy ego is skilled in imagination, feeling, intuition, and sensing, in addition to thinking….

“Underworld signifies transpersonal states of consciousness and identity associated with soul and characterized by depth, darkness, demons, the daemon, the subconscious, sacred woundings, dreams, the unknown or not-yet-known, shadow, death, and vision of personal and cultural destiny. This is Hades, the domain of soul encounter, the realm in which the conscious self is deepened and matured.

“Underworld experiences deepen individuality through the discovery of our ultimate place in the world. This is facilitated by practices that I refer to collectively as soulcraft and that include dreamwork and deep imagery journeys, wandering in nature, and communicating with birds, trees, the winds, and the land itself….

“The shared purpose of transcending the conscious self (upperworld), differentiating the conscious self (middleworld), and deepening the conscious self (underworld) is personal development or maturation, which fosters cultural vitality and evolution, which in turn promotes ecological and planetary vitality and evolution.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. pp. 43-4.

“To say that a culture is ecocentric is to say that its customs, traditions, and practices are rooted in an awareness of radical interdependence with all beings. The individual in an ecocentric society perceives the world as an organic web of relationships and recognizes each living thing as an integral participant in this evolving web. Everyone in such a society knows that each thing, including each person, is what it is by virtue of its relationships with everything else. Every thing is praised and held as sacred.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 45.

“Individual egocentrism is a type of arrested development that makes an anthropocentric society possible. Likewise, cultural anthropocentrism (‘the world was created for the use of us humans, especially my class, gender, religion, or nation’) encourages each citizen to cultivate a use-relationship with things and other people (egocentrism). Thinking of oneself and others as ‘consumers’ becomes a reasonable idea despite its profoundly deranged implications. In a soulcentric world, egocentrism after a certain age would be considered an aberration or a pathology.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 46.

“The Eight Stages of Eco-soulcentric Human Development [chart arranged as circle that proceeds clockwise starting with stage 1 between 3 and 4:30 if seen as a clock or southeast if seen as a compass]

“Birth [transition], Stage 1, Early Childhood, The Innocent in the Nest, Task: Ego formation and the care of innocence, Gift: Luminous presence, Center of Gravity: Spirit.

“Naming, Stage 2, Middle Childhood, The Explorer in the Garden, Task: Discovering the natural world and learning cultural ways, Gift: Wonder, Center of Gravity: Family and nature

“Puberty, Stage 3, Early adolescence, The Thespian at the Oasis, Task: Creating a secure and authentic social self, Gift: Fire, Center of Gravity: Peer group, sex, and society.

“Confirmation, Stage 4, Late adolescence, The Wanderer in the Cocoon, Task: Leaving home (the adolescent identity) and exploring the mysteries, Gift: Mystery and darkness, Center of Gravity: The underworld.

“Soul initiation, Stage 5, Early Adulthood, The Apprentice at the Wellspring, Task: Learning delivery systems, Gift: Visionary action and inspiration, Center of Gravity: Cultural depths.

“Induction, Stage 6, Late Adulthood, The Artisan in the Wild Orchard, Task: Manifesting innovative delivery systems for soulwork, Gift: Seeds of cultural renaissance, Center of Gravity: Giveaway as art form.

“Crowning, Stage 7, Early Elderhood, The Master in the Grove of Elders, Task: Caring for the soul of the more-than-human community, Gift: Wholeness, Center of Gravity: Web of life.

“Surrender, Stage 8, Late Elderhood, The Sage in the Mountain Cave, Nontask: Tending the universe, Gift: Grace, Center of Gravity: Cosmos (spirit). [ending transition is death which matches birth at 3 o’clock on wheel]” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 61.

“A rite of passage, then, is never necessary in order for a person to progress between developmental stages. But sometimes the rite helps a little, sometimes it’s a significant catalyst, and always it provides the opportunity for a family or community to celebrate or formally mark the transition.

“Separate from its occasional and minor role as a passage facilitator, a passage rite most always serves as a potent social accreditation of the transitioning individual, psycholgically supporting him and his family to openly act in accordance with his new status, something he might be reluctant to do otherwise.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 65.

“We might think of each of the nine transitional events on the Wheel as having these same three phases – separation, transition, and return – whether or not a rite of passage is involved. Each life passage involves a type of leave-taking, the leaving of a smaller home for a larger one. Each developmental transition begins with an ending, the death of the old stage, and ends with a beginning, the birth of the new. In the middle occurs that dynamic, precarious shifting of center of gravity.

“One life transition in particular – Soul Initiation – is so demanding and difficult that we could think of the entire stage that proceeds it (the Cocoon) as an extended preparatory period of separation, while the stage that succeeds it (the Wellspring) could be envisaged as an extended period of incorporation.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 67.

“The two tasks of the Nest [stage 1] – one focused on human nature (innocence) and the other on human culture (ego formation) – are in dynamic tension with one another, as is the case with the two tasks in every life stage.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 87.

“When parents notice the earliest signs of psychosocial puberty, they have the responsibility and pleasure of preparing, with the full participation of their child, a ceremonial rite of passage. Of the nine major life transitions on the Wheel, puberty is especially important to celebrate, because it is the first one in life in which the individual possesses conscious self-awareness on both sides of the passage. Consequently, a puberty rite provides the individual with an experiential template for all subsequent major life passages. A puberty rite also eases the transition and brings clarity for all family members, and the child is enabled to begin adolescence with less confusion and more pride and confidence. Parents have the opportunity to ceremonially conclude their role in parenting a largely dependent child, offer their blessings, and prepare for the very different role of parenting a much more independent youth – an adolescent.

“It’s crucial, however, to understand that a puberty rite is an initiation into adolescence, not adulthood.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 169.

“A puberty rite in a modern soulcentric family might include the following elements:

“A period of preparation, perhaps as long as a year. Preparations include:
Putting away childhood things….

“A number of instructional meetings with a group of adults of the same gender as the child (usually not including the child’s parent, because the puberty rite as a whole constitutes the ending of the family’s role as the hub of the child’s life)….

“Individual preparation activities, such as self-exploration and value clarification through creative writing music, dance, drawing, and painting.

“Fashioning of adolescent symbols and implements….

“The puberty rite itself, lasting anywhere from several hours to a couple of days, with activities such as:
Purification rites – for example, bathing, water immersion, sweat ceremonies, smudging with burning herbs or incense, prayers, and blessings.

“Men’s and women’s circles open only to the initiate(s), initiated adolescents, and adults, for lively exchanges on the significance of puberty and the opportunities and obligations of adolescence….

“The initiate’s ceremonial sacrifice, either private or witnesed, of some of the childhood objects and symbols.

“The initiate’s giveaway, to younger children, of other childhood items.

“The initiate’s gifts to parents, expressing gratitude for birthing and growing her as a child.

“Gifts to the initiate by members of the family and community – gifts that symbolize the end of childhood and the attainment of adolescence.

“Statements and symbolic enactments by parents, other adults, and older adolescents concerning the character of the initiate.

“Statements or symbolic enactments demonstrating that the initiate is leaving behind childhood.

“A ritual enactment with closest family members, perhaps witnessed by others, that symbolizes the cutting of the bonds of childhood that had kept her safe yet restricted within the womb of the family….

“At some point, perhaps in the middle of the night, a meeting with one or more nonfamilial adults – soul-initiated adults – of the complementary gender…. A nonfamilial adult of the initiate’s gender serving as witness and support, accompanies him or her….

“Solo time outdoors, perhaps in a place held sacred by the initiate or the community….

“A ceremony, with symbolic objects and/or ritual actions, in which the initiate claims Earth as her primary mother and the Sun or sky as her principal father….

“A ritual to reintegrate the initiate, as an adolescent, into the family, emphasizing the different status that the initiate now occupies, using symbolically significant clothing, words (for example, vows and lists of new responsibilities and freedoms), gestures, and/or other actions.

“A community feast or celebration.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. pp. 169, 170, 171, 172.

“Early adolescence is meant to be a kind of apprenticeship – not an apprenticeship to adulthood or to soul, but an apprenticeship in the art of differentiating a social self and of belonging to an extrafamilial social group The adolescent’s task in the Oasis is to compose one particular way of being human – her own way – that works well enough in her society. It is her first extended spin around the sociocultural block. As with all apprenticeships, she learns by doing. She learns what it is to consciously construct a social self by constructing a first one. Her mission is limited to the development of this first, provisional way of belonging to the wider human community.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 175.

“The task of creating a socially acceptable and authentic self divides into eight subtasks pertaining to values and authenticity, emotional skills, conflict resolution, status assignment, sexuality, sustenance, human-nature reciprocity, and childhood survival strategies.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 182.

“The tasks of Social Individuation absorb most of the attention of nearly all teens aged twelve through fifteen – which is only natural at this age. But in our society this pre-occupation extends well beyond the teen years – which is not at all natural. Our society’s egocentrism makes value clarification, for example, highly challenging at any age. Popular mainstream culture constantly broadcasts that the sole or foremost goal in life is socioeconomic advancement. Other dimensions of existence, such as psychological or spiritual self-development, service, art, sustainable living, and intimacy, are too often marginalized or ignored. Many people are motivated simply by the desire for psychological comfort, hoping in effect to not be challenged in any way by life. If comfort, security, and socioeconomic progress are the things that count, then authenticity, individuation, and love are secondary at best and, more often, irrelevant or derimental.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 183.

“Possible features of a Confirmation rite include the following:

“A preparation time in which the initiate simplifies her life. She drops out of social scenes, roles, and jobs that would not support the underworld journey. She ties up loose ends, completes as much unfinished interpersonal business as she can, and says her good-byes.

“A community ceremony in which the initiate’s social and psychological successes are affirmed. Her talents, achievements, unique styles, and sensibilities are noted. The community acknowledges her maturity and Thespian social contributions.

“Putting away, giving away, or ritually sacrificing objects and clothes associated with her early adolescence, or first adulthood.

“A ritual funeral for, or sacrifice of, the primary ego (the adolescent personality, which, in Western society, sees us through our first adulthood). This includes expressions of both grief and joy.

“The taking of vows, in which she dedicates this next stage of life to mystery, soul discovery, and the underworld journey.

“A ceremonial dedication or commitment to the initiation process that is about to begin. (The initiation process can span several years.)

“A ceremony of leave-taking, in which, perhaps, she changes clothes (symbolizing or embodying the shift from Thespian to Wanderer), performs purifications and/or exchanges gifts with family members and/or mentors. The ceremony might conclude with a symbolic leave-taking from the community or a literal departure for a few weeks or months, a year, or indefinitely.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. pp. 239-240.

“When the caterpillar enters his silk cocoon (for him, a tomb), he dies to his previous life and enters a liminal time of being neither Earth-crawling worm nor windborne flier. Likewise, upon entering our own Cocoons, we are neither adolescent Thespians nor initiated adults. We are betwixt and between. Within his cocoon, the caterpillar pupa, the chrysalis, does not feed, and within ours we do not draw further sustenance from society. Upon emerging from the Cocoon, the individual is reborn – as a true adult.

“The Cocoon results in the disintegration of almost everything we know about the world and ourselves. The butterfly, of course, understands this.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 242.

“At the Wellspring, there is a mentor of mystery, perhaps several. These mentors are the adults and elders who have mastered crafts for rendering the invisible visible, for carrying to others the same sort of gift the new adult has been called to manifest….

“As suggested by such an animated word as spring, the accent at the Wellspring is on action, on getting the business of the world done, but in every moment staying sourced in the mysteries, rooted in the enigmatic creativity of the unfathomable depths. And, as suggested by well, the Wellspring is a stage of life that conveys abundant health, well-being, and wholeness to the Earth community. The people look to the Wellspring as well as the wellsprings for something simultaneously natural and mystical, the elixir of life.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 304.

“Induction: Passage into Adult Artistry

“The Wellspring ends when you’ve mastered one or more delivery systems for your soul image or story and you stop looking outside yourself for instruction or role models for embodying soul. You begin to fashion novel and creative forms that arise out of your own depths – or the depths of the world, you’re not sure which. In a soulcentric setting, your community has already recognized for some time the performance of your vision in service to your people. And your soul-rooted individuation has progressed to the point that, more often than not, you behave socially as the person you experience yourself to be privately.

As a Soul Apprentice, you gradually understood your soul qualities in deeper ways, and you honed your skills at embodying those qualities through a particular craft. It is the former – your understanding – that is fundamental and essential and that you now carry with you into the second half of adulthood. After all, from time to time you need to change the cultural context in which you embody soul, or you might need to learn an entirely new craft. Soul is the constant; its form and sphere or embodiment varies.

“The end of the Wellspring is marked by the transition of Induction – your incorporation into a circle or guild of Artisans. Whether or not you undergo a formal or ceremonial initiation at this time, Induction is the spiritual passage your psyche experiences.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. pp. 353-4.

“In a soulcentric setting, Induction into the Wild Orchard might be marked and celebrated by a Rite of Induction. This rite of passage might include the following:

“The ritual surrender of the role of Apprentice, including a sacrifice or giveaway of symbols, objects, or clothing specific to your apprenticeship.

“An affirmation, by elders, of the personal qualities you have exhibited as an Apprentice, and a recognition of the signs of your readiness for the next stage of the Artisan.

“Formal reminders, by elders, of the responsibilities of the Aritisan and the nature of the Wild Orchard.

“The taking of vows.

“The bestowal of symbols, objects, and clothing representing the Artisan.

“A three- or four-day fast in wild solitude.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 354.

“The genuine Martyr is clear about what he holds sacred – namely, that which he discovered during the two stages of the West quadrant. He’s willing to sacrifice and suffer, if necessary, in order to protect or sustain the sacred. But what defines him is not his suffering but his loving and his nurturing. The Martyr knows what he’d be willing to die for, but more important, he knows what he lives for.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 360.

“In Buddhism, the Warrior-Martyr is a single, blended archetype called the bodhisattva, the hero or heroine who refuses enlightenment until all sentient beings are saved from suffering. One of the bodhisattva’s qualities is his great compassion for all beings. He suffers with other beings, which implies his Martyr facet. He does not remain aloof from the distress of others, because he knows all too well that there is no private salvation. His identity is ecocentric.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 361.

“Crowning: Passage into Elderhood [“Crowning” for Plotkin is the gender neutral equivalent of Croning]….

“At the North hour in life, your personality becomes firmly rooted in true character – your soul-infused expression of Self. More and more, you instinctively embody your character in your everyday behavior without deliberate intention to do so.

“At Crowning, you relinquish your conscious attachment to the embodiment of your soul powers – the attachment that was the very definition of your adulthood – as you turn your attention to domains much wider than your individual soul life, namely, the soul of the more-than-human community. But it’s not so much that you choose at this moment to make the web of life your top priority: it’s more as if the Mystery, sensing you’re ready, commands you to take up that task, and you assent.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. pp. 387-8.

“But what does change at Crowning – and this is a huge shift – corresponds to the movement from the West hemisphere of the Wheel to its East. You are transiting from the half of life focused on doing and manifesting your uniqueness (West, soul) to the half devoted to being (accepting, enjoying, celebrating, receiving, submitting, enduring) and reflecting the universal (East, spirit).

“This movement, then, is opposite the one you made at puberty – from childhood’s spiritual innocence to the adolescent quest for identity and uniqueness (and, consequently, doing).” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 388.

“The Master: Archetype of Early Elderhood….

“In our interview, Joanna [Macy in 2006 at age 76, taken as example of someone in early elderhood] affirmed that this tending to the web of life [systems theory that she liked and had written about a lot] had in fact become the center of her conscious sensibility.

“JM: I’ve written about the web of life and taught about it for the last thirty years, but it’s becoming more real to me.

“BP: It’s more where you live now?

“JM: Yes. Like I pray to it. Or I listen to it. And I do a lot of noodling about how, philosophically and metaphysically, the web of life can be a more-than-human intelligence, almost endowing it with personality. The Mother of All Buddhas (the Buddha’s central doctrine of mutual causality) blends in my mind with Gaia, and with the web of life, and with the goddess of all the little animals.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 391.

“Upon reaching Surrender [before passing into late elderhood], you stand at the northeast point on the Wheel. You’re taking leave of the North quadrant and making your return to the East, the quadrant you left almost a lifetime ago, at Naming – at age three or four. While your acquisition of an ego was celebrated at Naming, now you release your attachment to ego at Surrender. In a sense, Surrender is the undoing of Naming; it is when you forget your name, your way of self-designation that separates you from other things.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 416.

“What we in contemporary society think of as afflictions [health breakdowns] of old age might often be initiations into later life stages, commencements that we have forgotten how to appreciate.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 417.

“Although wise, the Sage does not personally experience himself that way. As his identity merges with the universe, it’s the universe that seems wise to the Sage.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 420.

“There are at least four categories of things that happen in the Sage’s sphere that nourish and even sustain the world: (1) wisdom sharing, (2) the coordination of the human realm with the cosmological realm, (3) mentoring by means of an enduring imaginal presence, and (4) preparation for death.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 424.

“In addition to the catastrophic loss of species and habitat in recent centuries, we have witnessed the correlated disappearance of authentic elders.” Plotkin, Bill. 2008. Nature and the Human Soul: Cultivating Wholeness and Community in a Fragmented World. Novato: New World Library. p. 435.

“If our society had a commonly held understanding of the meaning of love, the act of loving would not be so mystifying.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 3.

“Echoing the work of Erich Fromm, he [M. Scott Peck in The Road Less Traveled] defines love as ‘the will to extend one’s self for the purpose of nurturing one’s own or another’s spiritual growth.’” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 4.

“Extolling the transformative power of love in his essay ‘Love and Need,’ [Thomas] Merton writes: ‘Love is, in fact an intensification of life, a completeness, a fullness, a wholeness of life … Life curves upward to a peak of intensity, a high point of value and meaning, at which all its latent creative possibility go into action and the person transcends himself or herself in encounter, response, and communion with another….’ The teachings about love offered by Fromm, [Martin Luther] King, and Merton differ from much of today’s writing. There is always an emphasis in their work on love as an active force that should lead us into greater communion with the world.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. pp. 75-6.

“Spiritual life is first and foremost about commitment to a way of thinking and behaving that honors principles of inter-being and interconnectednes. When I speak of the spiritual, I refer to the recognition within everyone that there is a place of mystery in our lives where forces that are beyond human desire or will alter circumstances and/or guide and direct us.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 77.

“Peck [F. Scott in book The Different Drum: Community Making and Peace] defines community as the coming together of a group of individuals ‘who have learned how to communicate honestly with each other, whose relationships go deeper than their masks of composure, and who have developed some significant commitment to ‘rejoice together, mourn together,’ and to ‘delight in each other, and make other’s conditions our own’”. Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 129.

“When we see love as the will to nurture one’s own or another’s spiritual growth, revealed through acts of care, respect, knowing, and assuming responsibility, the foundation of all love in our life is the same. There is no special love exclusively reserved for romantic partners.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 136.

“Once the choice has been made to be honest, then the next step on love’s path is communication.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 157.

“To heal the gender war rooted in struggles for power, women and men choose to make mutuality the basis of their bond, ensuring that each person’s growth matters and is nurtured. It enhances our power to know joy…. The mutual practice of giving and receiving is an everyday ritual when we know true love. A generous heart is always open, always ready to receive our going and coming. In the midst of such love we need never fear abandonment. This is the most precious gift true love offers–the experience of knowing we always belong.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 164.

“Love is an action, a participatory emotion. Whether we are engaged in a process of self-love or of loving others we must move beyond the realm of feeling to actualize love. This is why it is useful to see love as a practice.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 165.

“The heartbeat of true love is th willingness to reflect on one’s actions, and to process and communicate this reflection with the loved one.” Hooks, Bell. 2001. All About Love: New Visions. NY: William Morrow. p. 185.

“We humans are among the largest organisms–our one-meter size scale is within a factor of 100 of the height of the largest trees but a factor of 10,000,000 from the size of the smallest bacteria.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 3.

“Reynolds carried out quantitative studies of the speed (v) of flow at which the transition between laminar and turbulent flow occurred in tubes of different sizes (diameter d) and with fluids varying in density (p) and viscosity (η). These led him to discover that turbulence did not occur if the dimensionless ratio pvd/η was less than about 2000, a result that he first published in 1883.

“This dimensionless ratio became known as the Reynolds number (Re). Its general definition is

Re ≡ pvL/η

“In this relation, L is some length that is relevant to the geometry of the flow–perhaps the diameter or radius of a tube through which the fluid flows or of a solid body moving through the fluid. Since this length is not precisely defined, the Reynolds number itself is not precisely defined until the length is specified for particular geometry….

“The Reynolds number can be thought of as representing the ratio of the force of inertia to the force of viscosity.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. pp. 42-3.

“Another way of thinking about the Reynolds number focuses on the effects of mass and viscosity. Inertial mass measures the tendency to resist temporal variation or change in direction of motion. In contrast, viscosity measures the tendency of adjacent (lateral to the direction of motion) parcels to move together. Thus, the Reynolds number is a measure of how sharply a parcel of fluid is likely to change velocity. At low Reynolds numbers, flow is laminar because high viscosity keeps adjacent fluid moving in parallel, at high Reynolds numbers, momentum allows nearby fluid to move in different directions, resulting in turbulence.

“The Reynolds number is valuable from several points of view. It measures the ratio of two kinds of forces in a fluid. It determines at what speed or size laminar flow transitions to turbulent flow.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 44.

“Consider some examples for organisms in water (p = 1 Mg ⋅ m-3 or 1000 kg ⋅ m-3 and η = mPa ⋅ s) ….

“Bacteria about 1 μm in diameter swim at speeds on the order of 10 μm/s. This generates a Reynolds number on the order of 10-5.
“A rotifer, 0.3 mm long, might swim at 0.6 mm/s, with a Reynolds number near 0.2….
“A fish, 0.1 m long, might swim at 1 m/s, with a Reynolds number near 105.
“A whale, 10 m long, might swim at 10 m/s, with a Reynolds number near 108.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. pp. 44, 45.

“In his first publication (1855), the German physiologist Adolf Eugen Fick applied to the diffusion of chemicals the mathematics that Fourier had used to describe the flow of heat. The equations are completely analogous, as both flows are proportional to the spatial gradient of some parameter (temperature or concentration). Indeed, we now understand that the mechanisms for both processes are basically the same, resulting from the random collision of molecules.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 70.

“Shannon notes that this definition of H [information = sum of probabilities times the log of the probabilities for n discrete “symbols”] is the same as that of entropy in Boltzmann’s kinetic theory. He even uses the same symbol, H, and calls it the entropy of an information source. This establishes a surprising connection between information and thermodynamics.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 117.

“From their [of organisms] environment, they receive inputs that are appropriately divided between causal inputs and informational inputs. Causal inputs are inherently important because of the chemical or physical effects that they exert and the work that they can do. In contrast, informational inputs are important only because they are associated with some causal input and can be used to predict the occurrence of the causal input at another place or a later time. Causal inputs exert forces, provide non-informational resources (e.g., nutrients, energy), or cause harm. Informational inputs do nothing but carry information, and a fundamental property of information is that it can be ignored or misinterpreted. Stimuli carrying only information must be amplified in order to have any influence on the whole organism.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 124.

“Each of the relevant photons [impinging on a cell/organism] carries energy in the range of 2 to 5 X 10-19 joules, for red to blue light….

“After being captured by photosynthesis, some of the energy passes through hundreds of chemical reactions, but it all eventually ends up as heat in the environment.

“At ordinary temperatures, this thermal energy is in the motion of molecules with an average kinetic energy of 6 X 10-21 J. Thus, the energy of each photon from the sun, moving in a particular direction, becomes degraded into the random motion of 40-80 molecules. Eventually, this energy is lost in thousands of infrared photons radiated into space in all directions, keeping the earth’s temperature in balance. This is the path of degradation of almost all the energy of the earth’s organisms.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 129.

“Air (density = 1.3 kg/m3; viscosity = 0.018 mPa  s) flowing at 1 m/s with a length scale of 1 m would generate a Reynolds number of 105, which explains why the air is always turbulent and winds are variable on our size scale….

Water (density = 1000 kg/ m5; viscosity = 1 mPa  s) flowing at 0.1 m/s with a length scale of 1 m would also generate a Reynolds number of 105, as in the atmosphere. Water has both a higher viscosity and a higher density, and these differences largely cancel out. Thus, water in natural environments is also highly turbulent. The only water not in turbulent motion is that confined to small spaces.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 142.

“With flow of speed (v), the time for transport over a distance (L) is t = L/v

“By diffusion, the time for transport is roughly t = L2/ D where D is the diffusion coefficient of the transported molecule in the fluid…. since this time is proportional to the square of distance, diffusion times are very short over small distances. In water, a small molecule would typically diffuse across a bacterial cell (L = 1 μm) in a millisecond, while it would take a day to diffuse across your eyeball, and a thousand years to diffuse across a swimming pool….

“In addition, close to surfaces, the speed of flow declines, so the relative advantage of diffusion is even greater.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 143.

“An important consequence of this rapid diffusion at the size scale of cells is that chemical mixing occurs faster than chemical reactions, and chemical gradients do not exist within microorganisms. It is only across membrane barriers that gradients are important.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 144.

“In air under standard conditions, the mean free path of gas molecules is near 0.1 μm and the collision frequency is about 5 X 109 s-1 ….

“In liquids, collisions are less well defined. A frequency of 1013 s-1 has been estimated. The observed diffusion coefficient of 10-9 m /s is consistent with this frequency if the step size is 10-11 m, which is about one-tenth the size of atoms. This small value is consistent with the concept of a liquid: the molecules are usually in contact with several neighbors and don’t move very far before suffering collisions.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 144.

“It is important to note that diffusion is much faster in ordinary gases than in liquids. The difference is about 10,000 fold…. … it is clear that the difference arises because of the much larger distance and time between collisions in the gas. In the 10-10 s between collisions in a gas, a molecule travels in a straight line nearly 10-7 m long. In this same time interval, a molecule in a liquid undergoes a thousand collisions and moves a net distance of only 10-9 m.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 144.

“For both the source and the sink [of initial concentrations – from a point source or as a point of absorption in a uniform field], the flux is proportional to linear size. Thus, larger organisms can obtain more nutrients or chemical signals. However, the supply of nutrients may not be sufficient. Requirements are roughly proportional to the organism’s volume, which varies with the cube of its linear size, while the flux is only proportional to the first power of size. So beyond some size limit, diffusion will not provide a flux of nutrients sufficient to support normal activity rates….

“One strategy employed by certain bacteria specializing in low-nutrient conditions is to grow a narrow protrusion that can access nutrients outside the region of nutrient depletion.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. pp. 150-1, 152.

“… an organism swimming at low Reynolds numbers carries a large layer of fluid along with it, and diffusion is the only mechanism of transport across this layer….

“… the size limit is around 10 μm diameter. This suggests that typical bacteria are too small to increase their exchange rates by swimming; they carry a halo of fluid depleted of nutrient around with them. In contrast, some fast-swimming protozoa may be able to obtain some increase in nutrient flux.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. pp. 152-3.

“Thus there is general agreement from a variety of approaches that swimming speed is much too slow for ordinary bacteria to significantly enhance their diffusion rates for nutrients. However, large bacteria and protists may obtain some benefits.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 153.

“In summary, organisms larger than about 400 μm cannot rely on diffusion and must do something to enhance transport, while organisms smaller than about 10 μm cannot do any better than diffusion. However, they can still improve their access to nutrients by moving to an environment with higher concentrations of nutrients. And it is likely that, for all organisms, the main benefit of swimming is to move in a guided direction to more favorable environments rather than to increase nutrient encounter rates by moving in random directions through a uniform environment.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 153.

“We know of no organisms that expend energy propelling themselves without some mechanism to guide their locomotion in a direction likely to be favorable.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 163.

“Magnetic bacteria have developed a method of extending the time over which they can maintain their orientation without attaching to the surface of a larger object. This allows them to take as much time as desirable to obtain directional information, without the limitation imposed by rotational Brownian motion. They can then swim forward and backward along this line, in response to chemical stimulation [called collimated swimming].” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 167.

“The time [for a small organism] to move some multiple of the diameter increases in proportion to the volume of the organism and as the square of the multiple [of diameter for distance covered].

“… Einstein estimated that a 1-μm-diameter particle is typically displaced 0.8 μm in one second. So Brownian motion moves a typical bacterium, about a micrometer in diameter, to an adjacent environment [1 multiple of its diameter] about every second, and this seems fast enough to be useful. But, if the organism’s diameter were just ten times larger, the time would be a thousand times longer or twenty minutes. If the organism were a millimeter in diameter, the time would be over thirty years, and this is clearly too long. So this analysis suggests that Brownian motion might provide for dispersal of the smallest bacteria but not for dispersal of much larger organisms, and not if dispersal over large multiples is important.

“These relations also suggest part of the reason viruses can prosper–their small size leads to rapid movement throughout the local environment by Brownian motion, without any work on their part.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 174.

“In many cases, important resources and threats are chemicals dissolved in the water in which the organism swims. If an organism cannot move far enough in a short enough time, it cannot get to an environment chemically different from the one at the original location, because molecular diffusion will equalize the concentrations within the region. This is especially relevant at small scale, where diffusion rapidly eliminates chemical differences.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. pp. 216-7.

“… we analyze the problem of following gradients of chemicals and other stimuli and demonstrate in more detail that self-propulsion is a waste of energy for the smallest bacteria.” Dusenbery, David B. 2009. Living at Micro Scale: the Unexpected Physics of Being Small. Harvard UP. p. 218.

“At a waterfront shop, less than a week after my return [from West Indies in 1985], I came across a faded picture of an old wooden boat. The caption read, ‘FOR SALE: Sixty-five-foot schooner, Crusader. Needs work, make offer.’ The next day I packed my Volkswagen bug and drove down the coast to Tillamook, Oregon. I met the owners at the head of the bay, followed them over Crusader’s deck and down her forward companionway. For several hours, we sat below and drank tea in the warmth of the woodstove, our noses filled with the smell of moist canvas, cedar, and punky fir. Even though Crusader was painted all orange and leaked over 100 gallons a day, I didn’t care. In spite of everything, or maybe because of it, she had magic, and I had already fallen in love.” White, Jonathan. 2016. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. xi.

Lynn Margulis: “A recent article in Science magazine said, ‘Margulis is well known as the fervent supporter of the controversial hypothesis that the earth is a single living organism.’ This kind of thing makes me angry because I never say the earth is a single, live organism. Lovelock might, but not me. It’s a bad metaphor. It leads to goddesses, mysticism, and other misconceptions about Earth. The earth is an ecosystem, or the sum of many ecosystems. I see a big difference between a single organism and an ecosystem. For example, an organism produces gases, but it can’t recycle its gaseous waste. It relies on the ecosystem for that.

Question from Jonathan White: “Lovelock likes to compare the earth with a giant redwood tree. The interesting thing to remember, he says, is that the middle of the tree is dead wood with just a thick skin of living tissue around the circumference. Beyond that there’s another dead layer, the bark, which protects the tree from the environment. Lovelock says the earth is very much like that. You have the middle, which is molten and dead, a thin skin of living tissue around the circumference, and beyond that, the atmosphere, which is just like the bark of a tree.

“Lynn Margulis: “That’s an interesting comparison that helps make my point. A tree is an extraordinarily complex community. It not only includes the life you can see–the bugs and worms and birds–but also the myriad of microorganisms that live on the tree and in the soil below. What we see is a composite organism but not an ecosystem. The tree needs the rest of the ecosystem of which it is a part to deliver its carbon dioxide and water and recycle the oxygen it produces as waste. I agree that a tree is a better analogy for the earth than a person, but there are still significant differences.” White, Jonathan. 2016. Interview with Lynn Margulis. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 63.

Lynn Margulis: “The neo-Darwinist view, which is our present paradigm for scientific thinking in the West, denies the need for chemistry, climatology, geology, comparative planetology, and the like. Instead, it promotes the capitalistic view that organisms succeed over time just because they leave the most progeny or are better at outwitting their neighbors.” White, Jonathan. 2016. Interview with Lynn Margulis. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 69.

Lynn Margulis: “Life, according to the neo-Darwinists, is a collective of individuals who reproduce, mutate, and reproduce their mutations. These mutations are assumed to arise by chance. The life-centered alternative to this view recognizes that, with the exception of bacteria, individuals with single genetic systems don’t exist. All other living organisms, such as animals, plants, and fungi, are complex communities of multiple, tightly organized beings. What we generally accept as an individual animal, such as a cow, is really a collection of entities that together form an ‘emergent domain.’ The hind-gut of a termite, for example, is loaded with over twenty-five different kinds of bacteria and protists. Each of these organism types evolved over millions of years to perform a role in the ‘domain’ that we recognize as a ‘termite.’” White, Jonathan. 2016. Interview with Lynn Margulis. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 70.

Lynn Margulis: “Life did not take over the globe by combat but by networking.” White, Jonathan. 2016. Interview with Lynn Margulis. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 71.

Lynn Margulis: “The past is all around us. Darwin’s biggest contribution was to show us that all individual organisms are connected through time. It doesn’t matter whether you compare kangaroos, bacteria, humans, or salamanders, we all have incredible chemical similarities. As far as I know, no one disagrees with this. Vernadsky showed us that organisms are not only connected through time but also through space….

“The fact that we are connected through space and time shows that life is a unitary phenomenon….” White, Jonathan. 2016. Interview with Lynn Margulis. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 74.

Richard Nelson: “In our society, we force ourselves into a greater and greater distance from the natural world by creating parks and wilderness areas where our only role is to go in and look. And we call this loving it. We lavish tremendous concern and care on scenery but we ignore the ravaging of environments from which our lives are drawn.” White, Jonathan. 2016. Interview with Richard Nelson. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 96.

Ursula Le Guin: We use language as a device for distancing. Somebody who is genuinely living in their ecosystem wouldn’t have a word for it. They’d just call it the world.” White, Jonathan. 2016. Interview with Ursula Le Guin. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. pp. 106-7.

Ursula Le Guin: “Coyote walks through all our minds. Obviously, we need a trickster, a creator who made the world all wrong. We need the idea of a God who makes mistakes, gets into trouble, and who is identified with a scruffy little animal.” White, Jonathan. 2016. Interview with Ursula Le Guin. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 120.

James Hillman: “‘Morality,’ ‘Being right,’ and having the ‘true’ sense of things–those words that are moral words in our world–come out of religious texts or from priests. In the tribal world, those words come out of the behavior of animals.” White, Jonathan. 2016. Interview with James Hillman. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 128.

James Hillman: “These two positions [conservationists and consumers] seem diametrically contradictory, but they stem from the same psychological ground. Neither group feels it is nature. The first group is the good shepherds, the caretakers, basically moralists, and moralists are always above what they are judging. The second group is the conquerors, Promethean and Herculean in their ability to overcome nature. But both groups stand apart, forever doing something to or for or with nature. If you feel yourself to be nature, no different from it, then you simply are like a tree or a squirrel in the tree, and you move along without an attitude of one kind or another.” White, Jonathan. 2016. Interview with James Hillman. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. pp. 134-5.

Gary Snyder: “The Buddhist way of talking about the delusion of the separate self is to say ‘no self.’ That’s what my phrase ‘no nature’ means–no inherent predictable characteristics.” White, Jonathan. 2016. Interview with Gary Snyder. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 152.

Dolores LaChapelle: “Seasonal festivals revive the topocosm, a Greek word for ‘the world order of a particular place.’ This includes not only the human community but the total community–the plants, animals, and soil of the place. It also includes more than just the present living community. These festivals make use of myths, art, dance, and games, all of which serve to connect the conscious with the unconscious, the right and left hemisphere of the brain, and the human with the nonhuman.” White, Jonathan. 2016. Interview with Dolores LaChapelle. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 169.

Dolores LaChapelle: “If you don’t have true rituals that involve the entire brain/body/senses and nature around you, then you have addiction.” White, Jonathan. 2016. Interview with Dolores LaChapelle. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 170.

Dolores LaChapelle: “In sacred rituals many different techniques are used, including chanting, drumming, dancing, singing, and fasting. The physiological effect of these ‘ways’ is complex, but essentially what happens is they help to supersaturate the left brain so that the right brain is able to fully function. This feeling is called tuning. Bonding develops out of this tuning, and bonding is the real basis of all society, both human and nonhuman.” White, Jonathan. 2016. Interview with Dolores LaChapelle. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 172.

Dolores LaChapelle: “One of the reasons I began doing rituals is to enable people who are unable or unwilling to endure the hardships out in nature to have a similar experience. I’ve found that we don’t have to take people out into the wilderness but that they can do ritual in their own backyard and experience the real wilderness inside themselves….

“And most important of all, during rituals we have the experience of neither opposing nature nor trying to be in communion with it.” White, Jonathan. 2016. Interview with Dolores LaChapelle. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 174.

Dolores LaChapelle: “Taoism doesn’t consider that the order of nature comes from rules or laws but from the spontaneous cooperation of all beings brought about by following the pattern of their own natures.

“In Ancient China, Li, or pattern, came from the way fields were laid out for cultivation. Li was also used to describe patterns in jade or the fibers in muscles. Eventually the word came to be used to talk about the principle of organization in the universe. If things do not conform to their own Li, or their natural pattern, they lose their relational position in the whole and become something other than themselves.” White, Jonathan. 2016. Interview with Dolores LaChapelle. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 176.

Matthew Fox: “He’s [Lynn White, author of ‘The Historical Roots of Our Ecological Crisis’] exactly right about that [i.e., saying that the roots of our ecological troubles are religious so that the solutions must also be religious]. My work is to show there is another tradition within Christianity that has been purposely forgotten, often condemned, or misconstrued. That tradition is ‘creation spirituality,’ which is not a human-centered path but a creation-centered one.” White, Jonathan. 2016. Interview with Matthew Fox. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 183.

Matthew Fox: “ When you consider how young we are as a species, it seems all the more ludicrous to limit our cosmology to our own history. What about all the wonderfully creative, exploding, spiraling, dancing, evolving life that happened before we arrived? On top of that, we call the whole thing original sin! To begin religious experience this way, instead of celebrating the blessing that the cosmos is, trivializes religion.” White, Jonathan. 2016. Interview with Matthew Fox. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 184.

Matthew Fox: “Creation spirituality was alive and well in medieval Europe during the twelfth and thirteenth centuries. It was a period of spiritual renaissance that involved an awakening of scientists and mystics who saw nature as a source of divine revelation. This was the period that gave us the beautiful Chartres Cathedral, which is presided over by the Mother Goddess, and the mystical teachings of Hildegard of Bingen, Thomas Aquinas, Meister Eckhart, and Francis of Assisi.” White, Jonathan. 2016. Interview with Matthew Fox. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. pp. 185-6.

Matthew Fox: “In the United States, we’re still living the myth of the frontier. Once we use up something, we throw it out or move on. Well, in Europe, much more so than here, there is no more ‘out’ and no more land to move on to.” White, Jonathan. 2016. Interview with Matthew Fox. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 202.

Paul Shepard: “The game changes from chance to strategy [in the switch to agriculture], from reading one’s state of grace in terms of the hunt to bartering for it, from finding to making, from a sacrament received to a negotiator with anthropocentric deities.” White, Jonathan. 2016. Interview with Paul Shepard. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 220.

Paul Shepard: “As long as people represent sacred power in a diversity of animals, it doesn’t lead to conflict between the genders. But once they begin to anthropomorphize their deities, that sexual dominance is echoed all through society, in art, in economics, politics, family dynamics, and so on.” White, Jonathan. 2016. Interview with Paul Shepard. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 222.

Peter Matthiessen: “We can’t consciously adopt Indian attitudes toward nature because traditional people don’t have any attitudes toward nature. They are nature. Wilderness is a false concept to them. They have no word for it.” White, Jonathan. 2016. Interview with Peter Matthiessen. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 239.

Peter Matthiessen: “Yes, I think that’s true [that we cannot be either opposing nature or in communion with it but rather finding ourselves within it]. In Buddhism we teach that all self, all separation from the One, is illusion. There’s a wonderful metaphor of a bottle of seawater floating in an ocean, and our ego is the glass bottle that separates our little bit of water from the whole. We’re not different from the seawater in which we’re floating, yet we assign our little bottle-selves a name, a social security number, a ZIP code. Every such idea or concept only fortifies the illusion of a separate existence.” White, Jonathan. 2016. Interview with Peter Matthiessen. Talking on the Water: Conversations about Nature and Creativity. San Antonio: Trinity University Press. p. 239.

“One can best feel in dealing with living things how primitive physics still is …” Einstein, Albert. Quoted in: Clark, Ronald W. 2007(1972). Einstein: The Life and Times. NY: Harper Perennial.

“Points summarizing the Regenerative Agriculture Philosophy as presented by Harwood.

“1. Agriculture should produce highly nutritional food, free from biocides, at high yields.
“2. Agriculture should increase rather than decrease soil productivity, by increasing the depth, fertility and physical characteristics of the upper soil layers.
“3. Nutrient-flow systems which fully integrate soil flora and fauna into the pattern of are [sic] more efficient and less destructive of the environment, and ensure better crop nutrition. Such systems accomplish a new upward flow of nutrients in the soil profile, reducing or eliminating adverse environmental impact. Such a process is, by definition, a soil genesis process.
“4. Crop production should be based on biological interactions for stability, eliminating the need for synthetic biocides.
“5. Substances which disrupt biological structuring of the farming system (such as present-day synthetic fertilizers) should not be used.
“6. Regenerative agriculture requires, in its biological structuring, an intimate relationship between manager/ participants of the system and the system itself.
“7. Integrated systems which are largely self-reliant in nitrogen through biological nitrogen fixation should be utilized.
“8. Animals in agriculture should be fed and housed in such a manner as to preclude the use of hormones and the prophylactic use of antibiotics which are then present in human food.
“9. Agricultural production should generate increased levels of employment.
“10. A Regenerative agriculture requires national-level planning but a high degree of local and regional self-reliance to close nutrient-flow loops.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. p. 14; reference: Harwood, R.R. 1983. “International overview of regenerative agriculture.” In: Proceedings of Workshop on Resource-efficient Farming Methods for Tanzania, Morogoro, Tanzania, 16-20 May 1983, Faculty of Agriculture, Forestry, and Veterinary Science, University of Dar es Salaam. Morogoro, TZ: Rodale Press.

“Indeed, the idea that soil, and soil life in particular, is under threat underpins most, if not all, calls for Regenerative Agriculture. Nonetheless, the term soil health is inherently problematic. Just like soil quality, soil health is a container concept, which requires disaggregation to be meaningful. While it can be understood as something positive to strive for, underlying soil functions need meaningful indicators which can be measured and monitored over long periods of time. Moreover, agronomic practices which benefit one aspect of soil health (such as soil life) often have negative effects on other functions (such as nitrate leaching, primary production or GHG emissions); there is usually not one direction in soil health, but multiple trade-offs.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. pp. 17-8.

“Many practices associated with Regenerative Agriculture, such as crop rotations, cover crops, livestock integration, are (or in some contexts were) generally considered to be ‘Good Agricultural Practice’ and remain integral to conventional farming. Some are more problematic: conservation agriculture, for example, can be practiced within an organic framework or as GMO-based, herbicide and fertilizer intensive. Others, such as permaculture, have rather limited applicability for the production of many agricultural commodities. Still others, such as holistic grazing are highly contentious in terms of the claims made for their broad applicability and ecological benefits in terms of soil C accumulation and reduction of greenhouse gas emissions. The potential of perennial grains has aroused substantial interest in relation to Regenerative Agriculture. Deep rooting perennial grasses such as intermediate wheatgrass, cereals (e.g. sorghum) or legumes (e.g. pigeonpea) have the advantage of supplying multiple products such as fodder as well as grain, and provide continuous soil cover that can arrest soil erosion and reduce nitrate leaching. On the down side, perennial grains tend to yield less than annual varieties and share constraints with monocultures in terms of pest and disease build up.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. p. 20.

“Among the practices associated with Regenerative Agriculture, agroforestry in its many shapes and forms perhaps has the greatest potential to contribute to climate change mitigation through C capture both above- and below-ground.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. p. 20.

“Recommended practices such as rotations and (multi-species) cover crops fit within IPM [integrated pest and disease management], as do approaches such as intercropping and strip cropping which are largely ignored in discussions of Regenerative Agriculture. IPM is knowledge intensive, requires regular crop monitoring and the skill to identify early signs of outbreaks of multiple pests and diseases. The reasons for the lack of uptake of IPM approaches are complex, but include the perceived risk of crop damage. Alongside IPM, integrated weed control (IWM) combines the use of mechanical weeding through tillage and cover cropping with a much more strategic use of herbicides. IWM is promoted as an environmentally friendly approach that can harness diversity to manage deleterious effects of weeds, but again, is highly knowledge intensive.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. p. 21.

“… given the high degree of diversity of agroecosystems, farm systems and policy contexts, the nature of these challenges can vary dramatically over time and space. This fact undermines any proposition that it is possible to identify one meaningful and widely relevant problem definition, or specific agronomic practices which could alleviate pressures on the food system everywhere.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. p. 21.

“The growing enthusiasm for Regenerative Agriculture highlights the need for agronomists to be more explicit about the fact that many of the categories and dichotomies that frame public, and to some degree the scientific debates about agriculture, have little if any analytical purchase. These include e.g. alternative/conventional; family/industrial; regenerative/degenerative; and sustainable/unsustainable. Regardless of their currency in public discourse, these categories are far too broad and undefinable to have any place in guiding agronomic research.” Giller, Ken. E., Renske Hijbeek, Jens A. Andersson & James Sumberg. 2021. “Regenerative Agriculture: An agronomic perspective.” Outlook on Agriculture. 50(1):13-25. doi: 10.1177/0030727021998063. p. 22.

“Rates of human-induced soil erosion are estimated to outpace soil formation rates by more than an order of magnitude. The consequential trajectory of soil thinning is one that, left uninterrupted, leads to the removal of the soil cover and the exposure of the underlying parent material. Given that the thickness of the pedosphere is a first-order control on soil functioning, with thicker soils having a greater capacity for water, carbon and nutrient storage, the continued thinning of near non-renewable soil profiles is one of the most significant threats to soil sustainability.” Evans, D.L., J. N. Quinton, J.A.C. Davies, J. Zhao & G. Govers. 2020. “Soil lifespans and how they can be extended by land use and management change.” Environ. Res. Lett. 15:0940b2. doi: 10.1088/1748-9326/aba2fd. p. 1.

“A compilation of 4285 plot-based gross erosion rates representing 10030 plot years, were amassed from 240 studies, comprising 255 unique locations across 38 countries….

“The distribution of lifespans for the plots under conservation management was shifted towards longer lifespans when compared to conventionally managed soils. For conservation managed soils, 48% of the estimated lifespans exceeded 5000 years compared to 23% for conventional agriculture, and 39% exceeded 10000 years compared to 18% for conventionally managed soils.” Evans, D.L., J. N. Quinton, J.A.C. Davies, J. Zhao & G. Govers. 2020. “Soil lifespans and how they can be extended by land use and management change.” Environ. Res. Lett. 15:0940b2. doi: 10.1088/1748-9326/aba2fd. pp. 2, 5.

“Analysing by land use suggests that land use change towards a forested site would be the most effective land use change for extending soil lifespans. The shortest lifespan in the forested dataset was 420 years, compared to 16 years for cropland soils. In 50% of cases, gross erosion rates in forests fell below those of soil formation, promoting soil thickening. This proportion of thickening soils was significantly greater than that for bare plots (15 times greater) and cropland plots (six times greater). These findings concur with similar work that has concluded that croplands erode, on average, more than order of magnitude faster than forest soils.” Evans, D.L., J. N. Quinton, J.A.C. Davies, J. Zhao & G. Govers. 2020. “Soil lifespans and how they can be extended by land use and management change.” Environ. Res. Lett. 15:0940b2. doi: 10.1088/1748-9326/aba2fd. pp. 5, 7.

“The analysis suggests that land use change from bare or conventional cropland to grassland would be similarly effective in lengthening soil lifespans. For grassland plots, we found that 2% of lifespans were <100 years, a 17-fold reduction in the proportion of <100 year lifespans compared to plots kept bare and a seven-fold reduction in comparison to cropland soils.” Evans, D.L., J. N. Quinton, J.A.C. Davies, J. Zhao & G. Govers. 2020. “Soil lifespans and how they can be extended by land use and management change.” Environ. Res. Lett. 15:0940b2. doi: 10.1088/1748-9326/aba2fd. p. 7.

“Without reducing the area of land designated for agriculture, we found that cover cropping was an effective method of extending lifespans. No plot in the cover-crop dataset had lifespans of <100 years. In 25% of cases, gross soil erosion rates fell below those of soil formation, promoting an estimated net soil gain of 0.031 … mm y-1. The proportion of thickening soils from cover crop plots was significantly greater than that of conventional management practices.” Evans, D.L., J. N. Quinton, J.A.C. Davies, J. Zhao & G. Govers. 2020. “Soil lifespans and how they can be extended by land use and management change.” Environ. Res. Lett. 15:0940b2. doi: 10.1088/1748-9326/aba2fd. p. 7.

“Our analysis showed that, for the majority of cases, fallowing increased soil erosion rates by more than an order of magnitude compared to those during the cropping period. This demonstrates that incorporating a protective cover into the fallowing period is essential to minimize soil erosion.” Evans, D.L., J. N. Quinton, J.A.C. Davies, J. Zhao & G. Govers. 2020. “Soil lifespans and how they can be extended by land use and management change.” Environ. Res. Lett. 15:0940b2. doi: 10.1088/1748-9326/aba2fd. p. 8.

“The organism outside of the biosphere is not a real construct, but a logical and abstract one according to its properties….” Vernadsky, Vladimir. 1931(2014). “On the Conditions of the Appearance of Life on Earth.” Translated from the French by Meghan Rouillard. 150 Years of Vernadsky (Volume 1): The Biosphere. 21st Century Science Associates. pp. 3-19. p. 3.

“Not only do we come closer to reality in considering the problem of the appearance of life on Earth as the problem of the appearance of the biosphere, but, we obtain a new and solid foundation for scientific work; we rely on an immense quantity of new empirical facts–geological and geochemical.” Vernadsky, Vladimir. 1931(2014). “On the Conditions of the Appearance of Life on Earth.” Translated from the French by Meghan Rouillard. 150 Years of Vernadsky (Volume 1): The Biosphere. 21st Century Science Associates. pp. 3-19. p. 6.

“Thus the first appearance of life during the genesis of the biosphere had to produce itself not in the form of some unique species or organism, but in the form of their ensemble, responding to living geochemical functions. Biocenoses had to appear from the outset.

“If we admit of abiogenesis on Earth, there exist two possibilities for abiogenesis: either the simultaneous formation of an ensemble of unicellular organisms, or determined biogeochemical function; or the formation of a nonexistent and unknown organic form, whose later disintegration into organisms of diverse geochemical functions would be produced very rapidly and by an unknown means, independently of the processes of evolution.” Vernadsky, Vladimir. 1931(2014). “On the Conditions of the Appearance of Life on Earth.” Translated from the French by Meghan Rouillard. 150 Years of Vernadsky (Volume 1): The Biosphere. 21st Century Science Associates. pp. 3-19. p. 16.

“Evo-devo, however, had taught us an important lesson. To understand innovability we cannot ignore the complexity of phenotypes.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 22.

“All in all, E. coli can use more than eighty different molecules as its only source of energy and as its only supplier of every single one of the billions of carbon atoms in its cells. It is similarly flexible about other elements, such as nitrogen and phosphorus. E. coli is like a self-building, self-multiplying, self-healing race car that can run on kerosene, Coca-Cola, or nail polish remover.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 61-2.

“… life’s symphony of innovation has three major themes. First, innovations created new combinations of chemical reactions, such as those that form life’s building blocks and that built the first replicators. Second, innovation required molecules that could help other molecules react. Third, innovation created new regulation, the key to coordinate complex life.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 66.

“To date, we have discovered more than five thousand different chemical reactions that some organism, somewhere on our planet, uses to produce the building blocks of life, …. The reactions that occur in E. coli–more than a thousand–are among them….” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 69.

“It [a specific metabolic genotype] is a text in a library vast beyond imagination, the library of all possible metabolisms….

“Because each reaction in the known universe of reactions can be either present or absent in a [a specific] metabolism, there are two possibilities (present or absent) for the first reaction, two for the second reaction, and so on, for each reaction in the universe. To calculate the total number of texts [possible metabolisms], we multiply the number 2 by itself as many times as there are reactions in our universe. For a universe of 5,000 reactions, there are 25000 possible metabolisms, 25000 texts written in the alphabet of zero and one, each of them standing for a different metabolism. This number is greater than 101500 , or a 1 with 1,500 trailing zeroes…. The metabolic library is also hyperastronomical.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 71.

“Two E. coli strains can differ in more than one million letters, or one-quarter of their DNA, such that one strain can harbor a thousand genes that the other strain lacks. Every million years–a blip of evolutionary time, 20 percent of the time since humans diverged from chimpanzees–an E. coli genome acquires some sixty new genes, all of them through horizontal gene transfer.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 80.

“At this point [after mapping the library of functional metabolisms and finding it dense with workable metabolisms], I was close to ecstatic. We had stumbled upon fundamental principles that govern the metabolic library’s organization. First, many metabolisms are viable on the same fuel molecules–it matters little which fuels you choose. Organisms can assemble biomass building blocks in many ways, through many different sequences of reactions. Second, many of these metabolisms are very different from each other, sharing only a minority of reactions. Third, the viable metabolisms we found were connected in a gigantic network–a genotype network. This genotype network reached far through the space of metabolism.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 101.

“… evolution does not just explore the metabolic library like a single casual browser. It crowdsources, employing huge populations of organisms that scour the library for new texts. Every time gene transfer alters the metabolic genotype of an organism, it takes a step through the library. Different readers–billions of them–walk off in different directions to explore the library….

“In the metabolic library readers die (and others get born) in an exploration that unfolds over generations.

“Viewed from afar, the library’s explorers, from bacteria to blue whales, might appear like giant clouds of dust grains–dwarfed by the library itself–drifting this way and that, from one stack to the next, endlessly meandering swirls of living things that try new combinations of chemical reactions over and over and over again. Some die. Others survive, and pass innovative combinations on to subsequent generations. This churning mass of life is evolution in action.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 101-2.

“Innovability in the metabolic library is near limitless, and for that both genotype networks [multiple, long paths of connectivity for different reactions but with similar and viable metabolisms] and diverse neighborhoods are required. They are the two keys to innovability. Genotype networks guarantee that evolving populations can explore the library. Without them the lethal punishment of losing viability would be inevitable. But without diverse neighborhoods in this library, exploring a genotype network would be pointless: The exploration would not turn up many texts with new meanings.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 105.

“To find out how rare ATP binding proteins are in the library, Keefe and Szostak used a chemical technology that can create many different proteins, each one with a different and completely random amino acid string, a process equivalent to pulling random volumes from the shelves of the protein library. The random proteins these researchers generated were all eighty amino acids long. Because there are more than 10104 such proteins, no experiment could create all of them, but this one created an impressive number, about 6 trillion, or 6 X 1012 random proteins.

“Keefe and Szostak found that four of them–unrelated to one another–can bind ATP. Four new ATP-binding proteins out of six trillion doesn’t sound like too many, but when the proportions are extrapolated to the number of potential candidates, the number is much larger. It comes out to more than 1093 proteins–a 1 with 93 zeroes–that can bind ATP. The problem of binding ATP has astronomically many solutions.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 118; reference: Keefe, A.S. & J.W. Szostak. 2001. “Functional Proteins from a Random-Sequence Library.” Nature. 410:715-8.

“Plants and animals dwell on different major branches of life’s tree, because their common ancestor lived more than a billion years ago. Their globins [oxygen-carrying proteins such as hemoglobin] are staggeringly different, which reflects their long and separate evolutionary journey. For instance, the globins from lupins and insects differ in almost 90 percent of their amino acids. Yet these globins not only bind oxygen, they also still fold into the very similar shapes….” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 122.

“When it comes to forming vast and far-reaching genotype networks, globins are not an exception but the rule. Enzymes with the same fold, catalyzing the same reaction, and sharing the same ancestor typically share less than 20 percent of their amino acids.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 124.

“The stunning fact is that some enzymes with this fold [TIM barrel to extract energy from glucose] do not have a single amino acid in common. They occupy opposite corners of the protein library–texts that do not share a single letter–yet carry the same chemical message. Proteins like these are a bit like innumerable versions of Hamlet, all of them equally stageable, while sharing only a few hundred–or even none–of the play’s four thousand lines.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 124.

“The neighborhoods of two proteins contain mostly different functions, even if the two proteins are close together in the library. For instance, even proteins that differ in fewer than 20 percent of their amino acids have neighborhoods whose proteins differ in most of their functions. The protein library has neighborhoods that are highly diverse, just like the metabolic library. And just as with metabolism, this diversity makes vast genotype networks ideal for exploring the library, helping populations to discover texts with new meaning while preserving old and useful meaning.

“Both metabolic and protein libraries are full of genotype networks composed of synonymous texts that reach far through a vast multidimensional hypercube, and both harbor unimaginably many diverse neighborhoods.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 126, 127.

“What is more, texts with the same shapes [for folded RNA molecules] are organized much like in the protein library. They form connected networks that reach far through the library, allowing you to revise any one text in little steps, radically, while leaving its molecular meaning unchanged. And just as in the protein library, different neighborhoods are more like medieval villages than cookie-cutter suburbs. Each neighborhood contains many different shapes, and any two neighborhoods do not share many of them. All this hints that innovability in RNA follows the same rules as in proteins. And recent experiments show that this is indeed the case.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 129.

“Some such regulators bind DNA strongly and also influence transcription strongly, others bind weakly and influence transcription weakly. Like a cabinet of counselors who jockey for influence over a king, these regulators jockey for influence over the polymerase’s ‘decision’ to express a gene. Some favor repression, others activation, some are influential, others less so, and the sum of their influences determines gene expression.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 144.

“If each gene in a forty-gene circuit can only be on or off, it contributes two possibilities to a gene expression pattern [in how regulating proteins can create diverse patterns of expression and repression between the forty genes]. To calculate the total number of possible expression patterns, we need to multiply two with itself, as many times as there are genes, to arrive at 240 possible phenotypes. This number is already greater than a trillion, but it grows much larger if we consider that a gene can be more than just on or off–it can express a small, medium, large, or very large amount of regulator protein. What’s more, several circuits often cooperate to shape any one body part, which multiplies the number of possible expression codes. Compared to the number of these possible meanings, the few hundreds of cell types and tissues of a complex body like ours are paltry.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 160-1.

“So we are back to a familiar story. The regulatory circuit library has the same layout as the metabolic and the protein libraries. Circuits with the same gene expression phenotype are organized in vast and far-reaching genotype networks.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 167.

“These similarities among different libraries are mysterious. How could innovability in metabolism, in proteins, and in regulation circuits have the same source, a library full of chemical meaning with a common cataloging system? The answer is held by an invisible hand that guided the world long before life’s origin–self-organization….” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 168.

“… in recent years we have also learned, thanks to genotype networks, that perfect order is as hostile to innovation as total disorder. Nature doesn’t just tolerate disorder. It needs some disorder to discover new metabolisms, regulatory circuits, and macromolecules–in short, to innovate.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 169-170.

“He [Waddington] called the phenomenon through which development can produce ‘one definite end-result regardless of minor variations in conditions’ canalization–another word for robustness.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 171.

“Unlike galaxies, which self-assemble through the gravitational attraction of cosmic matter, or biological membranes, which self-organize through the love-hate relationship of lipid molecules with water, genotype networks do not emerge over time. They exist in the timeless eternal realm of nature’s libraries. But they certainly have a form of organization–so complex that we are just beginning to understand it–and this organization arises all by itself. And as with galaxies and membranes, the principle behind their self-organization is simple: Life is robust. This robustness is both necessary for genotype networks–otherwise synonymous texts would be isolated from one another–and it is sufficient. Wherever metabolisms, proteins, and regulatory circuits are robust, genotype networks emerge.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 176.

“… evolution must meet two demands, seemingly at odds with one another. It must be simultaneously conservative and progressive….” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 176.

“Genotype networks are essential for exploration. But they aren’t made for conservation.

“This bears emphasizing, because the exciting new discoveries about genotype networks can tempt us to forget the critical importance of natural selection. Conservation is the job of natural selection–evolution’s memory-and its power to conserve even tiny improvements, given enough time, is so great as to seem absurdly unbelievable.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 176.

“… neutral change is critical for navigating genotype networks. Neutral change provides the browsers of nature’s libraries with a safe path to innovations through treacherous territory of meaningless texts. Without genotype networks and the neutral changes they allow, the exploration of nature’s libraries would be just about impossible.

“Another reason is that a change that is neutral when it first appears doesn’t have to stay that way.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 180-1.

“But common sense fails in this library [of regulation circuits, genes on or off from regulation]. We had already learned this from our discovery that there are innumerable circuits with the same expression code–the haystack has many needles–but the library is even more bizarre, as we found out by searching for circuits with specific new expression codes. In this search, we created arbitrary expression codes–thousands of them–and for each such code we used our computers to generate a pair of circuits, where the first circuit produced one of these codes, and the second produced the other. The two circuits differed also in most of their wiring pattern, in the who-regulates-whom among the circuit genes. We then changed the first circuit gradually, one wire at a time, requiring that each such gene regulation change preserve the circuit’s expression code. How close could we get to the second circuit? Very close, we found out, for example to within 85 percent of the second circuit’s wiring for circuits of twenty genes. In other words, starting from anywhere in the library–anywhere–you need not walk very far, only fifteen steps away from a genotype network, before finding the genotype network of any other circuit. It is as if your needle were always nearby, no matter where you started to search.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 183.

“In biology, increased complexity means increased robustness to environmental change.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 188.

“Duplicate genes, like humans, are created equal, but they do not stay that way for long. They accumulate mutations that alter their DNA and its molecular meaning, and lead to increased specialization on one environment…. The redundancy of many gene duplicates is more apparent than real, because they ensure robustness to changing environments.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 189.

“… it is useful to compare Buchnera [bacteria that live protectedly in aphids] to its cousin, Escherichia coli, that marvel of metabolic flexibility, able to survive on dozens of different food sources, and highly robust to changing chemical environments. E. coli’s complex metabolic network harbors more than a thousand chemical reactions, a large collection of skills for surviving in a changeable and uncertain world.

“The metabolism of Buchnera’s ancestors once resembled that of E. coli. But no longer. Now its metabolic network has a puny 263 metabolic reactions. Its alliance with aphids started when dinosaurs still walked the earth, and since then it has lost nearly three-quarters of the reactions that E. coli still harbors.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 191.

“With this recognition [that life’s complexity and robustness increase with its exposure to environmental change], a circle is closing. Environmental change requires complexity, which begets robustness, which begets genotype networks, which enable innovations, the very kind that allow life to cope with environmental change, increase its complexity, and so on, in an ascending spiral of ever-increasing innovability. At the core of this innovability is the self-organized multidimensional fabric of genotype networks, hidden behind life’s visible splendor, but creating this splendor. It is the hidden architecture of life.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 194.

“This idea–that analogs of genotype networks could accelerate innovation in technology–is not so far-fetched, as we shall see. A first hint is that innovation in nature and innovation in technology show many parallels….

“Failure in science and technology does not usually mean bodily death, but this does not mean that ideas die easily….

“One of nature’s antidotes against catastrophic failure has been accidentally co-opted by technological innovators: populations….

“And when the armies of technological innovators advance, they do so on many fronts simultaneously–again like nature. The American sociologist Robert Merton … is well remembered in the history of sciences for documenting the prevalence of inventions with multiple origins–he simply called them ‘multiples’….

“Multiple origins are possible because the problems of technology–like those of biology–have multiple solutions…..

“Another commonality of both technological and biological innovations is that they endow old things with new life….

“In 1982, the paleontologists Stephen Jay Gould and Elizabeth Vrba baptized the biological version of this phenomenon ‘exaptation’….

“Such co-option is a special case of a final parallel between nature and technology: Innovation is combinatorial. It combines old things to make the new. We encountered combinatorial innovations first in metabolism, where new combinations of old reactions turned toxins like pentachlorophenol into fuels to manufacture biomass, and allowed our ancestors to detox their bodies by synthesizing urea. In proteins they are new combinations of old amino acids, and in regulation circuits they are new combinations of interacting regulators. But a technological innovation like the aviation-transforming jet engine is just as combinatorial [compressor, combustion chamber, turbine]….

“Trial and error. Populations. Multiple origination. Combination. With all these parallels between technology and nature, it is little surprise that technologists would try to mimic nature’s innovability.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 196-201.

“Nature is better at recombination, much better, for one simple reason: standards….

“All the different things that proteins can do–catalyze reactions, transport molecules, support cells–emerge from strings of building blocks connected in the same way, through a standardized chemical connection called the peptide bond….” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 204, 205.

“Because the library [of small, random computer circuits of 16 gates that yielded logic circuits] hosts many more circuits than there are functions–1026 times more, to be precise–we knew that there must be multiple synonymous texts, circuits computing the same logic function, but we didn’t know how they were organized…. Karthik [postdoc researcher with Wagner] started random walks like this from more than a thousand different circuits, each one computing a different function that needed to be preserved.

“The networks of circuits he found reached even farther through the library than the genotype networks from earlier chapters: From most circuits one could walk all the way through the circuit library without changing a circuit’s logic function. Two circuits may share nothing, not a single gate or wire, except the logic function they express, yet they can still be part of a huge network of circuits connectable through many small wiring changes. What’s more, we found that this holds for every single function we studied. It is a fundamental property of digital logic circuits. The library of digital electronics is like biology, only more so.

“Karthik next turned to the neighborhoods of different circuits computing the same function, created all their neighbors, and listed the logic functions that each of them computed. He found that these neighborhoods are just as diverse as those in biology. More than 80 percent of functions are found near one circuit but not the other. This is good news for the same reason as in biology: One can explore ever more logic functions while rewiring a circuit without changing its capabilities….

“A fabric [multidimensional fabric of biological innovability, the complex, densely woven tissue of genotype networks] just like that of life’s innovability exists in digital electronics, and it can accelerate the search for a circuit best suited for any one task.

“Circuit networks thus have all it takes to become the warp drives of programmable hardware, in precisely the same way that genotype networks are the warp drives of evolution.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 213-4.

“When Karthik analyzed logic circuits that differed in their complexity–their number of logic gates–he found that the simplest circuits could not be rewired without destroying their function. Change one wire in such a circuit, and you destroy the circuits’s function. Every gate and every wire matters. Such simple circuits have no innovability, because they cannot explore new configurations and computations. For rewiring, one needs more complex circuits. The more complex they are, the more rewiring they tolerate…. This is one of nature’s lessons for innovable technologies: If we want to open nature’s black box of innovation, Ockham’s razor is much too dull. Like oil and water, simplicity and innovability don’t mix.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). p. 215.

“This doesn’t mean that simplicity and elegance are absent from powerful innovable technologies. Quite the opposite. But they hide beneath the visible world. The basic principle behind them is simplicity itself: With a limited number of building blocks connected in a limited number of ways, you can create an entire world. Out of such building blocks and standard links between them, nature has created a world of proteins, regulation circuits, and metabolisms that sustains life, that has brought forth simple viruses and complex humans, and ultimately, our culture and technology, from the Iliad to the iPad. The simplicity and the elegance of innovable technologies are hidden behind the visible world, just like nature’s libraries, whose faint reflection we see in the Tree of Life, like a shadow in Plato’s cave.” Wagner, Andreas. 2014. Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. NY: Current (Penguin Group). pp. 215-6.

“This time I feel around with my hand. Again we hear the scratching sound–louder this time, frantic. I reach deeper into the chimney and touch something smooth, soft, something round and moving. I shiver for a moment, then grasp it firmly. As my hand reappears, I see that it is a young swift. Its body radiates warmth. I sense the staccato rhythm of its heartbeat.

“I walk to the wide-open window, open my hand, and the bird vanishes like an arrow into the silvery light of the evening sky. Apparently he had flown down into the chimney and couldn’t get back out.

“Smiling, we look at one another. We can do nothing else–we have to smile. It is quiet, but then we hear the sound again. More rasping. I fumble about once more, reach deeper still into the cinders. I bring another swift into the light. I release it out the window to freedom where it arcs along the street between the houses and disappears around a bend. The swifts plunge into the air and are renewed to their element. In that moment, they are saved, even if they have already grown too weak to survive. I hear their exultant cries, their drawn-out shrills ringing in the evening. And the same exultation fills us, as we cannot help but fall into one another’s arms, happy to be saved.

“In that moment, I understand. The swifts are an element of the air, but they are also an element of happiness. The swifts are the children of the air’s love of itself. And for the first time, I suspect that we do not properly understand this love when we limit it to an emotion only felt in moments when, for example, we try to keep a particularly desirable person in our life. On that summer evening, I have the impression that love is nothing more or less than pure aliveness in flesh and blood, with a beating heart and outspread wings. Indeed, that every moment in which we encounter life and its desires with affection, this love unfurls, just as those young birds unfurled their oversized wings into freedom and aliveness.

“To love, I thought, means to be fully alive. But this has significant consequences. It became clear to me that this would cause us to completely rethink how we understand life and its significance. It would mean that, for some time, we might have understood very little–or have forgotten very much–about life and the feelings connected with it.

“And it could be that the planet is not actually suffering from either an environmental crisis or an economic one. Instead, it could be that the Earth is currently suffering from a shortage of our love. As the planet has entered the sixth wave of extinction, more and more people complain about feelings of meaninglessness. Depression and personality disorders are on the rise, and billions of us continue to live in the gloom of abject poverty.

“But this love–I thought, as the trail of the swift’s arrowlike flight seemed burned like an afterimage into the evening’s empty air–is indeed nothing other than the inexhaustible drive of both life-forms and the ecosystem to grow and to unfold. It is the desire for such unfolding and the joy experienced when that drive is fulfilled–and yet, it is also the happiness that my friend and I felt as we embraced one another after rescuing those little animals. It unfolds regardless of whether something good happens to me or another being, because it is the joy experienced whenever life increases in the world, somewhere.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 3.

“Love, as I reflected on it, was something like the inside of aliveness.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 4.

“The search for love is a central movement that characterizes life, and it remains as inexhaustible as it is unfulfilled. Its consistent failure could mean that we understand love as little as we understand the living world, the natural world, the equally threatened creative power of the Earth. We often love incorrectly. This is the starting hypothesis of this book–in private and in politics, in big ways and in little ones, in our culture and in our beds. We love incorrectly because what we consider love does not enliven us, nor does it enliven the world. But is it at all possible to love ‘correctly’?

“The answer that this book attempts to offer is this: To understand love, we must understand life. To be able to love, as subjects with feeling bodies, we must be able to be alive. To be allowed to be fully alive is to be loved. To allow oneself to be fully enlivened is to love oneself–and at the same time, to love the creative world, which is principally and profoundly alive. This is the fundamental thesis of erotic ecology.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 5.

“[Story about a heroine who speaks to a group of skeptical philosophers at a dinner party:] ‘To be a living bat is to be full of being; being fully a bat is like being fully human, which is also to be full of being. Bat-being in the first case, human-being in the second, maybe; but those are secondary considerations. To be full of being is to live as a body-soul. One name for the experience of full being is joy.’

“Joy is the sign of love; and love is the principle of a fulfilling equilibrium between the individual and the whole. The erotic manifests as that force that causes beings to inexhaustibly seek this equilibrium, to fail at that seeking, to neglect it, to temporarily achieve it. The power of the erotic suffuses the biosphere with life and imbues its members with the stamina to look–with new verve every day–for fruition, fulfillment, and joy.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 7; initial quote from story “Elizabeth Costello” by J.M. Coetzee where heroine makes that statement at a dinner of philosophers skeptical of experience.

“Life is the clearest example of the cosmos’s poignant and dramatic striving toward a future point of rest predicted by physical laws, while also taking countless detours along the way…. As the universe heads unavoidably toward what the physicists call ‘heat death’–that fade-out into solitude and uniformity–life freeloads aboard this gradual cool-down process to spawn its own oddities: coral reefs, little rotifers, naked mole rats, you and me.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 19-20.

“This constant babble of call and response pervades our geo- and biosphere. We are everywhere confronted by the erotics of the encounter…. The hedgerow at the edge of the woods results from the encounter of the dense forest and the clear open countryside. The blooming hedgerow shows how the woods answer the meadows.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 29.

“Biology is the science of that contact from which all experiences of touch emerge, the theory of interchange in an endless variety of forms, of metabolism–the exchange and transformation of matter—of amalgamation and of parasitization. Biology is the erotic science par excellence, because a living being is an erotic process: It transforms itself through contact with others, imagining new relationships out of each existing one, desiring more life, unrelentingly seeking a connection to the whole of which it is both concentration and unrepeatable instantiation.

“The erotic within the living world can be most clearly seen in three domains: the spheres of symbiosis, communication, and metabolism.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 33.

“… where the meadows [in hills of Italy] are still allowed to grow wild in the springtime. Within two or three weeks, the stalks swell into a multitude of meadow-grasses and blossoms as tall as my waist, fragrant and enveloping. I think then: It might have been this way once, when the plenitude of existence could spread everywhere and it seemed unavoidable that every corner of this biosphere would fill to the brim with life. When it was only natural to think of this cosmos as living, as enlivened at its deepest core, and not as an optimized assemblage of dead matter.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 34.

“The life in which we participate … is also not a merciless battlefield between unrelenting combatants, ‘red in tooth and claw’ and ‘at war, one organism with another.’ The world of biology is more like a wild playing field with anarchic elements, where the rules of creative togetherness are constantly being renegotiated, where gang wars break out between little groups of co-conspirators and schemers, but also where one finds acts of magnanimous sharing, heroic dedication, and dreamlike bliss.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 40.

“[Aldous] Huxley believed that we, and all other creatures, are seeking ‘grace’–a word that means both loveliness and blessing.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 43.

“The laws of desire frame the principles according to which life-forms experience all instances of bodily concern as existentially meaningful…. Its principles–the wish for continued existence, the visibility of this life wish as an emotional expression, and the necessary presence of other beings to enable one’s own life–make up the ground rules of desire according to which living matter pushes toward unfolding. These rules are true equally for processes of material exchange and for mental and emotional experiences.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 43-4.

“Every being is one of subjectivity’s masks, it is a form of being a subject–a feeling, longing, vulnerable, triumphant subject.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 45.

“As life-forms among the other beings of the natural world, we are ever observers of an aliveness that we also carry within ourselves. We see the outside of what we experience as value, meaning, and feeling ‘inside’–in our souls. We see this outside and know it to be an appearance occasioned by an inside, and that we can perceive this inside with our senses. The natural world is consequently more than just a reflection of soul. Filled to the brim with life and striving, it is a psyche whose outside gives us access to our inside. Every being is a figure of our inside; no: Our inside is one of its possible expressions. We–feeling, analogical, formative beings–can only understand this inside by seeing it as a living image of ourselves before us: as a happiness or a sorrow, which likewise fills us with happiness or sorrow.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 45.

“We human beings see with plants and animals just as poets see with words. Deep down, other life-forms are what make our own perception possible…. Without them, we are not, for all being is reciprocity and reflection.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 46.

“The audacious thought of the necessary imperfection of all creation.” Scholem, Gershom. Quoted in: Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 48; from: Juenger, Ernst & G. Scholem. 2009. “Briefwechsel 1975-1981.” Sinn und Form. 61(3):293-302.

“‘… [Kalevi Kull, biosemiotician, speaking about cells] its component parts are irreconcilable. Every cell is its own contradiction as long as it is alive.’

[Author Weber] “‘So, for the individual parts of a cell, does living mean having to help one another understand each other?’ I asked in response.

[Kull] “‘Precisely…. In a cell, dimensions that are fully irreconcilable come into contact with one another. The genetic data–which is an abstract code, and the cell body–which is a concrete, material being in space. Both are incompatible with one another. And this incompatibility means that one always has to be translated into the other.’

[Author] “‘Then there is always an excess that cannot be transferred,’ I thought aloud. ‘Understanding fails. But in the logic of this antithesis, it only has the chance to be ‘understanding’ because it must ultimately fail. Were it not for the ever-present possibility of death, beings would not need to be possessed by the urge to evolve, to go on existing. Without death, the being is a machine. Or more generally: Aliveness must be able to fail if it is to be truly alive. Only because of death does life become creative.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 50.

“The English philosopher Alan Watts says: ‘By and large Western civilization is a celebration of the illusion that good may exist without evil, light without darkness, and pleasure without pain, and this is true of both its Christian and secular technological phases.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 51.

“The deepest incompatibility is to be found between the autonomy that every life-form, even the simplest bacterial cell, introduces into the world, and matter that is organized according to the laws of cause and effect. The real scandal is that these willful cells exist at all, and that new ones are being created every moment out of substance that would gladly have rested on the ground as lifeless dust for the next billion years.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 52-3.

“In the Middle Ages, the philosopher Duns Scotus taught that every creature could reveal God simply by being wholly and uniquely itself….

“The concept that Scotus used for this phenomenon was the Latinate neologism ‘haecceitas,’ or ‘thisness’–which the British nature writer Robert MacFarlane also translates as ‘self-ablazedness.’ Thisness manifests the creative triumph over nothingness, a triumph that must, however, be perpetually wrested from that nothingness.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 54.

“At the end of the nineteenth century, the Irish romantic poet Gerard Manley Hopkins centered his work around his astonishment at the world’s endlessly repeated, yet always varied thisness. His language trembles with amazement at this constantly incredible gesture of revelation, and in the end, the only response suited to this incomprehensible phenomenon of a desire that abides as desire is to echo it.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 55.

“In order for desire to be able to unfold in a body as a creative, deeply vulnerable gesture, it must already carry its negation within itself. It must be an urge that knows of its own impending end and is thereby free to pursue the hazards of growth and attachment, and to risk itself in the process.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 56.

“So metabolism means: I subsist on what becomes my body, and I exhale into the air what was my body. I am the grain of the field that died for me, and I die constantly and transform myself into what the plants inhale, such that my body becomes their new bodies. The organism is a closed being, and at the same time matter flows through it. Matter drifts through the bodies of a vast array of organisms without ever being identical with them. A carbon atom in the calm grasses of the meadow was once a part of the air, and before that an insect, fruit, perhaps a human body, its breath, perhaps me.

“Isn’t that a genuinely erotic relationship? A bond that produces deep inwardness–and that demands, at the same time, complete self-sacrifice? The functioning of the circle of life on Earth depends solely on the fact that we all share in the great body of matter and pass through one another reciprocally. Life is touch in a much deeper sense than just touching skin to skin, colliding against foreign masses: It is touch as penetration of one by another.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 57.

“Life is a process in which an identity generates itself. But this identity resides not in matter, but in the desire with which it births itself in each new moment, in whose name it undertakes every attempt to unfold itself creatively. What composes us is a gesture, an act, a wish: the wish to continue existing.

“And this wish is precisely the opposite of matter, which is always striving for its final resting place. The desire for existence, which we can only realize through a substance that is continually seeking to escape this desire, is the deepest contradiction of the living.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 58.

“For a desiring subject, every crackle of reality contains a message, an answer to the anxious question of whether the next moment will simplify or hinder existence. Death is unavoidable, but only death makes the world legible.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 59.

“Living means learning to die.

“The universe is not purely gentle. It is just as deadly as it is gentle. And it can only be gentle because it is deadly. It can only be gentle insofar as its gentleness constantly puts up a fight against death. This is the message of erotic ecology, one that it sets against Darwinism, liberalism, and all of the dominant goal-oriented ideologies, all of the ideologies of efficiency, of combat, or war as the father of all things.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 65.

“And that objective [of living by combining symbiosis and death] is to increase the possibility for more desire for being, to increase the level of freedom, to love aliveness. This–not the factual bulimia found in schools–must be what composes the learning processes of our youth and young adulthood, but we have forgotten this.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 65-6.

“Learning to die means seeing reality without nudging it in some pleasant direction. That alone is what it means to really see. And that alone is what it means to be sculptural, to be creative without having to be ashamed of your imperfection. That alone is what it means to be wild, wild in the sense of animal who does what is necessary, wild like the whole of the natural world, which manages its own needs….” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 68.

“[Otto] Rank asserted that humanity’s lust for devastation, its evil, did not result from a destructive impulse built into our biology. Instead, in Rank’s view, destructive impulses are impossible to keep in check because we constantly act contrary to our drive for aliveness. And we counteract it because we cannot accept that this aliveness demands that we look death in the face, that we directly approach death as a central element of living reality.

“For Rank… modern humanity’s widespread refusal to surrender anxious self-defense in favor of aliveness (both one’s own and others’) is the true cause of evil. The ‘armored’ person is the problem, the person who is not open to others, who does not actually want life as such (life that includes death), but places his or her own survival above all else, no matter how narrow and ingrown it might be.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 69.

“In the understanding of aliveness that views life as an erotic phenomenon, as a phenomenon of being touched and being in relationship, it is not about welcoming death and then declaring it a remedy. It is not a question of nihilism. Nor indifference. Nor technocratic stoicism. Nor heroic romanticism. It is not a question of realism, which so often conceals an unimaginative cynicism. On the contrary, it is a question of equilibrium, of the living midpoint between glimmering light and devouring darkness. It is about despairing over the fact that suffering is unnecessary and then, for that very reason, choosing not to avoid our own suffering, for life’s sake….

“The attitude that truly follows aliveness’s call to the end knows to distinguish between death as a slave in one’s own existence and death as a wild animal that freely follows its own needs.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 73.

“Comprehending something means transforming. Learning means becoming something or someone else.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 80.

“Octavio Paz … writes: ‘The relationship between eroticism and poetry is such that it can be said, without affectation, that the former is a poetry of the body and the latter an eroticism of language.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 88; reference: Paz, Octavio. The Double Flame. p. 2.

“A kiss is softness sensed on the skin; a poem is that same tenderness, provided with a body by the velvet of a melody of words.

“In its imaginative potential, in the imaginative excess that it appends onto reality, the creative word holds the key to the understanding of what there is. But not because there is no true reality apart from our discourse on it. Rather, because living reality is already constantly reaching beyond itself in continuous, creative transformation. Our words and intonations and metaphors that make us shiver or shrug are part of this transformation. They are part of the body of the world. The world speaks itself.

“At this point, I would like to overturn the viewpoint, widespread in the humanities, that we hopelessly overlay worldviews onto an unknowable universe with our ‘interpretations.’ Not so. We are able to understand the nature of creative reality precisely because we, like all life-forms, are part of this reality. We are the world. We have both embodied and genuinely creative experiences, and we express these experiences with imagination, creativity, and freedom. We express our being in the world by the same means that the world forms itself. Reality is fluid and constantly bringing forth new beginnings–and so is our intercourse with it. A microcosm.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 88-9.

“This is why art is important to life–because it manages the uncontrollable within us without threatening to turn us into machines, without causing us to lose our aliveness.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 97.

“Many times, Goethe described the transformative force latent in all of reality. Experiencing this force and its effects and then describing this experience is more precise than the exhaustive analysis of an ostensibly objective science…. The doctrine lies not in the neutral analysis of the world, but rather in entering into relationship with it and allowing oneself to be transformed by this relationship. Goethe called such an attitude ‘tender empiricism.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 98.

“Language is the ability to name things, processes, feelings, and individuals, thereby making them into something different. At that point, they are no longer objects, but rather imaginative fields of energy….

“Language is a medium of metamorphosis between bodies and ideas and between different living bodies. In its potential to be a substance of transformation, the fabric of language corresponds to the nervous system of a living being.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 98, 99.

“The philosopher Plato recounted the saga that we are all searching for our ‘lost half.’ In Plato’s famous Symposium dialog, the priestess Diotima tells this story as a divine myth. In the beginning, all people were complete and whole like perfect spheres. But then they were split into two halves. From then on, each of us is looking for the missing piece that will allow us to become whole again….

“The age-old myth recounted by the priestess Diotima in Plato’s Symposium is thus already overshadowed by a cultural deficit: Beings that seek their second half exhibit the bitter privation of the needy who are not allowed to be themselves. The wise Diotima articulates a relational-ecological dilemma. She is expressing the condition of painful separation as a normal state of being in the world, but it is the outcome of a failure to relate. There is a reason for this failure. For Plato has her speak according to the spirit of separation that pervades his entire philosophy and that has exercised an incalculable influence on Western thought.

“Diotima’s stance follows the general program of Platonism: The world of bodies–in other words, the world in which we live–is already the result of a separation. Reality is isolated from actual things, from the ‘ideas.’ According to this thought, to live is to strive for a completeness that cannot be found here, but can be found only in a transcendent-ideal world. In Christianity, God was placed in this position of ideal truth, and ‘actual’ life came only after death. Modern science filled the Platonic ideal with its goal of eradicating all earthly evil through analytical understanding and technological improvement. In the current marketplace of love, the ideal has again been placed at the center of our desires. All of this has a common denominator: The real world is viewed as flawed. In love, a piece of the ideal world beyond is supposed to become real, but the result of this is an act of controlling, not one of allowing the other to be enlivened….

“In the history of philosophy, this notion is called the ‘radical transcendence of the ego.’ The I actually does not exist in this earthly world, suffering and loving in the experiences of the sensory body–rather, it exists somehow as an otherworldly abstract principle of knowledge. It is consciousness, spirit, rationality–and therefore structurally unrelated to the impenetrable drives here below….

“In my eyes, the philosophers’ ‘radical transcendence of the ego’ reflects a pathological condition of the soul, a trauma. It results from the pain of having one’s own aliveness trampled and disallowed. Most of us have experienced this. Such a trauma propagates itself. If the I is irrecoverably shut up in itself because it was not seen by a benevolent gaze, then it will turn everything with which it comes into contact into a means of aleviating the torment of this isolation. Every relationship partner turns into a resource for survival.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 114, 115, 116, 117.

“A first approximation of the rules of erotic exchange might go somewhat like this:

“1. Every participant can produce his or her aliveness only by him- or herself and cannot acquire it through another.
“2. In order to experience ourselves as alive, we must bestow aliveness on others. The You precedes the I.
“3. The other’s offering is a gift, not a reward for a service.
“4. Through giving back this gift–the other who sees me in my reality–I can become what I am.
“5. A relationship is successful when it increases the aliveness of all… [followed by 7 more rules].” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 122.

“The couples’ therapist David Schnarch identifies the basic problem of aliveness as a ‘two-choice dilemma.’ By this, he means the contradiction in life between fusing with the whole and individuating, the ecology of incompatibility inherent in life itself. After many years of practical work, Schnarch writes without illusion: ‘Our problem is not the two-choice dilemma itself but our refusal to face it, our unwillingness to meet life on its own terms.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 122-3; reference: Schnarch, David. Passionate Marriage. p. 300.

“For the influential American psychologist and author Ernest Becker, life is characterized by a basic ‘ontological’ or ‘creaturely’ tragedy. It is the clash between two basically irreconcilable needs–one for connection and one for autonomy…. In the ‘romantic solution,’ we fix our ‘urge to cosmic heroism onto another person in the form of a love-object’….

“But exactly this seeming solution is bound to fail in a painful way. Becker writes: ‘We enter symbiotic relationships in order to get the security we need, in order to get relief from our anxieties, our aloneness and helplessness; but these relationships also bind us, they enslave us even further because they support the lie we have fashioned.’ The object of love, according to Becker, becomes a god–and can therefore transform just as easily into the devil. For not the character of the other, but ‘life itself is the insurmountable problem.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 123; reference: Becker, Ernest. The Denial of Death. pp. 160, 165, 270.

“… the contradiction of life cannot be cleared up. Rather, the creative answer to living reality is to bring its duality into a dynamic balance.

“Seeking this balance–and constantly failing to achieve it–is the central drama of human connections.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 124.

“Because I can feel the world with my skin, I can also feel myself; and because I can feel myself, I can feel the world…. Reality actually only exists in this moment of touch from which both sides emerge; it exists only in the sensitivity, in the tangibility, and in the attention with which I perceive both myself and this sensibility to other at once. Does this not open up a fundamental, erotic connection to reality?” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 126.

“The erotic is the exchange of reciprocal perception through living bodies. It is the foundational moment of any relationship to reality. The world senses me: In my perception, I am sensed by the world. And I thereby experience myself, sensing, perceived as foreign by the foreign-familiar of my own body, constantly regifted to myself. Therein lies the erotic.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 128.

“Octavio Paz writes: ‘Love does not defeat death; it is a wager against time and its accidents. Through love we catch a glimpse, in this life, of the other life. Not of eternal life, but […] of pure vitality.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 129; reference: Paz, Octavio. The Double Flame. p. 273.

“It [play] is not actually training for the serious business of acquiring nourishment or forcefully defending territory, but for imaginative participation in the creative universe and for one’s role within it. So play comes very close to being a comprehension of one’s own aliveness. Play is an instance of expression and thereby one of the most important manifestations of erotic ecology.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 135.

“Children are themselves the essence of the living. They are prompted to be aimlessly creative in that undetermined zone between risk and security. In play they constantly define life as the creative transition between control and uncontrollableness….

“Play thus reveals itself as a practice of loving the world.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 136.

“For the idea of moderation, Camus invoked the ancient goddess Nemesis, who punished all dogmatic exuberance. Nowadays, Nemesis manifests herself in the parching heat storms over the Great Plains of Australia, in children’s blank expressions as they fix their eyes on little touchscreens. She is the goddess who does not condemn innovation but will take vengeance for exclusivity and all forms of dogmatic single-mindedness….

“Acting in moderation means not replacing the imperfections of creation with worse copies that are ostensibly error-free. By enduring the imperfections of creation, we are already following the goddess Nemesis. The errors intrinsic to all created things can only be endured if we respond to them, and create. As such, the experiences of the embodied present become the strongest argument for the conviction that the world, in all of its bitter imperfection, is the expression of something that cannot be improved.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 165, 166.

“Citing the thinker Friedrich Nietzsche, Camus calls for the following, as the central premise of moderation: ‘Instead of the judge and the oppressor, the creator.’” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 167; reference: Camus, Albert. The Rebel. p. 273.

“The British architect and author Christopher Alexander thinks that all forms of aesthetic beauty are really nothing other than various solutions to bringing the unavoidable tension within the process of being alive into dynamic equilibrium. Alexander charts a matrix of life gestures that each represent an artistic archetype and also depict a mediation between the whole and the isolated individual….

“If we follow Alexander in this line of thinking, then beauty becomes synonymous with life–a life that is stretched between irreconcilable opposites and seeks an equilibrium, a state of tension in which the opposites are preserved and can coexist without being dissolved and without being overtaken by one another.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 171, 173; reference: Leitner, Helmut. 2015. Pattern Theory: Introduction and Perspectives on the Tracks of Christopher Alexander.

“Although the East has approached paradox much more openly than the West, which has been denying it for three thousand years, inaction is not the answer we need. Paradoxically, we need both: action, and the knowledge that action is never enough–indeed, that there is always something absurd about taking action.

“Only the vision of a society that engages in this imperfect action, that admits both tragedy and the ‘astonishing beauty of things,’ in the words of Robinson Jeffers, will allow us to recognize a genuinely new reality. Only such a vision will be in the position to turn away from the dominant social technologies and economic theories and toward a practice of participation in which no optimum state can be reached, but in which we can constantly struggle to bring about an optimal equilibrium. Only such a vision accepts that we are part of everything and cannot separate ourselves from it through either our acts of destruction or our achievement of excellence.

“This variant of the ‘back to nature’ idea does not mean that we have to go back to living in huts. Above all, it means relearning to feel and to perceive, and accepting all of the feelings and perceptions–the terrible and the sublime–as reality. As our inner share of wildness, as our inviolable participation in a pulsing reality. With this attitude, it makes no sense to look for guilty parties. Here, acting in moderation becomes a gesture of immeasurably deep compassion.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp.176-7.

“The fireflies filled the air above the meadow and the trees [in Italy]. They flew like little stars, dancing zealously through space and flashing off and on. Their light mixed with the silver points of the heavenly bodies in the darkness of space, blurring the line between star and glowing insect. It was as though the stars sank into the grass and the smoldering insects ascended into the universe. For a brief second, I had stretched my head out into a living cosmos.

“What I saw was a festival of reproducing and of being devoured. I looked up between the stars and participated in a dance in which the participants ecstatically offered their bodies to others for use. The glowing insects danced through the night to find a mate and were consumed by late-flying birds and bats in the process. Everything gave itself away in the truest sense of the word, without wanting to, without thinking, without even being capable of having a thought about it. And it was no accident that it unfolded in this way–it was not some regrettably still-unperfected ideal.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 185.

“In the natural world, the most complicated, most valuable things are given away without a thought…. How can we comprehend the boundlessly deep miracle of the mayfly, on the surface of the water no less perfect than the wolf [magnificent but living only seven years], flawlessly and meticulously elaborated, yet nothing more than an empty shell after but a few days? And what does the may bug have to tell us, that beetle that enjoys a few early summer days after five endless years of larval existence below the earth?…

“All of this shows that the self, the delimited life of the individual, and its accumulated treasures cannot be the standard. The self is not the pinnacle of worldly affairs. That for which the incomprehensible filigree of the self is sacrificed must be infinitely more filigreed, filled with infinitely more self. Clearly, the wasting of so much preciousness is not at all significant to the greater whole….” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 187.

“The food chain is a clear negation of distinct individuality….

“Freedom has a price. And this price is death. Without death–which pulls a creature back in at some point–no self-preservation, no self-will, no insistence of one’s own position, no creation. Therein lies the deep logic of what Gershom Scholem once hesitantly suggested: that creation cannot know perfection. The freedom of creation, the creative autonomy that speaks from every blade of grass, only manifests if an individual stops taking first for herself and instead totally risks herself for it.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. pp. 188, 189.

“The first act of resistance to the current menace of life therefore is not eager protection of the bits and pieces that remain, but the confidence that we can be alive if we act as parts of the circle of giving.” Weber, Andreas. 2017. Matter & Desire: An Erotic Ecology. Rory Bradley, translator. White River Junction: Chelsea Green. p. 191.

“A main aspect of self-reorganizing dynamical systems is that the emergence of pattern and pattern switching occur spontaneously, solely as a result of the dynamics of the system: …. Self-organizing systems are, it seems, selfless.” Kelso, J.A. Scott. 2017. “On the Self-Organizing Origins of Agency.” Trends Cogn. Sci. 20(7):490-499. doi: 10.1016/j.tics.2016.04.004. p. 2.

“Coordination dynamics refers to the patterns that the system is capable of producing spontaneously at a given point in time along with the attractor landscape that defines the relative stability of these patterns as intrinsic dynamics. Intrinsic dynamics is important to know because it influences what can be changed or modified by new experiences and how such change occurs, e.g., whether change is smooth or abrupt.” Kelso, J.A. Scott. 2017. “On the Self-Organizing Origins of Agency.” Trends Cogn. Sci. 20(7):490-499. doi: 10.1016/j.tics.2016.04.004. p. 3.

“The ability of complex systems to softly assemble themselves into functional synergies or coordinative structures in a context-sensitive fashion offers significant selectional advantages.” Kelso, J.A. Scott. 2017. “On the Self-Organizing Origins of Agency.” Trends Cogn. Sci. 20(7):490-499. doi: 10.1016/j.tics.2016.04.004. p. 3.

“My opinion is that a coordinative structure is formed when the (notably prelinguistic) infant discovers itself as an agent (‘this is me’), that is, when the baby realizes it can make things happen. In this theory, the birth of agency and its causative powers (‘I do’, ‘I can do’) corresponds to a phase transition of a coordination dynamics whose key variables span the interaction between the organism and its environment. The idea is that when the baby realizes it is causing the world to change it experiences itself as an agent for the very first time. This igniting of agency has a eureka-like, ‘aha’ effect; mathematically, it corresponds to a bifurcation in a coupled dynamical system. Coupled dynamics refers to the coordinated relation between the baby’s movements and the (kinesthetic, visual, auditory and emotional) consequences they produce. Bifurcations are the mathematical equivalent of phase transitions, qualitative changes in coordinative states. The main mechanism underlying the origin of self as a causal agent involves positive feedback when the baby’s initially spontaneous movements cause the world to change, their perceived consequences have a sudden and sustained amplifying effect on the baby’s further actions.” Kelso, J.A. Scott. 2017. “On the Self-Organizing Origins of Agency.” Trends Cogn. Sci. 20(7):490-499. doi: 10.1016/j.tics.2016.04.004. pp. 3-4.

“In short, it does not seem too far of a stretch of the imagination to propose that evolutionarily constrained processes of self-organization – real organisms coupled to real environments living in the metastable regime of their coordination dynamics – are at the origins of (meaningful) information and agency itself. This step may signal an end to false contrasts about whether coordination in living things is a directed or self-organized process and point rather to their inherently complementary and unified nature.” Kelso, J.A. Scott. 2017. “On the Self-Organizing Origins of Agency.” Trends Cogn. Sci. 20(7):490-499. doi: 10.1016/j.tics.2016.04.004. p. 8.

“Neuroscientists have identified a particular attractor of neural connections in the brain that is activated during mind-wandering, called the default mode network….

“It might be helpful to think of our default mode network as a salience seeker; exploring neural pathways to seek out what’s important, it pounces on what’s salient and raises it to conscious attention so we can mull it over.” Lent, Jeremy. 2021. The Web of Meaning: Integrating Science and Traditional Wisdom to Find Our Place in the Universe. Gabriola Island, BC, Canada: New Society Publishers. p. 189.

“When we formulate an intention, this is equivalent to modifying the landscape within our attractors of consciousness.” Lent, Jeremy. 2021. The Web of Meaning: Integrating Science and Traditional Wisdom to Find Our Place in the Universe. Gabriola Island, BC, Canada: New Society Publishers. p. 191.

“When researchers developed a benchmark called the genuine progress indicator (GPI), which factors in qualitative components such as volunteer and household work, pollution and crime, they discovered a dramatic divergence between the two measures [against GDP globally]. GPI peaked in 1978, and has been steadily falling ever since, even while GDP continues to accelerate.” Lent, Jeremy. 2021. The Web of Meaning: Integrating Science and Traditional Wisdom to Find Our Place in the Universe. Gabriola Island, BC, Canada: New Society Publishers. p. 352.

“Intrigued by this experiment [dropping grains of rice one at a time on pile that then experiences avalanches at sizes predicted by power law], I decided to try it myself. I got similar results, but I notice something else that fascinated me. Most of the time when I dropped a few grains on top of the pile nothing much happened at first, but, as I kept watching, I began to see subtle changes occurring in different places all over the pile. It was as though the inert heap of rice had come alive. I realized that, unseen, the tiny impacts of the grains on top were resonating throughout the pile, causing innumerable other tiny reactions among adjacent grains, which in turn passed their movements on throughout the pile. It dawned on me then that each grain I dropped was contributing something unique to the eventual avalanche.” Lent, Jeremy. 2021. The Web of Meaning: Integrating Science and Traditional Wisdom to Find Our Place in the Universe. Gabriola Island, BC, Canada: New Society Publishers. p. 381.

“Agential thinking is intimately linked with the idea of fitness-maximization in biology. This idea has two variants, both controversial. The first is that evolved organisms will exhibit traits that are adaptive, hence maximize their fitness relative to some set of alternative traits. The second is that the process of natural selection itself involves maximization, in the sense of continually changing a population’s composition so as to achieve higher fitness. These two claims are related but distinct. The former concerns adaptation (the product), while the latter concerns selection (the process). Both tie in with agential thinking but of different sorts. The former relates to the paradigmatic sort of agential thinking in which the agent with the goal is an individual organism. The latter relates to the ‘mother nature’ sort of agential thinking, in which the agent with the goal is the evolutionary process itself.” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. p. 3.

“By contrast, type 1 is a legitimate expression of adaptationism, but it relies on a crucial presupposition. It presupposes that the entity that is treated as an agent exhibits a ‘unity-of-purpose’, in the sense that its evolved traits contribute to a single overall goal. Where this unity fails to obtain, as for example if there is substantial within-organism conflict, then agential thinking loses its grip; it becomes impossible to treat the organism as akin to an agent pursuing a goal.” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. p. 5.

“There are two possible attitudes that one might take towards agential thinking. The first sees it as mere anthropmorphism, an instance of the psychological bias which leads humans to see intention and purpose in places where they do not exist, and to favour teleological descriptions of the world over purely mechanical ones….

“The second attitude sees agential thinking as a natural and justifiable way of describing or reasoning about the process of Darwinian evolution and/or its products. After all, many evolved organisms engage in activities that seem clearly purposive, such as foraging, searching for mates, and warning others of danger. Such behaviours are functionally similar to the actions of rational humans, even if their proximate cause is quite different, in that they are efficient means of achieving a goal (e.g. survival or reproduction). So treating the organisms in question as agent-like, and describing their activities in intentional terms, is well-motivated even if not literally true, in that it picks out a real phenomenon in nature. Similarly, one might try to justify (a different form of) agential thinking on grounds of an objective similarity between natural selection and rational choice: both are to do with selecting between alternatives in accordance with a goal, and thus involve a form of optimization. On this view, agential thinking in biology is not (mere) anthropomorphism, but has a genuine rationale and plays a real intellectual role.

“My own attitude is intermediate between these two poles, as I think that agential thinking is not an undifferentiated whole.” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. p. 11.

“In A.I., an intelligent agent is defined as any entity that perceives or senses its environment and performs actions which alter the environment. Examples include simple control systems such as thermostats, software agents, and robots…. The simplest intelligent agent is a ‘reflex agent’ whose action depends only on its current percept; it thus implements a set of stimulus-response conditionals. More sophisticated agents have an internal model of their environment which they update, so can learn from experience; they have a goal which they are trying to achieve; and in some cases they can engage in search and forward planning in order to achieve their goal. The behaviour of such agents is not merely flexible but also goal-directed and autonomous.” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. p. 14.

“A different notion of agency is found in the economics literature, in the rational actor model. In this field, a rational agent is defined as one whose decisions or choices maximize their utility, or expected utility in the case of decision under uncertainty. Utility-maximization is not intended as a psychological description but rather as a behavioural characterization: it means that agents behave as if they were trying to maximize a utility function. (In effect, this is a de-psychologized version of the notion of agency as intentional action.)” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. p. 14.

“To summarize, we have distinguished four notions of agency: the minimal notion of doing something: the philosopher’s notion of agency as intentional action; the A.I. notion of agency as flexible/goal-directed activity; and the economist’s notion of agency as rational choice. The minimal notion and the A.I. notion apply widely in biology, the philosopher’s notion the least widely, while the economist’s notion has intermediate generality.” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. p. 15.

 

“Agential thinking in evolutionary biology comes in two types. The first type treats an actual evolved entity, paradigmatically an individual organism but possibly a gene or group, as akin to an agent with a goal…. The second type treats ‘mother nature’, a personification of natural selection, as an agent who chooses between phenotypes in accordance with a goal, such as fitness-maximization; or (in another version) who tries to solve design problems….

“Both types of agential thinking involve a form of teleology, or goal-directedness, but in different ways. In type 1, the telos belongs to an evolved organism (in the paradigmatic case); the point of treating the organism as agent-like is to capture the fact that its evolved traits, including its behaviour, are adaptive, hence conduce towards the goal of survival and reproduction. In type 2, by contrast, the putative telos belongs to the evolutionary process itself (‘mother nature’); the suggestion is that natural selection has an inherent tendency to move the population in a particular direction, so is goal-directed in that sense. Thus in the former case the teleological description applies to the products of evolution, while in the latter case it applies to the evolutionary process itself.” Okasha, Samir. 2018. Agents and Goals in Evolution. Oxford UP. pp. 15, 16.

“Are you still uncertain as to who counts as a COVID maximalist? They are the people who post and boast about all the prophylactic layers they don before leaving the house, about how many antigen tests their families use per week; the people who shame others on social media for letting their masks slip beneath their noses. The maximalists typically belong to a distinct social class (my own, incidentally) in which it is financially possible to stay at home and ‘work’ (i.e., manipulate the windows on our laptops in various prescribed ways) at a distance from our employers.

“When we ‘work’ like this, we are, of course, relying on the labor of a vast mass of people who are unable to obey the moral (or moralizing) commandments that the maximalists like to pretend are universal. The maximalists denounce red-state families going to Chili’s for a special night out, taking off their masks with carefree delight when the Awesome Blossom arrives, but do not stop to think for a second before ordering Indian food on UberEats. Of if they do acknowledge the delivery drivers and bikers, it is in a register that could easily be mistaken for regret that these people exist at all,. The state, the tech companies, and the volunteer forces these entities have in the maximalists would like to see everyone at home, streaming content all the time. This includes the delivery people, whose enduring presence on the streets often seems more a logistical problem than a human one, likely to be solved soon enough by drones.

“Substantive criticism of the COVID maximalists has come from a new current of right-wing Foucauldian thinkers, who correctly highlight the ways in which the power of the professional classes is being maintained through the aggressive monitoring of other people’s bodies and breath, even as it relies on the labor of people who lack the freedom to decide where their own bodies go or what air they breathe. These theorists have done much to bring Foucault’s notion of ‘biopolitics’ into widespread use since the beginning of the pandemic, and their analyses have been illuminating. But they have not fully appreciated the role of new automatisms, which, to some extent, suggest the most useful focus of analysis in the present moment….

“Increasingly, fundamental decisions about transport logistics, health care, and even electoral politics are made algorithmically, while the human beings found at various nodes within the digital networks are transitioning into a new existence that reduces them, at best, to a natural resource the system is charged with managing, and, at worst, to its biofuel, extracted in raw form as attention and converted into clicks or simply ‘eyeballs.’ It is significant, then, that at the same moment that the virus arrived and made the universality of biopolitics seem more plausible than when Foucault first insisted on it, politics was finally becoming significantly less biopolitical than it ever had been, as a considerable portion of the responsibility for maintaining society had been outsourced to machines.

“These machines remain as stupid as machines always have been; the much-vaunted ‘singularity,’ where the machines rise up and take over the planet as a result of incipient self-awareness, is nowhere in the sights of any serious thinker or prognosticator. Yet if we consider this singularity simply as a transition to a largely algorithmic model of social management, then we have already begun the shift. It has been with the double blow of the internet evolving and mutating over the course of the 2010s, together with the pandemic that arrived at the end of that decade, that the transition to a postbiopolitical order, an order in which human beings are no longer the ‘for which’ of politics, has appeared on the horizon–a future in which the emergency is over, but the technologies we developed to control it still control us.” Smith, Justin E.H. 2022. “Permanent Pandemic: Will COVID controls keep controlling us?” Harper’s Magazine. June. pp. 25-31. p. 30, 31.

“We have lived by the assumption that what was good for us would be good for the world. And this has been based on the even flimsier assumption that we could know with any certainty what was good even for us. We have fulfilled the danger of this by making our personal pride and greed the standard of our behavior toward the world – to the incalculable disadvantage of the world and every living thing in it. And now, perhaps very close to too late, our great error has become clear. It is not only our own creativity – our own capacity for life – that is stifled by our arrogant assumption; the creation itself is stifled.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “A Native Hill (from 1968).” pp. 3-37. Berkeley: Counterpoint. p. 24.

“Thousands of acres of hill land, here and in the rest of the country, were wasted by a system of agriculture that was fundamentally alien to it. For more than a century, here, the steepest hillsides were farmed, by my forefathers and their neighbors, as if they were flat, and as if this was not a country of heavy rains. We haven’t yet, in any meaningful sense, arrived in these places that we declare we own. We undertook the privilege of the virgin abundance of this land without any awareness at all that we undertook at the same time a responsibility toward it. That responsibility has never yet impressed itself upon our character, its absence in us is signified on the land by scars.

“Until we understand what the land is, we are at odds with everything we touch. And to come to that understanding it is necessary, even now, to leave the regions of our conquest – the cleared fields, the towns and cities, the highways – and reenter the woods. For only there can a man encounter the silence and the darkness of his own absence. Only in this silence and darkness can he recover the sense of the world’s longevity, of its ability to thrive without him, of his inferiority to it and his dependence on it.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “A Native Hill (from 1968).” pp. 3-37. Berkeley: Counterpoint. p. 32.

“It is arguable, I think, that our country’s culture is still suspended as if at the end of Huckleberry Finn, assuming that its only choices are either a deadly ‘civilization’ of piety and violence or an escape into some ‘Territory’ where we may remain free of adulthood and community obligation. We want to be free; we want to have rights; we want to have power; we do not yet want much to do with responsibility. We have imagined the great and estimable freedom of boyhood, of which Huck Finn remains the finest spokesman. We have imagined the bachelorhoods of nature and genius and power: the contemplative, the artist, the hunter, the cowboy, the general, the president – lives dedicated and solitary in the Territory of individuality. But boyhood and bachelorhood have remained our norms of ‘liberation,’ for women as well as men. We have hardly begun to imagine the coming to responsibility that is the meaning, and the liberation, of growing up. We have hardly begun to imagine community life, and the tragedy that is at the heart of community life.

“Mark Twain’s avowed preference for boyhood, as the time of truthfulness, is well known. Beyond boyhood, he glimpsed the possibility of bachelorhood, as escape to the ‘The Territory,’ where individual freedom and integrity might be maintained – and so, perhaps, he imagined Pudd’nhead Wilson, a solitary genius devoted to truth and justice, standing apart in the preserve of cynical honesty.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Writer and Region (from 1987).” pp. 81-97. Berkeley: Counterpoint. pp. 85-6.

“And so there is the Territory of self-righteousness. It is easy to assume that we do not participate in what we are not in the presence of. But if we are members of a society, we participate, willy-nilly, in its evils. Not to know this is obviously to be in error, but it is also to neglect some of the most necessary and the most interesting work. How do we reduce our dependency on what is wrong? The answer to that question will necessarily be practical; the wrong will be correctable by practice and by practical standards. Another name fo self-righteousness is economic and political unconsciousness.

“There is also the Territory of historical self-righteousness: if we had lived south of the Ohio in 1830, we would not have owned slaves; if we had lived on the frontier, we would have killed no Indians, violated no treaties, stolen no land. The probability is overwhelming that if we had belonged to the generations we deplore, we too would have behaved deplorably. The probability is overwhelming that we belong to a generation that will be found by its successors to have behaved deplorably. Not to know that is, again, to be in error and to neglect essential work, and some of this work, as before, is work of the imagination. How can we imagine our situation or our history if we think we are superior to it?

“Then there is the Territory of despair, where it is assumed that what is objectionable is ‘inevitable,’ and so again the essential work is neglected. How can we have something better if we do not imagine it? How can we imagine it if we do not hope for it? How can we hope for it if we do not attempt to realize it?” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Writer and Region (from 1987).” pp. 81-97. Berkeley: Counterpoint. pp. 90-1.

“The test of imagination, ultimately, is not the territory of art or the territory of the mind, but the territory underfoot. That is not to say that there is no territory of art or of the mind, only that it is not a separate territory. It is not exempt either from the principles above it or from the country below it. It is a territory, then, that is subject to correction – by, among other things, paying attention. To remove it from the possibility of correction is finally to destroy art and thought, and the territory underfoot as well.

“Memory, for instance, must be a pattern upon the actual country, not a cluster of relics in a museum or a written history. What Barry Lopez speaks of as a sort of invisible landscape of communal association and usage must serve the visible as a guide and as a protector; the visible landscape must verify and correct the invisible. Alone, the invisible landscape becomes false, sentimental, and useless, just as the visible landscape, alone, becomes a strange land, threatening to humans and vulnerable to human abuse.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Writer and Region (from 1987).” pp. 81-97. Berkeley: Counterpoint. p. 93.

“Neighborhood is a given condition [for Emerson], not a contrived one; he is not talking about a ‘planned community’ or a ‘network’, but about the necessary interdependence of those who are ‘next’ each other. We see how it invokes dance, acting in concert, as a metaphor of almost limitless reference. We see how the phrase ‘to suffer and to work’ refuses sentimentalization. We see how common work, common suffering, and a common willingness to join and belong are understood as the conditions that make speech possible in the ‘the dumb abyss’ in which we are divided.

“This leads us, probably, to as good a definition of the beloved community as we can hope for: common experience and common effort on a common ground to which one willingly belongs. The life of such a community has been very little regarded in American literature. Our writers have been much more concerned with the individual who is misunderstood or mistreated by a community that is in no sense beloved, as in The Scarlet Letter. From Thoreau to Hemingway and his successors, a great deal of sympathy and interest has been given to the individual as pariah or gadfly or exile.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Writer and Region (from 1987).” pp. 81-97. Berkeley: Counterpoint. pp. 94-5.

“Our society, on the whole, has forgotten or repudiated the theme of return [e.g., the prodigal son]. Young people still grow up in rural families and go off to the cities, not to return. But now it is felt that this is what they should do. Now the norm is to leave and not return. And this applies as much to urban families as to rural ones. In the present urban economy the parent-child succession is possible only among the economically privileged. The children of industrial underlings are not likely to succeed their parents at work, and there is no reason for them to wish to do so. We are not going to have an industrial ‘Michael’ [poem from Wordsworth] in which it is perceived as tragic that a son fails to succeed his father on an assembly line.

“According to the new norm, the child’s destiny is not to succeed the parents, but to outmode them; succession has given way to supersession. And this norm is institutionalized not in great communal stories, but in the education system. The schools are no longer oriented to a cultural inheritance, that it is their duty to pass on unimpaired, but to the career, which is to say the future, of the child. The orientation is thus necessarily theoretical, speculative, and mercenary. The child is not educated to return home and be of use to the place and community; he or she is educated to leave home and earn money in a provisional future that has nothing to do with place or community. And parents with children in school are likely to find themselves immediately separated from their children, and made useless to them, by the intervention of new educational techniques, technologies, methods, and languages. School systems innovate as compulsively and as eagerly as factories. It is no wonder that, under these circumstances, ‘educators’ tend to look upon the parents as a bad influence and wish to take the children away form home as early as possible. And many parents, in truth, are now finding their children an encumbrance at home, where there is no useful work for them to do, and are glad enough to turn them over to the state for the use of the future.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Work of Local Culture (from 1988).” pp. 102-117. Berkeley: Counterpoint. pp. 110-111.

“If there is no household or community economy, then family members and neighbors are no longer useful to one another. When people are no longer useful to one another, then the centripetal force of family and community fails, and people fall into dependence on exterior economies and organizations. The hegemony of professionals and professionalism erects itself on local failure, and from then on the locality exists merely as a market for consumer goods and as a source of ‘raw material,’ human and natural. The local schools no longer serve the local community; they serve the government’s economy and the economy’s government. Unlike the local community, the government and the economy cannot be served with affection, but only with professional zeal or professional boredom.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Work of Local Culture (from 1988).” pp. 102-117. Berkeley: Counterpoint. p. 112.

“The new norm, according to which the child leaves home as a student and never lives at home again, interrupts the old course of coming of age at the point of rebellion, so that the child is apt to remain stalled in adolescence, never achieving any kind of reconciliation or friendship with the parents. Of course, such a return and reconciliation cannot be achieved without the recognition of mutual practical need. In the present economy, however, where individual dependences are so much exterior to both household and community, family members often have no practical need or use for one another. Hence the frequent futility of attempts at a purely psychological or emotional reconciliation.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Work of Local Culture (from 1988).” pp. 102-117. Berkeley: Counterpoint. p. 113.

“In rural America, which is in many ways a colony of what the government and the corporations think of as the nation, most of us have experienced the losses that I have been talking about: the departure of young people, of soil and other so-called natural resources, and of local memory. We feel ourselves crowded more and more into a dimensionless present, in which the past is forgotten and the future, even in our most optimistic ‘projections,’ is forbidding and fearful.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Work of Local Culture (from 1988).” pp. 102-117. Berkeley: Counterpoint. p. 115.

“There is no denying that competitiveness is a part of the life both of an individual and of a community, or that, within limits, it is a useful and necessary part. But it is equally obvious that no individual can lead a good or a satisfying life under the rule of competition, and that no community can succeed except by limiting somehow the competitiveness of its members.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Economy and Pleasure (from 1988).” pp. 268-281. Berkeley: Counterpoint. p. 272.

“It is impossible not to notice how little the proponents of the ideal of competition have to say about honesty, which is the fundamental economic virtue, and how very little they have to say about community, compassion, and mutual help.

“But what the ideal of competition most flagrantly and disastrously excludes is affection. The affections, John Ruskin said, are ‘an anomalous force, rendering every one of the ordinary political economist’s calculations nugatory; while, even if he desired to introduce this new element into his estimates, he has no power of dealing with it; for the affections only become a true motive power when they ignore every other motive power and condition of political economy.’ Thus, if we are sane, we do not dismiss or abandon our infant children or our aged parents because they are too young or too old to work. For human beings, affection is the ultimate motive, because the force that powers us, as Ruskin also said, is not ‘steam, magnetism, or gravitation,’ but ‘a Soul’….

“It may be argued that our whole society is more devoted to pleasure than any whole society ever was in the past, that we support in fact a great variety of pleasure industries and that these are thriving as never before. But that would seem only to prove my point. That there can be pleasure industries at all, exploiting our apparently limitless inability to be pleased, can only mean that our economy is divorced from pleasure and that pleasure is gone from our workplaces and our dwelling places. Our workplaces are more and more exclusively given over to production, and our dwelling places to consumption. And this accounts for the accelerating division of our country into defeated landscapes and victorious (but threatened) landscapes.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Economy and Pleasure (from 1988).” pp. 268-281. Berkeley: Counterpoint. pp. 274, 277.

“More and more, we take for granted that work must be destitute of pleasure. More and more, we assume that if we want to be pleased we must wait until evening, or the weekend, or vacation, or retirement. More and more, our farms and forests resemble our factories and offices, which in turn more and more resemble prisons – why else should we be so eager to escape them? We recognize defeated landscapes by the absence of pleasure from them. We are defeated at work because our work gives us no pleasure. We are defeated at home because we have no pleasant work there. We turn to the pleasure industries for relief from our defeat, and are again defeated, for the pleasure industries can thrive and grow only upon our dissatisfaction with them.

“Where is our comfort but in the free, uninvolved, finally mysterious beauty and grace of this world that we did not make, that has no price? Where is our sanity but there? Where is our pleasure but in working and resting kindly in the presence of this world?” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Economy and Pleasure (from 1988).” pp. 268-281. Berkeley: Counterpoint. pp. 277-8.

“… the comparative few who still practice that necessary husbandry and wifery often are inclined to apologize for doing so, having been carefully taught in our education system that those arts are degrading and unworthy of people’s talents. Educated minds, in the modern era, are unlikely to know anything about food and drink or clothing and shelter. In merely taking these things for granted, the modern educated mind reveals itself also to be as superstitious a mind as ever has existed in the world. What could be more superstitious than the idea that money brings forth food?

“I am not suggesting, of course, that everybody ought to be a farmer or a forester. Heaven forbid! I am suggesting that most people now are living on the far side of a broken connection, and that this is potentially catastrophic. Most people are now fed, clothed, and sheltered from sources, in nature and in the work of other people, toward which they feel no gratitude and exercise no responsibility….

“The problem is that it is possible to starve under the rule of the conventional economic assumption; some people are starving now under the rule of that assumption.

“Money does not bring forth food. Neither does the technology of the food system. Food comes from nature and from the work of people. If the supply of food is to be continuous for a long time, then people must work in harmony with nature. That means that people must find the right answers to a lot of questions….

The economy, always obsessed with its need to sell products, thinks obsessively and exclusively of the consumer. It mostly takes for granted or ignores those who do the damaging or the restorative and preserving work of agriculture and forestry. The economy pays poorly for this work, with the unsurprising result that the work is mostly done poorly.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “In Distrust of Movements (from 1998).” pp. 282-291. Berkeley: Counterpoint. pp. 287, 288.

“… good economic behavior is more possible for us than it is for the great corporations with their miseducated managers and their greedy and oblivious stockholders. Because it is possible for us, we must try in every way we can to make good economic sense in our own lives, in our households, and in our communities. We must do more for ourselves and our neighbors. We must learn to spend our money with our friends and not with our enemies. But to do this, it is necessary to renew local economies, and revive the domestic arts. In seeking to change our economic use of the world, we are seeking inescapably to change our lives. The outward harmony that we desire between our economy and the world depends finally upon an inward harmony between our own hearts and the creative spirit that is the life of all creatures, a spirit as near us as our flesh and yet forever beyond the measures of this obsessively measuring age. We can grow good wheat and make good bread only if we understand that we do not live by bread alone.

“My third condition is that this movement [for reform] should content itself to be poor. We need to find cheap solutions, solutions within the reach of everybody, and the availability of a lot of money prevents the discovery of cheap solutions. The solutions of modern medicine and modern agriculture are all staggeringly expensive, and this is caused in part, and maybe altogether, by the availability of huge sums of money for medical and agricultural research.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “In Distrust of Movements (from 1998).” pp. 282-291. Berkeley: Counterpoint. p. 290.

“The idea of an economy based upon several kinds of ruin may seem a contradiction in terms, but in fact such an economy is possible, as we see. It is possible, however, on one implacable condition: the only future good that it assuredly leads to is that it will destroy itself. And how does it disguise this outcome from its subjects, its short-term beneficiaries, and its victims? It does so by false accounting. It substitutes for the real economy, by which we build and maintain (or do not maintain) our household, a symbolic economy of money, which in the long run, because of the self-interested manipulations of the ‘controlling interests,’ cannot symbolize or account for anything but itself. And so we have before us the spectacle of unprecedented ‘prosperity’ and ‘economic growth’ in a land of degraded farms, forests, ecosystems, and watersheds, polluted air, failing families, and perishing communities.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Total Economy (from 2000).” pp. 66-80. Berkeley: Counterpoint. pp. 69-70.

“But the ‘free market’ idea introduces into government a sanction of an inequality that is not implicit in any idea of democratic liberty: namely that the ‘free market’ is freest to those who have the most money, and is not free at all to those with little or no money. Wal-Mart, for example, as a large corporation ‘freely’ competing against local, privately owned businesses, has virtually all the freedom, and its small competitors virtually none.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Total Economy (from 2000).” pp. 66-80. Berkeley: Counterpoint. p. 70.

“The folly at the root of this foolish economy began with the idea that a corporation should be regarded, legally, as ‘a person.’ But the limitless destructiveness of this economy comes about precisely because a corporation is not a person. A corporation, essentially, is a pile of money to which a number of persons have sold their moral allegiance. Unlike a person, a corporation does not age. It does not arrive, as most persons finally do, at a realization of the shortness and smallness of human lives; it does not come to see the future as the lifetime of the children and grandchildren of anybody in particular. It can experience no personal hope or remorse, no change of heart. It cannot humble itself. It goes about its business as if it were immortal with the single purpose of becoming a bigger pile of money. The stockholders essentially are usurers, people who ‘let their money work for them,’ expecting high pay in return for causing others to work for low pay. The World Trade Organization enlarges the old idea of the corporation-as-person by giving the global corporate economy the status of a super-government with the power to overrule nations.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Total Economy (from 2000).” pp. 66-80. Berkeley: Counterpoint. pp. 73-4.

“In an essay on the origin of civilization in traditional cultures, Ananda Coomaraswamy wrote that ‘the principle of justice is the same throughout … [It is] that each member of the community should perform the task for which he is fitted by nature.’ The two ideas, justice and vocation, are inseparable. That is why Coomaraswamy spoke of industrialism as ‘the mammon of injustice,’ incompatible with civilization. It is by way of the practice of vocation that sanctity and reverence enter into the human economy. It was thus possible for traditional cultures to conceive that ‘to work is to ‘pray.’” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Total Economy (from 2000).” pp. 66-80. Berkeley: Counterpoint. p. 76.

“In a viable neighborhood, neighbors ask themselves what they can do or provide for one another, and they find answers that they and their place can afford. This, and nothing else, is the practice of neighborhood. This practice must be, in part, charitable, but it must also be economic, and the economic part must be equitable; there is a significant charity in just prices.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Total Economy (from 2000).” pp. 66-80. Berkeley: Counterpoint. p. 79.

“Industrialism begins with technological invention. But agrarianism begins with givens: land, plants, animals, weather, hunger, and the birthright knowledge of agriculture. Industrialists are always ready to ignore, sell, or destroy the past in order to gain the entirely unprecedented wealth, comfort, and happiness supposedly to be found in the future. Agrarian farmers know that their very identity depends on their willingness to receive gratefully, use responsibly, and hand down intact an inheritance, both natural and cultural, from the past. Agrarians understand themselves as the users and caretakers of some things they did not make, and of some things that they cannot make.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Agrarian Standard (from 2002).” pp. 132-142. Berkeley: Counterpoint. p. 135.

“If we believed that the existence of the world is rooted in mystery and in sanctity, then we would have a different economy. It would still be an economy of use, necessarily, but it would be an economy also of return. The economy would have to accommodate the need to be worthy of the gifts we receive and use, and this would involve a return of propitiation, praise, gratitude, responsibility, good use, good care, and a proper regard for future generations. What is most conspicuously absent from the industrial economy and industrial culture is this idea of return. Industrial humans relate themselves to the world and its creatures by fairly direct acts of violence. Mostly we take without asking, use without respect or gratitude, and give nothing in return. Our economy’s most voluminous product is waste – valuable materials irrecoverably misplaced, or randomly discharged as poisons.

“To perceive the world and our life in it as gifts originating in sanctity is to see our human economy as a continuing moral crisis. Our life of need and work forces us inescapably to use in time things belonging to eternity, and to assign finite values to things already recognized as infinitely valuable. This is a fearful predicament. It calls for prudence, humility, good work, propriety of scale. It calls for the complex responsibilities of caretaking and giving-back that we mean by ‘stewardship.’ To all of this the idea of the immeasurable value of the resource is central.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Agrarian Standard (from 2002).” pp. 132-142. Berkeley: Counterpoint. p. 136.

“Under feudalism, the few who owned the land owned also, by an inescapable political logic, the people who worked the land.

“Thomas Jefferson, who knew all these things, obviously was thinking of them when he wrote in 1785 that ‘it is not too soon to provide by every possible means that as few as possible shall be without a little portion of land. The small landholders are the most precious part of a state ….’ He was saying, two years before the adoption of our Constitution, that a democratic state and democratic liberties depend upon democratic ownership of the land. He was already anticipating and fearing the division of our people into settlers, the people who wanted ‘a little portion of land’ as a home, and, virtually opposite to those, the consolidators and exploiters of the land and the land’s wealth, who would not be restrained by what Jefferson called ‘the natural affection of the human mind.’ He wrote as he did in 1785 because he feared exactly the political theory that we now have: the idea that government exists to guarantee the right of the most wealthy to own or control the land without limit.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Agrarian Standard (from 2002).” pp. 132-142. Berkeley: Counterpoint. pp. 138-9.

“In any consideration of agrarianism, this issue of limitation is critical. Agrarian farmers see, accept, and live within their limits. They understand and agree to the proposition that there is ‘this much and no more.’ Everything that happens on an agrarian farm is determined or conditioned by the understanding that there is only so much land, so much water in the cistern, so much hay in the barn, so much corn in the crib, so much firewood in the shed, so much food in the cellar or freezer, so much strength in the back and arms – and no more. This is the understanding that induces thrift, family coherence, neighborliness, local economies. Within accepted limits, these virtues become necessities. The agrarian sense of abundance comes from the experienced possibility of frugality and renewal within limits.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Agrarian Standard (from 2002).” pp. 132-142. Berkeley: Counterpoint. p. 139.

“I don’t think that being landed necessarily means owning land. It does mean being connected to a home landscape from which one may live by the interactions of a local economy and without the routine intervention of governments, corporations, or charities.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Agrarian Standard (from 2002).” pp. 132-142. Berkeley: Counterpoint. p. 140.

“Since the beginning of the conservation effort in our country, conservationists have too often believed that we could protect the land without protecting the people. This has begun to change, but for a while yet we will have to reckon with the old assumption that we can preserve the natural world by protecting wilderness areas while we neglect or destroy the economic landscapes – the farms and ranches and working forests – and the people who use them. That assumption is understandable in view of the worsening threats to wilderness areas, but it is wrong. If conservationists hope to save even the wild lands and wild creatures, they are going to have to address issues of economy, which is to say issues of the health of the landscapes and the towns and cities where we do our work, and the quality of that work, and the well-being of the people who do the work.

“Governments seem to be making the opposite error, believing that the people can be adequately protected without protecting the land.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Compromise, Hell! (from 2004).” pp. 311-317. Berkeley: Counterpoint. pp. 311-2.

“Good buildings that used to house needful, useful, locally owned small businesses of all kinds are now empty or have evolved into junk stores or antique shops. But look at the houses, the churches, the commercial buildings, the courthouse, and you will see that more often than not they are comely and well made. And then go look at the corporate outskirts: the chain stores, the fast-food joints, the food-and-fuel stores that no longer can be called service stations, the motels. Try to find something comely or well made there.

“What is the difference? The difference is that the old town centers were built by people who were proud of their place and who realized a particular value in living there. The old buildings look good because they were built by people who respected themselves and wanted the respect of their neighbors. The corporate outskirts, on the contrary, were built by people who manifestly take no pride in the place, see no value in lives lived there, and recognize no neighbors.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “Compromise, Hell! (from 2004).” pp. 311-317. Berkeley: Counterpoint. p. 313.

“It is when knowledge is corporatized, commercialized, and applied that it goes out of control. Can science, then, make itself responsible by issuing appropriate warnings with its knowledge? No, because the users are under no obligation to heed or respect the warning. If the knowledge is conformable to the needs of profit or power, the warning will be ignored, as we know. We are not excused by the doctrine of scientific self-correction from worrying about the influence of science on the corporate mind, and about the influence of the corporate mind on the minds of consumers and users. Humans in general have got to worry about the origins of the permission we have given ourselves to do large-scale damage. That permission is our problem, for by it we have made our ignorance arrogant and given it immeasurable power to do harm. We are killing our world on the theory that it was never alive but is only an accidental concatenation of materials and mechanical processes. We are killing one another and ourselves on the same theory. If life has no standing as mystery or miracle or gift, then what signifies the difference between it and death?” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Way of Ignorance (from 2004).” pp. 318-332. Berkeley: Counterpoint. pp. 326-7.

“Scientists and artists must understand that they can honor their gifts and fulfill their obligations only by living and working as human beings and community members rather than as specialists. What this may involve may not be predictable even by scientists. But the best advice may have been given by Hippocrates: ‘As to diseases make a habit of two things – to help, or at least, to do no harm.’

“The wish to help, especially if it is profitable to do so, may be in human nature, and everybody wants to be a hero. To help, or to try to help, requires only knowledge; one needs to know promising remedies and how to apply them. But to do no harm involves a whole culture, and a culture very different from industrialism. It involves, at the minimum, compassion and humility and caution. The person who will undertake to help without doing harm is going to be a person of some complexity, not easily pleased, probably not a hero, probably not a billionaire.

“The corporate approach to agriculture or manufacturing or medicine or war increasingly undertakes to help at the risk of harm, sometimes of great harm. And once the risk of harm is appraised as ‘acceptable,’ the result often is absurdity: we destroy a village in order to save it; we destroy freedom in order to save it; we destroy the world in order to live in it.

“The apostles of the corporate mind say, with a large implicit compliment to themselves, that you cannot succeed without risking failure. And they allude to such examples as that of the Wright brothers. They don’t see that the issue of risk raises directly the issue of scale. Risk, like everything else, has an appropriate scale. By propriety of scale we limit the possible damages of the risks we take.” Berry, Wendell. 2017. The World-ending Fire: The Essential Wendell Berry. “The Way of Ignorance (from 2004).” pp. 318-332. Berkeley: Counterpoint. pp. 330-1.

“The L in the name [of LUCA] is important; it was not the first organism, but the last before the bifurcation that led to all modern organisms.

“We do not doubt that living organisms existed long before LUCA. However, it is sometimes suggested to be an organism close to the origin of life….” Cornish-Bowden, Athel & Maria Luz Cardenas. 2017. “Life before LUCA.” Journal of Theoretical Biology. 434(SI):68-74. doi: 10.1016/j.jtbi.2017.05.023. p. 69.

“Understanding how the transition to an organism with a large coding capacity can have happened is a more challenging problem than understanding how LUCA could have evolved to Homo sapiens. For the post-LUCA evolution we have at least a rough idea of how it happened and what mechanisms were involved, but pre-LUCA evolution is a black box, probably more difficult to understand than to understand how self-sustaining systems came to exist in the first place. If the theoretical ideas of Kauffman or Friston are valid then self-sustaining systems may be inevitable, but getting from these to LUCA still presents enormous difficulties, and some crucial points, such as the origin of the genetic code, remain speculative. Our view is that studying the pre-LUCA period and finding a plausible series of steps to LUCA is an urgent task, but it will not be solved as long as LUCA continues to be discussed as if it were an entity close to the origin of life.” Cornish-Bowden, Athel & Maria Luz Cardenas. 2017. “Life before LUCA.” Journal of Theoretical Biology. 434(SI):68-74. doi: 10.1016/j.jtbi.2017.05.023. p. 73.

“In particular, we believe that primitive compartments formed before the emergence of the last universal common ancestor (LUCA) could have provided a mechanism by which primitive chemical systems underwent speciation, and that primitive speciation events due to function of primitive compartments resulted in the origin of species (prebiotic species) preceding the origin of life.” Jia, Tony Z., Melina Caudan & Irena Mamajanov. 2021. “Origin of Species before Origin of Life: The Role of Speciation in Chemical Evolution.” Life. 11(154): 1-22. doi: 10.3390/life11020154. p. 3.

“The concept of species and mechanisms of speciation are highly contested in biology; in prebiotic chemistry, defining species and outlining the processes of speciation is similarly challenging. Herein, we offer a working definition of prebiotic species: delimited chemical systems of similar makeup and properties. The examples of prebiotic speciation include speciation prompted by geographic separation, compositional diversity of macromolecular assemblies, and most commonly, compartmentalization.” Jia, Tony Z., Melina Caudan & Irena Mamajanov. 2021. “Origin of Species before Origin of Life: The Role of Speciation in Chemical Evolution.” Life. 11(154): 1-22. doi: 10.3390/life11020154. p. 15.

“While we cannot say which set of chemical reactions or conditions ultimately led to emergence of the first living organisms, we can point out benefits to early speciation in protolife systems. The presence of multiple prebiotic species would allow the utilization of various resources, potentially lead to increased stability of each species, through compatible interactions, and offer a greater chance of survival in the aftermath of catastrophic events. Prebiotic speciation is, therefore, a topic that warrants further investigation.” Jia, Tony Z., Melina Caudan & Irena Mamajanov. 2021. “Origin of Species before Origin of Life: The Role of Speciation in Chemical Evolution.” Life. 11(154): 1-22. doi: 10.3390/life11020154. p. 16.

“‘But what grew before was your kind [Western societies] of family. The twenty [couples that a mutual adoption club for their kids] are all our [novel’s imaginary culture of people on island] kind.’ As though reading instructions from a cookery book. ‘Take one sexually inept wage slave,’ she [island person, Susila] went on, ‘one dissatisfied female, two or (if preferred) three small television addicts; marinate in a mixture of Freudism and dilute Christianity; then bottle up tightly in a four-room flat and stew for fifteen years in their own juice. Our recipe is rather different: Take twenty sexually satisfied couples and their offspring; add science, intuition and humor in equal quantities; steep in Tantrik Buddhism and simmer indefinitely in an open pan in the open air over a brisk flame of affection.’” Huxley, Aldous. 1962. Island. Harper Perennial. p. 107.

“‘Danger,’ he [Vijaya, from the island] said, and again, ‘danger. Danger deliberately and yet lightly accepted. Danger shared with a friend, a group of friends. Shared consciously, shared to the limits of awareness so that the sharing and the danger become a yoga. Two friends roped together on a rock face. Sometimes three friends or four. Each totally aware of his own straining muscles, his own skill, his own fear, and his own spirit transcending the fear. And each, of course, aware at the same time of all the others, concerned for them, doing the right things to make sure that they’ll be safe. Life at its highest pitch of bodily and mental tension, life more abundant, more inestimably precious because of the ever-present threat of death. But after the yoga of danger there’s the yoga of the summit, the yoga of rest and letting go, the yoga of complete and total receptiveness, the yoga that consists in consciously accepting what is given as it is given, without censorship by your busy moralistic mind, without any additions from your stock of secondhand ideals, your even larger stock of wishful phantasies….

“Then at the foot of the precipice you unrope, you go striding down the rocky path toward the first trees. And suddenly you’re in the forest, and another kind of yoga is called for–the yoga of the jungle, the yoga that consists of being totally aware of life at the near-point, jungle life in all its exuberance and its rotting, crawling squalor, all its melodramatic ambivalence of orchids and centipedes, of leeches and sunbirds, of the drinkers of nectar and the drinkers of blood. Life bringing order out of chaos and ugliness, life performing its miracles of birth and growth, but performing them, it seems for no other purpose than to destroy itself. Beauty and horror, beauty,’ he repeated, ‘and horror….’” Huxley, Aldous. 1962. Island. Harper Perennial. pp. 202-3.

“Dualism … Without it there can hardly be good literature. With it, there most certainly can be no good life.

“‘I’ affirms a separate and abiding me-substance; ‘am’ denies the fact that all existence is relationship and change. ‘I am.’ Two tiny words, but what an enormity of untruth! The religiously-minded dualist calls homemade spirits from the vasty deep; the nondualist calls the vasty deep into his spirit or, to be more accurate, he finds that the vasty deep is already there.” Huxley, Aldous. 1962. Island. Harper Perennial. pp. 215-6.

“[Character from the utopian island people speaking in novel:] Darwin took the old totemism and raised it to the level of biology. The fertility cults reappeared as genetics and Havelock Ellis. And now it’s up to us to take another half turn up the spiral. Darwinism was the old neolithic Wisdom turned into scientific concepts. The new conscious Wisdom–the kind of Wisdom that was prophetically glimpsed in Zen and Taoism and Tantra–is biological theory realized in living practice, is Darwinism raised to the level of compassion and spiritual insight.” Huxley, Aldous. 1962. Island. Harper Perennial. p. 239.

“[Character from the utopian island people speaking in novel:] Any irritated person who takes five deep breaths releases a lot of tension and so makes it easier for himself to behave rationally. So we teach our children all kinds of breathing games, to be played whenever they’re angry or upset. Some of the gams are competitive. Which of two antagonists can inhale most deeply and say ‘OM’ on the outgoing breath for the longest time? It’s a duel that ends, almost without fail, in reconciliation.” Huxley, Aldous. 1962. Island. Harper Perennial. p. 255.

“[Character from the utopian island people speaking in novel:] But they [politicians in the third world] want to throw their weight around; they want to have armies, they want to catch up with the motorized television addicts of America and Europe. You people have no choice…. You’ve irretrievably committed to applied physics and chemistry, with all their dismal consequences, military, political and social. But the underdeveloped countries aren’t committed. They don’t have to follow your example. They’re still free to take the road we’ve taken–the road of applied biology, the road of fertility control and the limited production and selective industrialization which fertility control makes possible, the road that leads towards happiness from the inside out, through health, through awareness, through a change in one’s attitude towards the world….” Huxley, Aldous. 1962. Island. Harper Perennial. p. 259.

“The feeling that peace is better than conflict is so deeply ingrained [among the people of Ladakh] that people turn automatically to a third party.

“This mechanism prevents problems from arising in the first place. The spontaneous intermediary, it seems, is always around in any context that might possibly lead to conflict. if two people are involved in trade, for example, they can be sure that someone will be there to help them strike a deal. This way they avoid the possibility of direct confrontation. In most situations, the parties already know one another. But if someone unknown to the others intervenes, it is not seen as meddling–the help will be welcomed.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 47.

“Polyandry [more than one woman to one man] has been a key factor in maintaining a relatively stable population in Ladakh over the centuries. This stability has in turn, I believe, contributed to the environmental balance and social harmony. That population control is an important factor in maintaining a balance with the environment is clear. The link with social harmony is perhaps less so. Nevertheless, it seems that social friction is likely to be reduced if the number of people depending on a fixed quantity of resources remains the same from generation to generation. Under those circumstances, the need for scrambling and fighting to survive is clearly minimized.

“The ratio of men to women in Ladakh is roughly equal, so if a number of men take one wife, it means that some women do not marry. Fewer married women means fewer children. Women who do not marry become nuns. And, in fact, a large number of men, usually one or more of the younger brothers, also remain unmarried, living as monks. Thus polyandry has worked hand in hand with the monasticism of Tibetan Buddhism….

“Interestingly enough, though polyandry is the preferred form of marriage, it is not the only one. There is some polygamy and monogamy as well. This unusual situation probably reflects a careful adaptation to scarce resources. By keeping social relationships so flexible, the relationship to the land can remain optimal.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. pp. 56-7.

“Whatever the system of marriage, landholdings are kept intact. The guiding principle behind the system of land inheritance is that it remains undivided instead of being split into smaller and smaller pieces. Whatever happens, whatever the configuration of children may be, the land is passed on to just one individual. This is the case even when there are no children at all: then, someone is adopted as heir.

“It is usually the eldest son who formally inherits the family’s holdings. Since land is neither sold nor bought, and private ownership of land does not exist as in the West, he does not become the owner of the land, but rather a sort of guardian. If there are no sons at home, or if other circumstances make it desirable, the eldest daughter inherits everything….” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 58.

“One of the central elements of Buddhism is the philosophy of sunyata, or ‘emptiness.’ I had difficulty understanding the meaning of this concept at first, but over the years, in talking to Tashi Rabgyas, it became clearer…. ‘When you think of a tree, you tend to think of it as a distinct, clearly defined object, and on a certain level it is. But on a more important level, the tree has no independent existence; rather, it dissolves into a web of relationships. The rain that falls on its leaves, the wind that causes it to sway, the soil that supports it–all form a part of the tree. Ultimately, if you think about it, everything in the universe helps make the tree what it is. It cannot be isolated; its nature changes from moment to moment–it is never the same. This is what we mean when we say that things are ‘empty,’ that they have no independent existence.’” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 73.

“… in fact they [the Ladakhis] seem to be totally lacking in what we would call pride. This doesn’t mean a lack of self-respect. On the contrary, their self-respect is so deep-rooted as to be unquestioned.

“I was with about fifteen Ladakhis and two students from Calcutta on the back of a truck taking us along the bumpy and dusty road from Zanskar. As the journey went on, the students became restless and uncomfortable and began pushing at a middle-aged Ladakhi who had made a seat for himself out of a sack of vegetables. Before long, the older man stood up so that the students–who were about twenty years younger than him–could sit down. When, after about two hours, we stopped for a rest, the students indicated to the Ladakhi that they wanted him to fetch water for them; he fetched the water. They then more or less ordered him to make a fire and boil tea for them.

“He was effectively being treated as a servant–almost certainly for the first time in his life. Yet there was nothing remotely servile in his behavior; he merely did what was asked of him as he might for a friend–without obsequiousness and with no loss of dignity. I was fuming, but he and the other Ladakhis, far from being angered or embarrassed by the way he was being treated, found it all amusing and nothing more. The old man was so relaxed about who he was that he had no need to prove himself.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. pp. 84-5.

“Before feeling my way into Ladakhi culture, I had thought that leaving home was part of growing up, a necessary step toward becoming an adult. I now believe that large extended families and small intimate communities form a better foundation for the creation of mature, balanced individuals. A healthy society is one that encourages close social ties and mutual interdependence, granting each individual a net of unconditional emotional support. Within this nurturing framework, individuals feel secure enough to become quite free and independent. Paradoxically, I have found the Ladakhis less emotionally dependent than we are in industrial society. There is love and friendship, but it is not intense or grasping–not a possession of one person by another. I once saw a mother greeting her eighteen-year-old son when he returned home after being away for a year. She seemed surprisingly calm, as though she had not missed him. It took me a long time to understand this behavior. I thought my Ladakhi friends reacted strangely when I arrived back after being away for the winter. I had brought presents I knew they would like. I expected them to be pleased to see me and happy at the gifts. But to them it was if I had not been gone. They thanked me for the presents, but not in the way that I was hoping. I was wanting them to look excited and confirm our special friendship. I was disappointed. Whether I had been away for six months or a day, they treated me in the same way.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. pp. 86-7.

“Once the society in which you operate has telephones, you are at a great disadvantage– economically as well as psychologically–if you do not have one. Delivering your messages in person is in practice not a real alternative. Likewise, once there are cars and buses, you no longer have the choice of walking or riding animals. You cannot wake up in the morning and say, ‘Now today shall I drive or walk to work?’ The pace of your life is determined for you.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 107.

“When one-third of the world’s population consumes two-thirds of the world’s resources, and then in effect turns around and tells the others to do as they do, it is little short of a hoax.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 149.

“The need to belong to a group is in itself an important reason for human-scale social units. Here we can learn directly from Ladakh, where families are large, but communities small. Children are nurtured by people of different generations, benefiting particularly from the special bond with their grandparents. Though the relationships in this larger family are close, they are not so intense as those of the nuclear family. Each individual is supported in a web of intimate relationships, and no one relationship has to bear too much weight. In Ladakh, I have never observed anything approaching the needy attachment or the guilt and rejection that are so characteristic of the nuclear family.

“While there are clearly exceptions, the extended family generally provides more space and flexibility and far less pressure on each individual, both emotionally and in terms of responsibility. It is particularly beneficial for the elderly and for women and children. Within the extended family, older people are appreciated for their wisdom and experience, and their slower pace does not prevent them from making an important contribution to the community.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. pp. 184-5.

“When you are dependent on the earth under your feet and the community around you for your survival, you experience interdependence as a fact of daily life. Such a deep experiential understanding of interconnectedness–feeling yourself a part of the continuum of life–contrasts starkly with the analytic, fragmented, and theoretical thinking of modern society.” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 189.

“As Tashi Rabgyas said after spending a few months in England, ‘It’s amazing how indirect everything is here. They write about the beauty of nature, they talk about it, and everywhere there are potted plants and plastic plants, and pictures of trees on the wall. And all the time television programs about nature. But they don’t ever seem to have contact with the real thing.’” Norberg-Hodge, Helena. 1991/ 2016. Ancient Futures, New Edition. Local Futures. p. 190.

“Its [modern science’s] wondrous mathematical synchronicities, the specifics of its chemical analyses, the complexity of its physics are beyond both the practical and intuitive knowledge of most lay naturalists (or mystics), no matter how seasoned.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. pp. 16-7.

“Rooted lives are radically intertwined with the vitality of the planet. In a time that evokes fear and paralysis, rooted ways of being-within-nature assure us that we are grounded in the natural world. Our bodies, our thoughts, our minds, our spirits are affected by the whole of the earthen community, and affect this whole in return. This is both a mystical sensibility and a scientific fact. It is an awareness that makes us tingle with its responsibility, its beauty, its poetry. It makes our lives our most foundational form of activism. It means everything we do matters, and matters wondrously.

“Amphibious, we wander at the singular, radical intersection of science, nature, and spirit. Here resides a multifaceted understanding of the interdependence of earthly life and the engaged activism that such an understanding inspires and requires. Here are the interwoven pathways of inward, wild stillness and outward, feral action. At this crossroads there is intelligence, and sacredness, and wildness, and grace.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 22.

“Ecology and Mysticism: Rooted mysticism is the apprehension of life’s radical interconnection. Mystical insight and ecological science are mutually reinforcing–both refer to an underlying unity that dissolves the notion of an absolutely separate individual.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 23.

“… Thich Nhat Hanh conceived the word interbeing in English to describe the interdependence of all life….” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. pp. 23-4.

“Where kin are relations of kind, kith is relationship based on knowledge of place…. Kith is intimacy with a place, its landmarks, its fragrance, the habits of its wildlings. Kithship enlivens kinship.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 26.

“Hope is that virtue by which we take responsibility for the future,’ and a quality that gives our actions ‘special urgency.’

“While ‘virtue’ might sound a bit prim and moralistic, I looked it up in the same old monastic lexicon and found virtue described as the power to realize good, to do so ‘joyfully and with perseverance in spite of obstacles.’” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 36.

“Julian’s [of Norwich’s] ‘wellness’ neither transcends human error nor absolves it, but awakens us to the truth that we are called to loving action within the complex awareness that all things are blessed in a wider fullness, whether events unfold according to our hoped for outcomes or not….

“She concludes that in the sacred whole we are equally supported ‘in well and woe… both are one love.’ Uncertainty feeds our intellect and our actions; without it, we would have only the simple banality of ‘knowledge,’ with no need for the unsettling motivation of hope at all.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. pp. 37, 38.

“Mind-unnecessary environments [the opposite of what nature requires of minds]” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 55.

“In newer studies, Kabat-Zinn and other clinical psychologists are turning the question around: what if, instead of working to focus on the present moment, it is just as mindful to follow the mind where it wants to go, to let it wander? Kabat-Zinn adopted Krishnamurti’s phrase choiceless awareness to describe this more meandering meditation.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. pp. 70-1.

“Wandering may be directionless but it need not be dopey. There is no reason to move about like meditative clouds. We can leap, dance, run like a coyote, wave our arms like an unruly child, like an octopus, like a tree. We can hum, sing, scream, or dwell in shadowy silence. We can pad forward, double back. We can be home for dinner. We can forget we have a home. Our paths go their own way–a new way, a strong way.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 72.

“Directionlessness leads to clear vision and creative flourishing. Decoupled from overt value in the usual measures, wandering is an unorthodox act, removing us from the anthropic realm of striving, judgment, and economic utility. It allows us to uncover our authentic direction–a squiggling, awkward thing at first, a back and forth curving that begins tentatively and grows more assured, more knowing, more graced.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 73.

“In the poetic rightness of etymology, the word alone comes from the Middle English–not separateness, but all + one. Both at the same time.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 105.

“Darkness twins with light as the primordial ground of existence. So many myths (Gilgamesh, Orpheus, Persephone, Aeneas, Dante) deploy the Greek journey of katabasis–descent into a dark underworld that will edify a heroic seeker’s eventual life after they return to the aboveground world. Yet for the majority of organisms on earth there is no ‘return’ to light; fullness of being is found in darkness itself. Ninety percent of life unfolds in complete and eternal darkness….” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 120.

“Why not allow astonishment to visit as it will, then walk into the world changed but perhaps silent….

“This is beholding. For spiritual traditions all over the world, such a stance–that of contemplative witness–is in itself prayer, art, and activism.” Haupt, Lyanda Lynn. 2021. Rooted: Life at the Crossroads of Science, Nature, and Spirit. NY: Little, Brown Spark. p. 163.

“Yet physical laws restrictively drive life toward particular solutions at all levels of its assembly. The outcomes are not always predictable, but they are limited. It does not matter at what level those requirements are operating, from the subatomic to the population scale; the results are various, but not boundless.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 4.

“Evolution is the process by which the environment acts as a filter to select units of organic mass in which a mosaic of interacting physical laws are optimized sufficiently to allow for reproductive success.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 5.

“The evolutionary process is restricted by intersecting principles that forge and hammer its products into predictable and narrow forms.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 54.

“The ladybug is a remarkably complex thing, and packed into this machine, whose mass is a million billion billion billionth of the Sun’s, are many more physical principles than those that define the structure and evolution of a star….

“We can imagine a giant sheet of paper with many hundreds of equations written down, curved arrows running hither and thither showing how the terms or solutions of one equation influence another. Feedback processes abound as this enormous network of equations shifts and changes, each minuscule alteration in one equation, like ‘the wave’ in a stadium, rippling through the rest. This is life.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 56.

“Evolutionary convergence is often just another way of saying, albeit more efficiently, similarity caused by the laws of physics.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 58.

“The mole is an engineering solution to the compromises needed to effectively shift soil by maximizing the force applied over a small area. It is an organic manifestation of P = F/A.

“As an evolutionary consequence of this law, moles look the same regardless of their provenance. The Talpidae, the true moles, which live in Europe, North America, and Asia, appear similar to Australian moles, or the marsupial moles, which are more closely related to kangaroos and koalas.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 61.

“Nothing is magical or strange about convergent evolution any more than there is something uncanny about the fact that when both liquid lithium and liquid water are heated, both substances turn into a gas. This latter observation is not bizarre cosmic coincidence; rather, it is just physical processes, the consequence of adding energy to the molecules or atoms of a liquid to overcome their forces of attraction and cause them to dissipate into gas. This is the same with convergent evolution; very often it results when similar physical principles operating on different organic forms drive those forms toward resemblance.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 62.

“Physical rules continue to shape the form of living things, endless in detail, restricted in form.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 82.

“If you want to increase your surface area, it is better to become a longer cylinder than a bloated sphere….

“When we study microbes in the laboratory or in the wild, we often find that when microbes are starved, they become filamentous…. Physics makes long microbes.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 94.

“In these places [goopy, viscous environments], being a spiral shape seems to make moving around easier, as the microbes propel their way through their gluey world.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 95.

“A cell that produced a substance that hardened its membrane [i.e., origin of cell wall] could now be shaped by mutations and selection pressures to become spherical or filamentous or curved, enhancing its efficiency at attaching to surfaces, gathering food, or spiraling through goo. We can think of the cell wall as an adaptation that allowed life to be shaped by diverse physical principles, be they the laws of diffusion, hydrodynamics, or viscosity, to maximize its chances for survival and reproduction.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 96.

“Thus, to make an animal, a concatenation of three extraordinary events had to occur. First, oxygen levels had to rise in the atmosphere to produce the gas that would unleash the energy-yielding capacities of aerobic respiration, the form of energy production used by you and me. Second, endosymbiosis had to happen. When a bacterium was engulfed, mitochondrial power stations could be made. They would multiply the capacity to make energy inside a single large cell, a feat needed to tap into the new energy reserves. Finally, those cells must have collected together into a single machine, to commit irreversibly to differentiate into various organs and at once to produce something that operates as one.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 102.

“Although tenacious, life is a phenomenon circumscribed very much in its empire, constrained like the animals in a zoo by a fence of extremes [temperature, pressure, salinity, etc. hard limits; author defends hard limits across astrobiological scenarios] that bounds it into a pocket of existence that occupies a trifling fraction of all the physical conditions, in their extremities, to be found across the known universe.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 108.

“Even with wildly optimistic assertions about its temperature tolerance, the percentage of a planet that life can master is a tiny proportion of the total volume. Changing its capacities by hundreds of degrees merely alters the volume of a planet it may occupy by a few tenths of a percent. Life is hardy and persistent once it gets hold of a planet, but its dominion is small. Between absolute zero and the temperature of the interior of a star, say, the Sun, life occupies only 0.007 percent of this temperature range.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 115.

“The biosphere is a like a zoo, surrounded by a wall [hard limits of temperature, radiation, etc.]. Within it, all manner of living things, minuscule and giant, have evolved, guided by laws into predictable forms….

“But in broad scope, life’s boundaries, the insuperable laws of physics, establish a solid wall that bounds us all together.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 124.

“Carrying out the chemical reactions for life in a liquid makes sense. In a fluid, molecules can be brought together close enough to carry out reactions. Importantly, many millions of molecules can move around and meet in many combinations…. In a solid, molecules and atoms are generally rigid and cannot move around easily. In gases, they are often too far apart, in other words, too diffuse.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 167.

“The water molecules attached to the surface of a protein, because of their hydrogen bonded network, become a ‘shell’ of tightly bound molecules encapsulating the molecule. It is a physical state a little like glass. This behavior too plays a vital role in holding proteins together, but also in ensuring the easy movement of many of them.

“In all these astonishing ways, water helps proteins to fold and enables their floppy chains of amino acids to coalesce in the right way.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 171.

“Life and it liquid are interwoven with such complexity and subtlety in so many ways that water is part of the machinery, not merely a medium in which other life-giving reactions happen to occur.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 172.

“Chemical reaction rates proceed according to a very simple principle expressed in the Arrhenius equation…. Using the rates of different reactions measured in the laboratory, he showed that this dependence was not a simple linear relationship…. The relationship is exponential….

“Drop the temperature of the environment from 100̊C to 0̊C, and the reaction rate decreases by just over 350 times. However, drop the temperature by another hundred degrees, from 0̊C to -100̊C, and the reaction rate decreases by a staggering 350,000 times!” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. pp. 175-6.

“The other four elements that, like nuts and bolts, hold living things together through their carbon networks–nitrogen, oxygen, phosphorus, and sulfur–intriguingly occupy a small quadrangle of the periodic table, huddled together near carbon…. All four have incomplete electron orbitals and will take part in bonding with other atoms to fill them. They inhabit a space in the periodic table where the size of the atoms is just right. because the electrons can form bonds that do not need too much energy to break up, these elements are useful in the constant assembly and disassembly that characterizes the building and growth of living things.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. pp. 205-6.

“We are left with a general picture of what the Pauli exclusion principle does to shape life. There is a core of elements whose electron structures are sufficiently good to create stable bonds, but which can nevertheless be broken with sufficient ease to generate the huge assortment of compounds useful to life. These core elements occupy a little quintet in the periodic table–carbon, nitrogen, oxygen, phosphorus and sulfur, with little hydrogen ubiquitously hanging on whenever there is a spare electron going….

“Surrounding the quintet are elements with similar chemical properties, but in which the atomic size and number of electrons make them either a little too unstable or a little too reactive to be good at producing that fine balance between stability and reactivity for making the molecules of life.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 212.

“Look at life’s choice of amino acids, and you find it rooted in the physical properties of those molecules. Observe the folding of proteins, and you find an almost infinite possible number of amino acid chains collapsed into just a few forms. Examine the structure of life, and cells are universal. Survey the forms of animals and plants, and simple relationships confine their shapes like rivets. Marvel at the arrangement of birds, ants, and fish, and within their bewildering hordes, simple rules are at work. From the most diminutive parts of life to whole populations, physical principles have been shown to hold life captive, to corral it into a small set of possibilities.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 249.

“For those who like the fine details, the variety and color of life, then I grant that contingency is everything…. However, on a deeper biological level, these are trivialities against the underlying physics that circumscribes life: the cell membrane, the aerodynamic forces that converge the wings of animals, the structure of jaws made for crushing food.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 251.

“This is a biosphere of symmetry, of predictable scales and pleasing ratios, a pattern in form and construction that runs deep from the very core of biochemical architecture to families of ants and birds. It is the immutable and unbreakable marriage of physics and life.” Cockell, Charles S. 2018. The Equations of Life: How Physics Shapes Evolution. NY: Basic Books. p. 257.

“In his last paper, Alexander Oparin, life’s origin pioneer, wrote: ‘The process of evolution of organic compounds that led to the emergence of life can be divided into two major stages: chemical and prebiological. Chemical evolution developed at the molecular level, obeying chemical laws to reach abiogenic synthesis of polymers that resulted in a spontaneous assembly of phase-separated thermodynamically open systems, or probionts. The appearance of probionts was accompanied by the development of a new law they obeyed, i.e., natural Selection.’” Kahan, Amit & Doron Lancet. 2019. “Protobiotic Systems Chemistry Analyzed by Molecular Dynamics.” Life. 9(38):1-13. doi: 10.3390/life9020038. p. 1; reference: Oparin, Alexander, K. Gladilin, 1980. “Evolution of self-assembly of probionts.” BioSystems. 12:133-145.

“Evidently, Oparin alludes to the idea that the transition from abiotic entities to such capable of natural selection was not centered on a single molecule, but rather constituted a multicomponent system. In this respect, Oparin may be legitimately considered as a pioneer of systems chemistry and its relationship to the origin of life. This distinction between what single molecules can do and what necessitates a molecular ensemble is indeed reflected in the general definition of systems chemistry. This field seeks insight into complex networks of interacting molecules deriving systems level characteristics that emerge through collective behavior.” Kahan, Amit & Doron Lancet. 2019. “Protobiotic Systems Chemistry Analyzed by Molecular Dynamics.” Life. 9(38):1-13. doi: 10.3390/life9020038. p. 2.

“An appreciable sector of life’s origins models adheres to the credo of systems chemistry, asserting that life likely began as a multi-molecular system capable of reproduction, selection, and evolution. Along these lines, early abiogenesis was followed by systems protobiology, a stage at which an assemblage of chemical compounds began to acquire life-like systems properties.” Kahan, Amit & Doron Lancet. 2019. “Protobiotic Systems Chemistry Analyzed by Molecular Dynamics.” Life. 9(38):1-13. doi: 10.3390/life9020038. p. 2.

“The GARD model [graded autocatalysis replication domain] for life’s origin is based on the notion that the first rudiments of life were not individual molecular replicators, but rather self-reproducing multi-molecular systems….” Kahan, Amit & Doron Lancet. 2019. “Protobiotic Systems Chemistry Analyzed by Molecular Dynamics.” Life. 9(38):1-13. doi: 10.3390/life9020038. p. 8.

“In other words, no speciation at the well-mixed macromolecular level is possible [growth of certain molecular types without any separation into wholes for selection as wholes]. The idea how to solve the problem originates from the notion of group selection. Rather than being well-mixed, compartmented parabolic [slower than exponential growth rates] replicators are in a different population dynamic situation [than non-compartmented, growing individual molecular types], since selective forces do not affect them directly but address the fitness of whole systems…. This is the fundamental reason for why life needs to be cellular–other important reasons being confinement, protection, concentration, import-export control, and so forth.” Strazewski, Peter. 2019. “The Beginning of Systems Chemistry.” Life. 9(11):1-7. doi: 10.3390/life9010011. p. 4.

“Chemistry is the science that produces and isolates new and pure substances from controlled chemical reactions…. Systems Chemistry is the discipline that studies the mechanisms of the dynamic upkeep of chemical substances. The main focus is the maintenance of those particular substances that would rapidly and almost completely degrade without the conserving mechanisms. The main challenge here is to find the right initial conditions for the upkeep effect to prevail ‘on its own’, yet very often while supplying the system with energy for a maximally long period of time…. A subtle difference between plain Chemistry and Systems Chemistry is that the researcher seeks more to back off from the latter than from the former, tries not to be the central scrutinizer nor the intelligent designer, and does not want to interfere once the system works, not more than absolutely necessary…. … traditional chemists concentrate on the substances, while systems chemists ponder on the dynamic interactions between different substances.” Strazewski, Peter. 2019. “The Essence of Systems Chemistry.” Life. 9(60):1-9. doi: 10.3390/life9030060. pp. 3, 4.

“In essence, Systems Chemistry is the study of chemical reaction conditions that provide synergies to make more of the stuff that is useful for the whole system.” Strazewski, Peter. 2019. “The Essence of Systems Chemistry.” Life. 9(60):1-9. doi: 10.3390/life9030060. p. 4.

“Lipid vesicles self-reproduction occurs with a growing vesicle taking a non-spherical form and eventually dividing into two or more spherical daughter vesicles. This process is commonly called growth and division (GD).” Lopez, Augustin & Michele Fiore. 2019. “Investigating Prebiotic Protocells for a Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective.” Life. 9(49):1-21. doi: 10.3390/life9020049. p. 11,

“Finally, a functional protocell should achieve the replications of the content and the container together in a core-and-shell reproduction.” Lopez, Augustin & Michele Fiore. 2019. “Investigating Prebiotic Protocells for a Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective.” Life. 9(49):1-21. doi: 10.3390/life9020049. p. 14.

“Furthermore, hybrid bilayers containing both fatty acids and phospholipids get, at the same time, the properties of permeability given by the former and the stabilization given by the latter.” Lopez, Augustin & Michele Fiore. 2019. “Investigating Prebiotic Protocells for a Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective.” Life. 9(49):1-21. doi: 10.3390/life9020049. pp. 14-5.

“Previously, this study emphasized the importance of considering protocells as systems constituted of a wide variety of compounds. Indeed, this diversity is at the origins of complex networks based on physical and chemical interactions from which synergies can emerge. The cooperations between these molecules are of paramount importance for protocells as they are involved in their formation, their metabolism, their replication and finally their evolution.” Lopez, Augustin & Michele Fiore. 2019. “Investigating Prebiotic Protocells for a Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective.” Life. 9(49):1-21. doi: 10.3390/life9020049. p. 15.

“Historically, the term chemical evolution began to be used shortly after the first steps in the field of prebiotic chemistry were taken [dates to 1964 with article by Ponnamperuma], yet with a loose meaning.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 1; reference: Ponnamperuma, C. 1964. “Chemical evolution and the origgin of life,.” Nature. 201:337-340.

“The … conceptual framework is the outline of a theory of autonomous chemical systems (ACSs), i.e., chemical systems which self-sustain and reproduce by their own, marking the minimal set of functions that they must present in order to engage in an evolutionary process…. This would be done by contrasting how the molecular mechanisms of a protocell ensure kinetic control (e.g., coordinating through catalysis the different reactions in time), spatial control (e.g., providing a semipermeable physical separation from the environment, which preserves minimal concentration thresholds of the relevant molecular species), thermodynamic control (e.g., favoring key reactions that are energetically disfavored, and variability control (e.g., preserving the main protocell features through its evolutionary process) [e.g., using different nucleobase pairing molecules to ‘recognize’ different molecules even if they are not part of nucleotides].” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 3.

“Engineering and the natural sciences (communication engineering, computational theory and quantum physics) place the focus on syntactic information, informational content understood as an abstract/mathematical magnitude. Cognitive and social sciences, on the other hand, emphasize semantic information (what information refers to) and pragmatic information (information that was not known by the receiver), and thus it is not redundant.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. pp. 4-5.

“Stochastic thermodynamics have recently shown how Shannon entropy has a precise physical meaning, determining the energetics of non-equilibrium processes in systems coupled to a thermodynamic reservoir. In that kind of situation, a chemical system in an improbable state would be an information carrier, as it reflects the action of prior work that perturbed the system to reduce its entropy from a more probable state. This relationship between negentropy and external work is key to understanding syntactic information….

“In the context of biomolecular networks, for example, linking the syntactic notion of information to physicochemical work is a necessary but not sufficient condition for information processing. In other words, any difference or alteration in entropy does not constitute by itself a referential relationship. This is because semantic information requires a process of interpretation to have meaning or to be a reference to something else.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 5.

“According to Kuppers, information processing in biochemical systems is then related to the changes induced (and thus, work exerted) by an informational molecule or molecular ensemble on an interpreting molecule or molecular ensemble, which can perform a function as a consequence of their interaction.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 5; reference: Kuppers, B.O. 1990. Information and the Origin of Life. MIT Press.

“A major condition for this attempt to naturalize the notion of semiosis, as a process connecting signaling and interpreting molecules/ensembles through physicochemical work, is that only out-of-equilibrium systems can perform work. The problem of information processing in prebiotic systems thus seems related to management of energetic flows, through populations of some kind of molecular sign users.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 6.

“… the ACS’s intrinsic dependence on specific external constraints (e.g., environmental conditions) links the system’s non-equilibrium dynamics to a pragmatic conception of information, i.e., to the emergence of functions that increase its persistence. The ACS autonomy in this context not only results from autocatalytic events, but also from functions that contribute to the system’s self-sustainment and reproduction. Any effective physicochemical interaction leading to a positive correlation of the ACS with the environmental conditions will tend to persist. Such correlation allows selection to operate over the functional outcome of the different informational interactions, and renders function and information as co-emerging primitive properties of ACSs, which enable transition to ever-increasing levels of dynamic complexity.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 6.

“The concept of chemosemiosis here supported is therefore narrower, and refers to heterogeneous chemical assemblies that lack template molecules with discrete sequence information but are still able to self-sustain and reproduce….

“On these bases, the qualitative and eventually quantitative analysis of a protocell performance (e.g., persistence and degree of aliveness) as a function of its semiotic activity would lead to what I call a chemosemiotic model. Protocell and chemosemiotic models are obviously related, but their perspective and utility should be different. The former focus on the components that constitute the protocell and their structural organization, while the latter will put the emphasis on the non-linear dynamics of the physicochemical interactions connecting those components.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 7.

“The theoretical framework outlined here is devoted to decipher such a missing link that exists between chemistry and biology, which requires connecting the dynamics of chemical interaction patterns with the dynamics of signification.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 13.

“Proposing that the physicochemical processes constituting ACSs present a semiotic character can also help to unify the two dominant views of chemical evolution, seen as either a natural process of self-organization or as a relational-constructive problem.” De la Escosura, Andres. 2019. “The Informational Substrate of Chemical Evolution: Implications for Abiogenesis.” Life. 9(66):1-16. p. 13.

“Many people who visit EcoVillage (of Ithaca) assume that we either have created or are trying to create a fairy tale like utopia in which people will live happily ever after. The truth is far richer, deeper, and more complex.” Walker, Liz. 2005. Eco Village at Ithaca. New Society Publishers. p. 77.

“The next Buddha will not take the form of an individual. The next Buddha may take the form of a community; a community practicing understanding and loving kindness, a community practicing mindful living. This may be the most important thin we can do for the survival of the Earth.” Quotation of Thich Nhat Hanh. Walker, Liz. 2005. Eco Village at Ithaca. New Society Publishers. p. 103.

“Data are discrete, objective facts, often without a context…. We can easily see that the singular data point is not all that telling or interesting unless we know much more about the background against which it should be gauged. For an airport in Saudi Arabia, 2.6 centimeters of rain in June is highly unusual, whereas the same amount is not even worth mentioning during monsoon season in Bangladesh. In the example, location and timing augment the data point with meaning. Generally, information consists of processed data augmented with metadata, which consist of such meaning, together with some context and background…. Knowledge is more difficult to define in unambiguous terms. It is a mixture of synthesized information, context, experience and possibly even value judgment. It explains how the information was obtained or generated, recognizes patterns in information, offers procedures for assessing a situation (know-how), and guides expectations regarding the future. Understanding interprets knowledge. It provides causality and rationale for a phenomenon, detail, or pattern in data. Understanding helps us explain why something is the way it is.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. pp. 35, 36.

“Stretched out, the DNA of a single human cell would be about 2 meters long, but if all DNA molecules in the human body could be strung out, the total length would be about twice the width of our solar system. Mind boggling!” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 58.

“Computational models of metabolic pathways generically consist of: pools, which can be imagined as containers for molecules; fluxes, which are quantities of material flowing among the pools through the reactions; and signals, which regulate some of the fluxes.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 73.

“Metabolic models commonly address two features of the actual pathway. The first is the steady state, where all metabolite concentrations remain the same, even though material is flowing through the system. Many healthy pathways operate close to this state of homeostasis….

“The second feature of a metabolic pathway system is its dynamics; the overriding question is: how do the metabolite concentrations of this pathway change over time?” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 73.

“An emerging branch of CSB [computational systems biology] strives to develop simulators of this genre for complex systems in biology and medicine. The premier example is a disease simulator. In direct analogy to a flight simulator, it is easy to imagine how the medical student of the future will learn the outcomes of various treatments of a disease and the typical, but also very rare responses from a small number of patients. The brain behind the simulator will be a complicated computer algorithm that is capable of creating realistic disease situations….” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. pp. 80-1.

“In other words, every parameter in the body has a normal range, within which its value does not really matter. Sensitive parameters have small ranges, whereas insensitive parameters have much larger ranges…. If we focus on three biomarkers, their ranges collectively result in a rectangular ‘normal’ box. Experience shows that combinations of extreme biomarker values are often not so good, and if we account for this observation, the corners of the box are no longer healthy and therefore should be avoided. If we cut them off our rectangular box, the result is something like a cut gemstone, which mathematicians call a simplex. We cannot visualize a simplex in thousands of dimensions, which would reflect our health domain, but even the three-dimensional simplex provides us with a concept of health (inside) and disease (outside),….

“Traditional medicine, of course, does not resort to simplexes, but usually focuses on the strongest driver of a disease.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. pp. 85, 86.

“More generally, a modern goal of medicine is to redirect traditional treatment strategies toward personalized medicine, which will eventually replace the current one-size-fits-all approach with treatments of interventions that are custom-tailored for a specific patient. Systems biology is on its way to play a major role in this trend because the full complexities of health and disease simply cannot be captured without computational approaches.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 88.

“The idea of Elementary Mode Analysis is that we should be able to get rid of many of these pathways [in the goal of optimizing the production by microbes of some chosen chemical], if the microbe did not have to suffer inclement conditions or face enemies. With modest experimental effort, these favorable conditions can be achieved in the laboratory, where food is ample, the temperature is always kept optimal, and everything the microbes need is provided. Thus, the first step is to compute which pathways are necessary for survival under optimal conditions, which pathways or whole metabolic modules are dispensable, and which pathways lead to the desired organic compound the metabolic engineer wants the microbe to produce.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 94.

“The number of different metabolites in the plant kingdom has been estimated to be between 200,000 and 1,000,000.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 98.

“One complication [in breeding] is that many plants do not have two sets of chromosomes as we do, but often more. For instance, bananas have three sets, potatoes four, wheat has six, and sugarcane eight. In fact, these multiple sets of chromosomes, which are sometimes obtained from other species, are the norm rather than the exception for crops that have been bred throughout the past centuries and millennia….

“The multiple copies of genes make experimentation and modeling cumbersome, because otherwise straightforward, routine techniques like knocking out or knocking down a gene must be done for all these copies. An additional challenge is the fact that the expression of genes in some crop plants is super-coordinated in the sense that any changes in gene expression for enzymes in some part of metabolism may also affect enzymes in other parts.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 99.

“Further confounding the search for potent laws, and indeed puzzling is the emergence of system properties that cannot be explained based on any of the system components alone but only through their interactions. This type of emergence is a central topic of systems biology, but it is difficult to explain.” Voit, Eberhard O. 2020. Systems Biology: A Very Short Introduction. Oxford UP. p. 115.

“The origin-of-life field is primed to become a systems domain. Most prebiotic chemistries explored to date have been limited to follow the widely accepted strategy of determining which biomolecules came first, the evaluation criteria relying on the biotic plausibility and the catalytic or template activity displayed by one or another type of molecule. However, this approach misses the crucial point that life, in all its manifestations, comprises a broad diversity of molecules in interaction.” Piedrafita, Gabriel, Pierre-Alain Monnard, Fabio Mavelli & Kepa Ruiz-Mirazo. 2017. “Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution.” Scientific Reports. 7:3141. doi: 10.1038/s41598-017-02799-6. p. 1.

“Thus, beyond the mechanisms and kinetics of the reactions involved, one needs to take also into account material constraints related to the spatial organization of those reactive processes, like the presence of dynamic interfaces, diffusion barriers, semi-permeable compartments, gradients or osmotic forces.” Piedrafita, Gabriel, Pierre-Alain Monnard, Fabio Mavelli & Kepa Ruiz-Mirazo. 2017. “Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution.” Scientific Reports. 7:3141. doi: 10.1038/s41598-017-02799-6. p. 1.

“… we argue for the importance of considering chemical and osmotic effects together, through an adequate coupling of membrane and proto-metabolic dynamics. More precisely, we show how the presence of an internal chemistry that produces lipid components spontaneously taken up by the membrane (mimicking endogenoous lipid synthesis, a fundamental biological feature under investigation in diverse labs) can simultaneously (i) enhance metabolic activity and (ii) lead to faster reproduction cycles of the protocells, thereby increasing their evolutionary potential. The key factor driving the process is the higher permeability that membranes with heterogeneous lipid compositions tend to display (as compared to pure ones).” Piedrafita, Gabriel, Pierre-Alain Monnard, Fabio Mavelli & Kepa Ruiz-Mirazo. 2017. “Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution.” Scientific Reports. 7:3141. doi: 10.1038/s41598-017-02799-6. p. 2.

“Given the permeability dependence on membrane lipid composition, protocell division times in the stationary reproduction regime were expected to depend in particular on the ability of protocells to partially transform their membrane composition, hence reaching heterogeneous lipid mixtures.” Piedrafita, Gabriel, Pierre-Alain Monnard, Fabio Mavelli & Kepa Ruiz-Mirazo. 2017. “Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution.” Scientific Reports. 7:3141. doi: 10.1038/s41598-017-02799-6. p. 2.

“Contemporary biomembranes are composed of a large variety of complex lipids, all metabolically synthesized according to the needs of each cell at any given time. Thanks to the presence of other functional ingredients (especially membrane proteins), biological compartments can afford lipids that confer them high stability at the expense of decreasing their overall permeability to hydrophilic solutes. The evolutionary pathway that permitted the emergence of such membranes from their prebiotic precursors is still unknown. But a monotonous transition towards increasingly more impermeable compartments should not be taken for granted, as it has been sometimes done. Protocells probably remained highly heterogeneous in terms of lipid composition from their earliest origins. In fact, there is no solid argument supporting pure or homogeneous prebiotic membranes. Scenarios like the one explored by [Cape et al.2011] seem to be more plausible, as evidenced by the meteorite amphiphile content or the large spectrum of products in simulated amphiphile syntheses. And it is quite probable that this membrane heterogeneity was later consolidated, because the changes toward modern (biosynthesized) lipids necessarily involved: (i) an increase in the hydrocarbon chain length (one cannot assume abiotic sources of fatty acids longer than 10 – 12 carbon chains); and (ii) an increase in the size and chemical complexity of the polar head (allowing among other things, the formation of diacyl structures). Therefore, the degree of heterogeneity in the composition of the membrane itself was possibly not such a significant change, but rather the emergence of an endogenous control of that heterogeneity through the coupling with metabolism).” Piedrafita, Gabriel, Pierre-Alain Monnard, Fabio Mavelli & Kepa Ruiz-Mirazo. 2017. “Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution.” Scientific Reports. 7:3141. doi: 10.1038/s41598-017-02799-6. pp. 6-7; reference: Cape, J.L., P.-A. Monnard & J.M. Boncella. 2011. “Prebiotically relevant mixed fatty acid vesicles support anionic solute encapsulation and photochemically catalyzed trans-membrane charge transport.” Chem Sci. 2:661-669. doi: 10.1039/c0sc00575d.

“In summary, our results confirm the adequacy of a systems approach to the question of origins of life, already reflected in the emphasis given to protocellular organization, but more manifest after showing how molecular mixtures add dynamic and structural richness to the basic phenomena. More specifically, lipid variety in the composition of prebiotic membranes could enable high ‘phenotypic’ diversity in primitive cells before the appearance of genetically-encoded transporters. In addition, as described in previous work (both experimental and theoretical), the non-genetic synthesis of short peptides could have also contributed to functionalize vesicle compartments during the first stages of protocell development. Thus, pre-Darwinian evolutionary processes should constitute the new focus of research in this field. Terms like ‘fitness’ or ‘survival’ ought to be substituted by other features related to the ‘dynamic robustness’ of the supra-molecular assemblies and investigated as the population-level consequences of their various physical-chemical interactions (in an environment with limited resources).” Piedrafita, Gabriel, Pierre-Alain Monnard, Fabio Mavelli & Kepa Ruiz-Mirazo. 2017. “Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution.” Scientific Reports. 7:3141. doi: 10.1038/s41598-017-02799-6. p. 8.

“As Putnam describes, communities dedicated to bridging bring different kinds of people together so that they can share assets, ideas, skills, and information…. On the other hand, communities focused on bonding connect similar types of people for solidarity, reciprocity, and social support.” Richardson, Bailey, Kevin Huynh & Kai Elmer Sotto. 2019. Get Together: How to build a community with your people. San Francisco: Stripe Press. pp. 32, 33; reference: Putnam, Robert D. Bowling Alone: The Collapse and Revival of American Community.

“‘A story of self communicates [for and towards a community] the values that are calling you to act,’ he [Marshall Ganz] writes in the course notes. ‘A story of us communicates values shared by those whom you hope to motivate to act. And a story of now communicates the urgent challenge to those values that demands action now.’” Richardson, Bailey, Kevin Huynh & Kai Elmer Sotto. 2019. Get Together: How to build a community with your people. San Francisco: Stripe Press. p. 72; reference: Ganz, Marshall. 2016. Organizing People, Power, Change. “Organizing Notes, Spring 2016.” [handout]

“Permaculture in its broadest application involves redesign of everything we do according to ecological principles.” Quote from David Holmgren in: Birnbaum, Juliana & Louis Fox. 2014. Sustainable [R]evolution: Permaculture in Ecovillages, Urban Farms, and Communities Worldwide. Berkeley: North Atlantic Books. p. 285.

“In these waning days of the American Century, Washington’s foreign policy establishment–the think tanks that define the limits of the possiblle–has splintered into two warring camps. Defending the status quo are the liberal internationalists, who insist that the United States should retain its position of global armed primacy. Against them stand the restrainers, who urge a fundamental rethinking of the U.S. approach to foreign policy, away from militarism and toward peaceful forms of international engagement. The outcome of this debate will determine whether the United States remains committed to an atavistic foreign policy ill-suited to the twenty-first century, or whether the nation will take seriously the disasters of the past decades, abandon the hubris that has caused so much suffering worldwide, and, finally, embrace a grand strategy of restraint.” Bessner, Daniel. 2022. “Empire Burlesque: What comes after the American Century?” Harper’s Magazine. July. pp. 24-33. p. 27.

“Gil Barndollar of Defense Priorities [a new think tank supporting the restrainers] has usefully summarized the restrainers’ limited set of foreign policy goals: helping to realize ‘the security of the U.S. itself, free passage in the global commons, the security of U.S. treaty allies, and preventing the emergence of a Eurasian hegemon.’ Because the major problems of the twenty-first century cannot be solved by U.S. military force, but instead require multilateral cooperation with nations that have adopted different political systems, there is no reason for the United States to promote democracy abroad or act as the global police force.” Bessner, Daniel. 2022. “Empire Burlesque: What comes after the American Century?” Harper’s Magazine. July. pp. 24-33. p. 30.

“If the coming of LUCA marked the crossing of the ‘Darwinian Threshold’, then it follows that pre-LUCA evolution must have been Pre-Darwinian and hence at least partly non-Darwinian.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 427.

“More concretely, I take the path from prebiotic chemical synthesis to LUCA has the following four areas with (near) consensus despite differences on specifics.

“First, prebiotic chemical synthesis of the building blocks of macro biomolecules (e.g., amino acids, nucleotides, lipids) must have preceded biological evolution, and it had been made possible by the environment of the Hadean Eon.

“Second, comparmentalization of biomolecules is essential because it restricts diffusion, increases stability, and allows for molecular crowding, which in turn facilitates interations, reactions, and hence the coevolution of biomacromolecules.

“Third, following Woese, progenotes (or FUCAs here [First Universal Cellular Ancestors]) must have preceded genotes (or LUCA here).

“Fourth, LUCA was already a fairly ‘modern’ cell with a sophisticated membrane system, a (nearly) fully functioning metabolism system, a nearly complete translation apparatus (with the standard genetic code being a core part of it), and perhaps a RNA/DNA hybrid-centric replication system, among other things.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 428.

“It is to Carl Woese’s penetrating mind that we now accept not only that the origin(s) of cell [sic] is different from the origins(s) of life but also that the former must have been an equally, if not more, decisive step in the making of the biotic world. Moreover, while both ‘what is life?’ and ‘what is a (proto-)cell?’ are hard questions, the latter is a bit easier because it is less philosophical.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 428.

“… I use persistence for non-cellular entities but survival for (proto-)cellular entities. Similarly, following Luisi, I use replication only for genetic replication but reproduction for vesicles and proto-cells that may grow and then divide, with or without genetic replication.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 429; reference: Luisi, P.L. 2006. The Emergence of Life. Cambridge UP.

“I now outline five key premises….

“(1) Persistence as survival came long before genetic replication, certainly before division as reproduction (with or without genetic replication). Before replicators and reproducers, there must be survivors, to paraphrase Szathmary and Maynard Smith (1997)…. This law that persistence comes before (cellular or not) metabolism, replication, and reproduction holds most forcefully in the Pre-Darwinian epoch….

“(2) Before FUCAs, variation had been a primary means toward persistence. From the very beginning of bioorganic evolution that eventually led to FUCAs and then LUCA, evolution was mostly about gaining more molecular and hence functional diversities so that protocells could survive in more diverse environments with a more potent arsenal. Moreover, variations back then were not generated by genetic mutation (which did not exist for a long time) alone, but by two additional processes: (1) prebiotic chemical synthesis, polymerization, and stereochemical mutualism, both outside and inside of vesicles; (2) absorption via breaking-and-repacking, acquisition or engulfing via proto-endocytosis, merger or fusion via proto-endosymbiosis, and other similar processes.

“(3) Natural selection can operate without genetic replication or even metabolism (at least not cellular metabolism), as long as different molecules, complexes, and vesicles have differential rate of persistence and reproduction within a system…. Four major non-Darwinian selection mechanisms, which most likely had appeared in the following order, had worked together in the process leading to FUCAs.

“(a) The first Pre-Darwinian selection mechanism is mostly chemical. It operates upon molecules and selects not only their chemical properties as monomers but also their capacities for forming polymers and complexes. Here, key yardsticks of ‘fitness’ include availability (i.e., steady supply from abiotic synthesis or meteoric bombardment), stability, solubility, polymerization, and stereochemical mutualism for forming larger complexes.

“(b) The second Pre-Darwinian selection mechanism is both chemical and physical. It selects the different capacities of different bioorganic molecules and complexes to interact with each other, and in turn, whether their interactions confer new (or emergent) life-facilitating properties, structural and functional. Among possible interactions, two were perhaps most central: (1) amino acids, alpha-helix forming peptides, and (poly-)nucleotides that can not only interact with and stabilize vesicles but also make vesicles selectively permeable; (2) peptides and RNAs that can not only interact with each other but also lead to new or enhanced properties (e.g., more efficient and reliable in terms of synthesizing RNAs and peptides) via their interactions.

“(c) The third Pre-Darwinian selection mechanism selects the different capacities of different vesicles (1) to absorb biomolecules and components via simple absorption and breaking-and-packing, (2) to engulf (or acquire) via proto-endocytosis and to merge (or fuse) via proto-endosymbiosis or similar processes. Vesicles with superior capacities in both absorption and merger/acquisition will enjoy advantages over those with less effective capacities, in terms of persistence, variation, and evolvability. A cool-and-hot cycle and a wet-and-dry cycle might have driven both processes.

“(d) The fourth Pre-Darwinian selection mechanism operates upon vesicles that now approach protocells. Among these now fairly stable vesicles, those that can not only absorb, acquire, and merge but also can produce primitive metabolism and replication and then divide (or reproduce) will hold critical selection advantage over those that cannot. Here, the key yardsticks of ‘fitness’ included persistence (as survival), absorption, growth, and division, first without and then with primitive metabolism and genetic replication.

“(4) Vesicles are evidently compartments of retention. More critically, however, vesicles’ absorption, acquisition, and fusion via breaking-and-repacking, proto-endocytosis, proto-endosymbiosis, and other similar processes are both processes of variation and processes of selection.

“(a) Absorption, acquisition, and merger are processes of variation because they produce different compartmentalization and hence different crowding, combination, and coevolution of biomolecules within vesicles. Absorption, acquisition. And merger [sic] entail extensive ‘horizontal biomolecules transfer’ (HBMT) rather than merely ‘horizontal gene transfer’ (HGT): HBMT thus subsumes HGT. Indeed, only with HBMT, could have pre-Darwinian evolution drawn from ‘global inventions’, and only with HBMT could have pre-Darwinian evolution overcome the seemingly insurmountable hurdle of bringing ‘the overwhelming amount of novelty needed to bring modern cells into existence’ (Woese 2004) ….

“(5) Reproduction and replication being tightly coupled had evolved from reproduction and replication not being linked at all and then to reproduction and replication being only loosely coupled. Only protocells with some kind of coupling of replication and reproduction via division become FUCAs, which then eventually evolved into LUCA.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. pp. 429-431.

“For simple bioorganic molecules to be assembled into more complex hetero-biomolecules, they have to be stereochemically compatible with each other: in other words, there must be ‘molecular mutualism’ (Lanier et al. 2017; Vitas and Dobovisek 2018). Key examples of such molecular mutualism include (1) that only some amino acids or peptides can interact with nucleotides and simple RNAs, non-covalently and (2) that only some peptides can form α-helixes and then insert themselves into lipid membranes to make lipid membranes more permeable. Moreover, once some kind of molecular mutualism is fixed, it may become difficult to change or unravel. A key implication of molecular mutualism is that simplicity does not always mean better. Because only certain configurations are compatible with certain assembling strategies for bringing different molecules together, those molecules that can interact, bind, or fit with each other properly, rather than those that are merely simpler, may be selected.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 432; reference: Lanier, K.A., A.S. Petro & L.D. Williams. 2017. “The central symbiosis of molecular biology: molecules in mutualism.” J Mol Evol. 85:8-13.

“For a period of time, the evolution of peptide-lipid membrane and the evolution of RNA-peptide (as the proto-translation machinery) might have proceeded independently from each other. The two processes might even have operated in different locations such as different terrestrial hydrothermal ponds or fields. Eventually, however, these two processes had to come together, and the moment in which these two processes merged was the first decisive step from replicators to reproducers that paved the way toward the first protocells or FUCAs. The fusing of the two processes was perhaps achieved by a peptide-lipid vesicle absorbing several RNA-peptide complexes (as proto-endocytosis), mediated via the interaction between RNA and lipids or peptide on the vesicle’s surface.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 433.

“Rather, FUCAs came to exist via drawing and fusing innovations from many precursors. It is through HBMT that is underpinned by acquisition and merger rather than HGT alone that FUCAs eventually came to possess a proto-machinery of survival and a proto-machinery of replication within the same protocell.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 433.

“Once FUCAs came to possess both a proto-machinery of survival (roughly, metabolism supported by proteins within a membrane) and a proto-machinery of replication (now supported by both peptides/proteins and RNAs), survival and replication began to co-evolve with each other.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 433.

“Eventually, a few lucky FUCAs with the right and tight coupling of metabolism, translation machinery, division with genetic replication, and energy efficiency will dominate the system, and these lucky few FUCAs merged into a single lineage or only one lineage of FUCAs survived: this lone surviving lineage became LUCA. Because LUCA possessed a tight coupling of cell division with genetic replication, it was a genote that had crossed ‘the Darwinian Threshold’.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 434.

“Without a (primitive) defense system against genetic invasion by mobile genetic elements, primitive cells would be extremely vulnerable to genetic invasion. In contrast, acquiring an even primitive defense system against genetic invasion inevitably reduces the rate of HGT.

“The arms race between HGT and defense against genetic invasions by genetic parasites via HGT therefore most likely began only with FUCAs the earliest. The acquiring of a defense system against genetic invasion also marks the coming of HGT as a reduced form of HBMT….

“LUCA already possessed a quite sophisticated defense system against mobile genetic elements, which eventually evolved into the core defense systems against mobile genetic elements in the two primary domains, including the pAgo system, the CRISPR-Cas system and the toxin-antitoxin (TA) system.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 434.

“The evolution of the complex translation apparatus requires input from ‘global inventions’ that can only be provided by HBMT via vesicles’ merger-and-acquisition. With HBMT, vesicles within a pool of vesicles or protocells could have easily drawn from ‘global inventions’, not only in genetic materials but also in metabolism and other ingredients, within the community of FUCAs as progenotes.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 437.

“Many artificial vesicles indeed can grow and divide without replication, by simply absorbing either ingredients or other (mini-)vesicles. They can also undergo structural changes under different conditions (e.g., different pH, different concentration, a wet-and-dry cycle, a hot-and-cool cycle, redox chemistry), thus facilitating acquisition and merger.” Tang, Shiping. 2021. “The Origin(s) of Cells(s): Pre-Darwinian Evolution from FUCAs to LUCA.” Journal of Molecular Evolution. 89:427-447. doi: 10.1007/s00239-021-10014-4. p. 437.

“If you want to go fast, go alone. If you want to go far, go together.” African proverb. Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 1.

“Forms of community:….

“Social Capital: The shared social norms, trust, and networks that impact how individuals and groups get along. A form of positive social glue. High social capital requires the investment of time and energy. It includes networks of bonding and bridging between individuals and groups.

“Political Capital: The ability of individuals and groups to influence the political agenda within the community. This can include the ability to help set the agenda, future policies, and allocation of resources. High political capital of citizens is supported by participatory democracy and broad empowerment of all members of a community.

“Cultural Capital: The local beliefs, values, traditions, language, history, and cultural heritage of a community. Cultural capital can give community members their sense of identity and sense of place.” Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 14.

“Some say that expert-driven societies have efficiency in operations but I claim, and have experienced, that this top-down approach is very ineffective at meeting citizens’ needs. Healthy systems of governance require dynamic feedback loops that are not possible without embracing public engagement including a broad diversity of stakeholders.” Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 19.

“Engaging in research and finding the information that is needed for building healthy communities starts with asking the right questions. I encourage every community to come together, at least once a year, to raise the questions that need to be asked. Let these questions guide your research and information gathering for the coming year.” Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 111.

“An ecosystem establishes a dynamic interdependence between a myriad of plants and animals that balances competition and cooperation, a process also referred to as symbiosis. This is an interdependent system that can respond to unanticipated changes, such as floods, droughts, and diseases, and recover! The health and vitality of a human community and the effectiveness of its organizational systems are similarly dependent on a continuous flow of information and communication with dynamic feedback loops. Without these, there will be inadequate accountability and critical changes that are urgently needed may be avoided or seriously delayed.” Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 177.

“Tell me, I’ll forget. Show me, I’ll remember. Involve me, I’ll understand.” Ancient Chinese Proverb. Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 215.

“Communities need social foundations that include shared norms, common interests, mutual respect, trust in each other, a belief in their community, and confidence in their ability to succeed.” Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 235.

“Whenever you’re in conflict with someone, there is one factor that can make the difference between damaging your relationship and deepening it. That factor is attitude.” Quote from William James. Gruber, James S. 2020. Building Community: Twelve Principles for a Healthy Future. Gabriola Island, BC, Canada: New Society Publishers. p. 259.

“Inherent intra-genome interactions should also give us pause with respect to the yet largely unknown, potential long-term health risks of viral-vector DNA vaccines, such as AstraZeneca/ Oxford University, and Johnson & Johnson adenovirus vector DNA vaccines against SARS-CoV-2 viruses….

“Any time that large quantities of foreign DNA are inserted into the cytoplasm and then penetrate the nucleus of eukaryotic cells, inevitably a minuscule fraction of the exogeneous DNA gets embedded and incorporated into the genome of a few of the trillions of host cells…. In many cases, this exogenous DNA insertion may merely lead to unused, non-coding DNA, but in a few cells, this also could very well lead to genome destabilization, and it also could trigger oncogenesis….

“So far, I am not aware of known evidence for either, but clearly so far nobody is looking for this evidence.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 19, 20.

“It is remarkable that the detailed mechanisms of generating change prior to natural selection have not been analyzed systematically and rigorously by evolutionary science.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 32.

“The frequently detected viral recombinations are another form of horizontal gene transfer (HGT). One could even consider viral recombinations the precursor to, or the most rudimentary form of ‘sexual reproduction’.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 46.

“In summary, if the Modern Synthesis theory of evolution was correct, humans probably would have millions of genes, or more. The fact that we only have ~21,000 genes also further demonstrates the importance of epigenetic, RNA, protein and other molecular information storage, and inter-generational cell code transfers for short-term inheritance over two or a few cellular or organismal generations.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 56.

“Moreover, phenome adaptations due to environmental feedback can lead to many more forms of short-term biological information storage during the lifetime of an organism, as exemplified by our adaptive immune system.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 56.

“… this book demonstrates how the clearly incomplete, and substantially incorrect Modern Evolutionary Synthesis theory, in combination with the insufficient tenets and dogmatic prohibitions of the Central dogma of Molecular Biology, together have held back a corrected and comprehensive understanding of evolutionary biology for decades.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 70.

“… we can ultimately only understand the cellular genomes, epigenomes, transcriptomes, proteomes and metabolomes, and many diseases and syndromes within an integrative and interactive systems biology framework.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 71.

“For the taxa of bacteria, the Modern Synthesis theory is plainly incorrect.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 75.

“This remarkably low number of remaining genes [37] in mitochondria as organelles is feasible, because many of their mtDNA genes have migrated to the nuclear genome of eukaryotic cells over evolutionary time frames. This is prima facie evidence that the nuclear genome has been actively rewritten and externally reprogrammed, by cell biology mechanisms that drive evolution, and that go far beyond random mutations.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 104.

“A broader understanding of Active Evolution is bound to lead to a less myopic and a less gene-dominated approach to society’s funding for biological and medical research. It is expected to lead to better success rates and faster progress in pharmaceutical and biotechnology research into needed new diagnostics and therapeutics, and in some cases even to cures. This is particularly true for various debilitating or deadly diseases, including cancer, neurodegenerative, neurodevelopmental and psychiatric disorders, cardiovascular disease and diabetes, where progress by our gene-dominated research enterprise has been slow or disappointing for patients.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 140-1.

“The Weismann threshold [change of terms for “barrier”] then is a protection against incessant ‘genetic and retroviral’ noise, and it effectively filters out low-frequency or low-level attempts to edit or reprogram the DNA of the germline. Yet, the Weismann threshold likely permits transfer of important, frequent and evolutionarily needed gemline DNA modifications. That only happens when the germline DNA edit signals arrive with high amplitude, frequently or over prolonged periods of time.

“This type of nature’s ingenious soma-to-germline biological noise and low-intensity signal filtering has not yet been experimentally demonstrated, to the best of my knowledge.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 175-6.

“In my 2005 EDITA presentations, I specifically questioned whether the prevalent, narrow ‘random DNA mutation change generator’ hypothesis could account for scientific observations, such as:…

“… the conundrum presented by the undeniable marvels observed by developmental evolutionary biologists, who criticized neo-Darwinism for focusing on just the extinction of unfavorable mutants, while paying no attention to the developmental mechanisms behind the creation of innovative phenotypes and morphologies.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 184, 185.

“In 2005, I therefore posed the question whether the environment, defined here as all external influences from outside the nuclear genome, other than regulation or control within the nuclear DNA, can induce, drive and actively direct evolutionary novelties and changes prior to selection….

“I realized that it was quite controversial to propose that the environment cannot only passively select, but that it also can induce and drive the creation of novelty, i.e., the evolutionary step of change that is needed prior to selection. The implications were then and are today far-reaching, because environmental drive implies directing evolutionary change towards successful subsequent environmental selection, i.e., a self-organizing process, rather than a random change process!” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 185-6.

“The EDITA Postulate states broadly:

“Externally driven irreversible and transferable adaptation (EDITA) is a generator of non-random change prior to natural selection, and it can generate heritable novelties.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 186.

“From a human perspective, infections are a disease, which humans tend to interpret as some sort of malfunctioning of nature, which is an oxymoron, of course.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 190.

“The scientific community is curiously hesitant to learn from cancer biology about general biological mechanisms and concepts. Similarly, we are hesitant to consider cancer as a prime example and model system of real-time evolution within an organism.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 190.

“Due to prior infections or vaccinations, humans acquire and refine a major part of their immunity during their lives in the non-heritable, somatic cells of the adaptive immune system. It is, however, evident that there are also significant differences in the heritable innate immune system of various ethnic groups depending on geographic origin.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 195.

“… if our genes represent the dictionary of life (‘words’), then regulatory DNA, epigenetics, non-coding RNA and enzymes provide the ‘grammar rules’ to regulate biological processes (‘sentences’), in our cells (‘paragraphs’), which are assembled into various tissue types (‘chapters’) of our organs (‘books’). They altogether make up a human being, or any other multicellular organism (‘library’), and the super-organism also includes the microbiomes and viromes. Altogether, these super-organisms constitute complex ‘life,’ with just our genes being very far from a complete ‘blueprint for life’.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 221.

“… epigenetics ‘rescues’ humans from implicit genetic pre-determination of our lives. The conclusions from the previously assumed predetermination of life by genes, as some ‘blueprint of life,’ and therefore the dominating role of genetic heredity has been pervasive. This appeared to put us into a genetic bio-fatalism trap for human dignity, partially free will and self-determination.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 232.

“In single cells selection can still prefer certain cell types and capabilities, which may be directly and causally linked to certain genes, and their interactions in the genome. By contrast, in complex, multicellular life the effect of natural selection on genes is even further shielded by organismal homeostasis, and by seemingly purposeful cellular collaboration and coordination, e.g., in embryogenesis or morphogenesis.

“As Levin has pointed out, some molecular or evolutionary biologists reject the attribution of supposedly anthropmorphic capabilities, like basic memory, basic ‘cognitive’ capabilities of tissues or organs other than the brain, or of purposeful direction in biological development and in regeneration in plastic organism, from re-growing lost limbs in salamanders, to basic wound healing or skin regeneration in humans, for philosophical reasons.

“Levin advocates that for a proper understanding of evolution, and the role of development, the experimentally demonstrated goal directedness has to be added to a new paradigm of evolution that goes beyond the Modern Synthesis. This teleological aspect of multicellular development can be modeled in a cybernetic sense, as described by engineers in control theory. We need to expand homeostasis to shape, morphology and anatomy, as evidently cells keep building reproducible patterns.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 239-240; reference: Levin, Michael. Tufts University. www.drmichaellevin.org.

“But what tips a system into cancer isn’t necessarily a particular mutation but the last mutation that causes the avalanche, a catastrophic phase-transition into cancer.” Quotation from Azra Raza, book The First Cell, and the Human Cost of Pursuing Cancer to the Last. Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 293.

“… one of the major conclusions of the October 2020 Cancer & Evolution Symposium was that cancer cells under ‘extinction pressure’ will react to aggressive chemo-, radiation-, targeted or immunotherapies with rapid, actively driven further genomic diversification.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 296.

“Even in the same patient, it is not the same disease at two sites or at two different points in time. Vicious and self-obsessed, it learns to grow faster and become stronger, smarter, and more dangerous with each successive division. It is a perfect example of intelligence at a molecular level, able to perceive its environment and take actions that maximize its chances of survival.” Quotation from Azra Raza, book The First Cell, and the Human Cost of Pursuing Cancer to the Last. Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 299.

“If the probability of cancer simply went up with the number of cells or cell divisions in an organism, then larger, long-lived animals would have a higher incidence of cancer than small, short-lived animals. However, it is well known that elephants or whales do not have a higher incidence of cancer than humans. This is known as Peto’s Paradox….

“Five years ago, a part of the answer to Peto’s paradox was discovered in that elephants have 20 copies of the tumor suppressor gene TP53 in their genome, compared to humans who have only one copy of TP53. The slower metabolism and lower rate of cell division in larger animals may be the other part of the answer. Conversely, mice have a higher incidence of cancer than humans, when normalized for body size and number of cells,…. Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 305-6.

“Kenneth Pienta, a cancer researcher and professor of urology at Johns Hopkins University Medical School, et al. have published an excellent paper in early 2020 about the role of evolution in cancer. They cover oncogenesis as a cancer protist speciation event, rapid speciation within the original cancer clade, and then evolving efficient evolability as a trait that later also favors metastasis, therapy resistance and lethality.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 312; reference: Pienta, Kenneth, E.U. Hammarlund, R. Axelrod, S.R. Amend & J.S. Brown. 2020. “Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer.” Molecular Cancer Research. doi: 10.1158/1541-7786.MCR-19-1158.

“In particular, Heng calls for a new ‘genomic paradigm,’ and asserts that thinking about genetics ‘one gene at a time’ is non-productive or even misleading, as most genes do not have independent functions, except in monogenic diseases. Heng illustrates that research and subsequent cancer diagnostics at the genome level is more likely to provide meaningful insights to enable progress in cancer therapy. Heng asserts that the entire genome, including its topology, defines a biological system and determines cell biology or disease function, and that the genome is far more than the ‘sum of the function of individual genes,’ which is today’s prevalent concept of genetics.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 317-8; reference: Heng, Henry. 2019. Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine. Academic Press.

“… cancer never invents anything new. Instead, it merely appropriates already existing functions of the host organism, many of them very basic and ancient. Limitless proliferation, for example, has been a fundamental feature of unicellular life for aeons.” Quotation from Paul Davies. November 2018. “A New Theory of Cancer: On a disease’s evolutionary history and the implications for treatment.” Australian magazine The Monthly. Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 326.

“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. To be sure, 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.” Quotation from Paul Davies. November 2018. “A New Theory of Cancer: On a disease’s evolutionary history and the implications for treatment.” Australian magazine The Monthly. Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 327.

“Davies urges us to understand cancer as an evolutionary atavism. Cancerous processes are always latently present, or an ‘accident waiting to happen’. In healthy, young individuals, these ancient ‘cancerous’ processes are dormant, because they are actively suppressed by multicellular control and apoptosis mechanisms….

“Davies’ insights that cancer has many elements of evolutionary atavisms thus complement the views that cancer results from rapid novelty generation via genome destabilization, and that cancer is driven by many of the same active processes of active organismal evolution.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. pp. 327, 328; reference: Paul Davies. November 2018. “A New Theory of Cancer: On a disease’s evolutionary history and the implications for treatment.” Australian magazine The Monthly.

“In any case, if Davies is partly correct, then a general cure for cancer will be impossible, because cures are only feasible for externally induced diseases, like infections, i.e., for true pathobiologies. But cures are inherently non-sensical for fundamental biological phenomena like dormant, atavistic cancer processes, or aging.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 329.

“Levin studies regeneration, morphogenesis and embryogenesis, including bioelectrical networks for storing and recalling pattern memories, e.g., on how to form a limb. In numerous experiments, he has observed staggering plasticity and preserved patterns of morphological homeostasis in regenerative animals, like salamanders, or in mouse or frog embryos. Levin adds the counter-intuitive observation that regenerative animals, or organisms in regenerative developmental phases, e.g., as an embryo, despite their high propensity to proliferate even much faster than cancer cells, actually have a lower incidence of cancer than non-regenerative animals, or later developmental phases.

“In addition, when implanted with cancerous cells, or if their genomes are modified with the insertion of aggressive oncogenes, like KRas, these regenerative animals, or animals in plastic developmental stages, e.g., in tadpoles, actually can ‘normalize’ or control cancer, and reintegrate cancerous cells, or cells with tumor driver genes, back into purposeful, non-cancerous morphological development. This is quite remarkable, and a valuable additional top-down perspective on cancer, as being, at least in part, a result of the loss of physiological control, as well as of the empirically observed cohesion between cells, within a tissue or an organism.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 330; reference: Levin, Michael. Tufts University. www.drmichaellevin.org.

“So far, this notion [cancer transmission between hosts] has been dismissed, as traditionally we consider only bacteria, fungi, parasites and viruses as infectious agents. However, genotoxin-carrying EVs [extracellular vesicles], or oncoviruses, also can spread cancer to other hosts, as has been empirically observed in many examples of contagious cancers that we discuss next. Except for several known special cases, modern medicine has dogmatically declared human cancers to be a non-infectious disease; discussing anything else in the case of humans is a societal taboo.” Laukien, Frank H. 2022. Active Biological Evolution: Feedback-Driven, Actively Accelerated Organismal and Cancer Evolution. North Hampton, NH: Evolution Press. p. 332.

“The Greek for flow, rhein, has given us the name for the science of flow and deformation, rheology. The different rates at which fluids flow under the same force–the sluggishness of honey and the quickness of water–was, for the ancients, and is in today’s experimental laboratories, the fundamental characteristic of soft materials.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 2.

“So materials falling under the labels of ‘colloids’, ‘polymers’, ‘liquid crystals’, ‘self-assembly’, ‘membranes’, ‘foams’, ‘granular materials’, ‘biological materials’, ‘glasses’, and ‘gels’ now find a common scientific home [in soft matter].” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 3.

“Soft materials exhibit large local rearrangements of their microscopic structural constituents under thermal agitation, while ‘hard’ materials suffer only small distortions under the same effects of heat.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 9.

“Structure between the length scale of several nanometres to micron is almost ubiquitous in soft matter systems.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 11.

“A classical particle in motion, he [Feynman] reasoned, moves in a well-defined path from starting point to finish. Throw a ball to your friend, and you can trace its trajectory. A quantum particle moves in an entirely different and strange way: in some, at least mathematical, sense it travels along all possible paths connecting the starting point A and the end point B. The probability that it arrives at the end point is then calculated from a sum over all those possible paths, each one contributing a particular number to the sum….

“The picture gives away the connection to the polymer problem. Suppose that one end of a polymer molecule starts at A; one way of getting at the problem of its overall size is to ask about the probability that the other end arrives at another point B. The polymer is not a quantum object, but the sum over paths arises in a similar way, in this case because it is a statistical object. A real polymer chain will be in rapid motion, due to the Brownian fluctuations of the solvent, so it will explore all possible states and configurations in the solution. Furthermore, any experimental measurement of the solution would average over many individual polymer chains. All would depend on the average property, and that would result from a sum over paths. The formal similarity between the quantum mechanics of a particle and the ‘statistical mechanics’ of a polymer lies at the heart of soft matter physics.

“To go a little further into this deep conceptual mapping between the quantum particles and polymers, the length of the polymer chain corresponds to the time variable in the motion of the quantum particle. Varying the temperature of the polymer system can be compared with varying the scale of the particle system between quantum and classical limits. For example, extreme tension applied to a polymer chain stretches it so that all fluctuations in its typical path lie close to a ‘classical’ trajectory of a straight line between its endpoints. Such a situation is equivalent to the physics of the large-mass limit in the quantum case, where this is the dominant classical trajectory of the particle.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. pp. 44-6.

“A polymer is an example of the class of objects known as ‘fractals’…. … fractals are symmetric under change of scale….

“Polymer coils are similarly fractal, but in a random, or statistical, sense; each sub-chain is statistically a random walk with the same properties as the entire chain.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. pp. 55, 56.

“De Gennes’s conception of the slithering Brownian motion of a free polymer chain in a network reminded him of a snake slithering in reptilian fashion along a tunnel or tube, inspiring the coming of a new word for this special dynamic mode, which he called ‘reptation’….

“… the same imaginative key–to think about one molecule at a time, constrained in its motion by its many neighbours–would also unlock the problem of the polymer melt, even when no molecule is special and where no permanent cross-links tie the stringy structure together. Each can only move along its own contour even when all other molecules are also in motion, and only when each molecule has crawled out of its straitjacket of entangling constraints–fortunately they may all do this simultaneously–will the composite material be able to flow a small amount. So repeated escape from the entangled structures and the re-creation of new entanglements is the molecular picture for how polymeric liquids flow. The polymer chains are all trapped in effective ‘tubes’ constructed from the entanglements with their near-neighbours, that trace their convoluted paths. The effective tubes survive just long enough, as those neighbours themselves slither away, to allow each chain to explore the tangled stringy surroundings by this special random toing-and-froing along their self-made tubes. The resulting continuous release of old entanglements between chains, and the creation of new ones, allows the entire system slowly to deform and to flow.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. pp. 59-60; reference: De Gennes, Pierre-Gilles. Nobel Laureate.

“The local formation of bilayers is a ‘first-order’ requirement of self-assembly. The bilayer membranes in turn, once formed, can take on many geometrical forms, depending on the ‘second-order’ molecular determinants such as a preferred curvature and surface-to-volume ratio.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 84.

“The classification of soft matter, which takes its cue from the shape of the underlying mesoscopic component, suggests a class of soft materials that would possess properties distinct from those of both colloids and polymers. For between the compact near-spherical particles of the first and the flexible strings of the second ought to lie molecules that are extended (like polymers) yet rigid (like colloids). Nanoscopic or molecular rods provide the theoretical notion that animates the exploration of the soft matter class of ‘liquid crystals’…. McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. pp. 91-2.

“The material of rod-like molecules … does something radically different [by having two melting points – first to cloudy liquid and then to clear liquid]. It moves from complete order (the crystal …) to complete disorder (the normal fluid …) by first freeing the three spatial degrees of freedom (and the one that allows the molecules to spin around their long axis) but keeping two of the rotational angles of freedom restricted. In this intermediate ‘semi-melted’ phase …, all the molecules point with their long axis in the same direction (longitude and latitude) just as they did in the crystal, but they are not free to move spatially to any place in the fluid–there is no spatial crystal lattice at all. At the lower melting temperature of cholesterol only the spatial lattice melted away, reacquiring its continuous symmetry but leaving the orientation of the rod-like molecules ordered. Only at the higher transition temperature do the remaining two degrees of rotational freedoms completely ‘melt’….

“The chemist and physicist working together really had discovered a new ‘phase’ of matter, in addition to the three classes of solid, liquid, and gas known from antiquity until that point. They needed a name for the new phase–‘nematic’ suggested itself from the worm-like nature of the molecular shapes that underlies its emergence.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 95.

“The Nagoya researchers had managed to encapsulate quantities of two proteins within the tiny self-assembled bag of surfactant membrane…. The components jostled about in the field of view under constant Brownian motion. Then something extraordinary happened–the vesicles began to distort from their natural spherical shape, throwing out extensions and becoming highly asymmetric…. The soft matter, rather than passively responding to its interactions and the environment in the usual inexorable slide towards thermal equilibrium, was actively moving and changing shape….

“They had managed to encapsulate within the vesicle a significant concentration of a protein molecule known as G-actin. Like the peptides…, appropriate solution conditions favour its self-assembly, and by a similar one-dimensional polymerization process. The G-actin units form extended, stiff polymers of filamentous or F-actin.

“The key to the research team’s special findings was, however, the third ingredient. A cross-linking protein, called myosin, possesses two sub-units that each bind to sites on the F-actin polymer strings–so acting just like the cross-links in a polymer gel. Myosin is no passive cross-linker, however, rather it draws on energy sources within the cell (and in particular the universal cellular ‘fuel’ molecule adenosine tri-phosphate) to actively pull its two attached filaments past each other. It is an example of a ‘molecular motor’…. But what the Japanese experiment and many others like it in recent years have shown is that the incorporation of active motor units such as myosin into artificial soft matter assemblies opens up an entire new world of materials, in which the local dynamics are driven chemically rather than simply by thermal motion [which chapter title calls ‘liveliness’].” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. pp. 115, 116-7.

“In this chapter we briefly review the current excitement of the new biologically inspired field of active soft matter. There is an extra motivation, for as well as exploring further emergent properties of soft matter in ‘active’ states, they can also be viewed as highly simplified versions of living matter, and so a first step on the long road of understanding the complexity of biology.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 119.

“… researchers in the 1990s began to notice, using subtle methods in optical microscopy, that behind a moving bacterium there appeared to be a long tail of denser medium. Analysis revealed that this tail was composed of a cross-linked gel of filamentous F-actin–the same self-assembled polymer used in the Japanese artificial cell mimics…. As the bacterium moves forward, the tail seemed continually to be forming around it. Not only was it using the surrounding host medium as an elastic framework to move through, the invader was taking the surrounding cell’s own supply of G-actin to create its propulsion system by building the continuously growing tail from it….

“They [French researchers] represented the cell interior as a weak elastic medium, within which a stronger elastic gel is being polymerized at the surface, but only at the rear, of the bacterium. The idea is that by creating new elements of the actin gel at its surface, the bacterium compresses the newly formed section of tail immediately surrounding it against the elastic resistance of the cell interior, so generating compressive elastic stresses there. Because these stresses impinge on the rear of the bacterium only, and not the front, there is a net (‘soap-squeezing’) force propelling it forward. As it does so, it leaves the actin tail behind in its wake, moving into a yet-unexplored region of the cell where it constructs a new section of tail….

“… the density of monomers in the tail slowly decreases away from the attachment point to the bacterium. This is an important clue to the additional trick played by actin polymerization: the monomers themselves have a ‘front’ and ‘rear’ end, and polymerize with a corresponding orientation along their polymers. Furthermore, the F-actin polymers grow at the site that displays bare ‘front’ ends of the monomers (abutting the bacterium) and tends to fall apart, or ‘depolymerize’, at the other terminus (far from the bacterium). This is wonderfully useful for the Listeria of course–for the continuous dissolving of the extreme rear end of the tail resupplies the cell with raw actin monomer that, after diffusing through the cell, can be reincorporated into the new filament….

“Yet pushing a bacterium through a high-viscosity cell medium most certainly requires work. For one thing, the friction of the Listeria through the fluid generates heat…. Although a polymerizing filament of gel does not look much like anything we would normally call a motor, it nevertheless manages to behave as one in the case of Listeria….

“The clue to the puzzle rests in the apparently harmless rule that the actin adds monomers at one end only [requiring ATP], while losing them at the other.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. pp. 120, 121, 122.

“Soft matter science started in the 20th century by providing a long-sought window onto the reality of the molecular world. It promises, a century later, to open up new insights into the biological world.” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 134.

“… through evolution, life itself has recruited the structures of soft matter for its own purposes. Polymers, membranes, liquid crystallinity, self-assembly form its fundamental constituents….” McLeish, Tom. 2020. Soft Matter: A Very Short Introduction. Oxford UP. p. 137.

“The goal of community is to make sure that each member is heard and is properly giving the gifts he or she has brought to this world.” Quotation of Sobonfu Somé. Hough, Susan. 2021. Walking With Sobonfu: A Guide to Claiming Your Authenticity and Deepening Your Sense of Community. Colorado Springs: Empower Press. p. 7.

“In Sobonfu’s words, a ritual is a ‘a ceremony in which we call in Spirit to be the driving force, the overseer of our activities… Dagara rituals are about healing, an acknowledgement of people and their gifts, and making Spirit visible or tangible.’” Hough, Susan. 2021. Walking With Sobonfu: A Guide to Claiming Your Authenticity and Deepening Your Sense of Community. Colorado Springs: Empower Press. p. 8.

“In my words, ritual is taking action when you want to shift, to move out of your head and into your heart. It’s not passive. It’s an opportunity to deepen your connection to yourself, your community, and your purpose. It can remove blocks and awaken you to your true self.” Hough, Susan. 2021. Walking With Sobonfu: A Guide to Claiming Your Authenticity and Deepening Your Sense of Community. Colorado Springs: Empower Press. pp. 8-9.

“In accounts of present-day life, lipid-mediated catalysis is largely non-existent…. However, primordial lipids appear to have been much more structurally and functionally diverse. This likely encompassed head groups with catalytic moieties, allowing a broad spectrum of chemical characteristics, including selective enhancement of reaction rates, as portrayed in the next section. Thus, protocellular lipids could harbour both catalysis and compartment-forming features, justifying the term ‘lipozymes’ for early lipid assemblies in a ‘lipid world’ scenario.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 870.

“Although the micellar scenario entails the loss of an aqueous core, with its payload of life-related polar compounds, lipid micelles can adsorb and/or enclose diverse molecules with a wide range of polarities.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 871.

“Numerous studies provide detailed information on the catalytic roles of diverse amphiphilic lipid molecules in a variety of micellar entities.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 871.

“In pioneering studies by Luisi and colleagues, fatty acid micelles were found to catalyse the hydrolysis of a precursor, leading to autocatalytic micellar reproduction.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 872; reference: Bachmann, P.A., P.L. Luisi & J. Lang. 1992. Autocatalytic self-replicating micelles as models for prebiotic structures.” Nature. 357:57-59.

“The above-mentioned portrayals [of micelles with distinct populations of catalytic moieties as head groups that make the micelles differentially persistent and reproducing] demonstrate a potential for catalytic micellar protocell precursors to store and transmit chemical information to the next generation, and to undergo compositional reproduction and selection, a basis for primal evolutionary attributes. As such, micellar protocell precursors constitute an appropriate departure point for a gradual evolutionary progression towards more complex protocells.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 875.

“Having lipid-attached amino acids and nucleobases on the same micellar surface could, thus, promote the co-evolutionary synthesis of peptides, oligonucleotides and other biomolecules, embodying even more life-like mutual interactions.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 875.

“On the one hand, we present extensive literature supporting catalytic properties of lipid micellar aggregates, thus bearing similarity to globular proteins in structure, size [micelles have similar size to average proteins of modern life] and underlying chemical functionalities. On the other hand, we reveal strong evidence that mixed lipid micelles can generate their own copies by growth and fission, mediated by collectively catalytic interactions. Such observations lend credence to the proposition that nanoscopic micellar protocell precursors could serve as evolutionary forerunners for more complex protocells.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 876.

“… for micelles, the same molecular assemblies that mediate collective catalysis and reproduction also delineate spatial containment. This contrasts with a process in which, en route to protocells, biopolymers have to join forces with a separately formed, chemically orthogonal lipid container [as with vesicles]. In other words, micellar aggregates made of appropriately functionalized lipids appear to be the only chemical entities that possess the three pillar attributes of the life-like function in one go – catalysis, reproduction and containment.” Kahana, Amit & Doron Lancet. 2021. “Self-reproducing catalytic micelles as nanoscopic protocell precursors.” Nature Reviews; Chemistry. 5(12):870-8. doi: 10.1038/s41570-021-00329-7. p. 876.

“Increasingly, even though both ecological psychologists and enactivists agree that agency must be explained by focusing on the relation between the organism and the environment instead of the individual’s representational states, they have evolved their own individual (and largely independent) approaches to it, focusing on different aspects of the organism-environment relation.” Segundo-Ortin, Miguel. 2020. “Agency From a radical Embodied Standpoint: An Ecological-Enactive Proposal.” Frontiers in Psychology. 11(19):1-13. p. 2.

“I have proposed that there is a mutual fit between enactivism and ecological psychology, and that both theories can complement each other to explain sensorimotor agency. According to this view, the environment, as conceived of by ecological psychologists, contributes to the emergence of agential behavior by providing the organism with information about affordances, and agential behavior depends on the enactment of habitual patterns that integrate structures at the level of the organism with action-specific ecological information.” Segundo-Ortin, Miguel. 2020. “Agency From a radical Embodied Standpoint: An Ecological-Enactive Proposal.” Frontiers in Psychology. 11(19):1-13. p. 11.

“In competent organisms, including starfish, planaria, salamanders, and deer, lost limbs, damaged organs, or even the entire body may be regenerated until this same stable, species- or variety-typical, adult morphology is restored. Thus, regeneration and regulative development are individual cases of a more general biological process: anatomical homeostasis, which is able to robustly achieve a specific large-scale geometry despite drastic perturbations such as amputation and from different starting conditions…. Similarly, some embryos can be cut in half, fused with others, or implanted with aggressive cancer cells, and still result in perfectly normal bodies. These kinds of examples illustrate how anatomical homeostasis can reach the same large-scale anatomy from diverse starting conditions and other perturbations. We will refer to such a stable endpoint of development or regeneration, averaged over species- or variety-typical outcomes, as the ‘target morphology’ of the species or variety.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. pp. 57-8.

“The Neo-Darwinian movement of the mid-20th century largely discredited ‘orthogenetic’ conceptions of evolutionary variation as somehow directed or constrained, replacing them with a conception of variation as strictly random.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 59.

“Here we introduce two lines of argument for a deep mechanistic coupling between variation and selection, and hence for a view of evolutionary processes as search processes in a space with invariant attractors. The first is that the processes we characterize as ‘evolution’ and ‘development’ differ primarily in scale. Indeed as pointed out previously, all of life since LUCA can be viewed as a single, continuous cell lineage; hence evolution can be viewed as a developmental process with LUCA as the ‘zygotic’ founder cell…. The second line of argument builds on Friston’s observation that all living systems face a thermodynamic requirement to minimize the variational free energy (VFE) – effectively, the unpredictability – of their environments. We have argued previously that the transition to multicellularity can be viewed as a VFE minimization strategy. Briefly, reproductive (i.e. stem) cells can be expected to produce ‘bodies’ comprising non-reproductive (i.e. somatic) progeny as protection against sufficiently-challenging environments. If the transition to multicellularity can be understood in effectively thermodynamic terms, as a general response to selective pressures that works independently of minor details or contingencies, might not the other major transitions be similarly understandable?” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 60.

“It is also now clear that ‘bottom-up’ sequence information is insufficient to specify the mature structure of most functional RNAs; a myriad of proteins, some specific to particular RNAs or classes of RNAs, are also required for correct folding. These ancillary proteins are therefore, also contributors of instructive information to the folding process. From the RNA’s perspective, they are parts of the environment that provide top-down information or, in the more usual language, constraints….

“There is now considerable evidence that proteins fold incrementally, with already-folded domains providing higher-level constraints on the folding of later domains as well as on domain assembly. Additional high-level constraints may be provided by chaperone proteins or other cofactors present in the ‘typical’ environment. Hence as in the case of RNA, information at multiple scales is required to achieve the molecular-scale target morphology.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 62.

“Single genomes can support multiple target morphologies, in unicells and facultative multicellulars as well as in obligate multicellulars including metazoa. Target morphology can be preserved despite significant genetic change, e.g. in planaria which maintained a fixed morphology and behavioral repertoire over 20 years of asexual reproduction despite the accumulation of non-synonymous codon substitutions in 74% of predicted genes. On the other hand, small changes in the genome, or in environmental conditions including bioelectric signaling, diet, toxins, parasites, and commensal bacteria etc. can produce large changes in final morphology as well as function.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 63.

“The processes that maintain homeostasis can, as Friston emphasizes, be considered inferential: they are processes that compare external conditions to the memory and adjust one or the other, what Friston calls ‘active inference.’ The most fundamental requirement of any such process is that ‘external conditions’ and ‘memory’ be separately accessible. Maintaining homeostasis, therefore, requires a boundary.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 65; reference: Friston, Karl J. 2013. “Life as we know it.” Journal of the Royal Society Interface. 10. 20130475.

“Within a VFE minimization or active inference framework, the primary driver of evolution is predictability. For a cell equipped with a memory, the most predictable state is the state of its own memory: homeostasis is precisely the process of keeping this state fixed.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 66.

“If the states of other cells are more predictable than the state of the open environment, any cell that associates closely with other cells achieves an increase in predictive success, i.e. a decrease in VFE. Hence facultative multicellularity is a direct prediction of the VFE minimization framework. Any evolutionary process capable of producing cellular life can be expected to generate facultatively multicellular life.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 66.

“By coupling reproductive cycles, obligate endosymbiosis assures that components that work well together stay together. From an information-processing perspective, this represents an increase in computational power, one that enables more efficient search of fitness landscapes that are rugged on multiple scales. A capability for more efficient search is, effectively, evolvability. Hence one can expect evolutionary processes to generate, via endosymbiotic or other reproductive-coupling processes, systems that are progressively more evolvable.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 66.

“Given such a starting point – a bounded ‘cell’ that can talk to other cells – an evolutionary process will display major transitions if it is able to replicate this basic organizational structure on larger and larger scales. The key to achieving larger scales is, however, built into the system. Aggregating small entities will produce a large entity, and small entities can be expected to aggregate for protection from their environment. The pre-adaptation needed by the small entities to act as a larger unit is communication. This communication can be cooperative, but can also be coercive. Both communication styles were discovered, on Earth, by bacteria. We would expect them to be discovered at an early stage in any evolutionary process.

“These considerations suggest that the ‘direction’ of evolution is not toward higher complexity per se as often believed, but rather toward larger scales. Dynamics at larger scales is not more complex than dynamics at smaller scales; large-scale dynamics rather replicates smaller-scale dynamics using larger components. Complexity at the whole-system level increases due to the hierarchization resulting from this embedding.” Fields, Chris & Michael Levin. 2020. “Does Evolution Have a Target Morphology?” Organisms. 4(1): 57-75. doi: 10.13133/2532-5876/16961. p. 68.

“Contextual organismality begins from the recognition that the condition of organismality is not fixed but instead depends on context. Its goal is to elucidate the ecological contexts under which entities act as organisms.” Diaz-Munoz, Samuel L., Amy M. Boddy, Gautam Dantas, Christopher M. Waters & Judith L. Bronstein. 2016. “Contextual organismality: Beyond pattern to process in the emergence of organisms.” Evolution. 70(12):2669-2677. doi: 10.1111/evo.13078. p. 2670.

“Thus, contextual organismality goes beyond a snapshot in evolutionary time to identify the ecological processes, mechanisms, and traits that solidify or dissolve organismality.” Diaz-Munoz, Samuel L., Amy M. Boddy, Gautam Dantas, Christopher M. Waters & Judith L. Bronstein. 2016. “Contextual organismality: Beyond pattern to process in the emergence of organisms.” Evolution. 70(12):2669-2677. doi: 10.1111/evo.13078. p. 2672.

“It is straightforward to envision that loose interactions, such as interspecific mutualisms, incorporate both cooperation and conflict and are context dependent. Indeed, context dependency is increasingly recognized to be a key feature driving the evolutionary dynamics of mutualism.” Diaz-Munoz, Samuel L., Amy M. Boddy, Gautam Dantas, Christopher M. Waters & Judith L. Bronstein. 2016. “Contextual organismality: Beyond pattern to process in the emergence of organisms.” Evolution. 70(12):2669-2677. doi: 10.1111/evo.13078. p. 2672.

“Honey bee colonies, long considered organisms or superorganisms, also represent a case in which a shift in cooperation-conflict levels occurs according to developmental timing. When a colony reproduces, potential honey bee queens are intensely aggressive and show no cooperation, as they engage in fatal physical combat to determine the reigning queen. After the sole queen is established, the group develops into a unit with low conflict and very high cooperation.” Diaz-Munoz, Samuel L., Amy M. Boddy, Gautam Dantas, Christopher M. Waters & Judith L. Bronstein. 2016. “Contextual organismality: Beyond pattern to process in the emergence of organisms.” Evolution. 70(12):2669-2677. doi: 10.1111/evo.13078. p. 2672.

“In contrast, the organismality of entities that are unequivocally considered organisms, such as human individuals, is largely unaffected by ecological context. The ‘largely’ qualifier is necessary, because particular circumstances such as pregnancy or autoimmune disease can increase conflict within a human, although not to the point of calling into question its existence as an organism. That is, the cooperative and low-conflict interactions among cells that make up human individuals persist under a wide variety of circumstances….

“Thus, a lack of context dependency can be used as an indicator of an organism, that is, a group that preserves high cooperation and low conflict among the parts across widely divergent contexts.” Diaz-Munoz, Samuel L., Amy M. Boddy, Gautam Dantas, Christopher M. Waters & Judith L. Bronstein. 2016. “Contextual organismality: Beyond pattern to process in the emergence of organisms.” Evolution. 70(12):2669-2677. doi: 10.1111/evo.13078. p. 2674.

“We believe structure, function, and evolution of biopolymers are explained and best-described by their relationships with each other. RNA and protein are Molecules in Mutualism.” Lanier, Kathryn A., Anton S. Petrov & Loren Dean Williams. 2017. “The Central Symbiosis of Molecular Biology: Molecules in Mutualism.” J Mol Evol. 85:8-13. doi: 10.1007/s00239-017-9804-x. p. 9.

“Mutualisms (i) sponsor co-evolution, (ii) foster innovation, (iii) increase fitness, (iv) inspire robustness, (v) are resilient and resistant to change, and (vi) involve partners that are distantly related with contrasting yet complementary proficiencies.

“Mutualisms are understood to operate on levels of cells, organisms, ecosystems, and even societies and economies. The eukaryotic cell is a culmination of mutualism between simpler prokaryotic cells. The majority of land plant families are mycorrhizal; this plant-fungi mutualism is traceable to the origins of land plants.” Lanier, Kathryn A., Anton S. Petrov & Loren Dean Williams. 2017. “The Central Symbiosis of Molecular Biology: Molecules in Mutualism.” J Mol Evol. 85:8-13. doi: 10.1007/s00239-017-9804-x. p. 9.

“Organismal-level mutualisms are generally characterized by large phylogenetic distances, for example between metazoans and the microbes that live within their alimentary tracts. Large phylogenetic distance yields great differences in metabolic or functional proficiencies. It is less likely that two primate species, for example, would develop a mature mutualism because the partner proficiencies are similar rather than complementary.” Lanier, Kathryn A., Anton S. Petrov & Loren Dean Williams. 2017. “The Central Symbiosis of Molecular Biology: Molecules in Mutualism.” J Mol Evol. 85:8-13. doi: 10.1007/s00239-017-9804-x. p. 11.

“By contrast [to other results from genome wide sequencing], the results for healthcare have been disappointing. Only in rare genetic diseases do we find strong associations. For most multi-factorial diseases we find low associations with individual genes. Some now favor the omnigenic hypothesis: all genes are involved one way or another in any particular function of the body.” Noble, Denis & Peter Hunter. 2020. “How to link genomics to physiology through epigenomics.” Epigenomics. 12(4):285-7. doi: 10.2217/epi-2020-0012. p. 285; reference to omnigenic hypothesis: Boyle, E.A. Y. Li & J.K. Pritchard. 2017. “An expanded view of complex traits: from polygenic to omnigenic.” Cell. 169:1177-86.

“… in yeast, as many as 80% of knockouts appear to have little or no functional effect in well-fed conditions, yet we know that the majority of the proteins involved are functional. The reason is that physiological/biochemical networks are very effective at buffering their functionality from genomic change. They have to be. That came about through the evolution of robustness; networks employ epigenetic control mechanisms to achieve this.” Noble, Denis & Peter Hunter. 2020. “How to link genomics to physiology through epigenomics.” Epigenomics. 12(4):285-7. doi: 10.2217/epi-2020-0012. p. 285.

“The progression genomics –> epigenomics –> physiology therefore also works in the opposite direction: physiology –> epigenomics –> genomics. In these causal relationships, genomics refers to DNA sequences, epigenomics refers to gene control through DNA and histone marking and physiology refers to the networks that can cause all of this control to happen.” Noble, Denis & Peter Hunter. 2020. “How to link genomics to physiology through epigenomics.” Epigenomics. 12(4):285-7. doi: 10.2217/epi-2020-0012. p. 285.

“In fact, many OOL models use the same general framework and are governed by common precepts. A primary theme of many OOL models is the specification of one, or in some cases two, ‘privileged function(s).’ Privileged functions are extant biological functions that are considered by OOL model builders to be so essential and fundamental to life that they must also be a requisite for the origin of life.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. p. 85.

“Conventional scientific models are falsifiable. OOL models are not.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. p. 86.

“The Universal Gene Set [‘the set of genes shared as orthologs throughout the tree of life, and found in essentially every living system’] is small and distinctly non-random. Koonin’s version of the Universal Gene Set, for example, contains around 65 genes. Fifty-three universal genes are directly involved in translation… The Pace and Doolittle versions are very similar to the Koonin Universal Gene Set.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. p. 88.

“However, 1.5-2.0 billion years after LUCA, with the Great Oxidation Event (GOE), the oxidative potential of the biosphere changed, the chemical stability of guanine declined. Rates of guanine degradation in biological systems increased markedly. In the oxidizing environment of the extant post-GOE earth, around 100,000 guanines per mammalian cell are degraded to 8-oxoguanine each day…. Oxidative damage to guanine in humans leads to mutagenesis, genetic instability, aging, and cancer. The inclusion of guanine in the Molecular Toolbox is a demonstration of evolution’s lack of foresight.

“For the last 2 billion years, biological systems have been under intense pressure brought on by chemical instability of guanine….

“Since the GOE, evolution has tinkered. Biology has produced elaborate and multilayered systems to repair 8-oxoguanine, and to chemically push it uphill, back to guanine…. The persistence of guanine demonstrates that the Molecular Toolbox is fixed; alterations of the toolbox are effectively prohibited.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. p. 89.

“A useful OOL model should account for and predict the contents and the robustness of the Universal Gene Set and the Molecular Toolbox. Why are the Universal Gene set and Molecular Toolbox so robust over time and environment?… The answers appear to be found in dependencies, which are relationships in which change in one element induces change in another element. Systems with the most extensive and far-reaching dependencies are most resistant to evolutionary change.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. pp. 89-90.

“The Universal Gene Set lacks genes for the privileged functions that define conventional OOL models. The Universal Gene Set lacks genes for RNA polymerase ribozymes and metabolic ribozymes and membrane biosynthesis. Ironically, the translation system, which dominates the Universal Gene Set, is an afterthought to each of the privileged function OOL models.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. p. 90.

“A primary attraction of conventional OOL models and their privileged functions is an appearance of simplicity…. These models invoke genetic-takeovers and toolbox replacements, which are required for transitions from privileged function worlds to extant biology. In fact, once the takeover processes are acknowledged and are reasonably considered, the privileged function models are seen to be extremely complex with poor predictive power; they require indeterminacy and plasticity in the rulebook that governs biological processes

“Occam’s razor, which states that the simplest hypothesis is most probable, supports a model in which the Universal Gene Set and Molecular Toolbox were robust not only post-LUCA but pre-LUCA and were not re-invented by Darwinian processes, and that genetic and catalytic takeovers are unlikely. In this scenario, RNA, DNA, and protein and the Molecular Toolbox co-evolved in a cooperative and symbiotic process, with joint participation of many molecular participants and processes during the OOL and during the conversion from chemical to biological evolution. In this scenario, there were no privileged functions. If these conservative assumptions are correct, then conventional models of the OOL, with their privileged functions, require reconsideration.” Lanier, Kathryn A. & Loren Dean Williams. 2017. “The Origin of Life: Models and Data.” J Mol Evol. 84:85-92. doi: 10.1007/s00239-017-9783-y. pp. 90-1.

“Natural selection is neither the only, nor the most general process that drives biological evolution. It is a manifestation of a more general but underestimated persistence principle, for whose temporal–and hence evolutionary–consequences we have proposed the name ‘stability-based sorting’ [SBS]….

“Our broad concept of stability that consists of (1) static stability and SBS in its strict sense and usual conception, i.e. the accumulation of temporally persistence unchanging entities and characters, and (2) sorting based on dynamic stability, i.e. selection, being a special case of this phenomenon in systems of entities replicating with heredity has broader scope than any other attempt to study these phenomena in the field of evolutionary biology or related disciplines.” Toman, Jan & Jaroslav Flegr. 2017. “Stability-based sorting: The forgotten process behind (not only) biological evolution.” Journal of Theoretical Biology. 435:29-41. doi: 10.1016/j.jtbi.2017.09.004. p. 38.

“Chemists in general are quick to personify their molecular and atomic building blocks. If you’ve not already got one in your hands, grab a recent copy of any chemistry journal. Substituents are directive, transitions are forbidden, some groups take their leave and others attack. Bonds can even negotiate with reactions….

“Molecules, our standard language suggests, are not only animate, but they have feelings – deep desires and profound aversions. Electron-deficient atoms want more electrons. Nucleophiles and electrophiles would love to find each other. And how many protein active sites cower in fear of water? We feel for our molecules.” Francl, Michelle. 2018. “It’s alive!” Nature Chemistry. 10:993-4. p. 993.

“If such a premise [metabolism on its own terms… as a chemistry that is strongly linked to biological phenomena, but not fully subordinate to them] is accepted and metabolism is postulated to stand at the interface between chemistry and biology, then one is forced to address: (i) the criteria to distinguish minimal forms of metabolism from simpler sets of chemical reactions; and (ii) a plausible scenario from which more complex expressions of metabolism could progressively develop, all the way to genetically-instructed metabolisms, like the ones we observe today in nature.” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. p. 2.

“Minimal metabolisms would stand at the interface between non-equilibrium complex chemistries and biological systems. As major prebiotic transitions unfold, the complexity of the corresponding phenomena should increase, together with the capacity to develop autonomous control mechanisms. Whereas chemical diversity decreases, in the sense that only a subset of all possible molecular compounds/types of reactions is exploited by living systems, functional diversity increases, in the sense that these systems manage to generate and couple together a wider variety of inter-dependent components and transformation processes.” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. p. 2.

“A basic feature, sometimes forgotten because it is rather uncontroversial, is the fact that metabolism is a non-reducible, systems construct. Indeed, all the traditional models on ‘minimal living organization’, conceive of it as a coupled set of diverse molecules and transformation processes that cannot be scaled down, by definition, to a particular component or reaction…. This feature (the non-reducibility to molecular mechanisms) may seem obvious now, in the era of systems biology, but it has a fundamental consequence for our purposes here: metabolism must be defined in relational terms (i.e., through an account that includes–and typically highlights–the relationships among the different components of a system, not just the components themselves).” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. pp. 2-3.

“… the main role of metabolism is the production of the material building blocks and the means of energy from which all living organisms continuously build and repair themselves. However, this fundamental, ‘enabling power’ of metabolism cannot be maintained in time unless it is realized in a way that it feeds back on itself. In other words, metabolisms constitute real phenomena only if, in addition to a network of coupled chemical transformations providing matter/energy resources, a complementary functional relationship with–at least, part of–the actual products of those transformations is established. Such a functional relationship is accomplished thanks to the constraining effects that an adequate combination of products happen to exert on the underlying dynamics, responsible for their synthesis.” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. p. 3.

“Thus, in our account, the two levels [of a truncated cone where two flat truncations correspond to constraints and processes that are each considered to be non-reducible networks where they are tied together by synthesis proceeding from processes and control stemming from constraints] would be populated by a diversity of molecular compounds in mutual dynamic transformation, although their relative stability, modes of interaction and causal effects would differ. In a first approximation, one could think about the ‘lower level’ [bottom and larger cross section of cone corresponding to synthesis processes] as the one in which basic metabolites diffuse, bump into each other, react and transform into other chemical species. In turn, the ‘higher level’ would be one in which some more elaborate products of those reactions (e.g., oligomers, supramolecular structures), whose characteristic lifetimes are longer than typical reaction times, come together to exert a number of constraining actions on the former. We can say that it is a functional bootstrapping because the recurrent loop between synthesis and control (the complex interconnection between those two circular areas of each plane) is precisely what causally explains the self-maintenance of the system….

“The main novelty of this proposal is the irreducible molecular and interactive diversity at each level and thereby, for the whole system. More explicitly stated, we put forward that any effective functional bootstrapping between synthesis and control, our key condition for metabolism, requires an inherent variety of components and interactions at each level of description. Depending on the physico-chemical couplings and mutual reinforcement relationships established among those various components and transformation processes, a number of different cyclic, self-constructing organizations could be put together, with different degrees of dynamic robustness.” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. p. 5.

“To address that search [for specific sets of reactants, transformation processes, constraints and overall conditions that satisfy above minimal metabolism concept], we just want to highlight that the graphical metaphor of the ‘truncated cone’ means that the exploration should involve chemical mixtures that bring about irreducible combinations of molecules and supramolecular structures with qualitatively different constraining effects on the reaction processes. For instance, in accordance with [previous work: Ruiz-Mirazo et al. 2017. “Chemical roots of biological evolution: The origins of life as a process of development of autonomous functional systems”], one should investigate chemical networks that produce catalysts (for kinetic control), self-assembling amphiphiles (for spatial control), common intermediaries to couple endergonic-exergonic processes (for energetic control), and template structure (for variability control).” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. pp. 5-6.

“Adopting this two-level perspective has important implications in terms of how we conceive–and thus, how we propose to investigate–the viability conditions for proto-metabolic systems, as well as their evolutionary development. With regard to the underlying network of physico-chemical transformation processes, among other features that one may consider, the fundamental requirement that stands out, from our approach, is controllability. Not an external (e.g., human) or ubiquitous (e.g. thermodynamic) type of controllability but, rather, the implementation of reaction networks that develop, locally, their own control mechanism and transform themselves through those mechanisms. This brings forward an important shift of focus that should be more explicitly addressed in the field. After all, why do metabolic processes take place in non-equilibrium conditions? Why do they tend, so often, to get organized in cycles? Why do they establish couplings through a small set of common molecular intermediaries? A unifying answer to all these questions is that the network becomes much easier to control under those circumstances. Hence controllability, endogenous or autonomous controllability, appears as an essential and pervasive feature, to be more carefully examined through experimental work.” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. p. 6.

“This dual perspective also prompts thinking about the development of metabolism in terms of a co-evolution or a co-determining process between reaction networks and concurrent molecular constraints operating on them, which can be helpful in order to identify the potential bottlenecks involved. For instance, it makes us realize that chemical transformations, if they are to become metabolic, should imply, right from the beginning, a landscape with significant kinetic (and probably also energetic) barriers. Although it might seem counterintuitive, one should investigate reactions that do not run, or hardly run, but nevertheless hold the potential to be run more efficiently, provided that they start producing the suitable catalysts, or that they couple with other, enabling processes. Direct thermodynamic control of a reaction is thus to be avoided–or very cautiously used–by experimentalists.” Lauber, Nino, Christoph Flamm & Kepa Ruiz-Mirazo. 2021. “‘Minimal metabolism’: A key concept to investigate the origins and nature of biological systems.” BioEssays. 43:2100103. doi: 10.1002/bies.202100103. p. 6.

“… Prebiotic Systems Chemistry … the emerging covalent and non-covalent interactions between molecules / supramolecules, leading to a network of reaction pathways and transformations with potential for feedback and chemical evolution.” Krishnamurthy, Ramanarayanan. 2020. “Systems Chemistry in the Chemical Origins of Life: The 18th Camel Paradigm.” Journal of Systems Chemistry. p. 42.

“The desire to connect one prebiotic data point (ribose, amino acids, and nucleobases in prebiotic chemistry and in meteorites) with the second biological data point (the same molecules in extant life), separated by millions of years by simple extrapolations, has led to an apparent straight line that has misled (and still is misleading) this field. … we are trying to solve the Origins of Life problem with what is observed in biology and then limiting the search to only those molecules in prebiotic chemistry, while ignoring the rest of the prebiotic inventory.”

“… it is not possible to solve the problem [father dies while willing his 17 camels to three sons with the following instructions: ½ to oldest, 1/3 to second son, and 1/9 to youngest son] with the given parameters and have a full camel at the end. As the anecdotal story goes, the three sons unable to solve the problem visit a wise old man who patiently listens to them and declares that he can solve the problem. The wise old man adds one of his own camels to the pack of 17 to make it 18. Then he reads the will of the father and gives ½ of 18 to the first son, 1/3 of 18 to the second son, and the 1/9 of 18 to the third son. If we add up those numbers 9+6+2, it comes out to 17 camels. The remaining camel was taken back by the wise old man, thus solving the seemingly unsolvable problem.” Krishnamurthy, Ramanarayanan. 2020. “Systems Chemistry in the Chemical Origins of Life: The 18th Camel Paradigm.” Journal of Systems Chemistry. pp. 46-7, 47.

“Thus, from a Systems Chemistry point of view, the interaction of mixture of α-hydroxy acids with α-amino acids, by the process of removal of water by drying, naturally led to the appearance of the peptide bond as consequence of a) the kinetics of ester bond formation, which then b) allowed the attack of the amino group of the amino acid to form the thermodynamically stable amide bond. In this process, the α-hydroxy acid was first consumed to form an ester and then was regenerated when the amide bond was formed. In other words, the α-hydroxy acid was catalyzing the peptide-bond formation, and therein lies the connection [to] the “18th camel story’! The α-hydroxy acid was the ‘18th camel’ that was added to solve the ‘17 camel problem’ of trying to make peptide bond starting from only amino acids based on the ‘will of the father’. What is more intriguing is that this principle of ester formation, followed by amine attack to make the peptide bond, is exactly the same chemistry that takes place within the ribosome….” Krishnamurthy, Ramanarayanan. 2020. “Systems Chemistry in the Chemical Origins of Life: The 18th Camel Paradigm.” Journal of Systems Chemistry. pp. 48-50.

“We were able to achieve a proof-of-principle demonstration of this [temporary catalysis by a chimeric component that leads to regular biotic chemistry], wherein a brew of the RNA ligands along with the chimeric RDNA ligands [nucleic acid backbones made of mixtures [of ribose sugar isomers, some DNA, some RNA] in the presence of the RDNA template produced much more (160%) of the final RNA product when compared to the mixture that lacked the chimeric RDNA ligands (108%). This result, combined with the others described above, clearly shows the advantages of the Systems Chemistry modus operandi, and what outcomes can be obtained – the very same ones that have been very difficult to attain when pursuing experiments based on an RNA-only scenario. The ‘18th camel’, in this example, would be the chimeric RDNA sequences, which (when added to the mixture) enable the emergence of the homogeneous RNA and DNA backbones, but they themselves (as chimeric sequences) are not present in the final biologically functionally relevant systems.” Krishnamurthy, Ramanarayanan. 2020. “Systems Chemistry in the Chemical Origins of Life: The 18th Camel Paradigm.” Journal of Systems Chemistry. p. 56.

“At first glance it may appear wasteful to continuously dissipate energy to sustain a self-assembled structure, but such dissipation has some important consequences. Firstly, it enables decoupling the mechanical properties of the assembly from its dynamics. For microtubules, the dissociation rate of tubulin-GTP is almost 3000 times lower compared to its hydrolysed diphosphate analogue, tubulin-GDP. This means that a microtubule is robust when fuelled by GTP (with persistence lengths of up to 8 mm for a long microtubule), whereas it can quickly disassemble when GTP is converted to GDP. The result is a strong yet dynamic structure, a combination which is not easily achieved through other means!

“Secondly, dissipative self-assembly using chemical fuels allows forming structures that are not determined by their thermodynamic stability, but rather by the rates of assembly and disassembly.” Ashkenasy, Gonen, Thomas M. Hermans, Sijbren Otto & Annette F. Taylor. 2017. “Systems chemistry.” Chem. Soc Rev. 45:2543-2554. doi: 10.1039/c7cs00117g. p. 2544.

“One can distinguish between different types of non-equilibrium systems, including kinetically trapped systems that reside in a metastable state, or systems that are in transition from a higher to a lower chemical potential. The most interesting systems, however, are those in continuously dissipative non-equilibrium steady-states. Such states are able to do work and show behaviour that, in isolation, would defy the second law of thermodynamics. But, as these systems are not isolated but linked to an energy input, behaviour such as unidirectional movement, population of thermodynamically disfavoured assemblies and oscillations … are made possible. The first requirement for such continuously dissipative systems is the presence of concurrent processes of formation/addition and destruction/removal of molecules and/or molecular assemblies. Such chemistry is underdeveloped. Once feedback is coupled to a formation/ destruction system exciting functional behaviour may emerge.” Ashkenasy, Gonen, Thomas M. Hermans, Sijbren Otto & Annette F. Taylor. 2017. “Systems chemistry.” Chem. Soc Rev. 45:2543-2554. doi: 10.1039/c7cs00117g. p. 2548.

“[The] Benefit of using photochemistry is that, unlike chemical fuels, these processes do not produce waste chemicals. In contrast, chemically fuelled processes have the advantage of allowing selective coupling to other processes in the system, which is more difficult when using photochemistry.” Ashkenasy, Gonen, Thomas M. Hermans, Sijbren Otto & Annette F. Taylor. 2017. “Systems chemistry.” Chem. Soc Rev. 45:2543-2554. doi: 10.1039/c7cs00117g. p. 2549.

“To date, three thermodynamic models have been established for characterizing complex chemical systems: (i) systems under thermodynamic control, where a minimum energy state is reached, (ii) systems under kinetic control that can be trapped in local kinetic minima or driven by irreversible processes, and (iii) systems sustained far-from-equilibrium propelled by continuous energy input. Each of these models can generate unique molecular networks, and have proven useful in the construction of receptors, sensors, and catalysts. Reaction networks involving kinetic feedback loops can show adaptive behaviours, and out-of-equilibrium networks can exhibit unique functions such as selective information storage and propagation, molecular oscillation, and fueled unidirectional macromolecular motions.” Bai, Yushi, Agata Chotera, Olga Taran, Chen Liang, Gonen Ashkenasy & David G. Lynn. 2018. “Achieving Biopolymer Synergy in Synthetic Systems.” Chemical Society Reviews. 47:5444-56. doi: 10.1039/C8CS00174J. p. 5444.

“Even though the field of integrated molecular networks remains young and advanced functionalization is just beginning, the design of amphiphilic peptide networks that enable self-guided assembly into well-defined architectures is yielding new functional peptide scaffolds. During the past decade, peptide fibril models have been used for scaffolding cell tissues, drug delivery, catalysis, self-replication, and bio-electronics. While peptide-based functionalization efforts provide a great starting point, they appear to be merely the very tip of a vast repertoire of future more complex integrated networks that are either compatible with or orthogonal to biology. Some critical investigations have now begun to address the three dimensions required for the design of such dynamic scaffolds: covalent macromolecular interactions -> supramolecular non-covalent assembly -> emergent functionality.” Bai, Yushi, Agata Chotera, Olga Taran, Chen Liang, Gonen Ashkenasy & David G. Lynn. 2018. “Achieving Biopolymer Synergy in Synthetic Systems.” Chemical Society Reviews. 47:5444-56. doi: 10.1039/C8CS00174J. p. 5449.

“A synthetic mimic of viral structure was developed by the synergistic co-assembly of a short peptide and plasmid DNA.” Bai, Yushi, Agata Chotera, Olga Taran, Chen Liang, Gonen Ashkenasy & David G. Lynn. 2018. “Achieving Biopolymer Synergy in Synthetic Systems.” Chemical Society Reviews. 47:5444-56. doi: 10.1039/C8CS00174J. p. 5451.

“Despite hypotheses for an RNA (only) world transition to living systems, biological systems are marvelously mutualistic networks of bio-polymer co-assemblies and life’s origins must reflect these synergies.” Bai, Yushi, Agata Chotera, Olga Taran, Chen Liang, Gonen Ashkenasy & David G. Lynn. 2018. “Achieving Biopolymer Synergy in Synthetic Systems.” Chemical Society Reviews. 47:5444-56. doi: 10.1039/C8CS00174J. p. 5453.

“While both peptide and nucleic acid precursors can form in prebiotic environments from simple building blocks, it is the synergistic assembly and mutualistic functions that must emerge to achieve the Central Dogma that provided the Darwinian threshold of cellular life.” Bai, Yushi, Agata Chotera, Olga Taran, Chen Liang, Gonen Ashkenasy & David G. Lynn. 2018. “Achieving Biopolymer Synergy in Synthetic Systems.” Chemical Society Reviews. 47:5444-56. doi: 10.1039/C8CS00174J. p. 5453.

“… the synergism hypothesis asserts that it was the functional (selective) advantages associated with various forms of synergy that facilitated the evolution of complex, functionally-organized biological and social systems.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 91.

“… chaotic systems may also spontaneously ‘crystalize’ stability and order under various circumstances. Indeed, in certain configurations of random Boolean (or on-off switching) networks, dynamical systems may spontaneously evolve stable patterns. In the three-dimensional ‘state spaces’ that are used to model Boolean network processes, these steady states are zero-dimensional points that are referred to as ‘dynamical attractors.’ In effect, these are models of self-organized synergy.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 94.

“Many years ago, Theodosious Dobzhansky voiced what still stands as the most important scientific objection to such orthogenetic and non-selectionist visions. The basic problem he noted, is that these theories implicitly downgrade the contingent nature of life and the basic problem of survival and reproduction. In fact, they explain away the very thing that requires an explanation: ‘No theory of evolution which leaves the phenomenon of adaptedness an unexplained mystery can be acceptable’. There’s the rub. Order is not a synonym for adaptation, and adaptation in nature depends on functional design.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 96.

“This is where the phenomenon of functional synergy (and the subcategory of symbiosis) fits into the evolutionary picture: It is the immediate, bottom-line payoffs of synergistic innovations in specific environmental contexts that are the causes of the biological/behavioral/cultural changes that, in turn, lead to synergistic longer-term evolutionary changes in the direction of greater complexity, both biological and cultural/technological.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 106.

“The process of complexification in evolution has been closely linked to the production of novel, more potent forms of synergy. That is, the ‘progressive’ differentiation and/or integration of various ‘parts,’ coupled with the emergence of cybernetic regulation and the development of hierarchical controls, has been driven by the ‘mechanism’ of functional synergy; synergistic effects of various kinds have been a primary cause of the observed trend toward more complex, multi-functional, multi-leveled, hierarchically-organized systems….

“Returning to another point raised earlier, we can now also see why it may be said that, at least in the process of evolutionary complexification, wholes have been more important units of selection than parts. It is wholes of various sorts that produce the synergies that then become the objects of positive selection (i.e., differential survival and reproduction); synergistic relationships – of various kinds and at various levels of organization – have been important ‘units’ of evolution. In other words, the Synergism Hypothesis is a theory about the causal role of the relationships among biological phenomena; it is a theory about relationships. Synergistic combinations, whether they arise through an integration of various parts (symbioses) or through the differentiation and ‘progressive’ specialization of an existing whole (or for that matter through various agglomerative processes with synergistic outcomes), may provide a competitive advantage.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 107.

“However, it should be stressed that synergy is not the same as functional synergy in terms of the problem of survival and reproduction, and self-organization is not equivalent to functional organization. Since there is no theoretical restriction on how synergy may arise in evolution, the only issue is whether or not self-organizing phenomena are exempted from, or conform to, the imperatives of functional viability; are these self-organized synergies compatible with the functional requirements for survival and reproduction, or do they exist ‘despite’ natural selection, as we have defined it here? I believe that, for the most part, it will prove to be the case that autocatalytic and self-organizing phenomena are also subject to the editorial screening of natural selection. Thus, to reiterate, functional synergy may be the bridge that connects self-organization and natural selection….

“In sum, a fully adequate theory of evolution must encompass both self-organization and selection.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 108.

“A common source of confusion in the contemporary literature on self-organization has to do with a widespread failure to differentiate between the two radically different kinds. One form of self-organization is non-purposive in nature and should be called ‘self-ordering,’ while the other form is ends-directed; it has a systemic purpose…. … the latter implies functional design – ‘adaptations’ (and structures) that are either directly or indirectly products of natural selection.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 108.

“With the emergence and increasing scope of cybernetic self-control, a subtle but important dividing line was crossed in evolution; self-organization was augmented by self-determination. Accordingly, a fundamental challenge for autocatalytic, self-ordering theories of evolution is this: Can hierarchical, cybernetic controls evolve spontaneously?” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 109.

“Thus, it may be useful to introduce the notion of teleonomic selection to characterize the proximate ‘mechanism’ of value-driven, self-controlled behavioral changes. As the evolved products of evolution have gained greater power to exercise teleonomic control over their relationships to the environment (and to each other), natural selection has become a dog that is increasingly wagged by its tail. Teleonomic selection has become an important instigator of evolutionary change, and complexification.

“One example of this ‘mechanism’ is the evolution of giraffes, which are frequently cited in elementary biology textbooks as illustrations of the distinction between Lamarckian and Darwinian evolution. Evolutionists like to point out that the long necks of modern giraffes are not the product of stretching behaviors that were somehow incorporated into the genes of their short-necked ancestors (as Lamarck posited). Instead, natural selection favored longer-necked giraffes once they had adopted the ‘habit’ of eating tree leaves. And that’s the point. A change in the organism-environment relationship among ancestral giraffes, occasioned by a novel behavior – a teleonomic selection – precipitated a new ‘selection pressure’ for morphological change.” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 110.

“The definition [of “information”] I favor is perhaps the most radical of all. I have proposed that information does not in fact exist; in reality it is an umbrella concept like ‘natural selection’ that we use to characterize certain properties, or functional aspects, of a wide variety of phenomena associated with the construction (ontogeny, phylogeny) and operation of thermodynamic/ cybernetic systems. The cybernetics pioneer, Norbert Weiner, equated information with the degree of organization (or negative entropy) in a cybernetic system. However, I prefer to define information functionally as: The capacity to exercise cybernetic control over the acquisition, disposition and utilization of matter/energy in and by living systems….

“… it can only be measured in terms of the results it achieves for specific living systems. An amino acid sequence that does not code for anything is not information. And neither, by this definition, is the DNA in a sperm that does not fertilize an egg; nor the insect pheromone (or chemical ‘signal’) that elicits no response; nor, for that matter, an unread book. Indeed, the quantity of what we call information in various contexts is much less important than its ‘power’ – its ability to exercise cybernetic control over matter/ energy (a relationship that is quantifiable).” Corning, Peter. 1995. “Synergy and Self-organization in the Evolution of Complex Systems.” Systems Research. 12(2):89-121. [numbering possibly inaccurate] p. 111.

“At the very least, the term ‘synergy’ could be utilized as a pan-disciplinary lingua franca for the functional effects produced by cooperative phenomena of various kinds [emergence, cooperativity, symbiosis, coevolution, symmetry, order, epistasis, mutualism, interdependencies, heterosis, phase transitions, system effects,… complexity … ‘dynamical attractors’]; a terminological shift would underscore the fact that the differently named phenomena studied by various disciplines are in fact variations on a common theme in the natural world.” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. p. 133.

“So-called ‘emergent phenomena’ are a particularly important class of synergistic effects. (We restrict the term ‘emergence’ to the subset of synergistic effects in which new physical ‘wholes’ are synthesized.)” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 138.

“Although symbiosis is often equated with mutualism, it also includes many examples of parasitism–relationships which may or may not be deleterious (negative synergy) for one of the partners, including many cases in which the functional consequences vary with the circumstances. For example, the so-called VAM (vesicular-arbuscular mycorrhizal) fungi that are models of mutualism with many species of plants do in fact enhance plant growth in low phosphorous soils, but in high phosphorous soils or in low light conditions (when photosynthetic activity is reduced), they may become parasitic and reduce plant growth.” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 142.

“Synergistic causation is configurational; synergistic effects are always co-determined.” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 144.

“A synergy perspective suggests a paradigm that explicitly focuses on both wholes and parts, and on the interactions that occur among the parts, between parts and wholes and between wholes at various ‘levels’ of interaction and causation. It might be called ‘a science of relationships,’ as distinct from a science of ‘mechanisms’ or ‘laws.’” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 145.

“Cooperative interactions in nature that produce positive functional consequences, however they may arise, can become ‘units’ of selection that differentially favor the survival and reproduction of the ‘parts’ (and their genes).” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 149.

“… the synergism hypothesis and the concept of synergistic selection (or ‘functional group selection’), like the concept of natural selection, represents an umbrella term for a broad category of causal influences. It is not a discrete ‘mechanism’ or concrete causal ‘agent.’ The causes of synergistic selection, like natural selection, are always situation-specific.” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 155.

“… by directing our attention to context-specific ‘historical’ relationships and interactions, rather than ‘mechanisms’ or reductionist ‘laws,’ the synergy paradigm encourages multi-leveled, multi-disciplinary research and theory that is free from the intellectual shackles of 19th century Newtonian physics. Furthermore, the synergy paradigm draws our attention to the functional aspect of cooperative effects.” Corning, Peter. 1998. “‘The Synergism Hypothesis’: On the Concept of Synergy and its Role in the Evolution of Complex Systems.” Journal of Social & Evolutionary Systems. 21(2):133-172. [numbering possibly inaccurate] p. 156.

“Reductionism, or detailed analysis of the parts and their interactions, is essential for answering the ‘how’ question in evolution – how does a complex living system work? But holism is equally necessary for answering the ‘why’ question – why did a particular arrangement of parts evolve?” Corning, Peter. 2012. “The Re-Emergence of Emergence, and the Causal Role of Synergy in Emergent Evolution.” Synthese. 185:295-317. doi: 10.1007/s11229-010-9726-2. p. 295.

“Perhaps the most elaborate recent definition of emergence was provided by Jeffrey Goldstein in the inaugural issue of Emergence. To Goldstein, emergence refers to ‘the arising of novel and coherent structures, patterns and properties during the process of self-organization in complex systems.’ The common characteristics are: (1) radical novelty (features not previously observed in the system); (2) coherence or correlation (meaning integrated wholes that maintain themselves over some period of time); (3) A global or macro ‘level’ (i.e., there is some property of ‘wholeness’); (4) it is the product of a dynamical process (it evolves); and (5) it is ‘ostensive’ – it can be perceived. For good measure, Goldstein throws in supervenience – downward causation.” Corning, Peter. 2012. “The Re-Emergence of Emergence, and the Causal Role of Synergy in Emergent Evolution.” Synthese. 185:295-317. doi: 10.1007/s11229-010-9726-2. p. 301.

“The Synergism Hypothesis represents an extension of this line of reasoning [‘the functional consequences produced by adaptively significant changes in a given organism-environment relationship]. I refer to it as Holistic Darwinism because the focus is on the selection of wholes, and the combinations of genes that produce those wholes. Simply stated, cooperative interactions of various kinds, however they may occur, can produce novel combined effects – synergies – that in turn become the causes of differential selection. The ‘parts’ that are responsible for producing the synergies (and their genes) then become interdependent ‘units’ of evolutionary change.” Corning, Peter. 2012. “The Re-Emergence of Emergence, and the Causal Role of Synergy in Emergent Evolution.” Synthese. 185:295-317. doi: 10.1007/s11229-010-9726-2. p. 308.

“So, the bottom-line question is this: Can the evolution of complexity be attributed to emergence or to natural selection? The answer, of course, is both.” Corning, Peter. 2012. “The Re-Emergence of Emergence, and the Causal Role of Synergy in Emergent Evolution.” Synthese. 185:295-317. doi: 10.1007/s11229-010-9726-2. p. 312.

“One illustration [of how natural selection is a consequence of organism-environment relationships inclusive of other organisms] is the English land snail (Cepaea nemoralis). These snails are subject to predation from thrushes, which have developed the clever habit of capturing the snails and then breaking open their shells by using stones as anvils. In other words, a synergistic behavioral innovation (tool use) in one species has become a cause of natural selection in another species.

“However, the impact of natural selection in the snails is also shaped by two additional factors, one genetic and the other ecological. It happens that C. nemoralis exhibit genetically determined variations in shell banding patterns, which in turn provide varying degrees of camouflage. The result is that the more cryptic phenotypes are less intensively preyed upon than those that are more visible to predators. However, the pattern of predation by thrushes (and the frequencies of the different snail genotypes) also varies greatly from one location to the next. The reason is that the thrush populations, being subject themselves to predators (like hawks) display a strong preference for well-sheltered localities. Paradoxically, the snails are much less subject to predation in more open areas. So it is a combination of genetic, ecological and behavioral factors that has shaped the course of natural selection in C. nemoralis.” Corning, Peter. 2014. “Systems Theory and the Role of Synergy in the Evolution of Living Systems.” Systems Research and Behavioral Science. 31:181-196. doi: 10.1002/sres.2191. p. 190.

“Finally, it should be emphasized that the Synergism Hypothesis is agnostic about how a selectively relevant synergy may arise, just as natural selection is agnostic about the sources of the ‘variations’ that can influence differential survival and reproduction. A synergistic effect could be self-organized; it could be a product of some chance variation; it could arise from a happenstance symbiotic partnership; or it could entail a purpose-driven behavioral innovation by some living organism.” Corning, Peter. 2014. “Systems Theory and the Role of Synergy in the Evolution of Living Systems.” Systems Research and Behavioral Science. 31:181-196. doi: 10.1002/sres.2191. p. 191.

“All has been consecrated.
The creatures in the forest know this,

the earth does, the seas do, the clouds know
as does the heart full of
love.

Strange a priest would rob us of this
knowledge

and then empower himself
with the ability

to make holy what
already was. Catherine of Siena, “Consecrated.” 14th century CE. Loorz, Victoria. 2021. Church of the Wild: How Nature Invites Us into the Sacred. Minneapolis: Broadleaf Books. p. 51.

“He [poet David Whyte] speaks of ‘the conversational nature of reality,’ which he says is the relationship that happens at the ‘frontier between what you think is you and what you think is not you.’” Loorz, Victoria. 2021. Church of the Wild: How Nature Invites Us into the Sacred. Minneapolis: Broadleaf Books. pp. 90-1; reference: Whyte, David from interview by Krista Tippett on podcast On Being. April 7, 2016. “David Whyte: The Conversational Nature of Reality.”

“In Landmarks, Macfarlane tells a story of how citizens of an island township called Lewis, on the Outer Hebrides of Scotland, saved their homeland by restoring intimate conversation with their landscape….

“Four residents knew they needed to do more than protest [the construction of a gas and energy facility in a nearby bog] with conventional activist tactics. They launched a two-year campaign to inspire residents to restore intimacy with their land through specific storytelling. Restoration through re-storying. They called for the sharing of detailed and loving experiences that people had with particular places, encouraging them to tell stories, recall poems, create paintings and photographs, remember songs, recall lost words, map favorite hidden spots, and recount histories about particular places in their township.

“The activists hoped to restore intimacy with the moor by encouraging particular conversations that reconnected the people and their place. And it worked.” Loorz, Victoria. 2021. Church of the Wild: How Nature Invites Us into the Sacred. Minneapolis: Broadleaf Books. pp. 92, 93; reference: Macfarlane, Robert. 2016. Landmarks. Penguin.

“… authentic conversation begins the moment you realize you are misunderstood!” Loorz, Victoria. 2021. Church of the Wild: How Nature Invites Us into the Sacred. Minneapolis: Broadleaf Books. p. 99; idea attributed to physicist David Bohm.

“Up until the fourth century, Boyle points out, theologians and bishops and translators consistently translated the Greek word logos into Latin, the language of the church, as sermo, which means not ‘word’ but ‘conversation’….

“Logos happens through relationship,. This action of conversing–this intimate, abiding, turning to one another–is a sensual, living, flowing, never-ending relationship. It is the original primal relationship that has existed since the beginning and is reenacted in all matter and being.” Loorz, Victoria. 2021. Church of the Wild: How Nature Invites Us into the Sacred. Minneapolis: Broadleaf Books. pp. 109, 110.

“To disbelieve that Mary [wild doe in the backyard of author] loves me is to diminish that sacred bond. That is not love. To approach her from a dominant position and disregard her innate intelligence, beauty, compassion, and capacity to love is to break the conversation…. I have no choice but to believe what my body and soul already feel; she does love me back.

“When asking this same question, Kimmerer comes to this exultant conclusion: ‘I knew it with a certainty as warm and clear as the September sunshine. The land loves us back. She loves us with beans and tomatoes, with roasting ears and blackberries and birdsongs. By a shower of gifts and a heavy rain of lessons. She provides for us and teaches us to provide for ourselves. That’s what good mothers do.’” Loorz, Victoria. 2021. Church of the Wild: How Nature Invites Us into the Sacred. Minneapolis: Broadleaf Books. pp. 139-40.

“If the struggle between the wolves is symmetrical–that is, if wolf A is stimulated to more aggressive behavior by the aggressive behavior of [wolf] B–then if B suddenly exhibits what we may call ‘negative aggression’ [e.g., conciliatory move, surrender signals], A will not be able to continue to fight unless he can quickly switch over to that complementary state of mind in which B’s weakness would be a stimulus for his aggression. Within the hypothesis of symmetrical and complementary modes, it becomes unnecessary to postulate a specifically ‘inhibitory’ effect for the surrender signal.

“Human beings who possess language can apply the label ‘aggression’ to all attempts to damage the other, regardless of whether the attempt is prompted by the other’s strength or weakness; but at the prelinguisitic mammalian level these two sorts of ‘aggression’ must appear totally different. We are told that from the lion’s point of view, an ‘attack’ on a zebra is totally different from an ‘attack’ on another lion.” Bateson, Gregory. 1972. Steps to an Ecology of Mind. NY: Ballantine. p. 325.

“The panic of the alcoholic who has hit bottom is the panic of the man who thought he had control over a vehicle but suddenly finds that the vehicle can run away with him [after applying brake on a slippery road]. Suddenly, pressure on what he knows is the brake seems to make the vehicle go faster. It is the panic of discovering that it (the system, self plus vehicle) is bigger than he is.

“In terms of the theory here presented, we may say that hitting bottom exemplifies systems theory at three levels:

“(1) The alcoholic works on the discomforts of sobriety to a threshold point at which he has bankrupted the epistemology of ‘self-control.’ He then gets drunk–because the ‘system’ is bigger than he is–and he may as well surrender to it [with self-control he first attempts the symmetrical pattern of conflict with drinking but the hitting bottom leads to a complementary attitude of surrender].

“(2) He works repeatedly at getting drunk until he proves that there is a still larger system. He then encounters the panic of ‘hitting bottom.’

“(3) If friends and therapists reassure him, he may achieve a further unstable adjustment–becoming addicted to their help–until he demonstrates that this system won’t work, and ‘hits bottom’ again but at a lower level. In this, as in all cybernetic systems, the sign (plus or minus) of the effect of any intrusion upon the system depends upon timing.

“(4) Lastly, the phenomenon of hitting bottom is complexly related to the experience of double bind. Bill W. [founder of Alcoholics Anonymous] narrates that he hit bottom when diagnosed as a hopeless alcoholic by Dr. William D. Sikworth in 1939, and this event is regarded as the beginning of AA history. Dr. Silkworth also ‘supplied us with the tools with which to puncture the toughest alcoholic ego, those shattering phrases by which he described our illness: the obsession of the mind that compels us to drink and the allergy of the body that condemns us to go mad or die.’ This is a double bind correctly founded upon the alcoholic’s dichotomous epistemology of mind versus body. He is forced by these words back and back to the point at which only an involuntary change in deep unconscious epistemology–a spiritual experience–will make the lethal description irrelevant.” Bateson, Gregory. 1972. Steps to an Ecology of Mind. NY: Ballantine. pp. 330-1.

“There is a Power greater than the self. Cybernetics would go somewhat further and recognize that the ‘self’ as ordinarily understood is only a small part of a much larger trial-and-error system which does the thinking, acting, and deciding. This system includes all the informational pathways which are relevant at any given moment to any given decision. The ‘self’ is a false reification of an improperly delimited part of this much larger field of interlocking processes. Cybernetics also recognizes that two or more persons –any group of persons–may together form such a thinking-and-acting system….

“By resisting this Power, men and especially alcoholics bring disaster upon themselves. The materialistic philosophy which sees ‘man’ as pitted against his environment is rapidly breaking down as technological man becomes more and more able to oppose the largest systems. Every battle that he wins brings a threat of disaster. The unit of survival–either in ethics or in evolution–is not the organism or the species but the largest system or ‘power’ within which the creature lives. If the creature destroys its environment, it destroys itself.” Bateson, Gregory. 1972. Steps to an Ecology of Mind. NY: Ballantine. pp. 330-1.

“Most amazingly of all, living organisms evolved systems to use the death of cells to their own advantage. All cells seem to carry ‘death’ gene programs that can be activated as needed. Many organisms, including humans, now rely on those programs to kill certain cells during development and to battle disease. The most dramatic occurs during metamorphosis of insects and frogs, but humans use the death of specific cells to hone our immune system and give us fingers and toes. Even single-celled organisms use quorum sensing to eliminate some cells to ensure the overall survival of the colony in harsh environments. Plants use it to cause leaves and fruit to drop in the fall.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. xi.

“… Cano and Berucki found spores that seemed to be related to a strain of bacteria … in a bee preserved in amber for the last 25-30 million years. Those spores were revived and started growing. More amazingly, using extremely stringent isolation procedures to prevent contamination, Vreeland, Rosenzweig, and Powers isolated bacterial spores from a salt deposit that formed 250 million years ago and found them to be still viable.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 17; references: Cano, R.J. & M.K. Borucki. 1995. “Revival and identification of bacterial spores in 25- to 40- million-year-old Dominican amber.” Science. 268:1060-1064; Vreeland, R.H., W.D. Rosenzweig & D.W. Powers. 2000. “Isolation of a 250 million-year-old halotolerant bacterium from a primary salt crystal.” Nature. 407:897-900.

“Plants can live for a very long time. Unlike animals that have a defined set of cells to produce sperm and eggs, plants do not. They produce seeds at multiple sites through the plant, and each of those sites generates cells that produce pollen and eggs. Somatic mutations (mutations in nonreproductive cells) can be carried into what will become reproductive cells so that those mutations can enter the germ line. Part of the reason for their longevity may be that their stem cells, which are located in the meristems (growing parts) of the plant, do not divide very often, even as they provide lots of precursor cells for the different parts of the plant. The relatively few divisions suggest that the stem cells do not age or senesce, and thus the plant can continue growing for a very long time. Also, the plant’s various meristems seem to operate independently of one another, which means that a mutation in one would only affect that specific branch; the rest of the branches would be safe.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 70.

“Amazingly, some organisms do not seem to age at all. When food is short or it is injured, the jellyfish Turritopsis dohrnii has an unusual ability to sort of re-create itself. Normally, the jellyfish begins as a fertilized egg that grows into a larva. The larva attached itself to a surface and develops a tube-shaped structure called a polyp. The polyp will later bud off a segment that will develop into a small jellyfish-like organism called an ephyra that grows into a full-sized medusa. When faced with a life-threatening stress, the medusa reverts to a blob of tissue that transforms back into a sexually immature polyp stage. So far, Turritopsis dolrnii is the only jellyfish with this ability.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 71.

“Naked mole rats also have much longer life spans than expected. They live up to thirty-two years, the longest of any rodent (compared to about four years for a house mouse…). Their mortality rate does not increase with age, and they are very resistant to cancer. The reasons for these abilities are unknown, but several ideas have been suggested. First, they can reduce their metabolism and avoid oxidative stress when food is short. Second, they express high levels of DNA repair genes. Third, the animals secrete a hyaluronan (a type of negatively charged polysaccharide or polymer of sugars that is five times larger than that seen in humans or mice. Hyaluronan is an important component of the extracellular matrix and contributes to proliferation of cells during growth and their migration to an appropriate position in the developing organism. The larger hyaluronan molecules might give the mole rats’ skin the elasticity needed to live in tunnels, where the skin is constantly exposed to rough surfaces, and that trait might also provide resistance to cancer and a longer life span. The naked mole rats have much more of this compound than other organisms because they have decreased activity of enzymes that degrade it and a unique sequence in the hyaluronan synthase 2 gene. If the amount of hyaluronan is lowered by genetic means, the rats become much more susceptible to cancer.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 71-2.

“The first organisms, which consisted of only a single cell, likely did not age. Scientists assume that they reproduced by simple cell division that resulted in two equal offspring. Over time, those organisms must have accumulated damage to their molecules and organelles, and the two daughter cells from cell division must have received approximately half of the damaged material. The two equivalent daughter cells were able to deal with the amount of damaged material that they inherited. If not, the line would have died out. This is the reasoning behind the notion that unicellular organisms do not age.

“The alternative to the early equivalent division is an asymmetric situation in which the damaged material is sequestered into one daughter cell and the other daughter cell receives the newly produced proteins and organelles. That outcome would require a more complicated mechanism to ensure the separation of old and new components. At some point in evolution, that additional mechanism did appear….

“For some time, scientists assumed that this evolutionary step took place with the eukaryotes. Bacteria, which are prokaryotes, were thought to reproduce by simple division to produce equivalent daughter cells. However, more recently, bacteria have been found that have asymmetric division: producing a mother cell and a daughter cell…. The ability to segregate damaged components into one daughter cell would likely be favored by natural selection.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 72, 73.

“… three [theories to explain aging] have emerged as good explanations of how aging might have evolved: mutation accumulation theory, antagonistic pleiotrophy, and disposable soma….

“The [mutation accumulation] theory states that the deleterious effects of genes that affect an organism early in life have a large negative selection value because they hinder reproduction. However, genes that are deleterious later in life have less or even no negative selection value–the organism has already reproduced, so genes with later effects are essentially meaningless for evolution.

“Medawar suggested that aging was caused by mutations that were detrimental only later in life….

“Medawar’s mutation accumulation theory, at least in its initial formulation, seems to be too simple to account for aging….

“While the mutation accumulation theory is widely respected, there are some who are critical of it.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 74, 75; reference: Medawar, P.B. 1952. An Unsolved Problem of Biology. London: HK Lewis.

“Thomas Kirkwood and Robin Holliday suggested that when resources are limited, organisms must make compromises about how they allocate those limited resources to various types of bodily functions, including growth, reproduction, and repair. If they use too many of their limited resources on repair, for example, reproduction doesn’t get enough, and their offspring will suffer and perhaps not reach reproductive age. Thus, reproduction is favored and receives most of the resources. With fewer resources available for repair, however, cellular damage may not be fixed. Cells are damaged, telomeres become shorter, and mutations accumulate. Eventually, senescence and then death set in. A variation on this theme asserts that time can replace limited resources. In other words, organisms that live longer have more time to devote to high-quality repairs than short-lived organism….

“There is considerable evidence for this theory. First, there seems to be an inverse correlation between size and life span in many animals, suggesting that resource trade-offs are made between growth and maintenance.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 76-7; reference: Kirkwood, T.B.L. & R. Holliday. 1979. “The evolution of ageing and longevity.” Proc R Soc Lond B Biol Sci. 205:531-546.

“Gavrilov and Gavrilova point out that many cells and organs seem not to age at all. For example, neurons do not seem to have increased risk of death as they get older. They question how a system that includes non-aging parts can age. Their mathematical models also show that some animals seem to stop aging after a certain point, including humans over 100 years old. Their reliability theory is a variation on a theory that has been used successfully in engineering and manufacturing. In biology, it suggests that humans are complex systems with many parts and multiple redundant systems. These ensure robust health early on, but as we grow older, those systems begin to fail one by one, and that results in aging. So aging is a trade-off.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 77-8; reference: Gavrilov, L.A. & N.S. Gavrilova. 2003. “The quest for a general theory of aging and longevity.” Sci Aging Knowledge Environ. 2003(28):RES.

“Nelson and Masel developed a model of aging and used it to test various outcomes. Their findings are consistent with theories of cell senescence. Senescence is selected against in unicellular organisms by competition among cells. That is not the case in multicellular organisms; because their existence depends on cooperation among cells, competition between the cells of a single organism is mitigated to ensure the survival of the whole organism. That cooperation leads to the accumulation of senescent cells.

“Others question Nelson and Masel’s conclusions.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 81; reference: Nelson, P. & J. Masel. 2017. “Intercellular competition and the inevitability of multicellular aging.” Proc Natl Acad Sci USA. 114:12982-7.

“The early signs [of approaching death for cancer patients] included decreased performance status, change in oral intake, and change in level of consciousness….

“Still, there are some generalities we can observe.

“First, appetite decreases. The body needs less energy, and so the patient slows or stops eating and drinking. They may sleep more as their metabolism becomes slower, and they have less energy. They might become less social, and they might not be able to sustain a conversation. Their vital signs will change: blood pressure drops, the rate of breathing slows, breathing may start and stop with long pauses, the heartbeat become weaker and irregular, and the urine might become brown or rust-colored as the kidneys begin to fail. Because they are eating and drinking less, their needs for elimination may be less or none at all. Their muscles will become weaker. Their temperature may drop, a sign the body is rationing blood circulation so that the internal organs get the lion’s share. Their hands and skin may be cool to the touch, and the skin may become pale or bluish. Their mental state will change: they may seem confused or they may experience hallucinations. The senses decline, with hearing thought to be the last sense to be lost. Sadly, they may experience pain.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 87.

“When a person dies, not all of the cells die at the same time. Some continue to live for hours or days, and continue to carry on their normal functions. Genes are turned on or off, and transcription of RNA and translation of proteins continue. Counterintuitively, some genes increase their expression….

“Another study showed that about 99 percent of all genes stop transcribing RNA at time of death, but 1-2 percent increased transcription. In zebrafish and mice, some genes increased activity immediately after death, but others showed increased activity twenty-four, forty-eight, or ninety-six hours after death… However, although the types of genes that were turned on did not seem to fit any pattern, the order in which they were turned on did show a pattern: the same genes were turned on at the same time. In fact, these sequences of activity are so regular that they can be used to determine the time of death.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 89.

“Once the oxygen that is supplied by fresh blood runs out, the tissue or the entire organism dies, and a relatively defined set of processes begins. Cells and tissues begin to break down in chemical processes called autolysis. Without oxygen, an anaerobic environment is established. This environment favors bacteria normally found in the body, and they begin to break down the body’s chemical components, including carbohydrates, proteins, and lipids. A cascade of biochemical reactions begins, and the process accelerates as the cells break open. Enzymes are released from their normal cellular compartments where their actions are controlled and begin to react with other molecules that they would not normally encounter. Microorganisms that had been held in check by the immune system and other defenses of the living organism now multiply and spread.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 99.

“Cells have organelles called lysosomes and peroxisomes that break down proteins. As long as the organism is healthy, those organelles remain intact, and their enzymes are safely contained.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 102.

“Programmed cell death (PCD) is critical for our reproduction, development, and survival. Several types of PCD occur. Apoptosis and autophagy are highly organized genetic programs. Necrosis is typically caused by external factors, such as infection or trauma, and is less regulated. Nectoptosis is a form of necrosis that is more organized.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 131.

“Thus there is no clear biochemical test of cell death. Like in human death, cell death lacks a clear ‘point of no return.’

“In the laboratory, cells are identified as dead or alive with the use of dyes that cannot pass through the intact plasma membrane of living cells. The membrane is compromised in dead cells, and so the dye enters the cell and can be easily seen with a microscope as a blue color….

“An international consensus suggested a morphological definition of cell death based on any one of these criteria: loss of the plasma membrane, complete fragmentation of the cell and its nucleus, and/or engulfment of the cell and its remnants by another cell. A more recent consensus modified this definition somewhat: ‘irreversible degeneration of vital cellular functions (notably ATP production and preservation of redox homeostasis) culminating in the loss of cellular integrity (permanent plasma membrane permeabilization or cellular fragmentation)’.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 131-2; subquote: Galluzzi, L., I. Vitale, S. Aaronson et al. 2018. “Molecular mechanisms of cell death: Recommendations of the Nomenclalture Committee on Cell Death 2018.” Cell Death Differ. 25:486-541.

“… most cells do not divide after the tissue or organ has reached its normal full growth. At that point, growth-suppressing proteins and microRNAs, which are short RNAs that hinder protein synthesis and cell division. There are times when cell division needs to turn on, however. Wound healing is one.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 133.

“Cells manage the health of their proteins by maintaining a network of molecular chaperones and the proteolytic machinery that can remove and recycle damaged proteins. This process is called proteostasis. Many age-related diseases are associated with dysfunctions in proteostasis. For example, most of the major neurodegenerative diseases feature dysfunction of proteostasis and aggregations of a specific protein.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 133-4.

“A multicellular organism requires considerable organization to position all of its cells, tissues, and organs so that they work together and function appropriately. When some cells lose the ability to do that, the organism needs a mechanism to fix the problem, and the ability to eliminate those cells would be beneficial. Thus, it is easy to imagine how such as system would evolve in multicellular organisms. However, a bigger surprise is that a similar system also occurs in unicellular organisms.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 139.

“And of course PCD is an important component of the defense against illness–under certain disease conditions, cells ‘commit suicide’ by turning on pathways that lead to death.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 139.

“PCD includes apoptosis, necrosis, and autophagy. These are the main three, but there are more. Apoptosis prepares the cell’s contents for recycling and use by other cells. Necrosis involves the death of cells by toxins or trauma and is generally less organized. It also prompts an immune and inflammatory response that can sometimes be problematic. Some researchers are reluctant to include necrosis in PCD because it seems less controlled. Autophagy is another form of PCD that allows the organism to optimize available resources by recycling damaged and worn-out proteins, organelles, and other cellular constituents. The cell activates this process when resources are limited.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 139.

“An average human loses 200 billion to 300 billion cells every day, and most of those are lost by apoptosis. It’s essential for the cells’ homeostasis that the debris from these apoptotic cells be cleaned up. One of the major cell types engaged in this cleanup effort is the macrophage. Macrophages engulf cell debris and degrade it. Macrophages are produced from immune stem cells in each type of tissue, which differentiate into tissue-specific macrophages, such as peritoneal macrophages in the peritoneal cavity, Kupffer cells in the liver, alveolar macrophages in the lung, and microglia in the brain. These cell types are sometimes referred to as ‘professional cleaners.’

“The macrophages do not just attack any cell they come upon. The apoptotic cell ‘identifies’ itself to the macrophage by releasing signal molecules…. Receptors on the surface of the macrophages recognize the signals. In a parallel manner, healthy cells show specific molecules on their surfaces, such as CD47 and CD31, that direct the macrophages to leave them alone.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 140-1.

“Apoptosis takes two forms. Intrinsic apoptosis is initiated within the cell itself. Extrinsic apoptosis is initiated from outside the cell via extracellular ligands, appropriately called death receptors. The two types are essentially independent of each other, except that they converge on the same enzyme cascades. In either case, apoptosis involves a fairly consistent series of steps.

“First, cells shrink. At the molecular level, apoptosis involves the major contractile proteins actin and myosis. Actin forms a ring around the membrane and, with myosisn, contracts to form the membrane protrusions that characterize apoptosis. Other protrusions then form, such as microtubules. The DNA is cleaved into pieces. The cell breaks into small pieces, each surrounded by a membrane containing the lipid phosphatidylserine. Macrophages sense the lipid and engulf those small pieces, and the contents are recycled for use by other healthy cells.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 141.

“While apoptosis involves a careful program of well-defined events, necrosis is generally thought of as accidental, occurring as the result of trauma, infections, cancer, infarctions, inflammation, and other conditions….

“In apoptosis, cells shrink and divide into small packets. By contrast, in necrosis the cells swell and break open, releasing their contents.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 144.

“A number of other forms of PCD occur, often in specific tissues or under specific conditions. Pyroptosis occurs in response to pathogens and heart attacks. It is different from other forms of PCD due to the different caspases involved….

“Cornification occurs in the epidermis and is essentially the final step in the differentiation that forms the outer protective skin layer….

“Mitotic catastrophe occurs during or just after failed mitosis–when a cell attempts to divide to form two identical copies of itself, but something goes wrong with the process, often because of damage to the cell’s DNA….

“Anoikis occurs in multicellular organisms where specific types of cells interact with the extracellular matrix to determine how much to grow and where to be….

“Excitotoxicity occurs in neurons….

“”Wallerian degeneration is not yet very well understood, but we do know that it causes part of a neuron or axon to degenerate without affecting the cell body.

“Paraptosis is triggered by IGF-1. It features cytoplasmic vacuolization and mitochondrial swelling but lacks the hallmarks of apoptosis….

“Pyronecrosis is similar to pyroptosis but differs in that pyroptosis requires the actions of caspase-1….

“Entosis was first described in Huntington’s disease. In it, cells begin to engulf their neighbors….

“Ferroptosis depends on the presence of iron and results in the oxidation of lipids. It is involved in tumors, nervous system diseases, kidney injury and blood diseases.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 145, 146.

“Apoptosis can be reversed, even at late stages after caspase release and mitochondrial fragmentation. The recovery of cells after apoptosis has been initiated is called anastasis. It can occur after a range of cellular threats, including cold shock, toxins, and protein starvation.

“When the process of apoptosis fails, fewer caspases are released, and not all the cell’s mitochondria begin to leak cytochrome c at the same time, with the rest remaining intact. When this happens, apoptosis ends. The cells store away mRNAs before apoptosis begins, and those are used to restart normal cell processes. In anastasis, more than 1,000 genes are upregulated. But survival does not come without a cost to the cells. Cells that begin anastasis at late stages of apoptosis might not be completely healed….

“While failed apoptosis is widely recognized, not everyone is convinced that anastasis is real.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 146-7.

“PCD is a critical mechanism in metamorphosis. In each transformation, specific cells are programmed to die, and other cells divide and expand to construct new tissues. These changes are controlled genetically and hormonally.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 148.

“Nearly 80 percent of insects go through some form of complete metamorphosis, but the extent of PCD differs from species to species. PCD in metamorphosis is by autophagy or apoptosis. Organisms use PCD to remodel cells and to recycle the cell contents. Apoptosis involves other phagocytic cells to recycle the components of the dead cell, but autophagy is accomplished by the cell itself. Apoptosis usually occurs earlier than autophagy, and hormones are intimately involved in regulation of metamorphosis.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 149.

“Neurons are postmitotic–that is, they have exited the cell cycle and no longer divide–so they must live essentially for the lifetime of the organism in order for those connections to be maintained. One of the hallmarks of most neurodegenerative diseases is the loss of neurons.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 154.

“It is estimated that between 50 and 200 T cell precursors for a specific antigen each expand 10,000- to 50,000-fold in response to a pathogen. However, when the danger is past, it is important for the system to go back to a homeostatic condition, so the additional cells must be removed efficiently.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 154.

“During maturation of the immune system, those cells that would react against the self are eliminated by apoptosis in the thymus.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 154-5.

“Although we generally see bone as a permanent structure, it is, in fact, a dynamic tissue: old bone is continually reabsorbed and new bone is synthesized. Two types of cells are involved in this process. Osteoclasts destroy existing bone material, and osteoblasts synthesize new bone. Clearly, a careful balance is critical, and apoptosis is used to maintain that balance.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 156.

“One way to look at it is that trees are mostly not quite alive. Some estimates, in fact, are that only about 1 percent of a mature tree is alive.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 162.

“Two general models have been suggested to explain senescence in plants. The first model involves a ‘death hormone’…. While at this point no unique ‘death hormone’ has been identified that invariably leads to senescence and death, this model remains at least a possible mechanism.

“The second model involves nutrients. Plants carefully balance their investments of resources and continually move nutrients from place to place within the plant, depending on the need. One might imagine the plant reallocating resources from dying areas of the plant to those that are doing better. The two most important nutrients are fixed nitrogen and sugars…. Cytokinins encourage growth, but the movement of sugars (such as from leaves to seeds) signals senescence (in this case, of the leaves). Strong sinks have more cytokinins that attract sugars from sources.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 162-3.

“The processes of death can be at different stages in the same leaf.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 163.

“Annuals commit all of their resources to seeds for the next generation. But perennials have a head start over seeds in that they already have part of their vegetative structure ready to go in the spring. In each case, the plant selects parts for retention and others for death. For annuals, all parts of the plant are discarded except for the seeds. In perennials, select parts (e.g., some stems, roots) are retained, and the remainder are pruned through programmed cell death.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 163.

“PCD is important for the proper development of all multicellular organisms, including plants. It is a critical mediator of reproductive structures, the remodeling of cells and tissues, and senescence. Apoptosis, autophagy, and necrosis all have roles.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 167.

“Abscission occurs in three steps. In the case of a deciduous tree’s leaves falling in the autumn, the first step involves chlorophyll. As the amount of sunlight decreases in the fall, levels of chlorophyll also drop. In addition to being responsible for the green color, chlorophyll is a valuable material for plants. For example, it contains nitrogen that is needed for amino acids, nucleotides, and other key compounds. The plant degrades the chlorophyll to recycle these materials. Other pigments are slower to degrade, and the leaf color changes from green to yellow or red. In the second step, an abscission or separation zone forms at the base of the petiole, and a protective layer is formed just below that. The cells then release suberin and lignin under the abscission zone to form a waterproof layer. Finally, the cells in the abscission zone import water, swell, and burst, causing the leaf to fall; in essence, the leaf is pushed off.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 169-170.

“Plants lack a complex adaptive immune system, such as that in mammals. However, they are hardly defenseless. They have several layers of defenses. First, a waxy cuticular layer provides a physical barrier against infectious agents, somewhat analogous to the way our skin protects us. Second, that cuticular layer contains antimicrobial compounds that can kill pathogens. Third, plants have a wound response that includes protease inhibitors and other compounds to discourage feeding on plant tissues. Fourth, plants release volatile compounds that attract beneficial insects that feed on the insects that eat plant tissues. Finally, plants have an effective innate immune system. They use a ‘zigzag’ model of plant immunity. In this model, plants use pattern recognition receptors to identify pathogens and nonpathogens by their molecular characteristics. The first component of this system involves disease resistance genes (R) that encode R proteins. The R proteins detect proteins associated with pathogens and bind and degrade them.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 171.

“Their [bacteria’s] main predators are viruses called bacteriophages (or simply phages). The phages outnumber bacteria ten to one, and a single bacterium can be infected by as many as ten different phages. The typical outcome of an infection is that the virus usurps the cellular machinery of the bacterium and uses it to produce the components of a new crop of virus. Ultimately, the bacterial cell bursts and releases the new viruses to infect other bacteria…. As many as 15 percent of all of the bacteria in the oceans are killed every day by phage infections.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 177.

“Bacteria uses QS [quorum sensing] to deal with many stressful situations. In the classic example, bacteria use QS to regulate the density of the colony. As the density passes a certain level, the colony throttles back on its growth and even allows some bacteria to die. In this way, even though some individuals are lost, the colony survives by living off the nutrients supplied from their dead comrades until conditions improve. Intriguingly, the bacteria seem to be communicating to regulate the density of the population by having some bacteria initiate a sequence that kills the cell.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 177-8.

“Amazingly, all free-living bacteria contain genes for cell suicide that are critical for their normal cell growth under different conditions.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. p. 178.

“Bacteria use PCD for many purposes. For example, they use it to prevent infection of the population. An infected cell initiates a death program; the cell dies, but this prevents the phage that infected it from reproducing and infecting other bacteria. They also use PCD when environmental conditions are not conducive to growth. Under those circumstances, bacteria produce spores that can survive in a sort of suspended animation until conditions improve. Death is a part of that process as well. Sporulation begins with cell division or mitosis that yields two cells, one small and the other large. The small cell will eventually become the spore, and the large cell provides support for the small one. When the spore is mature, the large cell activates enzymes that degrade itself and release the spore.” Howard, Gary C. 2021. The Biology of Death: How Dying Shapes Cells, Organisms, & Populations. Oxford UP. pp. 178-9.

“The concept of stability is a central one in science but the term is utilized in two quite different ways. Following the establishment of thermodynamics as a quantitative discipline, the term can be used in an energy/entropy sense. Thus a system of lower enthalpy and/or higher entropy is considered more stable. However, the term can also be used in a time sense, in the sense of persistence. A system that is persistent, unchanging over time, is also considered stable….”

“But the fact that the stability concept has two quite distinct facets – energy and time – has chemical consequences, in particular, when the two facets operate in a contradictory fashion, and such a situation is common. For example, a mixture of H2 and O2 is unstable in a Gibbs (free) energy sense, as it can readily react to give the thermodynamically stable product, water, but it can be highly stable in a time/persistent sense (kinetically stable) if the H2 + O2 mixture is kept under appropriate conditions (low temperature and the absence of a catalyst).” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16161.

“… stability in the sense of persistence is more general than stability in an energetic sense (thermodynamic stability). Stability in its most fundamental sense is about time rather than about energy; persistent systems may or may not be thermodynamically stable, however thermodynamically stable systems will necessarily be persistent.” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16161.

“Once it is appreciated that the more general facet of stability is its time facet, the one that extends beyond the more limited thermodynamic description, it leads directly to a logical law of nature, which we term the persistence principle: systems will tend from less stable (persistent) to more stable (persistent) forms, or, alternatively, and more concisely: nature seeks persistent forms. Note that the principle is logically true, in effect axiomatic, regardless of the reasons for the system’s persistence, thermodynamic or otherwise. The principle derives directly from its time formulation….” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. pp. 16161-2.

“But is there a mathematical basis for stability in the time/persistence sense beyond the one offered by the Boltzmann formulation? The answer is yes…. However, it is not probabilistic, but rather Malthusian, as it rests on the kinetic power of exponential growth. Let us summarize how this comes about….

“In simplest terms that stability kind is the stability associated with entities able to make copies of themselves at a rate that results in a non-equilibrium steady-state population of replicating entities being maintained over time – persistence through self-replication. Living systems, of course, exemplify this kind of stability in that populations of living things, whether humans, camels, mosquitoes, or bacteria, are maintained over time, due to the continual production of new entities (though in limited quantities due to resource limitations), which replace existing ones. Individual entities are continually being degraded by various processes, termed death (for biological systems), or degradation (for chemical systems). So it is the population of replicators that is stable/persistent, rather than the individual replicators that make up the population at any given moment. Thus DKS, being a kinetic form of stability, expresses a form of persistence that also lies outside the thermodynamic stability region….” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16162.

“If a particular replicating system replicates with some variation leading to competing replicating entities, then the competitive kinetics is explicit – competing exponential replicators cannot coexist. The more stable one in a DKS sense drives the less stable one into extinction. Thus there is a natural evolutionary process from DK less stable/persistent to DK more stable/persistent, the one governed by the math of exponential growth.” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16162.

“Through the [persistence] principle, abiogenesis and Darwinian biological evolution can be understood as one continuous process. The entire evolutionary process of the replicative change, beginning with some prebiotic persistent chemical replicating system and proceeding through to complex life, manifests the logical and irreversible drive toward greater persistence (stability) within the replicative world. Through the math of Malthusian kinetics we identify life as just the more evolved replicative expression of the persistence principle.” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16163.

“The underlying reason for the evolutionary process of complexification derives from the existence of a complexity-function relationship; an increase in efficiency of the replicative function almost invariably requires an increase in complexity.” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16164.

“In other words the physical manifestation of greater persistence in the replicative world over evolutionary time is primarily brought about through increasing complexity, functional complexity. In fact in a limited way complexity in the replicative world may be thought of as a rough analog of entropy in the ‘regular’ world though there are key differences. As noted earlier, complexity is difficult to quantify, in contrast to entropy. Moreover, though in the ‘regular’ chemical world entropy can reach a maximum value, beyond which a further increase is not possible, in the replicative world the degree of complexity has no formal upper limit – replicative function can always, at least potentially, be increased.” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16164.

“By governing the nature of material change in the replicative world, whether chemical or biological, the [persistence] principle reaffirms that the emergence of life and its subsequent evolution constitute one single continuous physico-chemical process. Thus biology’s central concept, natural selection, can be reduced to chemistry (as kinetic selection), then to physics (as dynamic kinetic stability), and finally to logic (drive toward persistent forms).” Pascal, Robert & Addy Pross. 2015. “Stability and its manifestation in the chemical and biological worlds.” Chem. Commun. 51:16160-65. doi: 10.1039/c5cc06260h. p. 16165.

“The products of anabolism are needed to mediate and regulate catabolism. The current search for separate prebiotic analogues of extant anabolic and catabolic chemistries largely does not address this critical feature of biology, which is how prebiotic systems chemistry gave rise to a mixture of reactions that tie together in a way that defies equilibrium.” Mansy, Sheref S. 2022. “Protometabolism as out-of-equilibrium chemistry.” Phil Trans R Soc A. 380:20200423. doi: 10.1098/rsta.2020.0423. p. 2.

“Until the last decade, membrane-enclosed organelles were associated exclusively with eukaryotic cells. Recent evidence indicates that membranous subunits with specific functions also exist in Prokaryota, e.g., bacteria and archaea. These new reports, and the recent findings showing the ability of surface-adhered model protocells to easily form subcompartments, support the possibility that primitive protocells, leading to the last common universal ancestor, already had separate structural subunits to support different prebiotic reactions.” Gozen, Irep. 2021. “Did Solid Surfaces Enable the Origin of Life?” Life. 11:795. doi: 10.3390/life11080795. pp. 800-1.

“Both synthetic and natural forms of solid surfaces have been recently experimentally explored in this context under laboratory conditions, which led to the discovery of unique lipid assemblies; subcomparmentalized protocells, protocell-nanotube networks, and protocell colonies.” Gozen, Irep. 2021. “Did Solid Surfaces Enable the Origin of Life?” Life. 11:795. doi: 10.3390/life11080795. p. 801.

“The basic premise of geobiochemistry is that life emerged on Earth where there were opportunities for catalysis to expedite the release of chemical energy in water-rock-organic systems. In this framework, life is a planetary response to the dilemma that cooling decreases the rates of abiotic processes to the point that chemical energy becomes trapped. Catalysis via metabolism releases the trapped energy, and life benefits by capturing some of the energy released.” Shock, Everett L. & Eric S. Boyd. 2015. “Principles of Geobiochemistry.” Elements. 11:395-401. doi: 10.2113/gselements.11.6.395. p. 395.

“The venerable field of biogeochemistry has the goal of understanding how biology affects geochemistry. The complementary emerging field of geobiochemistry aims to explain how geology affects biochemistry.” Shock, Everett L. & Eric S. Boyd. 2015. “Principles of Geobiochemistry.” Elements. 11:395-401. doi: 10.2113/gselements.11.6.395. p. 395.

“If we are to work from the assumption that ‘the biochemistry we have is one that the Earth allows’, then we are also implicitly assuming that–alongside differentiation, mantle convection, volcanism, tectonics, metamorphism, hydrothermal alteration, weathering, and climate change–life is a planetary process.” Shock, Everett L. & Eric S. Boyd. 2015. “Principles of Geobiochemistry.” Elements. 11:395-401. doi: 10.2113/gselements.11.6.395. p. 396; subquote: Manning, Craig. personal communication to authors.

“When reactions that are thermodynamically favorable meet profound mechanistic or kinetic barriers, catalysis emerges as a major factor in determining what actually happens. In essence, life is a collection of complex adaptive catalysts tuned to energy supplies that persist unexpended owing to abiotic complications that inhibit reaction progress. Without those abiotic mechanistic difficulties, life would not be possible. It follows that life is ‘allowed’ by the mechanistic complications of low-temperature geochemistry, and life owes its existence to interferences and hurdles in the relentless drive for the release of chemical energy.” Shock, Everett L. & Eric S. Boyd. 2015. “Principles of Geobiochemistry.” Elements. 11:395-401. doi: 10.2113/gselements.11.6.395. p. 396.

“‘Things that burst into flame are not good to eat’…. If a reaction can proceed abiotically at a rapid rate, there is no need for catalysis, and no option for that reaction to supply energy in support of microbial metabolism. Rates typically increase with increasing temperature, which is why one of the limits of the biosphere is assumed to be at high temperatures. If a reaction reaches equilibrium faster than microbes can intervene to take advantage of it, that reaction cannot support life.” Shock, Everett L. & Eric S. Boyd. 2015. “Principles of Geobiochemistry.” Elements. 11:395-401. doi: 10.2113/gselements.11.6.395. p. 400; subquote: Holland, Melanie. personal communication.

“Indeed, the most significant flaw in attempts to derive natural selection from thermodynamics is that the kinetic behaviour of complex systems can hardly be deduced from data governing free energy minima, data which ignores the free energy barrier heights separating reactants and products.” Pross, Addy & Robert Pascal. 2017. “How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution.” Beilstein Journal of Organic Chemistry. 13:665-674. doi: 10.3762/bpoc.13.66. p. 667.

“Key conditions for observing physicochemical behaviour governed by dynamic kinetic stability is that the system is self-reproducing and able to undergo exponential growth. These conditions further imply that the system is maintained in a far-from-equilibrium state and that the chemical autocatalytic process involved must be kinetically irreversible (i.e., the rate of the reverse reaction must be negligible on the timescale of reproduction generation).” Pross, Addy & Robert Pascal. 2017. “How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution.” Beilstein Journal of Organic Chemistry. 13:665-674. doi: 10.3762/bpoc.13.66. p. 670.

“The ‘autonomy of biology’ view of life, still deeply engrained within life science thinking, needs to be reassessed as it undermines attempts to understand biology’s deeper essence. The very fact that chemistry almost certainly evolved over time into biology is the clearest statement that the physical and biological worlds are merely two regions of a physicochemical-biological continuum. It also means that biological understanding in its deeper sense must lie in physics and chemistry. The awkward reality for biologists – that biology’s essence, secreted within those physicochemical origins lies largely outside the subject that purports to study it.” Pross, Addy & Robert Pascal. 2017. “How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution.” Beilstein Journal of Organic Chemistry. 13:665-674. doi: 10.3762/bpoc.13.66. p. 672.

“The ability to reduce everything to simple fundamental laws does not imply the ability to start from those laws and reconstruct the universe….

“The constructionist hypothesis breaks down when confronted with the twin difficulties of scale [and] complexity.” Anderson, P.W. 1972. “More is Different.” Science. 177(4047):393-396. p. 393.

“If ammonia starts out from the above unsymmetrical state [3 hydrogens forming a triangular pyramid to the one nitrogen], it will not stay in it very long. By means of quantum mechanical tunneling, the nitrogen can leak through the triangle of hydrogens to the other side, turning the pyramid inside out, and, in fact, it can do so very rapidly. This is the so-called ‘inversion,’ which occurs at a frequency of about 3 X 1010 per second. A truly stationary state can only be an equal superposition of the unsymmetrical pyramid and its inverse. That mixture does not have a dipole moment….

“In quantum mechanics there is always a way, unless symmetry forbids, to get from one state to another. Thus, if we start from any one unsymmetrical state, the system will make transitions to others, so only by adding up all the possible unsymmetrical states in a symmetrical way can we get a stationary state. The symmetry involved in the case of ammonia is parity, the equivalence of left- and right-handed ways of looking at things.” Anderson, P.W. 1972. “More is Different.” Science. 177(4047):393-396. p. 394.

“The essential idea is that in the so-called N -> ∞ limit of large systems (on our own, macroscopic scale) it is not only convenient but essential to realize that matter will undergo mathematically sharp, singular ‘phase transitions’ to states in which the microscopic symmetries, and even the microscopic equations of motion, are in a sense violated…. There is, of course, no question of the system’s really violating, as opposed to breaking, the symmetry of space and time, but because its parts find it energetically more favorable to maintain certain fixed relationships with each other, the symmetry allows only the body as a whole to respond to external forces.” Anderson, P.W. 1972. “More is Different.” Science. 177(4047):393-396. p. 395.

“At some point we have to stop talking about decreasing symmetry and start calling it increasing complication.” Anderson, P.W. 1972. “More is Different.” Science. 177(4047):393-396. p. 396.

“There may well be no useful parallel to be drawn between the way in which complexity appears in the simplest cases of many-body theory and chemistry and the way it appears in the truly complex cultural and biological ones, except perhaps to say that, in general, the relationship between the system and its parts, is intellectually a one-way street [reductionism works; predicting the emergence of complexity does not]. Synthesis is expected to be all but impossible; analysis, on the other hand, may be not only possible but fruitful in all kinds of ways….” Anderson, P.W. 1972. “More is Different.” Science. 177(4047):393-396. p. 396.

“The selection of a stable assembling species out of pool of non-assembling precursors is an attractive mechanism to the formation of protocells out of a pool of prebiotic molecules….

“We bring a library of primitive carboxylic acids out-of-equilibrium by high-energy condensing agents. We find the metastable anhydride products that can phase-separate into micron-sized droplets to be more persistent against deactivation than non-assembling ones. After several starvation-refueling cycles, the library self-selects the most competitive product by their survival in phase-separated droplets. The observed self-selection is rationalized by a first-order kinetic model, taking into account the persistence of species by compartmentalization. We found that it is more favorable for the self-selecting droplets to form when the library is brought out-of-equilibrium by periodic addition of batches as opposed to feeding it continuously. Our results suggest that persistence by phase-separation or compartmentalization offers a selection mechanism for energy dissipating out-of-equilibrium assemblies.” Tena-Solsona, Marta, Caren Wanzke, Benedikt Riess, Andreas R. Bausch & Job Boekhoven. 2018. “Self-selection of dissipative assemblies driven by primitive chemical reaction networks.” Nature Communications. 9:2044. doi: 10.1038/s41467-018-04488-y. p. 2.

“We used aqueous solutions of 300 mM propionic, 300 mM butyric, 300 mM valeric, and 100 mM caproic acid as precursors (C3, C4, C5, or C6, respectively). Condensing agents 1-ethyl-3-carbodiimide (EDC), N,N’-diisopropylcarbodiimide, and 1,1′-crbonyldiimidazole (CDI) were used as fuels that drive the chemical network out-of-equilibrium. Indeed, when we added a batch of these fuels to aqueous C5, the corresponding symmetric anhydride (C5C5) was temporarily found by high-performance liquid chromatography at the expense of the fuel. We focused the further experiments on EDC, the most active condensing agent….

“After the consumption of the fuel, we observed that the decay of the anhydrides was dependent on the carbon number. The higher carbon number anhydrides hydrolyzed slower with a drastic increase of stability for the C6C6. The dependence of the hydrolysis on the carbon number resulted in a significant difference in the remaining anhydride after 1 h: while for C3C3 and C4C4 almost no anhydride was detected, 1.5 and close to 3.5 mM remained for the C5C5 and C6C6 respectively.

“The different remaining concentrations after 1 h resulted from differences in the decay profile of the anhydride, which changed from an exponential decay for C3C3 and C4C4 to a linear decay for C5C5 and C6C6.” Tena-Solsona, Marta, Caren Wanzke, Benedikt Riess, Andreas R. Bausch & Job Boekhoven. 2018. “Self-selection of dissipative assemblies driven by primitive chemical reaction networks.” Nature Communications. 9:2044. doi: 10.1038/s41467-018-04488-y. p. 2.

“Next we changed the conditions to a regime, where the stabilization of products by phase-separation [from vesicle formation] could occur. For example, when we added 35 mM EDC every hour, C3C5 and C5C5 both peaked at close to 7 mM. However, C5C5 persisted for much longer than its competitors, and more than 2 mM C5C5 remained when we added a new batch of fuel, while all competitors had hydrolyzed. Addition of a new batch of fuel further increased the advantage of C5C5, which now peaked at around 10 mM. The advantage kept on increasing with every refueling round. Confocal microscopy showed the presence of oil droplets after addition of the first 35 mM EDC and confirmed that some droplets persisted before addition of new fuel. Refueling the experiment did not increase the number of droplets, but increased the radius of the existing droplets, as it was more favorable for freshly anhydride to assemble with persisting drops, rather than forming new ones.” Tena-Solsona, Marta, Caren Wanzke, Benedikt Riess, Andreas R. Bausch & Job Boekhoven. 2018. “Self-selection of dissipative assemblies driven by primitive chemical reaction networks.” Nature Communications. 9:2044. doi: 10.1038/s41467-018-04488-y. pp. 3-5.

“In conclusion, our results show that the ability of phase-separation is an effective mechanism for the selection of nonequilibrium products, even in complex reaction schemes with tens of interacting reactions. Selection is achieved by inducing compartmentalization, which results in separating the time scales of deactivation and therefore slowing down the deactivation of products. Compartmentalization by phase-separation has already been shown to be an essential mechanism in biology for cells for proper function, and our results suggest that there also [is] a more generic role of this mechanism in primitive chemical reaction networks. Moreover, work by others has shown that driven phase-separation can result in spontaneous self-division, as well as self-propulsion.” Tena-Solsona, Marta, Caren Wanzke, Benedikt Riess, Andreas R. Bausch & Job Boekhoven. 2018. “Self-selection of dissipative assemblies driven by primitive chemical reaction networks.” Nature Communications. 9:2044. doi: 10.1038/s41467-018-04488-y. p. 5.

“Only then [after first stars formed and exploded], as giant stars exploded into the first supernovae, did minute bits of condensed, crystalline matter form in the cooling, expanding, gaseous stellar envelopes. Possibly a dozen micro- and nanoscale mineral species appeared. Diamond and graphite were likely the most abundant crystalline phases in those carbon-rich environments, with a sprinkling of carbides, nitrides, oxides, and magnesium silicates. For perhaps tens of millions of years, these few microscopic primeval ‘ur-minerals’ were the only crystals in the universe.

“The diversification of minerals had to wait for the emergence of planets because planets are the engines of mineral formation.” Hazen, Robert M. & John M. Ferry. 2010. “Mineral Evolution: Mineralogy in the Fourth Dimension.” Elements. 6:9-12. doi: 10.2113/gselements.6.1.9. p. 9.

“The initial mineral evolution of Earth’s crust depended on a sequence of geochemical and petrologic processes, including volcanism and degassing, fractional crystallization, assimilation, regional and contact metamorphism, plate tectonics, and associated large-scale fluid-rock interactions. These processes, which produced the first continents and ultimately resulted in an estimated 1500 different mineral species, can be divided into three evolutionary stages.” Hazen, Robert M. & John M. Ferry. 2010. “Mineral Evolution: Mineralogy in the Fourth Dimension.” Elements. 6:9-12. doi: 10.2113/gselements.6.1.9. p. 11.

“… we argue that fully two-thirds of all known mineral species are the consequence of Earth’s transformation by living organisms….

“The ‘Great Oxidation event’ (GOE) (starting ~2.4 Ga), when atmospheric oxygen may have risen to >1% of modern levels, irreversibly transformed Earth’s surface mineralogy. More than 2500 minerals are hydrated, oxidized weathering products of other minerals, and these new minerals are unlikely to have developed in an anoxic environment.” Hazen, Robert M. & John M. Ferry. 2010. “Mineral Evolution: Mineralogy in the Fourth Dimension.” Elements. 6:9-12. doi: 10.2113/gselements.6.1.9. pp. 11-12.

“At the dawn of the Cambrian Period, Earth’s subaerial surface was, as it had been for most of the previous 4 billion years, mostly barren rock. The rise of land plants about 400 million years ago not only dramatically altered Earth’s surface appearance, but it also led to rapid production of soils, including an order of magnitude increase in the rate of clay mineral production.” Hazen, Robert M. & John M. Ferry. 2010. “Mineral Evolution: Mineralogy in the Fourth Dimension.” Elements. 6:9-12. doi: 10.2113/gselements.6.1.9. p. 12.

“… the nuclear genome, organelles, and microbiome of holobionts comprise a hologenome.” Bordenstein, Seth R. & Kevin R. Theis. 2015. “Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes.” PLOS Biology. 13(8):e1002226. doi: 10.1371/journal.pbio.1002226. p. 2.

“Hologenomic evolution is most easily understood by equating a gene in the nuclear genome to a microbe in the microbiome.

“Evolution for both genes and symbionts is fundamentally a change in population frequency over successive generations, i.e., the fraction of holobionts carrying that particular nuclear allele or microbe.” Bordenstein, Seth R. & Kevin R. Theis. 2015. “Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes.” PLOS Biology. 13(8):e1002226. doi: 10.1371/journal.pbio.1002226. p. 3.

“It [the hologenome concept of evolution] posits that hosts and their microbiota are emergent individuals, or holobionts, that exhibit synergistic phenotypes that are subject to evolutionary forces. Via fidelity of transmission from parents to offspring or stable acquisition of the microbiome from the environment, covariance between the host and microbiota can be established and maintained…. The microbiomes, and thus their encoded phenotypes, can change through differences in the relative abundances of specific symbiotic microbes, the modification of the genomes of existing resident microbes, or the incorporation of new microbial symbionts into holobionts, which can occur even within the reproductive lifetime of hosts. Importantly, genetic variation in the microbiome vastly exceeds that in the host genome and accumulates much more rapidly than variation in host genomes.” Bordenstein, Seth R. & Kevin R. Theis. 2015. “Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes.” PLOS Biology. 13(8):e1002226. doi: 10.1371/journal.pbio.1002226. pp. 5-6.

“As a final remark, given the ubiquity of catalysis in living systems, it seems that life does not so much ‘invent’ new chemistry, but rather uses chemistry that happens anyway, evolving efficient catalysts to speed up those reactions that are in some way useful for its own maintenance and reproduction. This way, a (self-)catalyzed reaction sub-network arises out of a background of all possible chemical reactions.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 4.

“Furthermore, RAF [reflexively autocatalytic and food-generated] sets often consist of many hierarchical levels of subRAFs…. This property provides one of the necessary conditions for autocatalytic sets to be potentially evolvable.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. pp. 4-5.

“A hypercycle is a special instance of the more general notion of autocatalytic sets, one in which all molecule types also catalyze their own formation in addition to the formation of one or more of the other molecule types.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 5.

“Indeed, an essential property of living systems is that they produce their own catalysis and, moreover, these catalysts mutually catalyze each other’s formation. This is exactly what allows living systems to evolve, diversify, and become more complex. We therefore argue that autocatalytic sets are a necessary (although not sufficient) condition for life-like behavior.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 5.

“We refer to a catalytic reaction system (CRS) as a set of molecule types (including a food set), a set of reactions, and a pattern of catalysis (describing which molecules catalyze which reactions). Note that an arbitrary CRS does not necessarily contain a subset of reactions that forms a RAF. However, when such a RA F subset does exist, there is a unique maximal one (containing all other possible RAFs) and this unique maxRAF….

“The maxRAF together with all of its subRAFs form a partially ordered set (poset) under set inclusion. The minimal elements of this poset are called irreducible RAFs (irrRAFs): Removing any reaction from an irrRAF results in a set that no longer is (or contains) a RAF. In other words, they are in some sense the ‘smallest’ RAFs, and presumably the first ones to emerge in a dynamical sense.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 5.

“… the main subRAFs of interest, from a dynamical point of view, are those that are closed. This means that any reaction for which all reactants and at least one catalyst are currently available from within the subRAF will be included in it.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 6.

“If there are closed RAFs in the poset other than the maxRAF, it implies that some reactions in the maxRAF do not immediately have all their reactants and/ or catalysts present (i.e., when the system is initialized with just the food molecules).” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 6.

“The first autocatalytic sets would have arisen with inorganic elements as their catalysts. Once these autocatalytic sets had established themselves, this opened up the possibility of producing more complex (organic) molecules, some of which could form more efficient catalysts, or incorporate the original inorganic elements as their cofactor making them more efficient and more specific. This, in turn, could then lead to yet more molecular complexity and catalytic efficiency, and so on until something resembling a modern-day metabolic network was formed.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 8.

“In fact, since RAF sets are defined in a graph-theoretical way, they are not restricted to chemical reaction networks only. In principle, the nodes in a ‘reaction graph’ could represent any kinds of entities and transformations between those entities. For example, in modeling early life, one can regard the formation of a lipid boundary leading to an early protocell as the generation of a ‘higher-level’ catalyst for the reactions that involve the molecules that are concentrated within the boundary (here, the catalyst is an aggregate structure rather than a single molecule).” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 8.

“Finally, the formal RAF framework can be applied to systems beyond chemistry, such as ecosystems, the economy, and cognition.” Hordijk, Wim & Mike Steel. 2018. “Autocatalytic Networks at the Basis of Life’s Origin and Organization.” Life. 8:62. doi: 10.3390/life8040062. p. 9.

“Comparison with compositions of modern granites suggested that Hadean granitoids–the inferred source of the Jack Hills zircons–contained a sedimentary component. Because most sediment forms through fluvial erosion, conditions at Earth’s surface at the very start of its history were cool and clement….

“Before the Jack Hills discovery … we imagined a Hadean Earth … covered by lavas and impact breccias, and blanketed by a primitive Jupiterian atmosphere. The Jack Hills zircons changed our ideas to such an extent that we now imagine that continents and oceans existed at that time. Furthermore, if there were water and if temperatures were moderate, it is only a small step to imagine that life emerged much earlier than previously thought possible on the surface of the Hadean planet.” Arndt, Nicholas T. & Euan G. Nisbet. 2012. “Processes on the Young Earth and the Habitats of early Life.” Annual Review of Earth and Planetary sciences. 40:521-49. doi: 10.1146/annurev-earth-042711-105316. p. 523.

“To summarize, by the late Hadean, say, 500 million years after accretion [4.56 Gya], the planet probably had many sites where the key biochemical necessities were available.” Arndt, Nicholas T. & Euan G. Nisbet. 2012. “Processes on the Young Earth and the Habitats of early Life.” Annual Review of Earth and Planetary sciences. 40:521-49. doi: 10.1146/annurev-earth-042711-105316. p. 533.

“Until recently, it was thought that the time before the late-heavy bombardment from ~3.9 Gya was inclement for life, and that even if life had begun in the Hadean, the bombardment would have sterilized the oceans. However, using thermal modeling, Sleep (2010) considers that by roughly 4.37 Gya some ‘Goldilocks’ regions existed in the oceanic crust where conditions were such that even a major ocean-heating event would not have destroyed newly emerged life. The latest date by which life must have started is set by the strong evidence in the Isua Belt in Greenland dating from ~3.8 Gya.” Arndt, Nicholas T. & Euan G. Nisbet. 2012. “Processes on the Young Earth and the Habitats of early Life.” Annual Review of Earth and Planetary sciences. 40:521-49. doi: 10.1146/annurev-earth-042711-105316. p. 534; reference: Sleep, N.H. 2010. “The Hadean-Archaean environment.” Cold Spring Harb. Perspect. Biol. 2:a002527.

“Most previous work on catalysis has been concerned with the acceleration of reaction rates by enzymes. A much more inclusive category of environmental influence on chemical reactions is a change in the reaction mechanism, i.e. a change in the path of the reaction. Accordingly, we will use the term catalysis in the broadest possible sense for any alteration of any detail of a chemical reaction by its environment, provided that the latter stays unchanged at the end of the reaction.

“Living organisms (and therefore their enzymes) need to preserve and use the energy generated in exothermic reactions. Evolution selects enzymes based on catalytic rate enhancement as well as the ability to preserve energy in high-grade, usable form. Balancing these two criteria results in the selection of an optimized reaction path in which a significant fraction of energy can be maintained in a high-grade form for subsequent use.” Szoke, Abraham, William G. Scott & Janos Hajdu. 2003. “Catalysis, evolution and life.” FBS Letters. 553:18-20. doi: 10.1016/S0014-5793(03)01008-1. p. 18.

“(a) B + Catalyst –> C + Catalyst + Heat

“(b) B + Catalyst –> C + Energised catalyst + Less heat
D + Energised catalyst –> E + Catalyst

“a: The case where no coupling is possible as ΔG is dissipated as heat. b: Reaction in which the catalyst captures part of ΔG. This feature allows energy transfer by coupling an exergonic reaction to drive an endergonic reaction uphill.” Szoke, Abraham, William G. Scott & Janos Hajdu. 2003. “Catalysis, evolution and life.” FBS Letters. 553:18-20. doi: 10.1016/S0014-5793(03)01008-1. p. 19.

“We simply envisage chemistry morphing smoothly into biology. However, there is a point further down the path that does have significance in which RNA and peptides exceed a certain length so that exploration of sequence space by the system can no longer be exhaustive, and nascent biology thus proceeds along a pathway dictated by contingency. Up to that point, prebiotic chemistry and early biology most likely followed a deterministic trajectory….” Sasselov, Dimitar D., John P. Grotzinger & John D. Sutherland. 2020. “The origin of life as a planetary phenomenon.” Science Advances. 6:eaax3419. doi: 10.1126/sciadv.aax3419. p. 1.

“Though scientific efforts in the last 60 years have provided many stimulating ideas and hypotheses and a host of experimental data, the evolution of inanimate chemical matter into living cells has remained an unsolved puzzle–or even a mystery.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 9.

“The important point is that non-covalent molecular forces bring about phase separations and hence purifications (i.e., the creation of lower entropy [purer] phases of matter)…. Phase separations can also be viewed as ‘self-assembly,’…. However, the usage of terms like self-assembly is ad hoc, and the meaning seems variable and imprecise. For instance, self-assembly could mean micelle formation from monomeric surfactant molecules–a thermodynamically spontaneous self-organizing process driven by the hydrophobic effect–or it could imply ‘far-from-equilibrium self-assembly,’ which does not explicitly recognize the role of non-covalent molecular forces at all.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 14.

“The top-down and bottom-up approaches [for explaining the origin of life] meet at the crowding transition, a key requirement for life to emerge. The crowding transition is identified by the commensuration of distances over which non-covalent molecular forces act–in the ~0.3 to ~3.0 nm range. This estimate is based on the range of action of three non-covalent molecular forces that can be considered as the most relevant: the excluded volume effect (biomacromolecular crowding), hydrogen bonding, and screened electrostatic forces.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 15.

“However, a host of other non-covalent attractions and repulsions were also known to operate inside the cell: quantum mechanical van der Waals forces, both attractive and repulsive; Debye’s polar (dipole) forces; and classical Coulomb electrostatic forces, either direct, as in ionic crystals, or screened, as in solutions of strong electrolytes of the Debye-Hueckel theory. By the 1960s other forces had been recognized, such as the hydrophobic effect and screened electrostatic forces in dilute polyelectrolyte solutions.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 19.

“… it is not so much that a bacterial nucleoid self-replicates; it is rather that the cell replicates the nucleoid…. The nucleoid is dead; only the cell is alive–only the cell creates information out of nucleic acids.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 20.

“The transition from prebiotic chemistry to ancient microbiology, between ~4.5 and ~3.5 billion years ago, is arguably the most important [major transition]. It defines the problem of life’s origins on Earth–the continuity between Earth’s prebiotic chemical evolution and its Archaean microbiological evolution, both driven by planetary cyclic energies.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 31.

“Given the multicomponent prebiotic composition of Earth’s carbon compounds, compartments likely phase separated naturally, for example, under hydration-dehydration cycles in sedimentary tidal matrices; in that sense, they also purified the primordial soup. Colloidal compartments localize chemical reactions and slow the dissipation of concentration gradients; they counteract the operation of the second law and thus are essential for life to emerge.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 35.

“‘Most chemists believe, as do I, that life emerged spontaneously from mixtures of molecules in the prebiotic Earth. How? I have no idea.’

“‘Solutions offered by supporters of geneticist or metabolist scenarios that are dependent on ‘if pigs could fly’ hypothetical chemistry are unlikely to help.’” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 36; subquotes are respectively: Whitesides, G.M. 2007. “Revolutions in chemistry.” C&EN. 85(13):12-17; Orgel, L.E. 2008. “The implausibility of metabolic cycles on the prebiotic Earth.” PLoS Biol. 6(1):e18)

“The cyclic environmental energies look the most plausible to me as the natural agents of life’s creation. Adopting Occam’s razor, I take a simplifying view that two natural cyclic energies arising from Earth’s rotation–solar radiation and seawater tides–were the most important; they stoked prebiotic chemical matter into a living state of first single-cell organisms.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 39.

“Shapiro described the issue [of demonstrating the OoL by increasing complexification of molecular structures], tongue-in-cheek, this way: ‘The analogy that comes to mind is that of a golfer, who having played a golf ball through an 18-hole course, then assumed that the ball could also play itself around the course in his absence.’” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 40; subquote: Shapiro, Robert. 2007. “A simpler origin of life.” Sci Am. 296: 46-53.

“At the core of the question [whether life arose from chemistry] is the tension between Darwin’s conclusion that all life arose from one (or a few) common ancestors and Pasteur’s refutation of the ‘spontaneous generation’ of even the smallest microbes (taken as extant representatives of common ancestors).” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 40.

“There is a widespread and long-standing physical, chemical, and biological consensus that no molecules are alive, something that has been known since Robert Brown distinguished the effects of colloidal diffusional motion (Brownian motion) from the biological motions of Leeuwenhoek’s animalcules.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 43.

“The problem of life’s origin cannot be solved by saying that ‘informational’ molecules are special–alive in the biological sense–and that they actually self-replicate and evolve. We know that they do not. This backward case of reductionism, of extending organismal reproduction, mutations, and natural selection to the behavior of molecules, is an extraordinary idea, unmoored from current textbook knowledge of chemistry.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 43.

“Additional findings have revealed that the replication of the bacterial nucleoid in vitro requires not only energy (ATP) but also crowded conditions, resembling those that the nucleoid encounters in a living cell.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 55.

“From a purely chemical point of view, a bacterial cell is exceedingly complicated. The cytoplasm contains in round numbers ~2,500,000 protein molecules of ~1,000 different kinds, ~200,000 transfer RNAs of ~50 kinds, and ~1,500 short-lived messenger RNAs of ~400 kinds…. The number of ribosomes can vary between 2,000 for a slow-growing population and 70,000 in a fast-growing population. These biomacromolecules are hydrated by a relatively concentrated (~4%) electrolyte–a multicomponent buffered solution of simple ions, particularly potassium ions and phosphate, and other low-molecular-weight metabolites from biochemical pathways, many of them phosphate esters.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 55-6.

“The crowding determines the rate of protein folding, the conformational stability, and the association of biomacromolecules into transient molecular machines, and it may cause protein misfolding.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 58.

“There is now a greater acceptance of the nineteenth-century view of bacterial cytoplasm as a colloidal gel (a two-phase sol-gel system), which is caused by the polymeric incompatibility of nucleic acids and proteins under crowded conditions. The transient gel phases are (presumably) super-crowded with biomacromolecules separated by narrow electrolyte channels. The sol has a morphology of large electrolyte ‘pools’ and wide ‘waterways’ with low viscosity. Within the sol, low-molecular-weight metabolites and small proteins diffuse relatively fast until they are ‘tagged’ by specific proteins or functional chemical groups (phosphate ester, methyl) and captured at biomacromolecular surfaces through attractive non-covalent forces.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 58-9.

“… the digital genetic program for bacterial organismal construction is largely silent on the kinds and amounts of nutrients, salinity, temperature, and pH–that is, on the environmental conditions necessary to make a cell work properly in a downward causation.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 60.

“Life is a relationship among molecules and not a property of any molecule.” Quotation of Linus Pauling. Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 65; quotation source: Hager, Thomas. Force of Nature. 1995.

“In general terms, non-covalent molecular forces are the ultimate reason for diverse kinds of phase separations, including the many nano-phases materializing within crowded bacterial cells as they grow and divide. It feels natural to imagine that such physicochemical sophistication could only have come about through the evolutionary processes of chemical reactions and concurrent phase separations, especially colloidal phase separations on nano- to micro-meter scales.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 65.

“Phase separations arise when molecular surfaces come into contact and when attractive non-covalent molecular forces, greater (on average) than the thermal energy kT, make them ‘stick’ together, at least transiently.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 66.

“There is a great variety of attractive non-covalent molecular forces responsible for the existence of liquid and solid phases. There are induced dipole-dipole (van der Waals) forces…. These forces explain the liquefaction of monoatomic (spherically symmetric) non-polar gases, such as helium, at temperatures close to absolute zero. There are Debye-type polar forces between small, overall neutral molecules with permanent dipoles, quadrupoles, and so on, exhibiting permanent polarity…. There are ‘naked’ coulombic electrostatic forces, as in ionic crystals, that can be as strong as covalent bonds; and there are screened electrostatic forces as defined by the Debye-Hueckel theory of strong electolytes, when a hydrated ion in a solution (or a charged surface) interacts with all the other dissolved ions nearby–often referred to as ionic cloud or atmosphere. Screened electrostatic forces come into play in all charged chemical systems, such as strong electrolytes and polyelectolytes, and also in systems with charged colloidal surfaces. In the latter case, these repulsive forces impart electrostatic stability to charged surfaces, particularly at low ionic strengths.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 67.

“Any phase transition, such as crystallization, can be regarded as a dynamic self-assembly, when highly disordered phases turn into more ordered phases–the consequence of dropping temperatures and/or chemical reactions that increase concentrations beyond solubility limits. In essence, a phase transition can be regarded as an act of creation of macroscopic matter from small molecules or ions: for example, those dissolved in water. In the case of low-molecular-weight multicomponent aqueous solutions, there are sequential phase separations of purified phases reflecting the solubility of the individual components in water. On molecular and supramolecular (colloidal) scales, such processes can be quite complex, involving super-saturation, nucleation rates vs. agglomeration rates, the evolving colloidal stability of the agglomerating supramolecular particles as they grow, and the complex dependence on process parameters, such as mechanical agitation and heat transfer. When a chemical system contains high-molecular-weight compounds (dispersed and/or dissolved), such as polymers, together with surfactant-like amphiphilic molecules, phase separations get very complicated. In particular, they can become quite slow, and the separated phases remain small–representing (partially purified) micro-domains or nano-phases. Often, such systems produce macroscopic, non-linear viscoelastic materials, with disconnected micro-domains or with thread-like micro-domains (interpenetrating networks), which can be crystalline, amorphous, or even liquid.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 67-8.

“What are the important molecular forces within the bacterial cell? From the many kinds of physicochemical non-covalent forces described and analyzed in the literature, three kinds of molecular forces are predominantly responsible for regulating phase separations during the bacterial cell cycle: (i) macromolecular crowding, a generalization of non-bonding (electron) orbitals that repel other molecules–they give a molecule (or a large polymer chain) its identity, a representation of its van der Waals shape; (ii) hydrogen bonding, accounting for the molecular complementarity of nucleobases in DNA and RNA, for the hydrophobic effect, and for the hydration of biopolymers; and (iii) screened electrostatic repulsions between macromolecular charges of the same sign exposed to the cytoplasmic electrolyte.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 68.

“Macromolecular crowding, which used to be a somewhat neglected and controversial concept, is now recognized as modifying biopolymer and metabolite diffusion in vivo, as well as biopolymer conformations and their associations into larger homo- and hetero-complexes of proteins and nucleic acids….

“Simple physical models of crowding show that cytoplasmic biomacromolecules are more or less touching in vivo, either repelling or transiently ‘sticking.’” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 70.

“From a biochemical perspective, transient macromolecular localizations were described as weak quinary structures nearly 40 years ago…. The term quinary is a continuation of describing proteins at different levels of structure: their primary structure (the sequence of amino acids along the peptide chains); their secondary structure such as Pauling’s helices and β-sheets; their tertiary 3-D structure, the structure of the total protein, showing all the ordered and disordered parts; and their quaternary structure, that of the protein’s homo- and hetero-complexes, including nucleoproteins. The difficulties of defining quinary structure are quite understandable from a physico-chemical standpoint because many non-covalent molecular forces act concurrently under high crowding throughout the cell. Quinary structures are weak and therefore disappear upon dilution via Brownian diffusion–they are the living structure of the cytoplasm.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 70-1.

“… there are about 2,000 different kinds of macromolecules and metabolites within the cell, operating at time-varying concentration and in parallel. They form a multitude of large biomacromolecular complexes, many of which can be strong and recovered from broken cells. These are the biochemical nano-machines, such as ribosomes, as well as large homo- and hetero-protein quaternary complexes of intermediate stability that can be isolated, reconstituted, and studied in vitro under specific conditions of temperature, pH, and ionic strength (and crowding if needed).

“Thus, under normal variations of environmental conditions (e.g., temperature, water activity, and nutrient availability), the non-covalent molecular forces organize a robust, amazingly well-orchestrated ‘quinary ballet’ of cytoplasmic molecular motions, which, remarkably, avoid any catastrophic–fatal–agglomerations.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 71-2.

“Hydrogen bonding is possibly the most important molecular interaction in biological physical chemistry, as suggested above by Pauling, because cellular life is based on water molecules, which create a biophilic continuous liquid medium, both inside and outside the cell. Thus, water is regarded as a bio-signature or an indicator of possible life in the cosmos because: (i) it can hydrogen bond with many compounds made of life’s CHONSP macro-elements; (ii) it is an excellent solvent for ions essential for life, such as K+, Na+, Ca2+ , and Mg2+, hydrogen-carbonate [HCO3]-1 and hydrogen-[HPO4]-2 and dihydrogen-phosphates [H2PO4]-1; and (iii) it can self-ionize and thus serve as a source of hydrated protons and hydroxyls.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 72.

“The enzymes and macromolecular machines that catalyze biochemical reactions are synthesized, assembled, and localized on much longer timescales than the nano- to pico-second persistence of biomacromolecular hydration. Therefore, the subcellular cellular architecture–the sol-gel quinary structure–originates from the (much slower) conformational, rotational, and translational molecular motions of large biomacromolecules, not from ‘bound’ (viscous or ice-like) biological water. In other words, the hydration of biomacromolecular surfaces is so fast that it can be considered equilibrated (decoupled) with respect to cellular physiological processes, such as the localizations of proteins and nucleic acids within the cell.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 76.

“When too many hydrocarbon molecules are added to water, they phase separate, giving rise to a measurable interfacial tension between the water and hydrocarbon phases, this phenomenon creates the superficial impression that hydrocarbon molecules are repelled by water molecules, hence the moniker ‘the hydrophobic effect’. Hildebrand criticized the term hydrophobic because the energy of adhesion between the interfaces is positive, that is, attractive; in other words, it is not hydrophilic enough.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 77; reference: Hildebrand, J.H. 1979. “Is there a ‘hydrophobic effect’?” Proc Natl Acd Sci USA. 76:194.

“The DNA double helix, with ionized phosphates outside, is one of the most highly charged known polyelectrolytes. It is stabilized by hydration and by electrostatic screening forces at a relatively high ionic strength to reduce the mutual repulsions between phosphates exposed into water.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 86.

“Curiously, Pauling, Watson and Crick, and others did not seem to ask the evolutionary chemical question of why cellular life is based on phosphates and other ionized groups–in fact, why cellular life is so overwhelmingly ionic….

“The two major reasons are: (i) to ensure that phosphorylated metabolites remain inside the cell because the plasma membrane is hydrophobic and (ii) to ensure sufficient hydrolytic stability of the genetic material.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 87.

“To summarize, the gene-carrying molecules of DNA and RNA are highly anionic. The metabolic proteins are charged at lower levels compared to nucleic acids, and their net charge can be anionic, cationic, or zero (i.e., zwitterionic at the isoelectric point). Their colloidal stability is significantly enhanced by hydrogen bonding with water molecules–by hydration, by phosphorylation, and by similar reactions that attach negative charges to biomacromolecules.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 89.

“… three non-covalent forces–hydrogen bonding, screened electrostatic interactions (Debye-Hueckel forces), and crowding (the hard core excluded volume effect)–as the most important for controlling and organizing cellular machineries. For these forces to functionally cooperate, they must act over a commensurate range of distances. These distances are estimated …, and they lie within the range of ~0.3 to ~3.0 nm (~3 to ~30 Å), which corresponds to up to about 10 hydration layers.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 92.

“The first conclusion [for comparing the three non-covalent forces in the commensurate range] is just a restatement of the data: cellular life can exist only under the reasonable hydration of 1 to 10 layers of water molecules, which correlate automatically with a crowding range of 15-45% volume fraction of biomacromolecules and with an ionic strength range of 0.01-1.00 M (and higher).

“The second conclusion is that life cannot exist at ‘high dilution,’ meaning more than 10 water layers, when crowding would drop below 15% volume fraction. In that scenario, weak quinary structures could not be maintained, and thermal diffusion would take over–the inexorable consequence of the second law, as biomacromolecules and low-molecular-weight metabolites have more space to exercise their random Brownian motions…. Low ionic strengths would prevent the chemical evolution of complementary mucleobases, that is, the hybridizations and associations depend on screening of the exposed phosphate esters of DNA and RNA and of the cationic and anionic charges of proteins. This physicochemical conclusion is in accordance with the seventh of the 10 commandments of the enzymology of bacterial DNA replication: in vitro protocols to study DNA replication require crowding….

The third conclusion is that an extrapolation in the opposite direction–toward anhydrous conditions below the first complete water layer–supports the contention that cellular life chemically arose and evolved as a cyclic process by phase separations during the hydration-dehydration cycles of tidal seawater. These cycles involve repeated drying and wetting (hydration of dried films, their redispersions, and partial dissolutions), which represents cyclic chemical evolution on a supramolecular (colloidal) scale.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp, 93, 94.

“… the topology of cellular biomacromolecular surfaces can be considered ‘smooth’ because of the fast molecular motions of biomacromolecular hydration in the nanosecond to picosecond range. The smooth biomacromolecular ‘patches’ (hydrophilic, hydrophobic, and negatively and positively charged) give rise to both stabilizing and agglomerating forces, which act on longer timescales, from about microseconds to seconds (minutes), that is, on timescales relevant to cellular physiological processes, including the bacterial cell cycle. The attractive forces bring about transient occurrences of biomacromolecular cytogels at higher-than-average levels of crowding. Consequently, reservoirs of dilute solutions of freely diffusing proteins, nucleic acids, and metabolites–the cytosol–appear in a complementary, topological manner. These considerations suggest a great variety of functional spatiotemporal cellular organizations involving fast sol-gel transitions during the growth of a bacterial cell.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 95-6.

“… the bacterial cell can be regarded as a scaffold of the plasma membrane that is stabilized by the excrescences of a coacervated nucleoid from the inside and by additional biomacromolecules on the outside. The nucleoid has two functions: (i) contributing to the mechanical stability of the cell and (ii) ensuring stable storage of genetic information. Proteins are largely phase separated in quinary (super-crowded) structures along the cytoplasmic side of the membrane (prokaryotic cortex) and along the nucleoid–the gelled part of the cell, or the cytogel; the remainder of the cell is a dilute cytosol.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 98.

“Another commonsense feature of the model is the improved mechanical strength of the cell. The sol-gel structure, with its layer of superclusters associated with the cytoplasmic side of the plasma membrane, strengthens the cell envelope by making it thicker and by having the character of a viscoelastic gel–the higher the sub-membrane super-crowding, the stronger the gel. The sub-membrane gel (bacterial cortex) also slows down the loss of water, making it the cell’s first-line defense against exposure to dry or hyperosmotic environments.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 101.

“Among these prebiotic molecules [soluble in seawater] were small amounts of life’s building blocks, such as amino acids, sugars, and nitrogen heterocyclic compounds–the future nucleobases. They were subject to natural phase separations in the tidal environments of prebiotic Earth, which created self-purified colloidal and macroscopic chemical matter that kept cyclically evolving toward living, single-cell organisms.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 105.

“Pieces of the jigsaw puzzle of the emergence [Spitzer’s rough schema to tackle key problems in origin-of-life study] of the first single-cell organisms [Caption of a figure]. After the formation of the Moon, Earth’s rotation slowed down and the Moon migrated away from Earth. (1) Earth cooled until water condensed and created the first seas and seashores. (2) Geochemical colloidal compartments appeared in tidal sediments. (3) Persisting compartments began to evolve, retaining chemical memory from previous cycles–a precondition for chemical evolution toward life. (4) Phase separations and chemical reactions, stoked by tidal and solar energies, drove self-purifying processes toward the phosphorus-dominated chemistry of proto-nucleic acids, -proteins, and -membranes. (5) The cyclic crowding transitions directed chemical evolution toward proto-microbiology and cellular life. (6) Progenotes became transiently alive by cycling environmental energies. (7) Progenotes evolved into proto-cells, with fast-evolving initial heredity in more stable enclosures; they became persistently alive. (8) Proto-cells became homeostatic and less dependent on cyclic environmental energies; longer nucleic acids and the confining membrane united to create the cellular scaffold of LUCAs.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 106.

“[Jigsaw piece #3] Because phase separations and chemical reactions in inter-tidal zones lag behind the frequency of environmental driving energies (e.g., diurnal solar radiation and the chemical wet-and-dry cycles of the tides), some sediments and their morphologies will persist and become subject to further chemical and colloidal evolution….

“It is essential that the driving environmental energies have a sustaining, stoking character (originating in planetary rotations) that allows the appearance and maintenance of physicochemical gradients, such as those of temperature and water activity that cyclically drive chemical reactions and phase separations. In comparison, one-directional (more or less steady-state) physico-chemical gradients have no stoking character; for example, the (roughly) unidirectional temperature gradients between the hot fluids of hydrothermal vents and cold seawater are far less likely to create any evolving and persistent colloidal chemical memory.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 113.

“[Jigsaw piece #4] The chemical complexity of prebiotic tidal sediments thus evolves on two scales: (i) on the macroscopic scale of large-scale atmospheric and oceanic currents and their tidal mixing and (ii) on the nano-scale and micro-scale of molecular diffusion, chemical reactions, and colloidal stabilization. The randomness and contingencies of the mixing processes between atmosphere, hydrosphere, and lithosphere are counteracted by the immobilization patterns of tidal wet-and-dry cycles. These cycles create abiotic proto-biofilms in which diverse molecules become cyclically ‘trapped’ and thus isolated from the contingencies of geo-scale mixing between atmosphere, hydrosphere, and lithosphere.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 114.

“Of all the macro-elements of life, the ‘cosmic’ (geo)chemistry of phosphorus holds the dominant position–the key to making the puzzle solvable.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 116.

“In the jigsaw puzzle [piece #5], they [the three key non-covalent forces] become commensurate in an evolutionary manner, cycling between ~0.3 and ~3.0 nm. The first ‘proto-life’ thus emerged as a collection of confined, cyclic, phase-separating processes–crystallizing or solidifying below 1.0 nm by dehydration and (partly) dissolving (and dispersing) above 1.0 nm by hydration. Under these cycling conditions, non-covalent forces begin to organize a host of proto-biochemical reactions and processes, the most important being water elimination reactions upon dehydration, alongside the evolution of an increasing degree of homochirality, substrate-enzyme recognition, and mutual hybridizations of proto-nucleic acids and their associations and proto-proteins. Importantly, under crowded conditions, non-covalent molecular forces begin to maintain the proto-cellular architectures of ‘becoming alive,’ that is, the cyclic, transient localizations of proto-biomacromolecules and their associations with proto-membranes.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 117.

“[Jigsaw piece #6] I have therefore modified and enlarged the concept of progenotes to accommodate physiochemical requirements. I will keep the Woesian term progenotes, which here means abiotic proto-biofilms, crowded with proto-biomacromolecules and cyclically energized by solar radiation and tidal seawater–where the prebiotic planetary chemistry of phosphorus is preeminent. Three modifications are necessary:

“(i) Progenotes had an, albeit imperfect, hydrophobic confinement that allowed them to persist long enough to function as open thermodynamic systems (chemical micro-reactors), and thus be able to locally and temporarily defeat the second law of thermodynamics. Without an evolving envelope, a progenote would dissipate. The confining envelope then also implies primitive membrane transport and related proto-regulatory processes.

“(ii) Without cyclic environmental energies–the prime movers for life to emerge in the first place–progenotes could not have arisen and evolved. Progenotes came into existence by cyclic crystallizations, aggregations, gel-formations, coacervations, and other colloidal, chemically reactive, phase separation processes….

“(iii) Woese’s imprecise mapping of prebiotic mRNA sequences into proteins by simple proto-ribosome was accompanied by other primitive processes: primitive nucleic acid replication, transcription into proto-mRNAs, the transcriptional regulation of proto-genes, and the ‘charging’ of transfer RNAs with amino acids. In other words, all the key processes of molecular biology were primitive but evolving on a daily basis under confined and crowded conditions.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 120.

“In summary, the progenotic era involves the principle of triple coevolution: (i) imprecise genetics; (ii) imprecise metabolism (i.e., the Woeseian mapping of proto-mRNAs into protein enzymes and proteins with structural and regulatory functions); and (iii) imperfect compartments (i.e., leaky and mechanically weak proto-cell envelopes with hydrophobic proto-proteins and proto-phospholipids). The progenotes in the tidal proto-biofilms thus began to create a unique ‘proto-biotic’ tidal environment-a proto-ecological niche–that was separate from but in contact with the atmosphere, hydrosphere, and lithosphere, and which brought in new abiotic molecules generated elsewhere. Within the tidal environments, progrenotic proto-biofilms were cyclically percolated by seawater, which itself was therefore coevolving with the progenotes as a storehouse of compatible chemical proto-nutrients.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 120-1.

“Progenotes in proto-biofilms were not in any sense biological organisms because their proto-metabolism directly depended on the rotation of prebiotic Earth–on its cyclic energies. However, using biological language, they could be described as proto-biotic colloidal compartments becoming cyclically alive, that is, being repeatedly ‘resurrected’ in an evolutionary manner, as if cultivated by cyclic environmental energies.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 122.

“The chief chemical characteristic of the progenotic era was the chemical evolution of phosphorylated carbon molecules (POCHNS) with low and high molecular weights toward future ATP, GTP, phospholipids, and proto-nucleic acids with ever-increasing molecular weight–the first proto-genes.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 122.

“Following Woese, there were also evolving polypeptides with increasing chiral purity, which could be phosphorylated and which were cyclically hydrogen bonding with available POCHNS molecules and proto-nucleic acids. Thus, the cyclic (daily) evolutionary processes selected molecules that could repeatedly hydrogen bond: if they were too polar (more water-soluble and diffusible), they would remain dissociated in the aqueous phases in a ‘disordered’ state; if they were too hydrophobic (water-insoluble), they would stay stuck in a more ordered solid phase. The cyclic temperature/water activity would have selected those proto-biomolecules that were ‘just right’; they persisted–dissociated and associated reproducibly–in response to cycling temperatures and to the osmotic forces of the tides.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 122.

“[Jigsaw piece #7] The next stage of the physicochemical evolution of progenotes is the era of evolutionary proto-cells, before LUCAs and the first single-cell organisms came into existence. The emergence of Hadean proto-cells signifies the transition from progenotes ‘becoming alive’ to proto-cells ‘becoming persistently alive,’ which indicates the beginning of heredity–the emergence of ancient proto-genes and proto-phages, but as yet no proto-genomes. Thus, proto-cells exhibited short-term heredity of ancient genes over a small number of generations–the origin of life, not yet as we know it, but as proto-cells stuck in tidal proto-biofilms, still quite dependent on diurnal and tidal energies for their short-term ‘reproduction.’” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 123.

“In principle, the chemical evolution of ‘getting’ nutrients would have had three mechanisms: (i) the evolving diffusion of small molecules through existing proto-cell envelopes, where amphiphilic peptides were mixed with low-molecular-weight amphiphilic and hydrophobic molecules, some being negatively charged with phosphate functionalities; (ii) the partial breaking and fast resealing of proto-cell envelopes on osmotic hydrations and dehydrations, allowing the cyclic exchange of molecules between the ancient cytoplasm and the tidal proto-biofilm environment, which also accounts for high proto-gene exchange; and (iii) the partial fusions of proto-cells on dehydrations with some ‘survivors,’ a case of engulfment or ‘predatory’ behavior in biological language, which, in addition to providing nutrients, would also have led to future horizontal (or lateral) gene transfer.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 126.

“[Jigsaw piece #8] Thus, the next evolutionary advance is critical to the origin of the first prokaryote-like organisms on abiotic Earth–the mechanical stabilization of proto-cells through the cycles of temperature and hydration. This remarkable innovation occurred when the replicating (growing) nucleoid became permanently attached to the growing cell envelope throughout the cell cycle. This attachment came about when random proto-cellular genes could permanently recombine and ligate into longer DNA double helices–the organismal genome physically represented by the nucleoid, spanning the whole proto-cell. Such an arrangement then drove the further evolution and localization of hydrophobic membrane proteins, including those responsible for membrane metabolism, that is, the generation of chemiosmotic potential to drive the membrane synthesis of ATP. The increasing sophistication of the cell envelope also stimulated the evolution of membrane sensors and transporters that could make the cell ‘aware’ of its changing environments and able to respond more precisely to those changing environments. The evolution of cell envelopes through direct contact with the nucleoid gave rise to internal homeostasis–the maintenance of a biomacromolecular living architecture, with its regulatory biochemical reactions, especially phosphorylations and methylations. Thus, the first proto-organisms became less dependent on the direct action of cycling environmental energies and more dependent on the chemical energies of nutrients transported through the cell envelope. The mechanical unity of the replicating nucleoid, localized and attached to a growing membrane, represents a self-renewing, evolving scaffold on which the cell could grow and divide and from which new organisms evolved vis-a-vis their changing external environments.

“These first organisms could be considered as LUCAs ‘rooting the Tree of Life,’ gaining a foothold in different geochemical (nutrient) environments. Such organisms were still genetically cooling, mutating fast, and becoming extinct at high rates, but they were evolving toward today’s long, persistent lineages in the two domains of Bacteria and Archaea.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 127.

“Taking into account known mechanisms through which genetic information can be modified and transmitted during the cell cycle, ancient Darwinian evolution in the Archaean eon can be classified physicochemically as micro-evolution, meso-evolution, and macro-evolution.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 132.

“In this case [micro-evolution], the genetic errors in the cell cycle do not involve the breaking and resealing of cell envelopes that would allow environmental (foreign) DNA to enter. The errors arise during the molecular template replication of DNA within any one cell cycle, for example, point mutations or ligations of broken DNA strands, without any foreign nucleic acids passing through the cell envelope during the replication and transmission of genetic information. Nowadays this mechanism has a very low rate of error and ensures the long-term genetic stability of biological species, that is, ‘precise’ heredity, with infrequent error, making Darwinian evolution observable over long but accessible periods of time. The evolutionary cell cycle process is highly evolved at a low “genetic’ temperature, being in operation for at least 3 billion years. It corresponds approximately to the gradualism of Darwin’s original conception, though some single point mutations could result in new phenotypes or be actually lethal.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 135-6.

“Fusions between living cells and dead environmental DNA and RNA, including viruses, can be distinguished as colloidal meso-evolution. This supra-macromolecular mechanism corresponds approximately to horizontal or lateral gene transfer and to the coevolution of plasmids and phages with the nucleoids of early prokaryotic-like organisms.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 136.

“Saltational macro-evolution represents direct cell-to-cell fusions under cycling temperatures and hydrating conditions. These fusions can occur, for example, in biofilms, when at least one cell is alive and survives the fusion process, or at least the large fused cell retains its structural integrity and can become alive by the cyclic stoking of tidal and solar energies. Such fusions give rise to more complex proto-eukaryotic cells involving new internal membranes, different kinds of protein-RNAs complexes (ribosomes) and multiple DNA nucleoids–to genetic and metabolic chimeras…. Nevertheless, the possibility of chimeric fusions to self-stabilize (rather than to fall apart) with the help of cyclic temperature and hydration gradients seems possible.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 136-7.

“… the meso- and macro-mechanisms of single-cell organismal evolution were quite common in the Archaean eon, indicating, that prokaryotic and eukaryotic cellular structures were evolving concurrently. The proto-eukaryotic genetic and structural chimeras, being physicochemically much more complicated, stabilized much later as eukaryotic single-cell organisms with vertical heredity.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 137.

“Darwinian evolution arose naturally and inevitably as a consequence of non-ideal cellular reproduction. There can be no doubt that Darwinian evolution is both gradual via molecular micro-evolution, as assumed by Darwin, and also supra-macromolecular or ‘saltational’ as intuited by Woese. The latter, in his words, involves the natural creation of new cellular ‘designs’–of genetic, metabolic, and structural chimeras brought to life by stoking environmental energies.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 137-8.

“The fact that extant life is based equally on phosphorus and carbon (membranes, genetics, bioenergetics, and protein regulation by phosphorylation-dephosphoroylation) suggests that phosphorus chemistry was extensive at the tidal boundary of atmosphere, hydrosphere, and lithosphere.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. p. 153.

“The sol-gel model, describing the spatiotemporal colloidal nature of the cell cycle, is summarized as follows.

“The nucleoid and the cell membrane (wall) at any given instant form a homeostatic scaffold that is being extended and filled with proteins–the ‘robots’ that replicate the nucleoid, enlarge the cell envelope, monitor and regulate the processes, and keep crowding the growing cytoplasm with more proteins (substantially of the same kind). Some proteins interact strongly (via electrostatics and the hydrophobic effect) with each other and with nucleic acids, creating molecular machines of a semi-crystalline nature. The semi-crystalline machines and proteins phase separate in crowded gels because of attractive, weak (soft) non-covalent forces. The gel phases form in the peripheral sub-membrane region and around the (coacervated) fibers of the nucleoid’s double helix. The crowding within the gels can be higher than the average crowding, with up to 50% volume fraction compared to 25% average volume fraction. Consequently, low-viscosity dilute cytosol (e.g., 5% volume fraction) is left behind between the gelled phases, as large, topologically complementary ‘pools’ and wide ‘waterways.’ These pools and waterways enable the fast diffusion of ions, metabolites, and small proteins throughout the cell. This fast diffusion has been experimentally documented in the last 20 years by employing chromophore-tagged biomacromolecules and fluorescence spectroscopies.

“The gelled phases are crucial for executing the biochemical reactions of molecular biology in a reproducible manner through each cell cycle because they transiently sequester and isolate many parallel biochemical reactions and physiological processes…. However, the super-crowded biomacromolecules in the gel phases are not randomly agglomerated. The gel phases are characterized by narrow aqueous channels formed by the hydrated surfaces of biomacromolecules. Where such surfaces are anionic, they contribute to the colloidal stability of the gel, preventing uncontrolled agglomeration. They also act as semi-conducting electrolyte switches to guide ions of different total charges (e.g. adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate) to where they fulfill their function within the gel phase, or they are released into the cytosol to quickly diffuse to different parts of the cytoplasm. Thus, the narrow electrolytic channels represent a ‘power and metabolite grid’ through which semi-crystalline molecular machines become functional within the gel.

“How are the sol-gel transitions controlled? Within the cell, there are a great number of signaling reactions that attach various tags to biomacromolecules (phosphorylations, methylations, acetylations, adenylations, etc.) and their reverse reactions that detach these tags. These post-translational modifications change the colloidal stability of interacting biomacromolecules (i.e., the morphology of the power and metabolite grid), making the cell operate on a spatiotemporal basis with transient functional gel phases. When the colloidal stability of the gel components increases (through, e.g., phosphorylations or demethylations), the gels themselves weaken and disperse into smaller gels or ‘dissolve’ into the dilute cytosol and cease to exist, having fulfilled their function. Reverse signaling reactions decrease the screened electrostatic repulsions and hydration, thus initiating the formation of new gel structures or increasing the size, strength, or longevity of an existing gel phase. The sol-gel transitions of the living state take place on a scale of about milliseconds to seconds….

“The complementary topologies of the gel phases and the cytosol, as well as those of the gelled biomacromolecules and the narrow electrolyte channels within the gels, are constantly remodeled in response to signals from the cell envelope and the outside environment.” Spitzer, Jan. 2021. How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. MIT Press. pp. 159-161.

“Although [Herbert] Spencer posited himself as an individualist in matters political (but of individuals embedded in a given cultural and social context), his basic evolutionary unit in his sociology was the collectivity, presented as a special kind of individual.” Gissis, Snait B. 2017. “‘Collectivity’ from a Historical Perspective.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 1-23. MIT Press. p. 7.

“To sum up, Spencer held a hybrid notion of individuality, in psychology, in biology, and in sociology, which could be viewed either as ‘collective individuality’ or as ‘collectivity of individuals’: a collective individuality contained multiple modes of relating and hierarchies of organizational complexity within its framework. Alternatively, the collectivity of individuals contained diverse kinds of individuals, differentially related to each other and to the collectivities they were members of. This collectivity could be looked upon as a special kind of individual. The first alternative was found to be more useful in biology while the second alternative turned out to be more useful in sociology.” Gissis, Snait B. 2017. “‘Collectivity’ from a Historical Perspective.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 1-23. MIT Press. p. 8.

“The Durkheimian image of science required, epistemologically and methodologically, ‘objective’ and stable objects of inquiry, a role which in his view collectivities could fulfill much better than individuals. However, ideology–the Durkheimian set of political and moral beliefs–demanded the notion of the autonomy of individuals. Durkheim attempted to take the middle road out of this dilemma, but at the cost of much internal tension in the body of his work, a tension which he attempted to resolve by the theoretical construction of a continuity between individuals and collectivities. In an ontological sense society did exist separately, apart from its components, the individuals, but not independently of them. Properties of individuals and relations among them were considered to be real but not independent of either a specific individual or of individuals in general, or of the collectivity. Thus, the facts of sociology were to be found in the relations among individuals but not solely in them. For Durkheim there could not be, nor be perceived, an individual without a/the collectivity, since that individual had already been socialized, collectivized. The collectivity existed through biological existence, but also by virtue of the feelings and the consciousnesses of the individuals, as well as by virtue of the cultural heritage of which they were constituent components.” Gissis, Snait B. 2017. “‘Collectivity’ from a Historical Perspective.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 1-23. MIT Press. p. 10.

“The variety of social life revealed a movement from states of acting and behaving and from states of thinking and feeling that are transient, unstable, and completely unfixed, applicable for short periods of time to individuals or to limited segments of the collectivity, to currents of opinion, then to patterns that are more solidified, that last for longer periods of time, become fixed and even permanent. The latter always encompass the entire collectivity and are reflected in the social behavior of individuals, for example, systems of beliefs, systems of customs. Durkheim called this process ‘crystallization’, a term that I interpret as indicating an effort to establish a continuity between the beliefs and experiential states of individuals and the persistent, more enduring collective practices, patterns, and institutions, and their material products.” Gissis, Snait B. 2017. “‘Collectivity’ from a Historical Perspective.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 1-23. MIT Press. p. 10.

“Collectivity captures something of the sense that more is different—a phase transition from aggregative to emergent properties. A fully integrated individual persists on some substantial timescale in such a way that its parts cannot easily go separate ways without consequences for the parts as well as for the whole, or at least without consequences for our interest in them. With collectives, the bonds holding constituents together do so less persistently than for individuals, or with less force, or with lesser consequences for the constituents if they separate, or in ways such that participation in the constituted grouping is less full or complete or, what in some cases amounts to the same thing: in less interesting ways….. In any case, the parts of a collective if we can legitimately call them that at all, seem borderline qua parts compared to the parts of integrated individuals.” Griesemer, James. 2017. “Landscapes of Developmental Collectivity.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 25-47. MIT Press. p. 30.

“We grapple with the metaphysics of individuality quite a lot, from our childhood beginnings as analysts and interpreters as well as experiencers of things, events and processes. Collectives that hang together draw our attention more than ephemeral collectives that form once and scatter without ever coming together again, like a swirl of autumn leaves.” Griesemer, James. 2017. “Landscapes of Developmental Collectivity.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 25-47. MIT Press. p. 30.

“I have been articulating for many years an account of reproduction that gives equal weight to two component processes: ‘progeneration’ and development.

“Propagule generation or progeneration is the production of offspring material entities from parent material entities….

“At least some of the materially overlapping parts in a progeneration process must confer developmental capacities on offspring entities for progeneration in this special sense to qualify as reproduction. Development in the most general relevant sense is just the capacity to acquire, manifest, refine, or maintain the capacity to reproduce. In other words, the capacity to reproduce is the capacity to progenerate developmental capacity again.” Griesemer, James. 2017. “Landscapes of Developmental Collectivity.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 25-47. MIT Press. pp. 35, 36.

“I have argued that most typical developmental processes are not a self-unfolding but rather involve the interaction of a developer with scaffolding….

“Scaffolding processes, as I use the term, involve the formation of heterogeneous, collective entities. The scaffold plays a different developmental role than the scaffoldee, and this heterogeneity of functional roles is essential to the proper functioning of each participant and of the collective. The scaffold used to build an arch, or a bridge, or to paint a building must have a structure quite different from the arch or the bridge or the building to do its job. And the entity formed from scaffold plus nascent arch, bridge, or building is quite different from either of its component participants.

“When scaffolding is involved in facilitating developmental processes, I think it is often apt or useful to consider the collective to be an entity in its own right, even if it is not so integrated, autonomous, or persistent as the sort of thing we usually call (biological) individuals. A nest may be a bird’s way of making another bird, or as Bateson pointed out, a bird may be a nest’s way of making another nest, but we might also say that bird-nest collectives are ways of making more bird-nest collectives.” Griesemer, James. 2017. “Landscapes of Developmental Collectivity.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 25-47. MIT Press. p. 38; reference: Bateson, P. 2001. “Behavioral development and Darwinian evolution.” In: Oyama, S., P. Griffiths & R. Gray (Eds). Cycles of Contingency: Developmental Systems and Evolution. pp. 149-166. MIT Press.

“… a challenge to the prevailing formulation [of the immune system as a defense for the individual] emerges when the immune system is understood as essentially a cognitive faculty that assesses the environment (internal and external) to allow for various kinds of interactions: some encounters evoke protective responses, and others mediate assimilation or cooperation. Shifting the focus from defense to a more general cognitive capacity reconceives the immune system as the mediator that effectively places the organism in its environment. On such a view, immune cognition must allow for both beneficial exchange with the environment and rejection of noxious elements. Tauber, Alfred I. 2017. “ Reconceiving Immunology as an Ecological Science.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 281-289. MIT Press. p. 281.

“… the governing host-defensive orientation of organismal autonomy remained largely unchallenged until an ecological sensibility penetrated immunology. That development portends a science that would account not only for individual organisms, but also for their interactions. On this view, immunity must be considered in two conceptual schemas: (1) mediating the autonomy of the organism as well as (2) facilitating (or allowing) participation in a larger ecology.” Tauber, Alfred I. 2017. “ Reconceiving Immunology as an Ecological Science.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 281-289. MIT Press. p. 283.

“Indeed, the biomedical model has so dominated immunology that comparative immunology represents a small portion of the literature, and research on the specific ways in which the immune system tolerates, or even fosters, cooperative relationships in the environment is smaller yet. However, when an ecological orientation is adopted, integration and coordination serve as organizing principles. In other words, balance becomes a regulative principle, and pathology results from the imbalanced state between host and pathogen.” Tauber, Alfred I. 2017. “ Reconceiving Immunology as an Ecological Science.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 281-289. MIT Press. p. 284.

“This older understanding [of the organism conceived as an autonomous, protected entity] was based on insular animals in competition with others and thus omits the biology of consortia. To study such collectives, immunity moves from the individual-based conceptions that have dominated the life sciences to considerations of symbiotic relationships characteristic of beneficial exchanges. Such an alternate formulation of the organism, based on a relational construction, places immunity as the mediator of cooperative associations. Accordingly, immune identity becomes the product of a dynamic process in which fixed self and nonself dichotomies are replaced with a spectrum of beneficial interactions mediated by immune tolerance. On this view, immunity escapes its older semantic defensive trappings to become the mediated state of immune balance. And with that shift the very basis of organismic identity undergoes a fundamental reordering.” Tauber, Alfred I. 2017. “ Reconceiving Immunology as an Ecological Science.” In: Landscapes of Collectivity in the Life Sciences. Gissis, Snait B., Ehud Lamm & Ayelet Shavit (eds). pp. 281-289. MIT Press. p. 286.

“The abundance of unfolded sequences is astonishing. According to a recent survey, about 5% of proteins in Escherichia coli, 23% in Arabidopsis and 28% in mouse are mostly disordered. Evidently many sequences of this kind are disordered only part of the time, actually folding up when they bind to their target in the cell. Flexible regions are useful if you have to assemble protein molecules into a large structure, such as a ribosome or a bacterial flagellum, since they allow subunits to wriggle into place rather than being forced into rigid holes.” Bray, Dennis. 2005. “Flexible peptides and cytoplasmic gels.” Genome Biology. 6(3):106. p. 1.

“For example [of failed attempts at operational definitions of life], a metabolic definition finds it hard to exclude enzymes (which are biologically functional but not living systems), while a thermodynamic definition does not exclude mineral crystals (which create and sustain local order and may reproduce).” Jortner, Joshua. 2006. “Conditions for the emergence of life on the early Earth: summary and reflections.” Philosophical Transactions of the Royal Society: B. 361:1877-1891. doi: 10.1098/rstb.2006.1909. p. 1878.

“This question [what is water? – which Leonardo da Vinci tried to do by attempting a phenomenological approach] could only be answered in the twentieth century with the establishment of the proper molecular composition and the structure of the H2O molecule, together with the globally condensed phase properties of the liquid, e.g. H-bonding, local order, radial and angular distribution, solvation, structure breaking, nuclear dynamics, phase transitions and response, providing a conceptual framework of an appropriate scientific theory.” Jortner, Joshua. 2006. “Conditions for the emergence of life on the early Earth: summary and reflections.” Philosophical Transactions of the Royal Society: B. 361:1877-1891. doi: 10.1098/rstb.2006.1909. p. 1878.

“Coacervate: An aggregate of macro-molecules, such as proteins, lipids, and nucleic acids, that form a stable colloid unit with properties that resemble living matter. Many are coated with a lipid membrane and contain enzymes that are capable of converting such substances as glucose into more complex molecules, such as starch. Coacervate droplets arise spontaneously under appropriate conditions and may have been the prebiological systems from which living organisms originated.” Daintith, John. 2008. Oxford Dictionary of Chemistry, Sixth Edition. Oxford UP. p. 130.

“… there is no one-to-one correspondence between genes and biological functions. Strictly speaking, therefore, to speak of a gene as the ‘gene for x’ is always incorrect. Many gene products, the proteins, must act together to generate biological functions at a high level. If we must use the expression ‘gene for x’ then we should at least add the plural and speak of the ‘genes for x’.

“Even this way of speaking is, however, seriously misleading. Not only do many genes co-operate in coding for the proteins that interact to produce any given biological function, each gene may also play a role in many different functions, which makes it difficult to label genes with functions.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 9.

“There are no privileged components [of a regulatory network] telling the rest what to do. There is rather a form of democracy, with every element at all levels having a chance to be part of a regulatory network. The co-ordinating hand is not so much an organist’s as a conductor’s. Or perhaps we should think rather of a ‘virtual conductor’–the system behaves ‘as if’ it has a conductor. The genes behave ‘as though’ they are being ‘played’ by this conductor–rather like some orchestras that play without a separate conductor.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. pp. 53-4.

“There is an interesting asymmetry between reductionists and modern integrationists in biological science. An integrationist, using rigorous systems-level analysis, does not need or wish to deny the power of successful reduction. Indeed he uses that power as part of his successful integration. Many reductionists, by contrast, seem for some reason to require intellectual hegemony.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 66.

“We need to take on board the reality that causation and explanation do not always run upwards from lower to higher levels. We have many dramatic examples now to show that causation can run in the opposite direction. Systems effects can even control the ultimate low-level processes of gene expression.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 66.

“The protein [for rhythm generator in a fruit fly] is involved in a negative feedback loop with the gene that codes for it. The idea is very simple. The protein levels build up in the cell as the period gene is read to produce more protein. The protein then diffuses into the nucleus where it inhibits further production of itself by binding to the promoter part of the gene sequence. With a time delay, the protein production falls off and the inhibition is removed so that the whole cycle can start again. So, we not only have a single gene capable of regulating the biological clockwork that generates circadian rhythm, it is also itself a key component in the feedback loop that forms the rhythm generator.

“We call such causal loops feedback loops because they form self-contained regulatory processes. Feedback is involved in the great majority of cases where downward and upward causation are linked together in biological systems. The linkage is a defining feature of feedback since the downward causation modifies the components responsible for the upward causation, which in turn modifies those generating downward causation … and so on….

“The basic rhythm generator in this case does seem to be dependent on a single gene and the protein it codes for. But does it carry out its work in isolation? Is it a ‘single gene module’? The answer is a resounding ‘no’. The further researchers get in unravelling the molecular feedbacks involved in circadian rhythms, the more gene and protein components appear to be involved….

“Moreover, these rhythmic mechanisms do not work in isolation. There has to be some connection with light-sensitive receptors (including the eyes). Only then will the mechanism lock on to a proper 24-hour cycle rather than free-running at say 23 or 25 hours. That is why, as Foster and Kreitzman have written: ‘What we see as a clock may well be akin to an emergent property of the system and all the genetic paraphernalia merely part of the fine tuning’….

“First, the protein that is coded by period is like all molecular components–it operates within the context of the complete cell. It depends for its production on the transcription/translation mechanisms and the ribosome machinery. Its ability to access the promoter region of the period gene depends on properties of the nuclear membrane.

“It is not only genes that never operate outside the cellular context. The same applies to individual proteins. It is conceptually convenient to ‘isolate’ the period-protein system, sure. This does indeed help us to appreciate its unusual characteristics as a molecular level oscillator. But this is an artificial conceptualisation. The real living system operates only in the context of the functioning of many other genes and proteins….

“Again, listen to what Foster and Kreitzman have to say: ‘what we call a clock gene may have an important function within the system, but it could be involved in other systems as well. Without a complete picture of all the components and their interactions, it is impossible to tell what is part of an oscillator generating rhythmicity, what is part of an input, and what is part of an output.’” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. pp. 70-1, 72; reference: Foster, R. & L. Kreitzman. 2004. Rhythms of life: the biological clocks that control the daily lives of every living thing. London: Profile Books.

“… integrative systems biology is just as rigorous and quantitative as reductionist molecular biology. The only difference is that it accepts that causality goes from higher to lower levels as well as upwards.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 77.

“The genes and proteins of the body to not in some way ‘know’ or ‘reveal’ what they are doing in higher-level functions. The assumption that they do is a strange one. We might indeed be forgiven for suggesting that it is itself a superstition of the order of vitalism.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 78.

“All levels can be the starting point for a causal chain, so any of them can be the starting point for successful simulation. In networks of interactions at many levels, there is in fact no alternative. Analysis must start somewhere, but it doesn’t really matter where.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p.79.

“But their mistake [imaginary example of tiny extraterrestrials thinking that a whole body of a multicellular was an “island” where a lot of different “species” [cells] have the same DNA] but other “islands” have different but all identical DNA and still a couple of hundred different “species”] has a large element of truth. To the cells themselves, the human body is rather like an island on which, from an evolutionary point of view, they are trapped. Organisms not only capture and enslave genes, viruses, and bacteria, they also capture whole cells.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 92.

“Why does a ‘Lamarckian’ form of inheritance flourish within the colonies of all the cell types in multicellular organisms with the sole exception of their germ cells?

“Maynard Smith has offered one possible explanation. He writes: ‘most phenotypic changes (except learnt ones) are not adaptive: they are the result of injury, disease and old age. A hereditary mechanism that enabled a parent to transmit such changes to its offspring would not be favoured by natural selection.’

“I am not so sure about this. Most genotypic changes (mutations) also are not adaptive. They are usually quite as bad as injury, disease, and old age, which is why natural selection rejects most of them. If natural selection can be so effective in filtering out bad genotypic changes, it could have been effective for bad phenotypic changes.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 95; reference: Maynard Smith, J. 1998. Evolutionary genetics. Oxford UP.

“For an important function like this heart rhythm there are several back-up mechanisms. There are so many, in fact, that physiologists have argued for decades about ‘Which is the real pacemaker mechanism?’ The answer is ‘It depends’. It depends on species, it depends on conditions, it depends on control mechanisms.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. pp. 107-8.

“Imagine fish evolving to become dry land species…. Almost certainly, the features of modularity and redundancy were critical. It is possible to slot pre-existing gene-protein networks into new control networks without upsetting them too much. That is modularity.

“Suppose mutations occur in some mechanisms, and eventually they are selected for functions quite different from those they originally supported. How, then, to maintain the function that they originally served? What were back-up mechanisms now become primary. That is the value of redundancy. This is the basic explanation for how nature can modify its ‘aircraft design’ while still ensuring that the aircraft continues to fly.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. p. 109.

“It is also that ‘I’ or ‘me’ or ‘you’ are not entities at the same level as the brain. They are not objects in the same sense that the brain is an object. In the sense in which my neurons are objects, in which my brain is an object, and in which all the other parts of my body are objects, ‘I’ am nowhere to be found. This does not mean that ‘I’ am not somewhere….

“… it did not make sense to say that cardiac pacemaker rhythm exists below the cellular level. There are no molecular oscillators that generate it. Instead, an integrative activity emerges from a multiplicity of protein interactions at the cellular level.

“We cannot locate the site of pacemaker rhythm at the sub-cellular and molecular levels. Yet, we have no difficulty in locating it at the level of certain cells within the whole organ. We know what it means to refer to the pacemaker of the heart and we can locate it anatomically. The fact that it cannot be found below the cellular level is irrelevant.

“If a particular biological function or entity does not exist at one level that does not mean to say it does not exist at all. To identify it may be quite simple once we have made the requisite explanatory shift. We just have to go up or down a level or two to find the context in which that entity can be said to exist. One of the important goals of integrative systems biology is to identify the levels at which the various functions exist and operate….

“My point is that the ‘self’ is an integrative construct, occasionally a fragile one. It is also a necessary construct. It is one of the greatest symphonies of the music of life….

“At the level of neurons and parts of the brain, what we normally mean by the self, that is, you or me, is more like a process than an object.” Noble, Denis. 2006. The Music of Life: Biology Beyond Genes. Oxford UP. pp. 128, 129, 133.

“We agree therefore with Rosen in Life Itself, that it is the organization of the organism itself that constrains the component parts, not the other way round. That organization forms the basis of active agency in organisms.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 2.

“But where are the great boundaries of the great systems of the body, the immune, nervous, circulatory, digestive, respiratory, reproductive, and hormonal systems? Merely to ask the question shows that the answer is not obvious. Anatomy is not necessarily the best basis for defining a functional boundary.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 2.

“The main reason for the failure to explain athletic performance from genetics alone is that the genome is controlled by the organism and its life-style experiences through extensive epigenetic control.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 4.

“The interface between DNA and epigenetic control is therefore another important boundary. It is one of the means by which the organism controls its genome as a ‘highly sensitive organ of the cell’. This boundary was first identified by Waddington, who was the originator of the term epigenetics. Since then many forms of epigenetic control have been discovered. This control is so effective in transmitting the adaptive properties of the networks that most gene knock-outs have very little effect. The exceptions are, of course, the rare genetic diseases, such as cystic fibrosis, where the networks do not have sufficient plasticity to cope with a knock-out. But, in general, plasticity is common.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. pp. 4-5; subquote: McClintock, B. 1984. “The significance of responses of the genome to challenge.” Science. 226:792-801; reference: Waddington, C.H. 1957. The Strategy of the Genes. London: Allen and Unwin.

“The molecules in cells are an aqueous suspension and must also be subject to Brownian motion. Water, and all molecules, will also be subject to quantum mechanical randomness. On some interpretations of quantum mechanics, all objects are subject to such randomness although it becomes negligible at a large enough scale.

“This is a boundary within the system. In a sense it is a boundary between levels or scales…. But here it is sufficient to note that the boundary is fuzzy. There is no precise cut-off scale at which molecular stochasticity, whether quantal or not, becomes negligible… We note that it is a good example of a boundary that cannot be given a precise anatomical location.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 5.

“… we have argued elsewhere for replacing the term e-mergence (suggesting privileging upward causation) with the neutral term a-mergence. In terms of causation, this requires replacing the linear sequence A causes B which causes C etc., with the existence of the state X, the occurrence of which means that A, B, and C etc., will also occur. This is the characteristic of high-level attractors. Once they occur, they take over the organization of the system. This fact becomes hidden when we insist on a linear causation viewpoint.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 6.

“This issue of simultaneity of action is fundamental. Another way of expressing it is to ask whether circular causality can be said to have a direction. Diagrams often strongly imply that they do, by giving the impression that, if one could be a nano-level observer, one would see one stream of causation running upward and another flowing downward. That picture is far from the reality. This is where the mathematical interpretation of circular causality is so useful in providing a totally different picture of the situation, since the integration procedures must proceed simultaneously. A nano-level observer would surely see something more like a cloud of happenings, which would not be resolvable into separate streams of happenings.

“In this respect, the Biological Relativity interpretation of multi-level causality resembles wave theories of quantum mechanics. Electrons circling a nucleus, for example, are referred to as a cloud because the wave interpretation does not, and cannot, identify where any particular electron may be. The cloud exists as a quantum mechanical state that is precisely and quantitatively described by quantum mechanical wave equations. What matters is the existence of that state, not where any particular electron may be.

“Similarly, it is the state of a multi-level biological system that matters, not just its breakdown into any particular separate sequences of causation. In any case everything else depends on the existence of the combined state of the system, which is unresolvable into two streams of causation. Not only would there not be two separate streams of causation, what is happening would not be evident in a single slice in time. The attractor or any other organization property would only be apparent in a phase space representation within which the organizational pattern can be appreciated in an extended time period….

“Representing organisms as high-level attractors and similarly organized states therefore corresponds much better to what we know experimentally. Most changes at the level of DNA are buffered by the high-level attractors.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 6.

“The standard theory of cancer formation is the somatic mutation theory according to which the accumulation of mutations cause some cells to proliferate abnormally to develop the cancerous tissue. A competing theory is the tissue organization field theory which attributes the cause of cancerous development to properties at a tissue rather than cell or genetic level. This theory locates the main action at the boundaries between individual cells and the state of the surrounding tissue. A key prediction of this explanation of cancer is that cancers may be ‘normalized’ by changing the boundary, i.e., by transplanting the cancerous or precancerous tissue into normal tissue. This has been shown to happen.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 7; reference to “tissue organization field theory”: Soto, A.M. & C. Sonnenschein. 2011. “The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory.” Bioessays. 33:332-340.

“Our paper shows that there are many kinds of boundaries in and around living organisms. Furthermore they are not usually, or ever, passive. They are an essential ingredient of functionality. The reason is that organisms are open systems, operating far from equilibrium. Boundaries are where many of those non-equilibrium processes take place. We cannot therefore understand the behavior of organisms or their parts from their composition alone, and certainly not from the genome alone. The consequences for physiological research are profound. Isolated components of organisms, whether molecules, cells, tissues or organs, do not necessarily behave in the same was [=way?] as those components in situ.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 9.

“Our article clarifies several aspects of the Principle of Biological Relativity.

“(1) The forms of causation involved in downward and upward causation are fundamentally different. Downward causation consists in constraints exerted by higher levels on the initial and boundary conditions within which the dynamics of lower level elements operate. By contrast, upward causation is the way in which those dynamics influence higher level states.

“(2) These two forms of causation do not form a temporal sequence. They occur simultaneously.

“(3) It is the state of organization of a higher level that can constrain lower levels. Causation by a state means that it does not make sense to separate out causation by any one element of the state.

“(4) Conditioned causation exists in attractors since any perturbation of the state will be resisted. The strength of an attractor can be measured by the speed with which it re-establishes itself. The strength of downward causation in organisms is generally high since organisms are very effective at resisting changes in phenotype in response to changes at the molecular level, including changes in DNA sequences. Some authors describe conditioned causation as entangled causation. This is a term borrowed from quantum mechanical theory. The analogy is correct to the extent that the causal states involved should not be separated and the entanglement involved resembles that in quantum mechanical states. But there is also an important difference, which is that entangled states in quantum mechanics are very fragile, collapsing in a fraction of a second, whereas the attractor states in biology are often very robust.” Noble, Raymond, Kazuyo Tasaki, Penelope J. Noble & Denis Noble. 2019. “Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When are the Boundaries?” Frontiers in Physiology. 10(827):1-12. doi: 10.3389/fphys.2019.00827. p. 9.

“… placing a macromolecule in a crowded environment produces a configurational entropic penalty. Any decrease in the volume of the macromolecule would increase the entropy and thus decrease its free energy. In practice, this means that excluded volume enhances the folding of a macromolecule, the oligomerization of proteins and the condensing of DNA. These effects of excluded volume have been explained through various theories…. All of these theories propose that high volume occupancy favours a more compact macromolecule owing to an entropic gain.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 309.

“Under normal physiological conditions of ionic strength and macromolecular crowding, hydrogen bonding, screened electrostatic forces and excluded volume repulsions act over a commensurate distance of ~1 nm; this intermolecular distance enables macromolecular surfaces, such as the surfaces of nucleic acids, proteins and membranes, to co-evolve and bacterial cells to maintain the dynamic structure of the cytoplasm.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 311.

“Relatively small changes in available cytoplasmic volume can have a major effect on the chemical equilibrium of a process (for example, the self-association of a protein) and enzyme kinetics. The rate of enzyme-catalysed reactions in a crowded environment is affected if the conformational change that is imposed on the enzyme by substrate binding decreases or increases the volume of the entire complex.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 311.

“In living cells, biopolymers are always exposed to soft interactions between themselves and surrounding molecules. The short distances between the biomolecules are in the range of screened electrostatic forces, hydrogen bonding and excluded volume. These forces stabilize the cytoplasm against random collapse (that is, against the nonspecific aggregation of macromolecules), and enable unequal crowding. The non-covalent repulsive and attractive forces that are caused by the uneven distribution of hydrophilic, hydrophobic and charged surface areas of macromolecules, enable the clustering of proteins and nucleic acids; this can result in the formation of subcellular structures such as metabolons, hyperstructures, intracellular bodies and filaments.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. pp. 312-3.

“We recently proposed that the bacterial and archaeal cytoplasms might form multiphase systems of supercrowded cytogel and dilute cytosol, in which the size of a molecule affects the cytoplasmic space it can visit… Large particles become caged in the supercrowded areas and only move long distances if the pools rearrange.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 313.

“Biochemical reactions are optimal in their natural crowded environment because proteins and nucleic acids have co-evolved together. Similar to pH and ion homeostasis, we propose that bacterial cells maintain homeostasis of macromolecule density (that is, of macromolecule crowding) to optimize the collective reaction and interaction rates of these molecules.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 313.

“With increasing macromolecular crowding the effective concentration of enzymes and biomacromolecules is increased, which accelerates biochemical reactions but slows down their lateral diffusion; the latter can become limiting.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 313.

“Thus, the range of volume fractions in the literature is smaller when they are based on the same parameters [after normalizing for “partial specific volume”], with Φ values ranging between 0.13 and 0.24. If optimal crowding exists, as we propose in this Opinion article, then bacterial cells probably control crowding when perturbed by changes in environmental conditions.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 314.

“In summary, bacteria may operate homeocrowding at Φ of 0.15-0.20 to achieve optimal growth rates. Osmotic downshifts decrease Φ and osmotic upshifts increase Φ, but bacterial cells can rapidly restore their cytoplasmic volume by activating mechanosensitive channels or osmoregulatory transporters.

“Macromolecular crowding that is too high or too low probably hampers cell function.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 315.

“If, as we propose, optimal crowding levels do exist, there must be mechanisms for achieving crowding homeostasis….

“We consider it likely that the osmoregulatory transporters and some of the more sensitive mechanosensitive channels have a role not only in osmotic regulation but also in the regulation of cell volume and thus the fine-tuning of macromolecular crowding.” van den Berg, Jonas, Arnold J. Boersma & Bert Poolman. 2017. “Microorganisms maintain crowding homeostasis.” Nature Reviews Microbiology. 15:309-318. doi: 10.1038/nrmicro.2017.17. p. 315.

“Spatial organization is a hallmark of all living systems. Even bacteria, the smallest forms of cellular life, display defined shapes and complex internal organization, showcasing a highly structured genome, cytoskeletal filaments, localized scaffolding structures, dynamic spatial patterns, active transport, and occasionally, intracellular organelles.” Surovtsev, Ivan V. & Christine Jacobs-Wagner. 2018. “Subcellular Organization: A Critical Feature of Bacterial Cell Replication.” Cell. 172:1271-93. doi: 10.1016/j.cell.2018.01.014. p. 1271.

“Over the course of evolution, diversification of cellular organization has also offered ways for bacteria to expand their metabolic capability and evolve new phenotypic traits. In some cases, cell specialization has come from the functionalization of specific cellular regions–in particular, the cell poles. In others, the development of new biological properties has been associated with cellular compartmentalization, generally through the formation of endomembranes and intracellular organelles.

“While the vast majority of bacterial proteins have dispersed distribution in the cell, some proteins accumulate at one or both cell poles in diverse non-spherical bacteria. These pole-localized proteins are involved in a variety of functions, including chemotaxis, motility, pathogenesis, cell differentiation, cell-cycle regulation, energy production, and secretion.” Surovtsev, Ivan V. & Christine Jacobs-Wagner. 2018. “Subcellular Organization: A Critical Feature of Bacterial Cell Replication.” Cell. 172:1271-93. doi: 10.1016/j.cell.2018.01.014. p. 1281.

“During each cell cycle, C. crescentus produces two distinct daughter cells: a motile cell with pili and a flagellum for exploring new territories, and a sessile cell with an appendage (stalk) and an adhesin (holdfast) for colonizing the local environment. In this organism, temporally orchestrated localization of regulatory and signaling proteins at a specific pole couples the synthesis or activation of polar organelles (flagelum, pili, holdfast, and stalk) with DNA replication, chromosome segregation or cell division. Functionalization of each cell pole with distinct regulatory pathways is necessary to accommodate the polar morphogenesis and the dimorphic lifestyle of this bacterium.” Surovtsev, Ivan V. & Christine Jacobs-Wagner. 2018. “Subcellular Organization: A Critical Feature of Bacterial Cell Replication.” Cell. 172:1271-93. doi: 10.1016/j.cell.2018.01.014. pp. 1281-2.

“Isn’t understanding ‘life’ a subject that falls in the intellectual purview of biology? No. Life is an expression of molecular chemistry–a remarkable network of molecules, catalysts, and reactions. It is also chemistry operating in a way that we (or at least I) do not understand.” Whitesides, George M. 2015. “Reinventing Chemistry.” Angew. Chem. Int. Ed. 54(11):3196-3209. doi: 10.1002/anie.201410884. p. 3202.

“A problem among scientists–especially those who think of themselves as doing creative, curiosity-driven work–is the perception that pure science and applications are somehow incompatible.” Whitesides, George M. 2015. “Reinventing Chemistry.” Angew. Chem. Int. Ed. 54(11):3196-3209. doi: 10.1002/anie.201410884. p. 3206.

“Pasteur is given credit for an approach that starts by identifying important societal problems with practical implications (death from rabies; illness from spoiled milk) for which there were no solutions and no relevant science, and then invents the new fields of science necessary to solve them. Pasteur did not apply known science; he invented new science to apply. The Pasteur’s quadrant approach [curiosity seeking and solving social problems] implies that it is possible to couple, simultaneously, the development of fundamental science to the solution of problems important to society. It uses very difficult problems to stimulate scientific discovery.” Whitesides, George M. 2015. “Reinventing Chemistry.” Angew. Chem. Int. Ed. 54(11):3196-3209. doi: 10.1002/anie.201410884. p. 3207.

“Pasteur’s quadrant research, ideally, is stimulated simultaneously by curiosity and problem solving, and is ambitious and uncertain along both axes. (And, hence, probably inappropriate for peer review: Pasteur himself would probably have a difficult time making it through the modern peer review system.) Embracing research in Pasteur’s quadrant will require modifying peer review.” Whitesides, George M. 2015. “Reinventing Chemistry.” Angew. Chem. Int. Ed. 54(11):3196-3209. doi: 10.1002/anie.201410884. p. 3207.

“Science and religion were very common subjects for many Victorian naturalists. Darwin himself was as well versed in the Bible as he was in natural theology, and there is no question that his own theory of natural selection had evolved, at least in part, from such arguments.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 23.

“… he [Richard Owen, scientist of 19th century and president of the Royal Society] imagined a principle of transcendental unity existing at a deeper level of reality than the physical. This Platonist approach led him to formulate the concepts of homology and analogy still used today. Homology refers to the same organ in different animals under every variety of form and function. Structures as different as a bat’s wing, a cat’s paw, and a human hand nonetheless display a common plan of structure, with identical or very similar arrangements of bones and muscles. There is a structural relationship. Homologies are basic structures that various creatures use for different purposes. Analogies refer to cases in which parts that have no structural resemblance serve a similar purpose in different animals: the flippers of dolphins and penguins are analogous structures, but the underlying structures are different. Analogies would have no significance for classification. Owen reasoned that there must exist a common structural plan, a bauplan or ‘archetype’ or for all vertebrates, the essence of the vertebrate form.

“Although historians and philosophers have traditionally placed Owen on the side of natural theology, conservatism, and staunch antievolutionism, this caricature has been recently challenged…. In the years following the publication of Darwin’s Origin of Species, Owen portrayed himself as a misrepresented evolutionist who had been unfairly and erroneously cast by Darwin as antievolutionist. In reality, he sought a middle ground between natural theology and materialistic evolution. He maintained that while each species had its origin in natural causes, the course of evolution was directed in accordance with predetermined law (such as First Cause or the Creator).” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 35-6.

“He [Haeckel] was a Christian before he read The Origin, translated into German in 1860. He then became the champion of materialism and anti-idealistic thinking. While materialists were shaking traditional beliefs in England, German thinking had been strongly influenced by the idealist philosophy of Friedrich Hegel, Immanuel Kant, Friedrich von Schelling, and others who had turned away from the materialism of the enlightenment. German Naturphilosophen maintained that an unknowable spirit or creative organizing force in nature gave it purpose and accounted for progressive perfection of God’s creatures. Haeckel aimed his polemics directly at their idealism and supernaturalism. Nothing caused nonevolutionists more trouble than organs and muscles that serve no purpose….

“Darwin himself felt that embryology provided some of the strongest evidence for the transmutation of species. If each species had been created independently by divine inspiration, he argued, then one would expect that the route from egg to infant would be direct. But embryologists had found exactly the opposite: there were extraordinary detours….

“Comparative embryology provided the criteria for homology and so was the means for uncovering the relationships and ancestry. One of the aims of this discipline was to see how far one could go in revealing ancestral forms common to all animals. Many who entered this field were inspired by the view, championed so forcefully by Haeckel, that the course of development, from embryo to infant, documented the path of evolution. In other words, that during the development of the embryo, key steps in evolution are repeated, or, in short, ontogeny recapitulates phylogeny.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 37.

“However, Robert Richards has argued that Darwin was both a progressionist and a recapitulationist like Haeckel, and that Mayr and Gould are guilty of distorting history to protect Darwin from any taint.

“The link between embryology and transformationism begins with the word ‘evolution’ (unfolding) itself. In the eighteenth century, the word was used by advocates of ‘preformationism’ to describe the unfolding of the organism from the egg during development…. With the development of a transcendental form of recapitulation theory during the first decades of the nineteenth century, the term ‘evolution’ came to refer to the sequence of events during development. As recapitulation came to imply phylogeny, Richards argues, the word ‘evolution’ took on both meanings and came to signify embryological progression as well as species transmutation. Both Charles Lyell and Herbert Spencer gave currency to the word ‘evolution’ to describe progressive change toward ever-increasing complexity.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 39; reference: Richards, Robert. 1992. The Meaning of Evolution: The Morphological Construction and Ideological Reconstruction of Darwin’s Theory. U of Chicago Press.

“In Haeckel’s view, nothing could be further apart socially and intellectually than scientific materialism and what he called the ethical materialism of the high priests and the privileged aristocracy of Europe. Scientific materialism affirms that everything in the world goes on naturally–that every effect has its cause, and every cause its effect. There are no supernatural processes,. Ethical materialism is based on the premise that only purely material enjoyment can give satisfaction; it proposes no other human aim than the most refined possible gratification of one’s senses. Haeckel claimed that it was absent among naturalists and philosophers, ‘whose greatest happiness is the intellectual enjoyment of nature, and whose highest aim is the knowledge of her laws.’ [But then he gave a big criticism of the elites who just wanted cynical tyranny] ….

“The materialism of Darwinism, based largely on a view of the natural wor[l]d as a place of persistent struggle, conflict, and war, confronted the optimistic view of natural theology of a harmonious natural world of give and take, of mutual cohabitation and a balance of nature in which each of God’s creatures was created to play its part for the benefit of all.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 41.

“Darwinian theory was summoned to support all types of political and ideological positions, from the most reactionary to the most progressive, including racism, militarism, laissez-faire economies, unfettered capitalism, Marxism, and anarchism.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 43.

“Although sociopolitical thought is usually omitted when the theory of natural selection is taught, cut and dried to biology students, it was crucial to the theory’s formulation…. Two fundamental social concepts are at the heart of Darwin’s theory: the concept of division of labor, which he used in his theory of divergence [of species], and Malthusian population theory, which he used as the driving force behind natural selection.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 50.

“Darwin used the concept [division of labor] in his theory for the origin of species through divergence. His argument began with the ecological premise that a locality can support more life if it is occupied by diverse organisms partitioning the resources. Divergence and specialization would be adaptive advantages because organisms avoid competition and elimination in the struggle for existence if they sepasrate into specialized niches in the economy of nature.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 50-1.

“The term ‘mutualism’ was introduced into biology in 1872 by the Belgian zoologist Pierre-Joseph van Beneden at the Catholic University of Louvain….

“This [the Paris Commune’s taking control in 1870] was the sociopolitical setting in which van Beneden first introduced the term ‘mutualism’ in his address in Belgium in 1872. He drew analogies from industry, human social relations, and morality to describe the social relations he saw in nature. He compared industrialists leading the life of noblemen to parasites….

“Moreover, the term ‘mutualists’ itself would surely have evoked thoughts of Proudhon and the mutualists of the Paris Commune.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 58, 60.

“If much of what is credited to Schleiden and Schwann had been stated by others before them, and if their assertions about the generation of cells was simply wrong, why are they credited as the founders of cell theory?….

“Although Schleiden and Schwann’s announcements about the importance of cells marked a turning point in the advance of biology, we can also appreciate the views of those who emphasized long ago that it was absurd to speak of them as the founders of the cell theory. Promoting a field and popularizing concepts is an important aspect of science, but this story illustrates another lesson. In a world of heightened individualism, we often search for heroic achievements made single-handedly, and scientists often attribute major discoveries to individuals. Yet science is in reality a collective activity.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 78-9.

“Like all genesis problems, spontaneous generation debates intermingled with philosophical and religious issues. Spontaneous generation was debated in Victorian England by T.H. Huxley, the physicist John Tyndall, and others in the context of materialism versus belief in a divine primordial creation. In his famous paper of 1869, ‘The Physical Basis of Life,’ Huxley lent support to the notion that microbes could arise from organic precursors (‘heterogenesis’). By the mid-1870s, he had abandoned heterogenesis and restricted the question of the origin of life to what he called abiogenesis, predicated on the idea that microbes had originated from inorganic molecules at the dawn of life on Earth. Pasteur saw both issues in the same manner. Spontaneous generation now or in the remote past was an argument for materialism and atheism. Thus, he allied his arguments against spontaneous generation with conservative religious views to attack materialism and the heresy of evolutionists.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 80-1.

“The cell theory of the organism was indeed a social theory, as expressed in the ‘cell state’ or ‘cell republic’ and expounded by Schlieden, Schwann, Virchow, his former student Haeckel, and Haeckel’s former student Oscar Hertwig (1849-1922), professor of anatomy at Berlin, who argued that because biology dealt with the organization of life, it was more akin to the social sciences than to physics and chemistry.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 84.

“The term ‘cell’ is a minsnomer. By the last decades of the nineteenth century, all biologists had come to recognize that whatever the cell was, it was not a hollow chamber surrounded by solid walls. The word was derived from Robert Hooke’s (1635-1703) microscopic observations of cork….

“With the compound microscope he made for himself, he was able to see that ‘the substance of Cork is altogether fill’d with Air, and that that Air is perfectly enclosed in little Boxes or Cells distinct from one another….

“The term ‘cells’ came into general use in biology at the beginning of the nineteenth century, when they were understood to be structural elements only, and literally conceived of as a chamber as the name correctly implied. The cell wall seemed to be the important part; the cell content was thought to be an unorganized fluid, or a homogeneous glutinous material without a trace of organization.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 86, 87.

“Experimental embryology began in the 1880s. Its aims were to discover the actual physicochemical processes by which the adult developed from the egg. Referred to by its founders as ‘developmental mechanics,’ it originated from the premise that organisms could be understood in the same way as machines.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 95.

“Since the middle of the nineteenth century, biology had been teeming with theories of the organism that postulated smaller corpuscular determinants or ‘elementary organisms.’ In effect, the internal organization of an organism was regarded as a series of Russian dolls. An animal or plant was regarded as a colony of cells; the cell was regarded as a colony of simpler units–nucleus, centrosome, mitochondria, and chloroplasts; the nucleus was regarded as a colony of chromosomes; the chromosomes, according to Weismann’s theory, were colonies of ids; the id was a colony of determinants; the determinant was a colony of biophores; and the biophore was a colony of molecules.

“The first generation of experimental embryologists rejected such conceptions of elementary organisms in a cell state; the adopted ‘the organism as a whole’ as a counterrevolutionary slogan while they redefined biological aims and explanations. They had three main objections to the previous concepts and approaches. First, models of the individual in terms of hypothetical ‘elementary organisms’ took as their starting point the very thing that many young biologists wanted to explain: life. The previous generation of theoreticians had simply bestowed the properties of life on a multitude of hypothetical entities, capable of assimilation., growth, and reproduction. Second, the concept of elementary organisms, whether cells or intracellular determinants, suffered from reductionism, the fallacy of reducing the properties of the whole to the parts of which it is composed. Instead of emphasizing ‘determinants,’ experimental embryologists focused on forces, flows, structures, and interactions. Third, the postulated elementary organisms of Weismann, Darwin, or Spencer were purely speculative. The new generation of experimental embryologists aimed to discover the actual causes of development….” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 95-6.

“The fact that each of the cells of a dividing egg was capable of developing into a complex organism, and yet did not do so when left in its natural state, indicated to embryologists that the organism as a whole controls the formative processes going on in each part. The organism had supracellular properties. Cells, they argued, were the instruments, not the agents, of morphogenesis. Development was not the result of a colony or republic of cell individuals bound together by the division of labor and mutual dependence. Organisms made cells, not the inverse. Cells were the result , not the cause, of development.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 98.

“The fate of a cell was a function of its position in the whole. The principle of ‘the organism as a whole’ became a central tenet of embryology; its capital problem was to find a physicochemical basis for it. Embryologists did not have the answers, but they did develop a common general conception; epigenesis. In epigenesis theory, the organism was conceived of in terms of the behavior of a particular protoplasm in a particular environment.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 101.

“Embryologists’ thinking about heredity and evolution was far removed from that of neo-Darwinian biologists, and from that of geneticists who studied chromosomal genes in the early twentieth century. The two main reasons for this stemmed from research begun in the nineteenth century. First, experimental embryologists were not concerned with adaptive changes to adult organisms….

“Second, while geneticists and neo-Darwinian evolutionists maintained that changes in the nuclear chromosomal genes of eggs and sperm were the basis of evolution, many embryologists insisted that the cytoplasm of the egg played the primary role in heredity and development. Although often overlooked by historians of evolutionary biology, embryologists argued that the large, ‘fundamental’ organismic characteristics that placed the organism in its proper phylum, class, order, and family were determined by the egg cytoplasm, while the smaller differences–between, say genera, species, varieties, and individuals–were due to changes in the chromosomes of egg and sperm.

“Embryologists’ and geneticists’ paths began to diverge when embryologists refuted Weismann’s nuclear theory of development. When Hans Driesch separated the first two cells of a sea urchin egg, each cell formed a complete sea urchin larva. This and other experiments showed that the fate of cells was determined in part by their relationship to other cells, indicating that development was not due to qualitative changes in the chromosomes, as Weismann had inmagined.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 103-4.

“As a result of gastrulation, the embryo is sorted into three distinct cell layers, or germ layers (endoderm, ectoderm, and mesoderm), which give rise to the basic body plan and differentiate into the many tissues and organs of the adult body….

“Each of these cell layers, and therefore the organs and tissues to which they gave rise, were traceable back to visible substances in specific locations in the cytoplasm of the fertilized egg. The arrangement of the cytoplasmic materials in eggs was so definite and so constant that characteristic organization patterns could be recognized for different phyla.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 105.

“Holism was (and is) usually opposed to ‘reductionism,’ a term borrowed from chemists who used it to describe the reduction of a compound to a simpler substance by removing oxygen–for example, the removal of oxygen from metal ores, which ‘reduced’ the metal ore to pure metal (e.g., 2Fe2O3 + 3C -> 3CO2 + 4Fe). Reductionism designated the practice of describing a phenomenon in terms of an apparent, more ‘basic’ or primitive phenomenon, to which the first is held to be equivalent. Embroyologists added to holism the principle of ‘emergence.’ Physicists and chemists had shown how new properties could arise through the combination of smaller units into larger ones. New atoms with new properties are formed by new combinations of protons and electrons, new molecules by new combinations of atoms. Similarly, embryologists argued, the distinctive properties of life and the formation of new materials and qualities in the course of development arise or emerge from the interactions of parts….” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 111.

“The Nobel Prize-winning biologist Peter Medawar was one of the first to do so [examine the structure and rhetoric of scientific papers] when, in 1963, he posed the question, ‘Is the Scientific Paper a Fraud”’ He did not mean to suggest that the scientific paper misrepresents ‘facts’ or that the interpretations found in a scientific paper are wrong or deliberately mistaken. What he meant was that ‘the scientific paper may be a fraud because it misrepresents the thought process that accompanied or gave rise to the work that is described in the paper. The typical scientific paper embodied ‘a totally mistaken conception, even a travesty, of the nature of scientific thought’:

“‘First, there’s a section called the ‘introduction’ in which you merely describe the general field in which your scientific talents are going to be exercised, followed by a section called ‘previous work’ in which you concede, more or less graciously, that others have dimly groped towards the fundamental truths that you are now about to expound. Then a section on ‘methods’–that’s O.K. Then comes the section called ‘results.’ The section called ‘results’ consists of a stream of factual information in which it’s considered extremely bad form to discuss the significance of the results you’re getting. You have to pretend that your mind is, so to speak, a virgin receptacle, an empty vessel, for information which floods into it from the external world for no reason which you yourself have revealed. You reserve all appraisal of the scientific evidence until the ‘discussion’ section, and the discussion you adopt the ludicrous pretense of asking yourself if the information you’ve collected actually means anything; of asking yourself if any general truths are going to emerge from the contemplation of all the evidence you brandished in the section called ‘results’”….

“The conception underlying this style of scientific writing is that scientific discovery is an inductive process. The scientific paper gives the illusion that discovery begins with simple, unbiased, unprejudiced, naive, and innocent observation. Out of this unbridled evidence and tabulation of facts, orderly generalizations emerge. Yet, scientists know full well that discoveries do not occur in this way. They know what meaning to place on their results before they conduct their experiments.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 127-8; reference and subquote: Medawar, Peter. 1963. “Is the Scientific Paper a Fraud?”

“The phrase ‘the evolutionary synthesis’ was introduced by Julian Huxley (1887-1975) in his book Evolution: the Modern Synthesis (1942) to indicate two generally accepted conclusions: that evolution can be explained by natural selection acting on variations resulting from gene mutations and recombination, and that phenomena observed by paleontologists, systematists, and field naturalists can be explained in a manner consistent with known genetic mechanisms.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 143.

“The paleontologist George Gaylord Simpson (1902-1984) went further [in defining species as an interbreeding population], defining species as ‘a phylogenetic lineage (ancestral-descendant sequence of interbreeding populations) evolving independently of others, with its own separate and unitary evolutionary role.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 151.

“Mayr called this hypothetical form of speciation [by geographical separation] ‘allopatric’ in contrast to ‘sympatric’ speciation (splitting of a single population in the same geographical area). He rejected the latter, arguing that it would be ‘subject to so many limitations that it is surely rare, if not exceptional.’ Plants were an exception. Instantaneous speciation within a single population of plants could occur by chromosomal changes such as polyploidy (that is, the occurrence of three or more complete sets of chromosomes). Polyploidy is virtually unknown in animals.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 151-2.

“Biologists’ discussions about the construction of the evolutionary synthesis are exemplary. There was no scientific revolution in the sense of one paradigm’s being dramatically replaced by another through an accumulation of anomalies. And there were many competing specialties or paradigms, none of which were entirely overthrown and replaced by an incommensurable one. The model for scientific change was a synthesis, a breaking down of disciplinary boundaries, resolving misunderstandings, mistrust, feelings of superiority, and intolerance between members of different specialties. The evolutionary synthesis is a lesson about the hazards of specialization and about the need for intellectual breadth and willingness to learn outside one’s own specialty. Mayr summarized this well when writing about the conflict he perceived between naturalists and experimentalists (geneticists):

“‘When I read what was written by both sides during the 1920s, I am appalled at the misunderstandings, the hostility, and the intolerance of the opponents. Both sides display a feeling of superiority over their opponents ‘who simply do not understand what the facts and issues are.’ How could they have every come together? Just as in the case of warring nations, intermediaries were needed, evolutionists who were able to remove misunderstandings and to build bridges between hierarchical levels. These bridge builders were the real architects of the synthesis.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 155; subquote: Mayr, Ernst. 1980. “Prologue: Some Thoughts on the History of the Evolutionary Synthesis.” in: The Evolutionary Synthesis: Perspectives on the Unification of Biology. Ed by: William B. Provine and Ernst Mayr. Harvard UP. pp. 1-48. p. 40.

“Embryologists generally did not participate in the evolutionary synthesis, not because they were excluded in any institutional manner, but because the two paradigms were so dramatically different. Ontogeny is controlled and purposeful; evolution, according to neo-Darwinism, was stochastic and random….

“The modern synthesis did not deal with the great transitions in life: the genesis of bacteria and of protists, and the multicellularity of plants and animals. It did not touch on microbial evolution and the role of microbial symbiosis in development and heredity.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 156.

“The first breakthrough in understanding how genes actually function in the cell begins with a tale of discovery, neglect, and discovery no less remarkable than that of the birth of genetics itself [i.e., Mendel]. The achievement, it is said, was made by an outsider, the British physician Archibald Garrod (1857-1936), who, in 1908, made the astonishing discovery that a gene controls biochemical reactions by directing the formation of a single enzyme. Geneticists have maintained that Garrod’s insight was unappreciated and overlooked for several decades until it was rediscovered in the 1940s by George Beadle (1903-1989) and Edward Tatum (1909-1975)….

“Beadle himself popularized the story of Garrod’s neglect in the 1950s. He referred to Garrod as the ‘father of chemical genetics,’ and in his Nobel lecture he insisted that he had only ‘rediscovered what Garrod had seen so clearly so many years before.’

“Garrod had said just enough for Beadle. The story of Garrod’s creative insight and subsequent neglect was important for bolstering his one-gene: one-enzyme hypothesis. The notion of the independence and the inevitability of the truth is embedded in the notion of rediscovery: the true concept of gene action, lost and found, would be vindicated, just as Mendel’s laws had been. Thus began, in 1950, the legendary myth about the long neglect of Archibald Garrod.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 157, 158, 162.

“In 1935 he [Max Delbrueck] coauthored a famous paper, ‘The Nature of Genetic Mutations and the Structure of the Gene,’ in which he suggested that ‘the gene is a polymeric entity that arises by the repetition of identical atomic structures.’

“Delbrueck’s ideas about the gene and the search for the secret of life were popularized by the Austrian Nobel Prize-winning theoretical quantum physicist Erwin Schroedinger in his famous book What is Life? (1944). The book was written for the layperson, much of it was not original, and much of what was original was known to be erroneous even at the time.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 169-170.

“In the 1940s, Waddington attempted a rapprochement between genetics and embryology, calling the gap between them ‘so frequently lamented as one of the main flaws in the structure of biological theory.’ In keeping with the classical theory of epigenesis, he coined the word ‘epigenetics’ for the study of the processes that operate between genotype and phenotype….

“To offset the random effects of natural selection and to emphasize a two-way relationship between genotype and phenotype, he introduced the concept of canalization. In his now-famous geographical metaphor of the ‘epigenetic landscpe,’ Waddington compared the development of an organism and its relationship to the environment to a ball rolling through valleys and hills. In the landscape, there are well-worn trails that represent the ontogenetic pathways a particular species has followed in the past. The landscape is active, like the shifting environment. It may jostle the ball off its path and force it to make a detour, but the ball pushes back to restore its internal energy balance and still reaches the same place: an individual of the species.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 173-4.

“Haldane was one of several socialist biologists who quit the Communist Party because of Lysenkoism. But he thought it would be difficult to get a fair hearing for the inheritance of acquired characteristics in the context of the cold war. As he commented in 1954, ‘It is apparently vain to hope that the existence of such a series of organisms will prevent dogmatic assertions both as to the non-existence of this phenomenon and as to its universality.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 177.

“In the United States, the inheritance of acquired characteristics became a heated political issue, with Communism on the Left and McCarthyism on the extreme Right. As one journalist put it in 1950:

“.The argument has long since ceased to be a scientific one, however. Not to accept Lysenko, lock, stock and gene, in the U.S.S.R. is close to heresy. To admit in the U.S. today to the possibility of some basis of fact in the Lysenko approach is tantamount to having subversive thoughts. And, unfortunately, science can never flourish without completely free inquiry, so that a proper evaluation of Lysenko will have to wait for the expiration of the Cold War.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 178.

“The controversy over Lysenkoism was especially complicated in France. In the country of Lamarck, the inheritance of acquired characteristics was a favored theory. Neo-Lamarckians, who were often associated with the political Right in France, also had high hopes for Lysenkoism insofar as it tended to show that Lamarck was right. On the political left, some leading biologists, such as Georges Tessier, director of the Centre National de la Recherche Scientifique (CNRS), were Communists, and some were also heroes of the resistance movement during the German occupation of France.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 179.

“One gene can give rise to dozens of proteins. At first thought to be an exceptional occurrence in humans, by the end of the century alternative splicing was estimated to occur in about 40 percent of human genes, and this, genomic researchers argue, partially explains the earlier inflated gene number predictions. Alternative RNA splicing is recognized as one of several important forms of genetic regulation during cellular differentiation. Different portions of the transcribed RNA are excised in specific tissue cells. In addition to the alternate proteins arising from the same sequence of DNA (gene), these individual proteins that are produced often become modified after they are made (post-translational modificaions), and these modifications alter the function of the protein.

“Because of such mechanisms for regulating and modifying protein synthesis and other post-translational modifications, there may be 300,000 proteins in the human body–ten times the number of genes.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 204.

“The complexity of genetic information and its modifications with RNA editing greatly complicated the definition of the gene. The gene was first defined as simply as a unit of inheritance, then as a locus on a chromosome, and then as a specific nucleotide sequence of DNA, but the ‘gene’ has become increasingly abstract. As Sharp noted in his Nobel lecture of 1994, what exactly the gene is had become somewhat unclear. Molecular biologists have generally returned to the old concept of the gene popular in the early twentieth century–that genes are operational entities. Raphael Falk commented that ‘living systems are essentially complex and integrative systems. It is meaningless to identify entities of such systems on an ontological basis. The gene is a generic term. This is the pragmatic approach adopted by many practicing molecular biologists.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 204-5; subquote: Falk, Raphael. 2000. “The Gene: A Concept in Tension.” in: The Concept of the Gene in Development and Evolution: Historical and Epistemological Perspectives. Ed: Peter Beurton, Raphael Falk, and Hans-Joerg Rheinberger. Cambridge UP. pp: 317-348. p. 340.

“However, neither mitochondrion nor chloroplast is formed anew from proteins: each is formed only from a preexisting organelle. If these organelles were removed from the cell, they could not be formed again, because their reproduction requires a preexisting supramolecular structure.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 208.

“If not the genome, then what orchestrates the hubbub of filaments, membranes, and polymers into recurring patterns recognizable as cells? Those biologists who exclude cell form from being ‘hardwired’ into the genome really do not know, and they have searched for new metaphors and concepts to understand cell organization and hereditary information.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 209.

“Embryologists and cytologists had used the term ‘polarity’ to refer to the visible directionality of cellular processes. Cell polarity is also especially noticeable in tip-growing organisms such as fungal hyphae, pollen tubes, and growing nerve cells. These cells orient their activities toward a unique site, called the apex. Building blocks of the cell, made elsewhere, are translocated to the apex, where they are assembled into new plasma membrane, new cell wall, new cell cortex, and so on.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 209-210.

“In other words, at least two kinds of mechanisms operate to maintain cell structure. One is a local constraint involving microscopically visible cell structures acting as a scaffold–ciliary units, for example, which are specified by local interactions at the molecular level. The other mechanism is a global one that pertains to cell structure as a whole….

“The idea of a morphogenetic field was prominent in embryology of the 1920s and 1930s and was revitalized somewhat in the 1980s. Embryologists defined the field as a ‘group of cells whose position and fate are specified with respect to the same set of boundaries. A particular field of cells will give rise to a particular organ when transplanted to a different part of the embryo and the cells of the field can regulate their fates to make up for the missing cells in the field’….

“On the other hand, biological structuralists such as Goodwin and Webster maintained that morphogenetic fields are not specified by genes–they exist independent of the entities or the final gradients that bring them to light–and they argued that there were internal structural constraints on evolutionary change. For them, the structure, the field, and the changes that occur in them were governed by ‘generative principles’ embodied in the processes that set them up.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 212, 213.

“The perpetuation of global cell patterns (cellular organization and form) thus presents not a puzzle, but a mystery. That cellular organization is a mode of heredity distinct from that encoded in genes continues to disturb the conceptual foundations of the modern consensus–perhaps, as some have suggested, as an outrageous assault on established truth, and tinged with vitalism to boot.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 214.

“Epinucleic mechanisms of inheritance, from structural inheritance to steady states, are often lumped together and discussed under the rubric of ‘epigenetic inheritance’ so as to distinguish them from the more well-known inheritance based on nucleic acids, a genetic system. However, this bipartite labeling tends to obscure important differences. To refer to structural inheritance as epigenetic inheritance belies the fact that the term ‘epigenetic’ was coined as an antonym for preformation, and yet the phenomenon of structural inheritance is an argument precisely for preformation. We can avoid the contradiction by referring to structural inheritance as such, or as extranucleic inheritance, and distinguishing it from epigenetic inheritance and nucleic inheritance.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 215.

“Every eukaryote is a superorganism, a symbiome composed of chromosomal genes, organellar genes, and often other bacterial symbionts as well as viruses. The symbiome, the limit of the multicellular organism, extends beyond the activities of its own cells. All plants and animals involve complex ecological communities of microbes, some of which function as commensals, some as mutualists, and others as parasites, depending on their nature and context. It is estimated that there are about 1014 cells in our bodies: 10 percent of them are our own eukaryotic cells, and 90 percent are bacteria comprising about 400 to 500 kinds.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 235.

“Different people have used the term ‘symbiosis’ to mean different things. For some, it has meant mutualism–two or more different organisms cooperating for a common good; for others, it has included parasitic relations as well.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 240.

“In addition to the main circular DNA genome or genophore (erroneously called the chromosome), bacteria contain various other bits of DNA in the form of bacteriophage, as well as small circular pieces of DNA called plasmids. Whole plasmids and fragments of the genophore can be transferred between different kinds of bacteria by conjugation. Bacterial genes can also be transferred by the uptake of DNA fragments from dead bacteria (transformations) and by viral infections (transductions).” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 243.

“The beneficial effects of microbial symbiosis continued to conflict with the very history that had brought science and medicine into intimate association [war against microbial infections].” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 244.

“The influential cell biologists Roger Stanier spoke for many in 1970 when he commented that ‘evolutionary speculation constitutes a kind of metascience, which has the same fascination for some biologists that metaphysical speculation possessed for some medieval scholastics. It can be considered a relatively harmless habit, like eating peanuts, unless it assumes the form of an obsession; then it becomes a vice.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 246; reference: Stanier, Roger. 1970. “Some Aspects of the Biology of Cells and Their Possible Evolutionary Significance.” in: Organization and Control in Prokaryotic Cells: Twentieth Symposium of the Society for General Microbiology. Ed.: H. P. Charles and B.C. Knight. pp. 1-38. Cambridge UP. P. 31.

“Perhaps the most dramatic new discovery is the widespread occurrence of hereditary symbiosis in insects. Bacteria of the genus Wolbachia are maternally inherited through the cytoplasm of their hosts and are disseminated throughout the body cells of their hosts. Surveys based on molecular phylogenetic techniques for screening have so far found Wolbachia in more than 20 percent of all known insect species, including each of the major insect orders. They are thought to be the most common hereditary infection on Earth, rampant throughout the invertebrate world; besides insects, hosts include shrimp, spiders, and parasitic worms…. … they appear to have evolved as specialists in manipulating reproduction and development of their hosts. They cause a number of profound reproductive alterations in insects, including cytoplasmic incompatibility between strains and related species, parthenogenesis induction, and feminization (that is they can convert genetic males into reproductive females and produce intersexes).” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 248.

“Most of the ideological influence from society that permeates science is a great deal more subtle. It comes in the form of basic assumptions of which scientists themselves are usually not aware yet which have profound effect on the forms of explanation and which, in turn, serve to reinforce the social attitudes that gave rise to those assumptions in the first place.” Lewontin, Richard. 1991. Quoted in: Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 252.

“Ever since the word ‘symbiosis’ was used for contiguous associations between different kinds of organisms in 1876, two competing definitions have persisted. Some biologists have used it, with Anton de Bary, to include parasitic relationships, and others have used it to mean solely mutualistic relations. By the early twentieth century, the word was most often used in opposition to parasitism to mean mutualism. Some experimental biologists wee reluctant to use the term because it had an unscientific aura of teleology insofar as it seemed to imply ‘cooperation for a common good.’” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 261-2.

“That the (‘lower’) microbial partner was a thief, stealing the host’s rightful inheritance and living at the expense of the (‘higher’) host’s labor, was a common assumption. Even when relations seemed more stable and mutualistic, biologists emphasized that they could easily become parasitic, depending on environmental conditions….

“The alternative perspective–that the microbial partner was actually a slave (a view that contrasted with the germ theory of disease)–arose from the lack of evidence for any apparent benefit to the microbial partners in many cases of so-called mutualism….

“Over the past century, a host of anthropomorphic metaphors–slavery, consortium, and the relations between men and women, among nations, and between humans and domesticated plants–have been used by biologists to describe and understand symbiosis.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. pp. 262-3.

“Most of the great controversies and conceptual oppositions of the nineteenth century are still present at the beginning of the twenty-first century: religion and vitalism versus evolution and materialism, structuralism versus functionalism, reductionism versus holism, gradualism versus saltationism, selectionism versus nonadaptationism, the inheritance of acquired characteristics, and nurture versus nature. What has changed is not so much the nature of the ideas but the evidence supporting them and the intensity of the debates.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 267.

“The advancement of biology has taken various forms. It has proceeded by the removal of contradictions (e.g., blending inheritance and Darwinian theory) and has often been expressed in terms of the resolution of paradoxes (none more persistent than differentiation among cells possessing identical genomes). Biology developed by opening black boxes (the molecular biology of the gene) and by making better statistical predictions (exemplified in Mendelian laws and in population genetics). It also progressed through establishing causal connections between previously unconnected phenomena (in particular, the role of the cell and its constituent parts in development and heredity).” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 267.

“Whatever the merits of the concept of the organism as an integrated whole, one could question its fruitfulness as a research program. The limits of progress by reductionism and oversimplification have become ever more conspicuous in recent decades as concepts of evolution, individual organism, and gene function have become more complex.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 267.

“At any particular time, there is a hierarchy of specialities with assertions about the importance of one approach over another. This struggle for authority in science is not simply a matter of rhetoric, but of efficacy of techniques and/or institutional power, which have combined in different ways to determine relationships between groups in various global and local settings; and they have shaped the modern life sciences ever since Lamarck.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 269.

“Evolution by association is as apparent between specialties as it is between individuals. Specialties do not survive long in isolation. Information is not just passed on vertically from one generation of specialists to the next, it is also passed on horizontally between specialties. This has been a macromechanism of change in the evolution of biology. New disciplines and even entire fields have resulted from the integration of ideas and techniques from once-independent specialties. The emergence of evolutionary theory in the nineteenth century itself is a triumph of synthesis of comparative morphology, paleontology, geology, and natural history. The fusion of cytology, breeding, and statistical reasoning formed classical genetics. The merger of genetics, population biology, and natural history led to the Darwinian renaissance of the 1930s and 1940s. The intermingling of techniques from physics and chemistry with those of microbiology and genetics resulted in the field of molecular biology.” Sapp, Jan. 2003. Genesis: The Evolution of Biology. Oxford UP. p. 271.

“A successful development of systems and synthetic biology approaches, and their application to human biology and medicine in a predictive, preventive, personalised and participatory manner led to the emergence of ‘systems medicine’ during the past ten years…. … case studies include neurological, cancer, respiratory, allergic and infectious diseases supporting pharmaceutical research and development to tackle patient needs.

“A prominent example of the impact of systems biology in advancing our understanding of the underlying mechanisms of disease development is reported in chronic obstructive pulmonary disease, one of the leading cause of morbidity worldwide. Studies across multiple molecular, cellular, tissular and organ levels indicate a significant impact on clinical practice, patient and healthcare management. The experience gained in such projects highlights the need for a profound revision of the training of life scientists and medical doctors to accomodate the cross-disciplinary nature of systems medicine….

“Thus, understanding biological systems and treating diseases can now be envisioned through the identification and manipulation of global perturbed networks rather than unique failing components.” Auffray, Charles, Denis Noble, Laurent Nottale & Philip Turner. 2020. “Progress in integrative systems biology, physiology and medicine: towards a scale-relative biology.” The European Physical Journal A. 56:88. doi: 10.1140/epja/s10050-020-00090-3. p. 3.

“Our assessment is that most mathematical and physical theories are unsuitable, as they do not properly address the space and time scales characteristic of biological systems and are unable to make experimentally testable predictions relevant to the most fundamental biological questions such as the origin of biological structures and of life itself. A key exception to this is the theory of scale relativity, which represents a theory of self-organisation across all scales in nature.” Auffray, Charles, Denis Noble, Laurent Nottale & Philip Turner. 2020. “Progress in integrative systems biology, physiology and medicine: towards a scale-relative biology.” The European Physical Journal A. 56:88. doi: 10.1140/epja/s10050-020-00090-3. p. 4.

“The fundamental challenge in modelling biological systems relates to computational complexity. Due to intrinsic disorder (chaos) in a biological system, modelling at even the smallest scales (e.g., the folding of an intrinsically disordered protein) can prove intractable. It therefore follows that it is impossible to model a complex biological system at all scales simultaneously. A solution to this challenge requires a systematic process of renormalisation at each scale, to reduce computation complexity. The theory of scale relativity offers such an approach and we see the beginnings of a coherent theoretical framework, which allow one to take into account effects occurring within and across multiple scales and organisational levels. Without such an approach, the predictive power of systems biology and its application to address fundamental and medical questions will remain limited….

“From a biological perspective, the seeds of a new approach begin with a proposal by Prigogine et al. that ‘many body’ complex systems can be regarded as irreducibly probabilistic, in a manner analogous with quantum mechaniscs (QM).” Auffray, Charles, Denis Noble, Laurent Nottale & Philip Turner. 2020. “Progress in integrative systems biology, physiology and medicine: towards a scale-relative biology.” The European Physical Journal A. 56:88. doi: 10.1140/epja/s10050-020-00090-3. pp. 4-5; reference: Prigogine, I. 1997. The End of Certainty: Time, Chaos, and the New Laws of Nature. NY: The Free Press.

“Consciousness and the neural structures that support it and the capacity to make intentional choices are great consumers of energy. Their evolution required payback in terms of selective advantages, which I believe the nervous system has given us. Consciousness, like life itself must be functional to justify its cost…. Conscious processes evolved because they serve a purpose…. If so, one of the most important transitions in evolution was actually driven by organism agency, not by natural selection.” Noble, Denis. 2021. “The Illusions of the Modern Synthesis.” Biosemiotics. 14:5-24. doi: 10.1007/s12304-021-09405-3. pp. 7-8.

“…we are now able to see what we call extracellular vesicles (EVs, sometimes also called exosomes) pouring out of living cells. They are little packets of chemicals including DNAs and RNAs that give a snapshot of the regulatory state of the cells from which they come. Other cells in the body can receive this information, which can then influence their behaviour.” ” Noble, Denis. 2021. “The Illusions of the Modern Synthesis.” Biosemiotics. 14:5-24. doi: 10.1007/s12304-021-09405-3. p. 10; source reference to claim: Edelstein, LR, JR Smythies, PJ Quesenberry & D. Noble (Eds). 2019. Exosomes: A Clinical Compendium. Elsevier.

“The illusions [Central Dogma, etc.] all depend on giving credence to a one-way form of causation in living organisms. Can that possibly be true? The answer is no, since living organisms are necessarily open systems….

“The idea can be viewed as an extension of the general principle of relativity, which is that we should avoid privileging any particular view of the universe. Physicists have applied that principle to speed of movement. All movement is relative to other bodies – there is no privileged position from which to measure speed…. There is no centre from which to view everything.

“Organisms are part of the universe. The processes that gave rise to them are the very same processes to which the principle of relativity applies. Why then should living systems be an exception to the principle? Specifically, why on earth assume that there is a centre: a privileged level from which the forces that shape living organisms emanate? And why should that be thought to be a molecule, however long, and particularly one that is dead outside living organisms?” ” Noble, Denis. 2021. “The Illusions of the Modern Synthesis.” Biosemiotics. 14:5-24. doi: 10.1007/s12304-021-09405-3. p. 16.

“Constraints? Where do those appear in any differential equations? They arise from a necessary mathematical fact: the equations have no solution unless you specify the initial and boundary conditions. Those form the constraints in such a mathematical model. They arise from the organisation of the higher level. The principle therefore achieves two necessary criteria: no privileged level of causation, and the top-down form (the constraint) is just as necessary as the mechanical upward form. The top-down causation is attributable to formal organisation, within which the bottom-up dynamic causation is constrained to occur.” ” Noble, Denis. 2021. “The Illusions of the Modern Synthesis.” Biosemiotics. 14:5-24. doi: 10.1007/s12304-021-09405-3. p. 17.

“The Weismann Barrier is a statement about cells, specifically the supposed isolation of the sperm and egg cells. The Central Dogma is a statement about molecules. From the viewpoint of a molecule a cell is as vast as the area of a country like England. Inheritance at the cellular level, including the intricate architecture, is vastly more than inheritance of DNA. To conflate molecular and cellular inheritance is a deeply confusing illusion.” ” Noble, Denis. 2021. “The Illusions of the Modern Synthesis.” Biosemiotics. 14:5-24. doi: 10.1007/s12304-021-09405-3. pp. 17-8.

“The Modern Synthesis in its various forms, but particularly strongly in the founding form of a synthesis between the Weismann Barrier and Mendelian Genetics, represents the organism-world relationship in a limited way. It views the environment as the passive filter of natural selection rather than seeing organisms as an essential and active driver of the environment. As I have noted earlier, both the EES [Extended evolutionary synthesis] and the EIS [Extended inclusive synthesis] seek to correct this limitation. The reason I go further than the EES is that I also show that the Modern Synthesis has been undermined, not supported, by molecular biology. It doesn’t make sense to retain a theory that has been so fundamentally undermined on its central assumptions, i.e. the Weismann Barrier, the isolation of the genome from the organism and the environment, and the exclusion of Lamarckian forms of inheritance, since these were the central motivations of the Modern Synthesis.” ” Noble, Denis. 2021. “The Illusions of the Modern Synthesis.” Biosemiotics. 14:5-24. doi: 10.1007/s12304-021-09405-3. p. 21.

“… functional theories about the workings of the cells, tissues, organs and systems of a living organism can make micro-level predictions that can be tested experimentally. But the converse does not necessarily or even usually hold. The multitudinous directions of movement of particles will not yield conclusions about the functioning of the whole, as we know well from thermodynamics, where constraint of such movements by containers generates the high-level properties of temperature, volume and pressure, and where most of the lower-level stochasticity is ironed out.” Noble, Raymond & Denis Noble. 2022. “Physiology restores purpose to evolutionary biology.” Biological Journal of the Linnean Society. XX:1-13. p. 2.

“The nerve impulse and heart pacemaker rhythm emerge from high-level constraints… One of the reasons is that the lipid bilayers are so thin that the electric field generated across them is enormous. They can support fields up to 10 000 volts per cm before they break down. Such field strengths are sufficient to cause membrane-bound proteins to change shape depending on which way the field works. Many transporter proteins forming channels and carriers in cell membranes can be regulated and so form electric switches. If the field changes, as found during electrical events like nerve impulses, the channels can open and close. Switching of sodium, potassium and calcium ion channels underlies nearly all forms of action and rhythm potentials in cells.” Noble, Raymond & Denis Noble. 2022. “Physiology restores purpose to evolutionary biology.” Biological Journal of the Linnean Society. XX:1-13. p. 3.

“The nature of the evolutionary process also changes. Evolution itself evolves. If a process made possible by one of the transitions can enable evolution to be more rapid, then that newly-enabled process will automatically dominate. That is another reason why restricting evolution to blind natural selection cannot be correct. Rapid radiations, such as the Cambrian explosion, are then more easily understood. Similar insights are now proving valuable in understanding the rapid evolutionary radiation of genomic forms in cancerous tumours.” Noble, Raymond & Denis Noble. 2022. “Physiology restores purpose to evolutionary biology.” Biological Journal of the Linnean Society. XX:1-13. p. 7.

“Nor is the ladder of life idea incompatible with a tree of life, which itself is not incompatible with a network of life. That is what we must now suppose since organisms extensively exchange DNA and other factors between themselves. The branches of the tree communicate with each other. Each analogy, ladder, tree and network can be viewed as useful, but partial, metaphors. The mistake of the hardened form of the Modern Synthesis was to insist that only one of the metaphors was correct.” Noble, Raymond & Denis Noble. 2022. “Physiology restores purpose to evolutionary biology.” Biological Journal of the Linnean Society. XX:1-13. pp. 7-8.

“The Modern Synthesis in its original version, as formulated by Julian Huxley in 1942, did not completely exclude physiological function in the process of evolution:

“‘Contrary to the views of the Weismann School, selection alone has been shown to be incapable of extending the upper limit of variation … mutation alone has been shown to be incapable of producing directional change … the third process of recombination is almost equally essential, not only for conferring plasticity on the species and allowing for a sufficient speed of evolutionary change, but also for adjusting the effects of mutations to the needs of the organism’….

“In this text he refers to recombination in sexual reproduction, but the idea nevertheless contains the seeds of realizing that other recombination processes could also ensure that evolution proceeds much faster and in a directed sense to meet ‘the needs of the organism’….

“It was the restrictive, hardened, form of the Modern Synthesis that developed in the 1960s, through the publication of Adaptation and Natural Selection (Williams, 1966), and in the 1970s through the The Selfish Gene, that finally sealed the fate of purpose in biology.” Noble, Raymond & Denis Noble. 2022. “Physiology restores purpose to evolutionary biology.” Biological Journal of the Linnean Society. XX:1-13. pp. 8-9; subquote: Huxley, J. 1942. Evolution: the modern synthesis. MIT Press. p. 29.

“The deconstruction of the Central Dogma of molecular biology had to wait for further molecular biological discoveries in order to understand that:

“(a) DNA cannot possibly be a self-replicator in the way ‘how crystals are formed.’ (Dawkins, 1976: p. 17).
“(b) there cannot, therefore, be a hard separation of ‘replicator’ and vehicle’, and
“(c) organisms have the ability to selectively modify their genomes and so to influence the direction of their evolution.” Noble, Raymond & Denis Noble. 2022. “Physiology restores purpose to evolutionary biology.” Biological Journal of the Linnean Society. XX:1-13. p. 10.

“Summary

“• Synthesising life’s building blocks using the same pathways and intermediates as extant biology is a near impossible task without enzymes.

“• “However, the building blocks can be synthesised from hydrogen cyanide and its derivatives under prebiotically plausible conditions, but some of these conditions are incompatible with life.

“• Therefore, it is proposed that the origin and early evolution of life took place in an environment containing previously synthesised building blocks.

“• The pathways and intermediates of extant biology could then have been introduced in a patchwork fashion as environmental supplies of building blocks became depleted and early organisms adapted to their changing conditions.” Wu, Long-Fei & John D. Sutherland. 2019. “Provisioning the origin and early evolution of life.” Emerging Topics in Life Sciences. 3:459-468. doi: 10.1042/ETLS20190011. p. 466.

“If the amount of computer memory required to represent the quantum wavefunction of one particle is N then the amount required to represent the wavefunction of k particles is Nk. It is possible to perform approximate calculations for larger systems…. But the schemes for approximating are not first-principles deductions but are rather art keyed to experiment, and thus tend to be the least reliable precisely when reliability is most needed, i.e., when experimental information is scarce, the physical behavior has no precedent, and the key questions have not yet been identified….Predicting protein functionality or the behavior of the human brain from these equations is patently absurd. So the triumph of the reductionism of the Greeks is a pyrrhic victory: We have succeeded in reducing all of ordinary physical behavior to a simple, correct Theory of Everything only to discover that it has revealed exactly nothing about many things of great importance.” Laughlin, R.B. & David Pines. 2000. “The Theory of Everything.” PNAS. 97(1):28-31. p. 28.

“The fact that the essential role played by higher organizing principles in determining emergent behavior continues to be disavowed by so many physical scientists is a poignant comment on the nature of modern science. To solid-state physicists and chemists, who are schooled in quantum mechanics and deal with it every day in the context of unpredictable electronic phenomena such as organogels, Kondo insulators, or cuprate superconductivity, the existence of these principles is so obvious that it is a cliché not discussed in polite company. However, to other kinds of scientist the idea is considered dangerous and ludicrous, for it is fundamentally at odds with the reductionist beliefs central to much of physics.” Laughlin, R.B. & David Pines. 2000. “The Theory of Everything.” PNAS. 97(1):28-31. p. 30.

“For the biologist, evolution and emergence are part of daily life. For many physicists, on the other hand, the transition from a reductionist approach may not be easy, but should, in the long run, prove highly satisfying. Living with emergence means, among other things, focusing on what experiment tells us about candidate scenarios for the way a given system might behave before attempting to explore the consequences of any specific model. This contrasts sharply with the imperative of reductionism, which requires us never to use experiment, as its objective is to construct a deductive path from the ultimate equations to the experiment without cheating. But this is unreasonable when the behavior in question is emergent, for the higher organizing principles–the core physical ideas on which the model is based–would have to be deduced from the underlying equations, and this is, in general, impossible.” Laughlin, R.B. & David Pines. 2000. “The Theory of Everything.” PNAS. 97(1):28-31. p. 30.

“In his book ‘The End of Science’ John Horgan argues that our civilization is now facing barriers to the acquisition of knowledge so fundamental that the Golden Age of Science must be thought of as over…. Horgan’s book might more properly have been called the “End of Reductionism, for it is actually a call to those of us concerned with the health of physical science to face the truth that in most respects the reductionist ideal has reached its limits as a guiding principle.” Laughlin, R.B. & David Pines. 2000. “The Theory of Everything.” PNAS. 97(1):28-31. p. 30; reference: Horgan, John. 1997. The End of Science: Facing the Limits of Knowledge in the Twilight of the Scientific Age. Reading, MA: Addison-Wesley.

“The central task of theoretical physics in our time is no longer to write down the ultimate equations but rather to catalogue and understand emergent behavior in its many guises, including potentially life itself. We call this physics of the next century the study of complex adaptive matter. For better or worse we are now witnessing a transition from the science of the past, so intimately linked to reductionism, to the study of complex adaptive matter….” Laughlin, R.B. & David Pines. 2000. “The Theory of Everything.” PNAS. 97(1):28-31. p. 30.

“We reason that the mechanisms driving the universal adaptations of multicellulars should themselves be universal, and propose a mechanism based on properties of matter and systems: energy, entropy, and interaction. Energy from the sun, earth and beyond creates new arrangements and interactions. Metabolic networks channel some of this energy to form cooperating, interactive arrangements. Entropy, used here as a term for all forces that dismantle ordered structures (rather than as a physical quantity), acts as a selective force. Entropy selects for arrangements that resist it long enough to replicate, and dismantles those that do not. Interactions, energy-charged and dynamic, restrain entropy and enable survival and propagation of integrated living systems. This fosters survival-of-the-fitted – those entities that resist entropic destruction – and not only of the fittest – the entities with the greatest reproductive success. The ‘unit’ of evolution is not a discrete entity, such as a gene, individual, or species; what evolves are collections of related interactions at multiple scales. Survival-of-the-fitted explains universal adaptations, including resident microbiomes, sexual reproduction, continuous diversification, programmed turnover, seemingly wasteful phenotypes, altruism, co-evolving environmental niches, and advancing complexity. Indeed survival-of-the-fittest may be a particular case of the survival-of–the-fitted mechanism, promoting local adaptations that express reproductive advantages in addition to resisting entropy.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 1.

“… there is one physical law to which adaptation is required a priori for living – all creatures in any environment have to deal with entropy. Therefore, adaptations that restrain entropy are ubiquitous in living systems, extending Schroedinger, we propose that cooperative, ‘social’ interaction is one such adaptation.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 5.

“We define an interaction as a relationship between two or more entities involving a transfer or exchange of matter, information and/or energy.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 5.

“Amazingly, living systems can utilize different combinations of their given component parts and processes to achieve a relatively uniform output. No single internal plan monopolizes a particular system. In other words, living systems can be said to be poly-determined–a given arrangement or behavior can be produced by multiple, diverse networks of interaction.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 10.

“Diversification is another name for individuality–no two are exactly the same; hence, evolution, as it were, has fostered individuality.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 10.

“A species acts as an attractor stabilized by poly-determination….

“A poly-determined species remains stable despite the differences between its component organisms. Diversification and poly-determination endow a species with robust behavior and continuity that actually exploits entropic variation.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 11.

“Niches are multi-scale fractals: niches within niches within niches. Life cannot rest at one scale: entropy must be dealt with at all habitable scales: molecular, genetic, metabolic, cellular, organismal, environmental, etc.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 14.

“Life is organized by recurrent time and the clocks of life are timed to the cycles of nature manifest in the repetitive movements of the earth, moon and sun, which are expressed through cycles of precipitation, tides, seasons, temperatures, weather, dark and light, and even the frequencies of light.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 14.

“Look at it this way: our psychological and institutional individuality, like our body, is created by group interactions and relationships, not merely with microbes, but with the people and the world in which we reside; our identity is the outcome of our history of bonding with others. Echoing Levins and Lewontin, we construct our niche by the nature of our interactions–we and our worlds co-evolve. We achieve a self by constructing a shared, interactive environment. Thy neighbor is part of thy evolving self.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 16; reference: Levins, R. & R.C. Lewontin. 1985. The Dialectical Biologist. Harvard UP.

“Entropy would seem to account for the most universal adaptations of evolution we have discussed here. In contrast, Natural Selection might drive more local, species-restricted adaptations.” Cohen, Irun R. & Assaf Marron. 2020. “The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.” F1000Research. 9:626. doi: 10.12688/f1000research.24447.3. p. 17.

“Yet, as soon as we try to understand what microbes do and don’t do we are forced to look beyond the individual cell. We are forced to study the larger wholes of which cells are part, in both time – i.e. cell genealogies – and space – i.e. cell collectives. It is in these larger wholes where we think lies a true understanding for the remarkable capacity of microbes to deal with their environment and where much attention should be placed in the future.” van Gestel, Jordi & Roberto Kolter. 2019. “When We Stop Thinking about Microbes as Cells.” Journal of Molecular Biology. 431(14):2487-2492. doi: 10.1016/j.jmb.2019.05.004. p. 2487.

“One of the first to call for a drastically different view on organisms was John Tyler Bonner. In his quest to understand microscopic eukaryotic life, he postulated that not the individual, but the life cycle, is the central unit in biology: ‘The life cycle is the central unit in biology. The notion of the organism is used in this sense, rather than that of an individual at a moment in time …. Evolution then becomes the alternation of life cycles through time; genetics the inheritance mechanisms between cycles, and development all the changes in structure that take place during one life cycle’. In other words, the developmental organization of any organism, microbes included, can only be understood in the context of its life cycle, which unfolds through the repetitive cycles of environmental change that organisms experience in nature – e.g. cycles in nutrient availability, acidity, humidity, temperature, light, competition, predation, etc.” van Gestel, Jordi & Roberto Kolter. 2019. “When We Stop Thinking about Microbes as Cells.” Journal of Molecular Biology. 431(14):2487-2492. doi: 10.1016/j.jmb.2019.05.004. p. 2487; reference: Bonner, John Tyler. 1965. Size and Cycle: An Essay on the Structure of Biology. Princeton UP.

“Microbes can, for example, transition between being host-living and free-living, parasitic and mutualistic, surface-attached and dispersing, vegetative and dormant, stressed and stress free. Most of these cycles span across generations. This means that cell genealogies undergo the phenotypic transitions that characterize the life cycle, rather than the individual cells that constitute these genealogies. These phenotypic transitions come about through the myriad of signal-response systems that enable microbes to adjust their phenotype in response to the environment. As a consequence, these signal-response systems are often tightly linked to the environmental changes that microbes experience in nature, making it misleading or even impossible to decouple them from their environment.” van Gestel, Jordi & Roberto Kolter. 2019. “When We Stop Thinking about Microbes as Cells.” Journal of Molecular Biology. 431(14):2487-2492. doi: 10.1016/j.jmb.2019.05.004. p. 2487.

“Microbes can not only anticipate environmental changes, they can – to a certain extend[t] – even anticipate evolutionary changes. Many microbes have a versatile set of genome-editing mechanisms that can be induced in anticipation of natural selection, including error-prone DNA poloymerases, phase variation through invertases, horizontal gene transfer through competence, CRISPR-Cas systems and diversity-generating retroelements.” van Gestel, Jordi & Roberto Kolter. 2019. “When We Stop Thinking about Microbes as Cells.” Journal of Molecular Biology. 431(14):2487-2492. doi: 10.1016/j.jmb.2019.05.004. p. 2488.

“Learning is defined as a process leading to an experience-dependent behavioural response of a system. It requires that:

“(i) A sensory stimulus that originates either from the activities of the system or from the external biotic or abiotic world leads to a change in the internal state of the system (the stimulus is encoded).
“(ii) A memory trace of this change is retained (storage); retention requires active stabilization and involves valence mechanisms of positive or negative reinforcement.
“(iii) Future interactions with the stimulus or associated stimuli lead to a change in the threshold of the behavioural response (recall).” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 2.

“Learning thus includes (by this definition) sensor-effector coupling, attribution of valence (intrinsic reinforcement), storage and recall involving a change in response threshold (so the system can be said to ‘anticipate’ the effects of learned stimuli). It enables complex (experience-dependent) decision-making within the lifetime of the individual, and can lead to changes in response thresholds when the signal is produced by another biological entity (social learning; communication)…. Cognition, which includes both learning and the processes and actions enabled by learning, is the outcome of the evolution of learning.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 2.

“Habituation, the decrease in a reflexive behavioural response to a repetitive stimulus, enabled organisms to ignore irrelevant stimuli, thus, saving energy. Sensitization, in which an increase in a reflexive behavioural response follows a strong stimulus leading to decreased threshold of response, is the mirror image of habituation, enabling a more effective (e.g. more rapid) response to a salient stimulus.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 2.

“We suggested that learning by habituation and sensitization in non-neural organisms is based on epigenetic molecular mechanisms such as chromatin-marking (e.g. DNA methylation and histone modifications), self-sustaining metabolic loops, RNA-mediated memory and memory based on three-dimensional molecular templates, all of which enable an induced phenotype cell state to persist even when the inducing stimulus is no longer present.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 2.

“In this paper, we focus on informational transitions in cognition, which involve new mechanisms that integrate neural information, evaluate and store it, and coordinate the actions of the organism. We recognize five major neural transitions, with the first two, on which we expand, occurring in phylogenetically early animals. The five transitions are: (i) the transition from non-neural to neural organisms that learn by neural habituation and sensitization; (ii) the transition to animals with a central nervous system (CNS) and flexible but limited associative learning (LAL); (iii) the transition to animals with open-ended (unlimited) associative learning, with hierarchically organized brains enabling mental representations (subjectively experienced mappings of world, body and prospective actions); (iv) the transition to imaginative animals with additional hierarchical levels of neural and mental representations; and (v) the transition to symbolizing, culturally learning humans.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 3.

“It is widely agreed that the nervous system evolved in multicellular animals, and that one of its major functions was rapid and flexible sensory-motor coupling through coordination of the animal’s locomotory movements, and also the movement of its internal organs (e.g. the gut…). The first neural transition was, in fact, muscular-neuronal.

“The nervous system’s coordinating functions are enabled mainly by the plasticity conferred by the evolution of novel types of developmental exploration-stabilization processes. Exploration-stabilization processes are manifest at all levels of biological organization and are based on a common principle–the generation of variations from which only a subset is eventually stabilized (selected). Examples are the selection of genetic mutations in populations; selective stabilization of biochemical networks within a cell; developmental selection processes that occur during ontogeny in plants and animals and lead to homeorhesis; stabilization of exploratory motor behaviours. In all cases, variations that confer benefits, or, more generally, that lead to a set-point (an attractor state) are stabilized/ selected. As the nervous system evolved, new levels of developmental selection were introduced: in addition to selection among neurons during embryogenesis, differential stabilization of synaptic connections takes place. Synaptic connections are overproduced, and most are pruned: connections that have the highest functional efficacy persist through the activity of internal reinforcing (valence) mechanisms. The net result is that only certain synaptic connections among the many initially produced are stabilized and retained. An additional level of developmental neural selection is selection of patterns of synaptic links among neuronal maps, a process that occurs at a higher hierarchical level, during later stages of neural evolution. In moving neural animals, there are thus (minimally) two additional levels at which developmental selection through differential reinforcement is manifest: synaptic-neural and behavioural.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 3.

“Four significant interrelated innovations distinguish the neural communication system from other communication systems (such as the hormonal or the circulatory systems). These are: (i) highly targeted short- and long-range interactions based on contact wiring; (ii) a new common ‘currency’ of communication; (iii) high-speed signal transmission, and (iv) a new (synaptic) memory system.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 3.

“Neurons are morpholgically differentiated cells, with three major specialized elements; the cell body (the soma) and the projections leading to and from it (dendrites and axons). The projections can link together many different neurons, forming endless numbers of small- and medium-sized neural circuits embedded within huge nerve networks. The number of connections between a given neuron and other neurons may be vast, and the distances between two connected neurons may span dozens of centimetres and even reach several metres. Crucially, connections among neurons and between the sensors and effectors they link involve contact wiring, enabling targeted signal transduction, which is far more efficient and directed than signal transduction in non-neural organisms.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 3.

“Crucially, the action potential is the same whether carried by sensory or motor nerves, and all modes of sensory stimuli–photons, chemicals, heat, sound waves and other mechanical types of energy–are translated into this common communication currency, the electrical impulse.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 4.

“The synapse is the basis of a new type of information storage. The synapse comprises the ends of two neurons and the tiny physical gap in between; it is the ‘point’ of contact between neurons (or one neuron and a muscle cell or a gland cell). Signal transduction (from electrical to chemical) occurs at the synapse through the release of neurotransmitter molecules that diffuse across the gap and bind to receptors of the postsynaptic neuron. The postsynaptic cell may have many points of input from different neurons, and the chemical information it receives is translated into local electrical changes that are summated and transmitted passively to its soma. If the summated change crosses a threshold, an action potential is triggered in the postsynaptic neuron. The synapse thus operates as a filter and a point of control, allowing only strong enough signals to be transmitted further.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 4.

“The area near the postsynaptic cell membrane is inhabited by hundreds of proteins that play various roles in modifications of the synapse, endowing it with great plasticity. They may, for example, modify the neuron’s excitatory parameters and hence its responses to future stimuli. The modifiable synapse is the basis of a new type of memory–synaptic neural memory–which enables a new (neural) type of learning based on a novel type of developmental selection: differential stabilization of synaptic connections. Neural animals, therefore, have two-tiered learning: in addition to the epigenetic memory and learning within neurons, their learning is also based on inter-neuronic synaptic memory.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 4.

“In animals with nerve nets, the scope of learning by habituation and sensitization is far greater than that in non-neural organisms. First, the co-evolved new type of motor effector, the muscle cell, greatly extends the range of sensor-effector reflexes and patterns of exploratory motor activity that can be modulated by habit[u]ation and sensitization. Second, since habituation and sensitization in neural animals involve the strengthening or weakening of synaptic connections, highly targeted, rapid and long-range habituated and sensitized responses can be established, and can be influenced by many combinations of neural inputs.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 4.

“Another crucial neural function, reafference, requires lateral inhibitions between motor and sensory neurons: every moving multicellular organism must distinguish between stimuli emanating from its own activity (e.g. vibrations that result from its movement in water) and stimuli that are independent of its own activity (e.g. identical vibrations generated by a predator). While the latter require generation of the flight response, the former require that the flight reflex is inhibited.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 4.

“Classical conditioning entails the formation of an association between a conditioned stimulus (CS) and an unconditioned stimulus (US). A US is defined as a stimulus that elicits a reflex response (an unconditioned response, UR). For example, the smell of food (US) innately elicits salivation (UR). Conversely, the sound of a metronome does not elicit salivation prior to learning and is, therefore, considered a conditional neutral stimulus (CS) with respect to salivation. The CS-US association is typically formed when the US repeatedly follows the CS, usually in close temporal proximity. Owing to the formation of the CS-US association, a conditioned response (CR) is acquired: the next presentation of the CS will elicit the CR, even in the absence of the US. Thus, the organism has learned to respond to the CS (e.g. salivate) as if the US were about to arrive.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 5.

“In Skinnerian or operant conditioning, the probability of eliciting a certain action changes as a function of its reinforcement history: actions that were followed by a positive (or negative) outcome will be more (or less) likely to occur in the future, under similar circumstances.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 5.

“But, however the two processes were conceptualized, it was clear that under most ecological conditions, it is very difficult to tease apart classical and operant conditioning, because both usually occur during a single learning episode…. This difficulty led Colomb & Brembs to replace the traditional distinction, based on the processes involved in each type of learning, with a classification based on what is learned: sensory world stimuli (world-learning) or one’s own behaviour (self-learning). This distinction is useful, but the question about the mechanistic and evolutionary relation between world- and self-learning remains. We suggest that world-learning, and self-learning are functionally entangled in most learning conditions (the animal learns both about the world and about its own reinforced actions), that they share the same neural and cognitive architecture, that they have co-evolved and that they require a brain.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 5; reference: Colomb, J. & B. Brembs. 2010. “The biology of psychology: ‘simple’ conditioning? Commun. Integr. Biol. 3:142-145. doi: 10.4161/cib.3.2.10334.

“With LAL [limited associative learning], spontaneous and stochastic exploratory activities and preexisting simple reflex reactions can be flexibly combined, reinforced and recalled…. However, although the animal can learn about the value of stimuli and actions, it cannot discriminate between differently organized multimodal, compound, novel stimuli or complex action patterns; it can only learn if there is a temporal overlap between the CS and the US, or the action and the reinforcer; it has a very limited ability for cumulative learning, and cannot make decisions requiring a motivational trade-off among learned actions, or learned and reflexive actions.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. pp. 5, 6.

“… after bilaterality evolved (probably more than once) in tiny, slow-moving ciliated animals during the Ediacaran, it was maintained in their macroscopic descendants, and is now present in 99% of animals. Once a single forward direction of movement was defined, the front parts of the animal were the first to meet (or seek) environmental stimuli. As a result, sensory neurons were concentrated in the anterior part of the body, the head, with coordinating motor circuits concentrated both in the brain and along the rest of the body. Such differentiation between the sensory and motor regions required integration of sensory inputs and coordination of motor outputs within regions as well as coordinated interactions between regions.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 6.

“But the CNS controls more than behaviour. As Cabej stressed, the CNS also controls morphogenesis and differentiation, and its regulation of development is the key to the understanding of the morphological evolution of animals.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 6; reference: Cabej, R.N. 2013. Building the most complex structure on earth: An epigenetic narrative of development and evolution of animals. Amsterdam: Elsevier.

“In all animals capable of conditional associative learning, there is also some differentiation within the brain into sensory and motor integrating centres and recurrent interactions between them.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 6.

“Increased size was correlated with an increased lifespan, which made learning by association worthwhile because events are likely to re-occur when one lives longer. Phyla with neural centralization evolved during the early Cambrian era, and the capacity for conditional associative learning in a subset of extant brain-possessing animal phyla suggests that it was at the early Cambrian that the first limited manifestations of conditional associative learning originated. Since even simple forms of conditional AL dramatically expand the capacity for learning during ontogeny, it enabled animals to exploit and construct new niches, promoted new types of interactions and arms races, led to adaptive responses that became fixed through genetic accommodation processes and drove the evolution of sense organs and of more complex motility.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 6.

“The learning capacities that distinguish UAL [unlimited associative learning] at the behavioural levels are (i) the ability to discriminate among novel (non-reflexive and not previously learned) compound stimuli that differ in the configuration of the elements of which they are composed (within the same modality and from different modalities) and among different motor action patterns; (ii) the ability to learn cumulatively, through second-order conditioning, pointing to a flexible value system; (iii) escape from immediacy–the ability to learn about a stimulus even when there is a temporal gap between the CS and the US or the action pattern and the reinforcer, pointing to working memory.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 6.

“A survey of the learning literature suggests that these learning capacities [UAL types] are present in three phyla: in almost all vertebrates, some arthropods (including honeybees and cockroaches) and some cephalopod molluscs (the coleoid cephalopods: octopods, squid and cuttlefish). The underlying embodied cognitive architecture of these animals includes: appendages with many degrees of freedom of movement; the addition of association areas in the brain that integrate information within and between sensory modalities and motor controlling systems, enabling the mapping of the world and the body through integration of precepts and action programmes; dedicated memory circuits for the storage of compound precepts; dedicated and flexible value systems; regions dedicated to the integration of learned world and body maps enabling stable distinction between world and self.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. pp. 6-7.

“… UAL can be considered as an evolutionary transition marker of sentience or minimal consciousness and the driver of its evolution….

“”UAL was the basis for the evolution of more complex types of cognition. It culminated in the evolution of what Dennett called Popperian organisms, animals that can select among imagined, alternative actions without having to try them out…. This imaginative planning and self-monitoring, which Tomasello identifies with thinking, is a qualitatively new type of cognition–an elementary form of meta-cognition.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 7; references: Dennett, Daniel. 1995. Darwin’s Dangerous Idea: Evolution and the Meanings of Life. NY: Simon and Schuster; Tomasello, Michael. 2014. A Natural History of Human Thinking. Harvard UP. p. 9.

“Neural learning was conceptualized as an evolutionary process involving cumulative selection processes within the brain, and the evolutionary process itself was conceived as a learning process–learning theory can explain how past experiences can lead to an incremental evolutionary adaptation, which is used to direct future adaptive behaviours. We can, therefore, look at the relation between learning and evolution from three perspectives: evolution as learning, learning as evolution and the evolution of learning.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 7.

“The relative evolutionary significance of exploratory-spontaneous activity versus reflexive responses to external stimuli, and the relative importance of responses to external stimuli versus responses to internal and proprioceptive stimuli are important and debated questions. The perspective we present here suggests that these responses co-evolved: spontaneous activity is a basic property of all living organisms, as is the ability to respond to a changing world. There is little benefit in increasing the sophistication of motor movement if this does not lead to an increased ability to cope with the incessantly changing external conditions that a rapidly moving animal encounters. The ability to distinguish between self-generated and world-generated stimuli, which is necessary for movement and is the basis of the distinction between self and world, depends on close coupling between interoception, proprioception and exteroception. This coupling suggests that the different aspects of sensations coexisted and co-evolved in the first moving neural animals.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. pp. 7-8.

“In addition to the formal similarity among different types of learning, all the cognitive mechanisms and many of the molecular factors involved in perception, motor activity, memory and valence signals that have been identified in non-neural organisms are present in somewhat modified forms in neural animals.” Ginsburg, Simona & Eva Jablonka. 2021. “Evolutionary transitions in learning and cognition.” Philosophical Transactions of the Royal Society: B. 376:20190766. doi: 10.1098/rstb.2019.0766. p. 8.

“Humans and other animals operate in a world of sensory uncertainty…. Our brains must effectively deal with the resulting uncertainty to generate perceptual representations of the world and to guide our actions. This leads naturally to the idea that perception is a process of unconscious, probabilistic inference.” Knill, David C. & Alexandre Pouget. 2004. “The Bayesian brain: the role of uncertainty in neural coding and computation.” Trends in Neurosciences. 27(12:712-719. doi: 10.1016/j.tins.2004.10.007. p. 712.

“For our purposes, the point … is that an optimal integrator must take into account the relative uncertainty of each cue when deriving an integrated estimate. When one cue is less certain than another, the integrated estimate should be biased toward the more reliable cue…. … computing with likelihood functions provides the most direct means available to account ‘automatically’ for the large range of differences in cue uncertainty that an observer is likely to face.

“This is the basic premise on which Bayesian theories of cortical processing will succeed or fail – that the brain represents information probabilistically, by coding and computing with probability density functions or approximations to probability density functions. We will refer to this as the ‘Bayesian coding hypothesis’.” Knill, David C. & Alexandre Pouget. 2004. “The Bayesian brain: the role of uncertainty in neural coding and computation.” Trends in Neurosciences. 27(12:712-719. doi: 10.1016/j.tins.2004.10.007. p. 713.

“We have described psychophysical evidence that shows human observers to behave in a variety of ways like optimal Bayesian observers. The most compelling features of these data in regard to the Bayesian coding hypothesis are: (i) that subjects implicitly ‘adjust’ cue weights in a Bayes’ optimal way based on stimulus and viewing parameters; (ii) that perceptual and motor behavior reflect a system that takes into account the uncertainty of both sensory and motor signals; (iii) that humans behave near-optimally even when the sensory information is characterized by highly non-Gaussian density functions, leading to complex patterns of predicted behavior; and (iv) that relatively simple Bayesian models can account for otherwise complex patterns of subjective, perceptual biases, even when the prior density functions built into the models do not explicitly code the biases. We argue that these data strongly suggest that the brain codes even complex patterns of sensory and motor uncertainty in its internal representations and computations.” Knill, David C. & Alexandre Pouget. 2004. “The Bayesian brain: the role of uncertainty in neural coding and computation.” Trends in Neurosciences. 27(12:712-719. doi: 10.1016/j.tins.2004.10.007. pp. 717-8.

“Over the past years, we have pursued this perspective [of the brain as an inference machine] in a Bayesian framework to suggest that the brain employs hierarchical or empirical Bayes to infer the causes of its sensations. The hierarchical aspect is important because it allows the brain to learn its own priors and, implicitly, the intrinsic causal structure generating sensory data. This model of brain function can explain a wide range of anatomical and physiological aspects of brain systems; for example, the hierarchical deployment of cortical areas, recurrent architectures using forward and backward connections and functional asymmetries in these connections.” Friston, Karl, James Kilner & Lee Harrison. 2006. “A free energy principle for the brain.” Journal of Physiology – Paris. 100:70-87. doi: 10.1016/j.jphysparis.2006.10.001. p. 70.

“It is fairly easy to show that both perceptual inference and learning rest on a minimisation of free energy or suppression of prediction error. The notion of free energy derives from statistical physics and is used widely in machine learning to convert difficult integration problems, inherent in inference, into easier optimisation problems. This optimisation or free energy minimisation can, in principle, be implemented using relatively simple neuronal infrastructures.” Friston, Karl, James Kilner & Lee Harrison. 2006. “A free energy principle for the brain.” Journal of Physiology – Paris. 100:70-87. doi: 10.1016/j.jphysparis.2006.10.001. p. 71.

“The purpose of this paper is to suggest that inference is just one emergent aspect of free energy minimisation and that a free energy principle for the brain can explain the intimate relationship between perception and action.” Friston, Karl, James Kilner & Lee Harrison. 2006. “A free energy principle for the brain.” Journal of Physiology – Paris. 100:70-87. doi: 10.1016/j.jphysparis.2006.10.001. p. 71.

“The free energy principle states that systems change to decrease their free energy.” Friston, Karl, James Kilner & Lee Harrison. 2006. “A free energy principle for the brain.” Journal of Physiology – Paris. 100:70-87. doi: 10.1016/j.jphysparis.2006.10.001. p. 71.

“We start with evolutionary or selectionist considerations that transform difficult questions about how biological systems operate into simpler questions about the constraints on their behaviour. These constraints lead us to the important notion of an ensemble density that is encoded by the state of the system. This density is used to construct a free energy for any system that is in exchange with its environment. We then consider the implications of minimising this free energy with regard to quantities that determine the systems (i.e., brains) state and, critically, its action upon the environment. We will see that this minimisation leads naturally to perceptual context (i.e., attention), perceptual learning about the causal structure of the environment and, finally, a principled exchange with, or sampling of, that environment.” Friston, Karl, James Kilner & Lee Harrison. 2006. “A free energy principle for the brain.” Journal of Physiology – Paris. 100:70-87. doi: 10.1016/j.jphysparis.2006.10.001. p. 71.

“Recent formulations try to explain adaptive behaviour in terms of minimizing an upper (free energy) bound on the surprise (negative log-likelihood) of sensory samples. This minimization usefully connects the imperative for biological systems to maintain their sensory states within physiological bounds, with an intuitive understanding of adaptive behaviour in terms of active inference about the causes of those states.

“Under ergodic assumptions the long-term average of surprise is entropy. This means that minimizing free energy–through selectively sampling sensory input–places an upper bound on the entropy or dispersion of sensory states. This enables biological systems to resist the second law of thermodynamics–or more exactly the fluctuation theorem that applies to open systems far from equilibrium. However, because negative surprise is also Bayesian model evidence, systems that minimize free energy also maximize a lower bound on the evidence for an implicit model of how their sensory samples were generated. In statistics and machine learning, this is known as approximate Bayesian inference and provides a normative theory for the Bayesian brain hypothesis. In short, biological systems act on the world to place an upper bound on the dispersion of their sensed states, while using those sensations to infer external states of the world. This inference makes the free energy bound a better approximation to the surprise that action is trying to minimize.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. pp. 1-2.

“We start with the following lemma: any ergodic random dynamical system that possesses a Markov blanket will appear to actively maintain its structural and dynamical integrity. We will associate this behaviour with the self-organization of living organisms…. Here, ergodicity means that the time average of any measurable function of the system converges (almost surely) over a sufficient amount of time. This means that one can interpret the average amount of time a state is occupied as the probability of the system being in that state when observed at random. We will refer to this probability measure as the ergodic density.

“A Markov blanket is a set of states that separates two other sets in a statistical sense. The term Markov blanket was introduced in the context of Bayesian networks or graphs and refers to the children of a set (the set of states that are influenced), its parents (the set of states that influence it) and the parents of its children. The notion of influence or dependency is central to a Markov blanket and its existence implies that any state is–or is not–coupled to another.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. p. 2.

“The existence of a Markov blanket implies that its states (e.g. motion in Euclidean space) do not affect their coupling or independence…. For example, the surface of a cell may constitute a Markov blanket separating intracellular and extracellular states. On the other hand, a candle flame cannot possess a Markov blanket, because any pattern of molecular interactions is destroyed almost instantaneously by the flux of gas molecules from its surface.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. p. 2.

“The existence of a Markov blanket induces a partition of states into internal states and external states that are hidden (insulated) from the internal (insular) states by the Markov blanket. In other words, the external states can only be seen vicariously by the internal states, through the Markov blanket.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. p. 2.

“Furthermore, the Markov blanket can itself be partitioned into two sets that are, and are not, children of external states, We will refer to these as a surface or sensory states and active states, respectively. Put simply, the existence of a Markov blanket S x A implies a partition of states into external, sensory, active and internal states: x ∈ X = Ψ x S x A x Λ. External states cause sensory states that influence–but are not influenced by–internal states, while internal states cause active states that influence–but are not influenced by–external states. Crucially, the dependencies induced by Markov blankets create a circular causality that is reminiscent of the action-perception cycle. The circular causality here means that external states cause changes in internal states, via sensory states, while the internal states couple back to the external states through active states–such that internal and external states cause each other in a reciprocal fashion.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. p. 2.

“The central role of Markov blankets speak to an important question: is there a unique Markov blanket for any given system? Or simulations focused on the principal Markov blanket–as defined by spectral graph theory. However, a system can have a multitude of partitions and Markov blankets. This means that there are many partitions that–at some spatial and temporal scale–could show lifelike behaviour. For example, the Markov blanket of an animal encloses the Markov blankets of its organs, which enclose Markov blankets of cells, which enclose Markov blankets of nuclei and so on. Formally, every Markov blanket induces active (Bayesian) inference and there are probably an uncountable number of Markov blankets in the universe. Does this mean there is lifelike behaviour everywhere or is there something special about the Markov blankets of systems we consider to be alive?

“Although speculative, the answer probably lies in the statistics of the Markov blanket. The Markov blanket comprises a subset of states, which have a marginal ergodic density. The entropy of this marginal density reflects the dispersion or invariance properties of the Markov blanket, suggesting that there is a unique Markov blanket that has the smallest entropy. One might conjecture that minimum entropy Markov blankets characterize biological systems.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. p. 10.

“The contribution of this work is to note that if systems are ergodic and possess a Markov blanket, they will–almost surely–show lifelike behaviour. However, this does not address the conditions that are necessary for the emergence of ergodic Markov blankets.” Friston, Karl. 2013. “Life as we know it.” Journal of the Royal Society: Interface. 10:20130475. doi: 10.1098/rsif.2013.0475. p. 11.

“… studies of gene expression, the immune system, protein chaperones, metabolic networks, and circadian clocks have similarly reported that exceptionally robust biological systems often harbor rare yet devastating fragilities. The theory of Highly Optimized Tolerance proposes that these rare yet devastating fragilities arise from fundamental trade-offs between robustness, complexity, and performance.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 3.

“‘… a property of a (system) is robust if it is (invariant) with respect to a (set of perturbations).’ The conclusions from studying robustness will therefore depend on how each element in the square brackets [must refer to the parentheses in the text above] is defined.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 3; subquote: Alderson, D.L. & J.C. Doyle. 2010. “Contrasting views of complexity and their implications for network-centric infrastructures.” IEEE Trans. Syst. Man Cybern. A Syst. Hum. 40:839-852.

“Biological components such as proteins, complexes, circuits, and pathways, often display a range of closely related functions. Some of these functions sometimes partially overlap with other components, i.e., they are degenerate. This is illustrated using bi-functional components that are either (purely) redundant, i.e., perfectly identical in functional capabilities, or degenerate, i.e., diverse in their bi-functionality while also having overlap in one of their functions (partial redundancy).” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 6.

“Robust regulatory control can spontaneously emerge in networks of positively and negatively reinforcing regulatory interactions with several studies reporting widespread links between robustness and regulatory complexity.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 6.

“The attention of the scientific comunnity has been particularly drawn toward evidence that the organization of biological systems into a scale-free network (SFN) is a major contributor to biological robustness. Concisely stated, SFN are networks in which the degree distribution of node connectivity can be approximated by a power law. A number of studies have reported the presence of SFN in biological networks with follow-up studies suggesting that this topological feature is significant to structural robustness or integrity. Integrity is measured by the proportion of nodes that remain members of a single connected network after the removal of a single node and its associated links. Assuming that a network is static, it can be proven that the integrity of a SFN is robust to the loss of randomly selected nodes, which typically have low connectivity, yet is fragile to the removal of highly connected hubs. Thus it was speculated that the robust-yet-fragile (RYF) nature of many biological systems might originate from their SFN topology.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 7.

“In metabolism, the bow-tie architecture provides a formal description of the large ‘fan in’ of catabolized nutrients that produce a small number of activated carriers (e.g., ATP, NADH) and precursor metabolites (the ‘knot’ of the bow-tie), that then ‘fan out’ in the synthesis of numerous building blocks (e.g., nucleotides, sugars, amino acids) and eventually larger macromolecules. This architecture provides exceptional robustness toward variable nutrient inputs through the many degenerate metabolic pathways that can be used to produce a few common building blocks….

“The core of the bow-tie architecture is generally seen as its Achilles heel: if sufficiently perturbed or hijacked for alternative uses then catastrophic failure is likely.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 7.

“Although rarely discussed, phenotypic regulation is not the only means by which robustness can be achieved. Alternatively, organisms and biological subsystems can exert influence on their surroundings to reduce exposure to damaging perturbations or to track resources that are relevant to system function. Here I discuss underlying similarities between four different strategies for achieving robustness: (1) adaptive phenotypic plasticity (modifying traits); (2) homeostasis (enforcing trait stability); (3) environment shaping (modifying the environment); (4) environment tracking (enforcing environment stability).” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 9.

“Adaptive plasticity can also sometimes support survival through reduced functionality, as illustrated in the remarkable behavior of microscopic tardigrades. By transitioning to a nearly suspended metabolic state, tardigrades can persist for years under tremendous extremes in temperature (-200, 150̊C), pressure (0, 1200 atm), dehydration, and direct solar radiation.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 10.

“More generally, environment tracking can help to ensure that suitable phenotype-environment pairings are preserved. Common forms of environmental tracking include chemotaxis, migration, seed dispersal, predator avoidance, and adaptive foraging. Evolution can also facilitate environment tracking through changes to life history traits such as the timing of reproduction (e.g., seasonal flowering and seeding times), hibernation, and the duration of development.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 11.

“Robustness involves a matching between system and environment. Distinct pathways for achieving this matching are differentiated in this review based on whether regulated changes take place in the system or the environment. The four pathways described – homeostasis, adaptive phenotypic plasticity, environment tracking, and environment shaping – can also be distinguished by the manner in which adaptive and self-organizing processes are integrated to achieve robustness.” Whitacre, James Michael. 2012. “Biological robustness: paradigms, mechanisms, and systems principles.” Frontiers in Genetics. 3(67):1-15. doi: 10.3389/fgene.2012.00067. p. 12.

“Although it may seem that the presence of a physical boundary, such as a nuclear membrane, is the only way compartments can be formed and provide trafficking control within cells, cells in fact have another option: liquid-liquid phase sepration (LLPS). Indeed, a large number of organelles including nucleoli, Cajal bodies, promyelocytic leukemia (PML) bodies, processing bodies (P-bodies), and stress granules are membrane-less. It has become clear recently that these organelles are formed through LLPS…. These cellular bodies are dissolved during mitosis and reformed in the next round of the cell cycle. They are also reversible, unlike aggregates, and appear to be in a viscoelastic-dynamic fluid state, which gives them plasticity and flexibility.” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 519.

“RNA also serves as a seed in defining the location of the phase-separated compartment. For example, the largest nuclear structure for ribosome biogenesis, the nucleolus, is formed near ribosomal RNA (rRNA) transcription sites. When rRNAs are artificially transcribed elsewhere in the chromosome, a new nucleolus-like condensate is formed at that site….” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 520.

“RNA granules, composed of RNA and RNA-binding proteins (RBPs), such as stress granules (SGs), P-bodies, Cajal bodies, and nuclear speckles, play an important role in the cytoplasm and nucleus….

“In order to preserve the function of cells within an organism, these cells must survive various environmental stresses such as high temperature or oxidative stress. Under the stress conditions, SGs are formed in the cytosol in order to suppress translation. There are two reasons cells produce SGs under stress: (1) to save limited resources and energy for essential functions that more directly combat stress; and (2) to avoid increasing defective ribosomal products because of misfolding or premature termination.” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 520.

“Due to the toxicity of aberrant SGs, cells require the ability to modulate the disassembly of SGs. Several studies in yeast and fruit fly models revealed that a protein quality control system is utilized to clear SG assembly.” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 521.

“The fundamental structural unit of chromatin is the nucleosome, which consists of negatively charged DNA containing a phosphate backbone wrapped around an octameric assembly of positively charged histone proteins. It is predicted that only approximately half of the negative charges of the DNA are neutralized by the positive charges of the histones….

“They [Nozaki et al] suggested that the behavior of chromatin domains is like ‘liquid drops’ rather than static and regular solid-like structures more physically constrained in nucleus. This observation led us to speculate that chromatin domains are phase-separated through self-assembly inside the nucleus and that it may provide chromatin with platform plasticity so that chromatin can conduct its many functions such as gene expression, DNA repair, and cell cycle-specific matters.”” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. pp. 522, 523; reference: Nozaki, T., R. Imai, M. Tanbo et al. 2017. “Dynamic organization of chromatin domains revealed by super-resolution live-cell imaging.” Mol Cell. 67:282-293.e7. 10.1016/j.molcel.2017.06.018.

“One potential prebiotic compartment candidate system that could have been produced on early Earth (for example, from simple peptides, nucleotides, or polyesters) exhibits ‘life-like’ behaviors and shows compatibility with modern biomolecules having structures derived from LLPS of polymeric systems. In vitro laboratory simulations of LLPS processes result in formation of co-existing liquid (or liquid-like) droplets within a bulk liquid through primarily energetically favorable processes (such as entropic effects and hydrogen bonds) rather than through production of energy intensive covalent bonds. These droplet systems are membrane-less and can be composed of simple heterogeneous polymer systems more closely resembling synthetic products from early Earth, suggesting that LLPS compartments may have been able to form easily on early Earth. As discussed in other sections of this review, LLPS are ubiquitous in biology as subcellular compartments used to segregate and compartmentalize important biomolecular analytes [sic] in various biological processes. This hints at the presence of a direct link between primitive LLPS systems and those observed in modern biology.” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 526.

“Aqueous two-phase systems (ATPS) are LLPS systems typically composed of one or more co-existing polymers such as poly (ethylene) glycol (PEG) and dextran. Such ATPS spontaneously separate into two distinct phases depending on the concentration of the components (the higher the concentration of both components, generally the greater the phase separation), the solution conditions, and temperature.” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 526.

“Coacervate droplets are another membrane-less droplet structure well-represented in extant biology. Protamine, RNA granules, chromatin, and nucleoli are all examples of modern cellular coacervates, some of which control human disease. Such membrane-less coacervate droplets are fundamentally different in nature than ATPS, generally forming from interactions between two or more oppositely charged species such as ATP and poly-lysine or RNA and polyamines.” Yoshizawa, Takuya, Ryu-Suke Nozawa, Tony Z. Jia, Tomohide Saio & Eiichiro Mori. 2020. “Biological phase separation: cell biology meets biophysics.” Biophysical Reviews. 12:519-539. doi: 10.1007/s12551-020-00680-x. p. 527.

“A state-of-the-art functional genomics study in yeast points to the current inability to appraise ‘biological noise’, leading to focus on few genes, transcripts and proteins subject to major detectable changes, while currently inaccessible small fluctuations may be major determinants of the behaviour of biological systems.” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. p. 1125.

“In biology, however, while it has allowed substantial progress in our understanding of what living systems are made of [from ‘the analytical reductionist framework’], there is a growing recognition that it has failed to provide the basis for equivalent deep understanding of biological functioning. As a result, biologists and physicians have not gained a similar understanding of their subject of interest as physicists and chemists have….

“Before our journey in the quest for knowledge, triggered by curiosity as well as our sense of duty to bring useful applications for the benefit of mankind, is stalled, many of us feel that we need to redefine our strategy.” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. p. 1128.

“Fifty years ago, when Jim Watson started his work that led to the discovery of the structure of DNA, he reported in his famous book The double helix, that he went to the library and he had to read less than 10 papers on the important question of that time, whether the genetic material was DNA or protein. Reading those few papers, he could make up his mind that the hypothesis that was the most likely to be true in his opinion was that DNA was the substance of heredity, and therefore he should work on the structure of DNA. Today, a beginner who wants to work on DNA will have to choose among over 7000 000 papers registered in PubMed….

“We suggest that this is a strong indication that, whereas we now know a great deal about the elements of living systems and the basic principles of their organization, and have a wealth of information on biological function, the fact that there are thousands of definitions of ‘function’ points to our limited understanding of how living systems really function.” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. pp. 1131-2.

“We have been able so far to look only at the top of the iceberg of the data pool [of bioinformatics gargantuan data collection], whereas in fact most biology related to complex genetic regulatory networks is likely to reside in the bottom part of that iceberg.” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. p. 1135.

“We propose adding to the four Cartesian precepts [objectivity, reductionism, building causal combinations up to form complexity, exhaustive descriptions] new precepts to operate in systems biology beyond reductionism

“The first is contextualization, complementing the basic principle of objectivity, which identifies objects within the environment in which they function and transform themselves, and associates them with a function, rather than just identifying them in isolation with clearly distinct characters and properties, independently of their environment….

“The second is relatedness, which complements (or perhaps contradicts) the precept of decomposition or division ‘in as many parts as it may be possible’. It consists of identifying interactions that modify the nature of behaviour of interacting objects, pointing to the fact that what is important are the interactions and not the objects themselves. An extreme view is that, in fact, there is no such thing as an object, because it is changing all the time, and that therefore everything is interaction….

“The third is the precept of conditionality complementing the precept of causality. It is intended to identify the rules that determine the behaviour of interacting objects leading to their organization, as pointed out by Edgar Morin around a quarter of a century ago. That has to be compared with the idea of just reordering the parts by linking them in long chains of simple reasoning, because nature is not organized only through those types of chains….

“Finally, more emphasis should be placed on the precept of pertinence than on exhaustivity….” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. pp. 1136-7; reference: Morin, Edgar. 1977. La methode. La nature de la nature. Paris: Le Seuil.

“A first conjecture [for systems biology] is that living systems have the ability to organize themselves as the result of a conjunction occurring through an interface between the variable part of a mostly stable organization, and the stable part of a chaotic network of small fluctuations.

“These small fluctuations, which are inaccessible to the tools currently available, may be the major determinants of the behaviour of biological systems, because they convey collectively the most information.” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. p. 1137.

“A second conjecture [for systems biology] is that living systems operate in a space with a changing number of dimensions (biological space-time), and that it is this very ability that makes them able to self-organize.” Auffray, Charles, Sandrine Imbeaud, Magali Roux-Rouquie & Leroy Hood. 2003. “Self-organized living systems: conjunction of a stable organization with chaotic fluctuations in biological space-time.” Phil. Trans. R. Soc. Lond. A. 361:1125-1139. doi: 10.1098/rsta.2003.1188. p. 1138.

“But there is another way of explaining the living system; not as a hierarchical, sequential transformational system, but as a highly concurrent reactive system. A reactive system, in contrast to a transformational system, does not behave according to a pre-programmed chain of linked instructions. Rather, such a system reacts in parallel to many concurrent inputs, and its behaviours, outputs and effects, are not just a function of the values of its inputs but also of their variety, of the order in which they arrive, of their timing, of their arrival speeds and so forth. A reactive system expresses a dynamic narrative in which the DNA code is one of the many formative inputs. Structural proteins, enzymes, carbohydrates, lipids, intracellular signals, hormones, and other molecules play key roles in forming and informing the system….

“Reactive systems call our attention to their emergent properties.” Cohen, Irun R. & David Harel. 2007. “Explaining a complex living system: dynamics, multi-scaling and emergence.” Journal of the Royal Society: Interface. 4:175-182. doi: 10.1098/rsif.2006.0173. p. 176.

“Emergence is difficult to define in biological terms. A recent survey lists five different definitions of emergence. The notion of ‘levels’, however, is shared by all the five definitions. Emergence, in other words, is a matter of scale.” Cohen, Irun R. & David Harel. 2007. “Explaining a complex living system: dynamics, multi-scaling and emergence.” Journal of the Royal Society: Interface. 4:175-182. doi: 10.1098/rsif.2006.0173. p. 176.

“The cell emerges from its component interactions at the scale at which the cell functions as an object with its own interactions with other cells and molecules. In other words, interactions at one scale create objects at a higher scale; that is, transition from interaction to object is the essence of emergence.” Cohen, Irun R. & David Harel. 2007. “Explaining a complex living system: dynamics, multi-scaling and emergence.” Journal of the Royal Society: Interface. 4:175-182. doi: 10.1098/rsif.2006.0173. p. 176.

“If e.g., an am[o]eba is surrounded by a self-generated electric field [as experiments show], it means that an ionic current leaves the cell at a particular location of the cell and enters at one or more other sites, this to close the current loops. This apparent polarity is due to the fact that the ion transporting proteins (ion pumps and ion channels) which reside in the plasma membrane are not spherically symmetrically distributed over the whole surface of the cell….

“The transcellular ionic current system enables that charged macromolecules which are in solution in the cytoplasmic fluid/gel can be forced to undergo ‘electrophoretic transport.’” De Loof, Arnold. 2016. “The cell’s self-generated ‘electrome: The biophysical essence of the immaterial dimension of Life?” Communicative & Integrative Biology. 9(5):1-19. e1197446. doi: 10.1080/19420889.2016.1197446. p. 7.

“In analogy with ‘genome,’ ‘proteome’… etc., ‘electrome’ stands for the totality of all inorganic-ion (H+, K+, Na+, Ca2+, Cl-, HCO-)-based electrical acts (= ionic currents) of any living entity, from the level of the cell to that of the whole organism.” De Loof, Arnold. 2016. “The cell’s self-generated ‘electrome: The biophysical essence of the immaterial dimension of Life?” Communicative & Integrative Biology. 9(5):1-19. e1197446. doi: 10.1080/19420889.2016.1197446. p. 9.

“The major levels which contribute to the establishment of a given ionic environment (ionic concentrations, potential and ionic gradients, ionic currents, secondary chemical gradients) in the cytoplasm and/or in cell organelles e.g. the nucleus, the mitochrondria and the endoplasmic reticulum are multiple. The major categories are:

“– Factors operating at the plasma lemma: here the different types of proteinaceous ion transporters (ion channels, ion pumps, cotransporters etc.) and the ways their activity is regulated are particularly important.
“– The way channels and pumps are distributed, either spherically symmetrically or asymmetrically, determines whether cells can drive an ionic current through themselves.
“– Multicellular organisms: not only the total number of cells matters, but the way cells are connected also matters: single cells, electrically coupled cells in multicellular systems etc.
“– Factors operating in the cytoplasm, e.g., is a particular ion free or is it bound to macromolecules, or is it stored in membrane sacs like a large part of Ca2+? Where in the cell do the cell organelles, e.g. the nucleus, reside?
“– The membrane properties of membrane-bound cell organelles, e.g., do they harbor ion pumps and channels?
“– For effects on gene expression, the ionic environment around the chromosomes is important.
“– The lipid composition and fluidity of membranes. Electrophoresis in the plane of the membrane.
“– The connection between ion transporters and elements of the cytoskeleton, in particular actin.
“–This list is not exhaustive.” De Loof, Arnold. 2016. “The cell’s self-generated ‘electrome: The biophysical essence of the immaterial dimension of Life?” Communicative & Integrative Biology. 9(5):1-19. e1197446. doi: 10.1080/19420889.2016.1197446. pp. 9-10.

“The theoretical framework of field theory can be summarized with four principles:

“1. Fields. Following Levin, a field is a physical structure that is non-local, and that influences smaller entities contained at any point within it….

“2. Upper direction. What is common to all of these physical structures, and what makes them fields, is a second principle of field theory, upper direction. A field directs the entities within its spatial boundaries and does so from above [i.e. downward causation]….

“3. Persistence and plasticity. Borrowed from Sommerhoff and Nagel, these terms describe the behaviour of teleological entities. Plasticity is the tendency for a teleological entity to orient itself toward its goal from any starting point within the field. A bacterium adopts a trajectory toward higher concentration in the food field from any starting point in the field. That is plasticity. Persistence is the tendency for the entity to return to a trajectory toward the goal following perturbations, such as those arising from lateral interactions….

“4. External direction. The fourth principle is that direction of the goal-directed entity is always external. That is, it arises from the field, which is spatially larger than and envelopes the goal-directed entity. The external chemical field is what orients the bacterium. The temptation might be to think that the bacterium itself–the complex molecular mechanism inside it–is responsible for its goal-directed behaviour. But that is a mistake.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. pp. 6-7; references: Levin, M. 2012. “Morphogenetic fields in embryogenesis, regeneration, and cancer: non-local control of complex patterning.” Bio Systems. 109:243-261; Sommerhoff, G. 1950. Analytical biology. Oxford UP; Nagel, E. 1979. Teleology revisited and other essays in the philosophy and history of science. Columbia UP.

“A goal-directed entity that is perfectly directed by a field is not free. A homing torpedo that is guided by the sound field coming off a target ship and propels itself in a straight line toward the ship without deviating is not free….

“The first kind of freedom comes from lateral direction. If a bacterium in a food field bumps into a tiny sand grain, the grain can reorient it, sending the bacterium in the opposite direction, toward a lower concentration of nutrient. The impact is a lateral one, delivered by an entity of about the same scale as the original bacterium. There are many such lateral forces in nature, which means that teleological entities seldom take the shortest possible route to their ends….

“The second type of freedom arises when upper-level fields overlap. We call it field-overlap freedom. Imagine a beachball floating in a middle of a large river. As the river flows, the ball moves downstream directed by the water in the river. In this toy example, the river is a field in which the ball is (partly) immersed, carrying the ball downstream. Now let’s overlay another field. Imagine a wind picks up, blowing the ball against the current. The river and the wind are both upper-level fields. Both are physical, at least partly envelop the ball, and are larger than it. When fields overlap in such ways, an entity is ‘free’ from one field insofar as it is directed by the other field….

“Thus, in field theory, overlapping fields produce a kind of freedom, that is, freedom from some specified upper-level field….

“The third type of freedom aligns more closely with conventional usage. It is the freedom that is exhibited when an entity moves independently of some particular field, not on account of some lateral interaction or an overlapping field, but because there’s a field operating entirely within the entity itself. Consider the bacterium again. In fact, real bacteria do not swim directly up a gradient. Instead they make a series of straight runs, followed by tumbles that reorient them randomly. On-average movement up the gradient is achieved only because the cell’s internal mechanisms detect the gradient and lengthen the straight runs when it happens to take the organism in the right direction. In our terms, the lengthening of the straight run is not free. That is determined by the field. What is free is the choice of direction of the straight runs, as well as the tumbling. These are field independent. And they are type-three freedom in that their causes lie inside the organism, in the molecular mechanisms governing the flagellum, rather than in any lateral bumps or overlapping fields originating outside it.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. pp. 7-8.

“Here we introduce the notion of autonomous goal-directed entities, entities for which some of their goal-directed behaviours arise from hierarchically nested structures inside them. But right at the outset, we need to acknowledge that this concept will seem to place us in a troublesome contradiction. On the one hand, we have claimed that in goal-directed systems, direction is always external. On the other, we have described autonomous freedom as behaviour in which the behaviour originates within the entity, in which external factors do not direct. But in fact there is no contradiction, because of the way that an autonomous entity is structured. It has fields that are internal to it, fields that act downwardly on its parts but that produce whole-entity effects, and that do so without guidance from fields external to the whole entity.

“Hormonal regulatory systems offer good examples. Thyroid hormones circulating throughout the organism constitute a large-scale, organism-wide field. Receptors for these hormones are present on a wide variety of contained tissues: brain, heart, liver, muscles and other organs. The hormone field acts downwardly on each of them….” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. pp. 8-9.

“This viewpoint invites us to see organisms as multilevel field structures, a nested series in which one field is immersed within another field, which is immersed in another, and so on. This nesting extends far below the scale discussed in the examples above. A kidney is regulated from above by various hormones in the circulatory system, and in turn regulates its own cells within it, and these cells in turn have membranes that regulate the flow of molecules into and out of themselves.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. p. 9.

“Consider a simple multilevel, autonomous entity, like a self-driving car. The recent technological advances made in self-driving vehicles provide an excellent, non-biological example of autonomous freedom. One can program a self-driving car to begin at its current location and arrive at another provided by a GPS waypoint or destination. The GPS guidance provided to this car is comprised of a series of networking satellites bouncing cellular signals. This is an upper-level field, external to the car, that guides it to its destination…. Yet, during the actual trip, sensors contained within the car actively detect obstacles in its path, telling the car to veer right or left, to avoid this pothole or that pedestrian. At this level in the hierarchy, the car possesses some degree of autonomous freedom, that is, freedom with respect to the GPS field. This is autonomous freedom in that it arises from some combination of small fields and their internal mechanisms, all located entirely within the car: the braking system directing the brake calipers, the steering system directing the steering linkage, etc. And these systems are contained within the larger computational system that directs the local, moment-to-moment movements of the car…

“And at the same time, the moment-to-moment operation of the entire local response system could be entirely independent of the GPS guidance system that chooses and executes the overall route. Local guidance is autonomously free and yet determined, at the same time….

“Perspective is critical in making sense of these hierarchically deep nested systems. Freedom at one level looks like noise from a perspective one level up. From the perspective of the GPS system directing the car to its destination, the various swerves and speed changes to avoid potholes and pedestrians look like random deviations, like noise.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. p. 11.

“… hierarchy lies at the heart of teleology and freedom. Without it, there is no teleology and there is no freedom.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. p. 11.

“In a non-hierarchical system in which all causation is lateral causation, if it is also deterministic, then in our terms there is no freedom, no freedom of a lower level relative to a higher one and no teleology….

“In sum, an appropriate hierarchical relationship is essential for both freedom and teleology. And consistent with everyday intuitions about teleology and freedom, teleology is not only compatible with freedom. Freedom is required.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. p. 13.

“Notice that freedom, as we’ve conceived it with these three types, is not a binary concept where certain entities are free and others are not. Freedom exists on a spectrum. A ball in a funnel is fairly free laterally, while having almost no autonomous freedom. Hume’s prisoner, chained to a wall, has little lateral freedom though they retain some of their autonomous freedom. They can think about whatever they like.” Babcock, Gunnar & Daniel W. McShea. 2022. “Resolving teleology’s false dilemma.” Biological Journal of the Linnean Society. XX:1-18. p. 13.

“… classical mechanics identifies the state of a physical system with the current values of certain observables of the system (e.g., the position x and the momentum p). Quantum mechanics, on the other hand, makes a very sharp distinction between states and observables.” Gillespie, Daniel T. 1973. A Quantum Mechanics Primer: An Elementary Introduction to the Formal Theory of Non-relativistic Quantum Mechanics. London: International Textbook Company. p. 40.

“Perhaps a more accurate description of the measurement process is to say that the very act of measuring à essentially develops a value of Ã; it evidently accomplishes this by the simple expedient of forcing the state vector into one of the eigenvectors of Â, so that then à will indeed have a value. In this view, ∣(αk,Ψt)∣2 is the probability that a measurement of à on the state [vector] Ψt will develop the value Ak. Gillespie, Daniel T. 1973. A Quantum Mechanics Primer: An Elementary Introduction to the Formal Theory of Non-relativistic Quantum Mechanics. London: International Textbook Company. p. 61.

“… the state vector of a quantum system evolves with time in a completely predictable manner, and in this sense it may be said that quantum mechanics, like classical mechanics, is a ‘deterministic theory.’ However, in quantum mechanics the state of a system not only changes with the passage of time, but it also changes as a result of being measured.” Gillespie, Daniel T. 1973. A Quantum Mechanics Primer: An Elementary Introduction to the Formal Theory of Non-relativistic Quantum Mechanics. London: International Textbook Company. p. 84.

“If we choose to regard the entire universe as a single system, governed by one super-Hamiltonian operator, then since there is nothing ‘external’ which can make a measurement on this system, we may justifiably assert that the state of the whole universe evolves with time in a completely deterministic way. If, however, we wish to consider only a portion of the universe as our system, omitting for example ourselves and our measuring apparatus, then we must evidently contend with a certain amount of indeterministic behavior every time we make a measurement upon the system.” Gillespie, Daniel T. 1973. A Quantum Mechanics Primer: An Elementary Introduction to the Formal Theory of Non-relativistic Quantum Mechanics. London: International Textbook Company. p. 84.

“Suppose first that the state vector of the electron coincides with one of the eigenvectors δxo(x) of the position operator X. … we may say in this case–and only in this case–that the observable position ‘has the value x0,’ or more simply that the electron ‘is at the point xo’…. Now it must be emphasized that this property of ‘having a position’ or of ‘being spatially localized’ is essentially the defining property of a particle. And it is only when the state vector of the electron coincides with one of these infinitely localized position eigenvectors δxo(x) that we can meaningfully assert that the electron ‘has a position and therefore ‘is a particle.’

“Suppose, on the other hand, that the state vector of the electron coincides with one of the eigenvectors θpo(x) of the momentum operator P. … we may say in this case–and only in this case–that the observable momentum ‘has the value po,’’ or more simply that th electron ‘is moving with momentum po.’ Instead, θpo(x) is seen to have an infinite, periodic, spatial extension, with fundamental period or ‘wavelength’
λo = h/po

“Now the property of periodic spatial extension is essentially the defining attribute of a wave, just as the property of sharp spatial localization is the defining attribute of a particle….

“We may summarize these results by saying that, when the state vector of the electron coincides with an eigenvector of X, then the electron has the attributes of (and therefore ‘is’) a particle; on the other hand, when the state vector of the electron coincides with an eigenvector of P, then the electron has the attributes of (and therefore ‘is’) a wave.” Gillespie, Daniel T. 1973. A Quantum Mechanics Primer: An Elementary Introduction to the Formal Theory of Non-relativistic Quantum Mechanics. London: International Textbook Company. pp. 101, 102.

“If we measure the position of an electron, then regardless of the state vector of the electron just prior to the measurement, immediately after the measurement it will coincide with one of the position eigenvectors, δxo(x). We will then have ΔX [the uncertainty of position] = 0, so that the position of the electron is well-defined and can be said to ‘have a value.’ Evidently, the position measurement has endowed the state vector of the electron with the property of sharp spatial localization, so that the electron may truly be regarded as a ‘particle.’ However, the electron then has no wavelike attributes: for since ΔX = 0 then … requires that ΔP = ∞, which means that the electron cannot be said to ‘have a momentum or wavelength.’ Thus, the measurement of the observable ‘position’ has developed the particle nature of the electron, but it has at the same time destroyed the wave nature of the electron.” Gillespie, Daniel T. 1973. A Quantum Mechanics Primer: An Elementary Introduction to the Formal Theory of Non-relativistic Quantum Mechanics. London: International Textbook Company. pp. 103-4.

“The immune system plays a key role in delineating (and constantly redrawing) the boundaries of a biological individual, determining which elements can be part of that individual, and insuring its cohesion.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 2.

“An infectious microorganism is not intrinsically pathogenic: it can be harmful in one species and benign in another, and its virulence often varies between different individuals in a population. Even within an individual, pathogenicity depends on pathogen localization, host physiological and immunological state at the moment of the infection, the presence of other microorganisms, and the past interactions with this pathogen or others, among many other factors.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 6.

“The vaccinated organism responds quicker and more strongly if it reenters into contact with the same pathogen. This capacity is called immunological memory, a phenomenon that has long been used to make a distinction between two arms of immunity, namely innate and adaptive immunity.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 7-8.

“Beyond humans, all animals, plants, unicellular eukaryotes, bacteria, and archaea are constantly under the potential threat of pathogens and have evolved multiple mechanisms to cope with those pathogens. Contrary to the long-held view that only vertebrates possess an immune system, in the last thirty years or so immune systems have been found in all the species in which their presence has been thoroughly investigated.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 8.

“Defining what counts as an immune process and delineating the field of immunology has indeed become extremely challenging nowadays. Focusing on defense against pathogens would be too narrow. On the other hand, extending the definition of immunity so far as the overall physiological regulation of the body (as sometimes suggested by recent studies on the role of the immune system in metabolism, tissue repair, homeostasis, development, and so on) would be so broad that it might cease to be scientifically fruitful, as almost everything in biology could be said to be immunological, at least to some degree.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 12-3.

“In 1998, Clint Hallam, a patient from New Zealand who was operated on in Lyon, France, received the world’s first hand graft. The operation was a technical success, and initially the recipient seemed to feel all right. Yet he soon started to consider as ‘other’ (foreign) the transplanted hand, which became unbearable to him. Hallam interrupted immunosuppressive treatment, organ rejection started, and eventually he asked that his hand be amputated.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 13-4.

“… Burnet postulated that, if foreign material was implanted early in the embryo, no antibodies would develop against that particular foreign material. This was later confirmed by experiments made by Peter Medawar’s group, showing that a tissue implanted early in the mouse embryo could subsequently be tolerated. For Burnet, therefore, the self is acquired, not innate: the organism acquires at an early ontogenetic stage the capacity to recognize its own constituents and to avoid their destruction.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 15-6; reference: Burnet, F.M. & F. Fenner. 1949. The Production of Antibodies, 2nd Ed. Melbourne: Macmillan.

“A degree of autoreactivity characterizes the lymphocytes generated and selected in primary lymphoid organs as well as naive lymphocytes circulating in the periphery. Effector T cells are selected only if they react weakly to self elements (and not if they do not react at all).” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 17.

“… many effector immune responses that occur routinely at the periphery during the lifetime of an organism target endogenous (‘self’) elements, as illustrated by the phagocytosis of dead cells, the clearance of cellular debris, many immune-mediated repair mechanisms, and the downregulating action of regulatory T cells, among many other phenomena. In other words, the claim that the immune system does not respond to self components is not true. There exists in fact a continuum from autoreactivity (interactions between immune receptors and endogenous motifs) to autoimmunity (the triggering of an effector response targeting endogenous motifs) and to autoimmune diseases (only the latter situation is pathological; it consists in the destruction of endogenous components, in a sustained manner and on a large scale….” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 17-8.

“Contrary to what was thought for many years, these microbes [from the microbiome] are not ‘invisible’ to the host immune system. The immune system interacts and develops an active dialogue with them, which leads to the triggering of a complex balance of effector and immunoregulatory mechanisms. In many cases, the host immune system facilitates the establishment and stability of certain components of the microbiota. Importantly, microbial molecular patterns that were conceived for a long time as pathogenic signatures can also mediate tolerogenic immune responses. All this confirms the centrality of the phenomenon of immunological tolerance, especially to the microbiota, in today’s immunology.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 18.

“In most cases, the symbiotic dialogue between the host and microbes is mediated by immune interactions, which confirms the central role of the immune system as an interface with the environment as well as between components of the organism. One striking result is that microbes, long seen as what the immune system must reject, can often participate in the immunological defense of the host against pathogenic entities, thus creating a form of ‘co-immunity.’” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 20.

“… the self-nonself theory is inadequate or at least incomplete, because many self components trigger immune responses and many nonself components are actively tolerated by the immune system.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 20.

“At the most general level, the issue of biological individuality consists in asking what makes up a countable, relatively well-delineated, and cohesive entity in the living world. (Being countable and well-delineated concerns what can be called external unity, whereas cohesion has to do with internal unity.)” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 20.

“The main claim of this section is that immunology makes an important contribution to the definition of biological individuality insofar as it sheds light on all three dimensions discussed above, namely countability, delineation, and cohesion. The three main activities of the immune system participating in the individuation of biological entities can be called ‘filtering over entry,’ ‘filtering over presence,’ and ‘promotion of cooperation’ (by ‘filter’ I mean allowing or, on the contrary, restraining the entry or presence of something, as explained below)….

“‘Filtering over entry’ refers to the fact that the immune system constantly patrols the interfaces of the organism with the environment (skin, gut, and so on) and determines which exogenous elements can enter the organism and which can’t. It thus plays a decisive role in the delineation of the organism’s boundaries and the possibility of counting it as one single entity….

“In a process that can be called ‘filtering over presence,’ the immune system constantly monitors the motifs expressed by the cells present in all tissues and body compartments as well as their intracellular content and determines which elements are tolerated, and therefore can remain part of that living thing, and which elements are rejected, and therefore cannot remain part of that living thing….

“Lastly, the immune system plays an important role in the promotion of cooperation between the components of the organism. It does so in two different ways. First, the immune system can ensure long-distance communication between remote components of the organism…. .. the immune system is unique in its capacity to send cells to every compartment of the organism. Second, the immune system can eliminate noncooperative elements (‘cheaters’), for instance, cancer cells, via the detection of abnormal molecular patterns, cell stress, aberrant cellular proliferation, and or damage caused to the organism.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 21-3.

“… the process of dual filtering [checking on ‘what comes from the inside’ and ‘what comes from the outside’] presented here is dynamic and never-ending. There is, therefore, a constant re-delineation, through the action of the immune system, of the constituents and boundaries of a living thing.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 24.

“According to the immunological account proposed here, every living thing is a chimera, a heterogeneous and mixed entity composed of genetically diverse components. On the one hand, it is a composite entity, comprising biotic elements that originate both from the organism and from outside the organism (bacteria, viruses, fungi, and so on). On the other hand, it is a very special composite entity, exhibiting a high degree of integration, with well-delineated boundaries, tight interactions, and strong cooperation between its components. Because of its three key activities of filtering over entry, filtering over presence, and promotion of cooperation, the immune system is essential in determining the constituents and boundaries of the living thing and therefore in turning a set of heterogeneous components into an integrated individual.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 24.

“Interestingly, in some cases, the highest degree of immunological integration is realized at the level of a colony rather than intuitively defined individuals. For example, some data in a number of social insects such as termites and honey bees suggest that key immunological processes occur at the colony level, which has led to the concept of ‘social immunity’ and has sometimes been used to support the superorganism hypothesis.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 26.

“Several researchers working on immunosurveillance noted that the action of the immune system could lead to the selection of more resistant tumor cells. Highly immunogenic tumor cells are eliminated by the immune system, but this process leaves behind tumor variants of reduced immunogenicity (or that have acquired other mechanisms to evade or suppress the immune response) and have a higher fitness in the immunocompetent host (a process similar to the selection of more resistant pathogens). Therefore, Robert Schreiber and colleagues proposed to use the term immnoediting instead of the traditional action of immunosurveillance, reflecting the fact that the immune system not only monitors tumors but also shapes them, with both beneficial and detrimental consequences for the host.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 32-3; reference: Schreiber, Robert, R.D., L.J. Old & M.J. Smyth. 2011. “Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion.” Science. 331:1565-1570. doi: 10.1126/science.1203486.

“From a conceptual viewpoint, therapies based on immune checkpoint inhibition constitute indeed a radical change in perspective. At least two important features of immune checkpoint therapies are worth emphasizing. First, the target of the treatment is the immune system, not the tumor itself (as was the intention with traditional treatments such as surgery, chemotherapy, and radiotherapy…. Second, the objective is to break the state of immune tolerance that has been established between the tumor and the immune system in the local tissue.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 36.

“Does the immune system dysfunction when it promotes cancer progression via a deficit in elimination or containment and/or via maintenance processes and/or via repair processes? The first situation corresponds to a dysfunctional immune system….

“In the second situation, however, the immune system acts normally and immune-mediated decohesion is due to an abnormal context. Pathogens, wounds, mechanical pressure, and local modifications due to carcinogenic environmental factors, among several other causes, can create an abnormal local context (characterized by inflammation, perturbation of the extracellular matrix, and so on). This local context influences the immune system, which in turn responds as it usually does, that is, by maintaining or repairing the tissue – even if the final, pathological, outcome is cancer promotion. It has long been known, for instance, that tumors resemble ‘wounds that do not heal,’ which means that, in cancer, normal repair mechanisms are triggered but generally without reaching the ‘resolution phase’. Furthermore, the tumor itself can be a major source of perturbation of the local context: it can influence the immune system through a variety of cytokines and can also increase inflammation and wounding, modify blood vessels, reshape the extracellular matrix, or exert a mechanical pressure, among many other possibilities. This is often described as the ‘hijacking’ or ‘co-option’ by the tumor of physiological pathways and of the tissue microenvironment.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 39-42.

“The main cellular actors of the brain immune system are microglia, the resident immune phagocytes of the CNS. They constitute about 10 percent of the total cells in the adult CNS.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 46.

“My analysis of this literature [ties between the immune system and the nervous system] has led me to single out five dimensions of neuroimmunology, each corresponding to a different question: interaction, similarity, overlap, origins, and control.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 54.

“The nervous and the immune systems are often said to be similar, that is, to share several important features. Similarity can be at a structural level. Both systems communicate via soluble ligands and receptors. Molecules that mediate such communication include cytokines, chemokines, neuropeptides, neurotransmitters, neurotrophins, and their receptors. Perhaps more distinctively, both systems make use of specific structures called synapses. The term appeared in neurobiology in the late nineteenth century and was subsequently adopted by immunologists in the 1980s to describe the extended communication surface platforms established between two immune cells, particularly antigen-presenting cells and lymphocytes. Both types of synapses are stable adhesive junctions between two cells across which information is transmitted via secretory molecules.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. pp. 55-6.

“Immune systems are much more widespread than nervous systems in the living world and much older in life’s history. Plants and prokayotes have an immune system but they don’t have a nervous system. Metazoans all have an immune system but not all have a nervous system….
And if one decides to focus on adaptive immune systems, then the reverse is true; countless animals, such as arthropods, for example, possess a nervous system without having an adaptive immune system.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 58.

“Multicellularity presupposes internal communication and in metazonas three types of long-distance communication channels can be distinguished. The first resembles our electric networks; it corresponds to the nervous system, and more specifically to neurons, which can send information at a very high speed with a relatively diverse content. The second resembles our water and/or sewage networks; it corresponds to the blood and lymphatic vessels, where endocrine signals, in particular, circulate. It delivers information at a relatively high speed with a relatively diverse content. These first two systems (nervous and vascular) are rigid: they can be modified (via neurogenesis and angiogenesis, for example) but only at an extremely slow rate. The third system resembles our mail carriers; it corresponds to immune cells, which are the uniquely mobile cells of the organism and which can deliver information with extremely diverse content everywhere in the organism, often over long distances though at a limited speed. In addition to carrying information, immune cells can perform all sorts of activities, including pathogen clearance, tissue remodeling, and tissue repair, among many others.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 59.

“… it would nonetheless be inadequate to consider only the nervous system when trying to identify the biological basis of feelings, emotions, behaviors, and cognitive states. Understanding these processes requires an integrative approach in which the immune system could play an important role. Accordingly, neuroimmunology lends more weight to the idea of embodied cognition, that is, the idea that bodily elements distinct from the brain play a significant role in cognitive processing.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 62.

“First, the immune system is an informant for the nervous system…. Second, the immune system is an executant for the nervous system: it realizes distinctive activities indispensable for the functioning of the nervous system, such as elimination of dead cells, repair, and so on. Third, and most crucially, the immune system is a messenger for the nervous system: not only does the nervous system resort to the molecular communication pathways of the immune system (cytokines) but it makes use of the unique feature of immune cells, namely their mobility, which allows them to reach any part of the organism and to deliver complex messages there.” Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge UP. p. 63.

“We talk about atoms being in two places at once, behaving like spread-out waves and existing in a superposition of two or more different states at once. By way of making things easier for you, the reader, we can settle on a single term that encompasses all these concepts: that of quantum ‘coherence.’ Thus, when we refer to ‘coherent’ effects we mean something is behaving in a quantum mechanical way, exhibiting wave-like behavior or doing more than one thing at the same time. Thus, ‘decoherence’ is the physical process whereby coherence is lost and the quantum becomes classical.

“Quantum coherence is normally expected to be very short-lived unless the quantum system can be isolated from its surroundings (fewer jostling particles) and/or cooled to a very low temperature (much less jostling) to preserve the delicate coherence.” McFadden, Johnjoe & Jim Al-Khalili. 2014. Life on the Edge: The Coming of Age of Quantum Biology. NY: Broadway Books. p. 118.

“Glance up at the sky for one second and a column of light 186,000 miles long descends into your eye. In that same second, the earth’s plants and photosynthetic microbes harvest the solar light column to make about 16,000 tonnes of new organic matter in the form of trees, grass, seaweed, dandelions, giant redwoods and apples.” McFadden, Johnjoe & Jim Al-Khalili. 2014. Life on the Edge: The Coming of Age of Quantum Biology. NY: Broadway Books. p. 119.

“… the only theory that provides an explanation of how flies and humans can distinguish the smells of normal and deuterated compounds [chemicals where hydrogen has been replaced with the heavier deuterium atoms] is based on the quantum mechanical mechanism of inelastic electron tunneling. Experiments have recently shown that, as well as flies and humans, other insects and even fish are able to sniff the differences between hydrogen and deuterium bonds.” McFadden, Johnjoe & Jim Al-Khalili. 2014. Life on the Edge: The Coming of Age of Quantum Biology. NY: Broadway Books. pp. 164-5.

“They [Mohseni et al] showed that transporting the quantum coherent exciton [an electron during photosynthesis that has been knocked out of its orbit by a photon plus the hole it leaves behind] can be either retarded or assisted by environmental noise, depending on just how loud that noise is. If the system is too cold and quiet, then the exciton tends to oscillate aimlessly without actually getting anywhere in particular; whereas in a very hot and noisy environment something called the quantum Zeno effect kicks in, which retards quantum transport. Between these two extremes is a a Goldilocks zone where vibrations are just right for quantum transport.” McFadden, Johnjoe & Jim Al-Khalili. 2014. Life on the Edge: The Coming of Age of Quantum Biology. NY: Broadway Books. p. 295; reference: Mohseni, M., P. Rebentrost, S. Lloyd & A. Aspuru-Guzik. 2008. “Environment-assisted quantum walks in photosynthetic energy transfer.” Journal of Chemical Physics. 129(17). 174106.

“The quantum Zeno effect, as it came to be known, describes how continuous observations can prevent quantum events from happening. For example, a radioactive atom, if observed closely and continuously, will never decay–an effect often described in terms of the old adage ‘the watched pot never boils’….

“To see how Zeno’s paradox is relevant to life, we will return to the energy transport step of photosynthesis. Let’s imagine that a leaf has just picked up a solar photon and converted its energy to an exciton…. It is the exciton’s waviness that is essential for efficient quantum transport, for this enables it, like a water wave, to explore multiple paths simultaneously. But if its quantum waviness breaks on the molecularly noisy rocks of decoherence inside the leaf, then its waviness will be lost and it will become a localized particle stuck in a single position. The noise essentially acts as a kind of continuous measurement, and if it is very intense then decoherence will take place very quickly, before quantum coherence has a chance to help the exciton wave reach its destination. This is the quantum Zeno effect: constantly collapsing the quantum wave into the classical world.

“When the MIT team estimated the influence of molecular noise/vibrations in the bacterial photosynthetic complex, they discovered that quantum transport was optimal at temperatures around those at which microbes and plants perform photosynthesis.” McFadden, Johnjoe & Jim Al-Khalili. 2014. Life on the Edge: The Coming of Age of Quantum Biology. NY: Broadway Books. pp. 296-7; reference: Lloyd, S., M. Mohseni, A. Shabani & H. Rabitz. 2011. “The quantum Goldilocks effect: on the convergence of timescales in quantum transport.” arXiv preprint. arXiv:1111.4982.

“… I hope to convince you that the conceptual problems and raging disagreements that have bedeviled quantum mechanics since its inception are unsolved and unsolvable, for the simple reason that the theory is wrong. It is highly successful, but incomplete.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. xvii.

“So I will endeavor to reassure readers that quantum mechanics can be understood completely within a realist perspective in which the external world can be completely comprehended as independent from us.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 11.

“We can follow John Bell and call a real property of a system a beable: it is part of what is. Bell coined the word as a contrast to the term observables, which is what anti-realists want out of a theory.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 26.

“Given the quantum state of an isolated system at one time, there is a law that will predict the precise quantum state of that system at any other time.

“This law is called Rule 1. It is also sometimes called the Schroedinger equation. The principle that there is such a law is called unitarity.

“Thus, while the relation between the quantum state and the behavior of an individual particle can be statistical, the theory is deterministic when it comes to how the quantum state changes in time.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 31.

“… Rule 2:

“The outcome of a measurement can only be predicted probabilistically. But afterward, the measurement changes the quantum state of the system being measured, by putting it in the state corresponding to the result of the measurement. This is called collapse of the wave function.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 35.

“… quantum states exist for two particles in which we know something about how the particles are related to each other, but nothing about each particle individually. We call such states entangled. The phenomenon of entanglement is something new, which comes into physics with the quantum and has no classical analogue.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 38.

“Stranger still was how quantum properties can be entangled and shared among systems that are widely separated in space. This was the ultimate lesson of the story told by Einstein, Podolsky, and Rosen. But it was only in John Bell’s retelling that the true moral of the story was revealed to be the radical nature of quantum nonlocality.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 49.

“Contextuality occurs in situations in which our system is described by at least three properties, which we can call A, B, and C. A is compatible with both B and C, so A may be measured simultaneously with either B or C. But B and C are not compatible with each other, so we can measure only one at a time.

“So we can measure A and B or we can measure A and C. We make a series of experiments in which we make both choices, and we record all the answers. When we do we will find–assuming that quantum mechanics is correct–that the answers to A depend on whether we chose to measure B or C along with A. The conclusion is that nature is contextual.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 56.

“Quantum mechanics was invented in order to explain certain puzzling experimental results concerning light, radiation, and atoms. The three new phenomena we discussed in this chapter–entanglement, nonlocality, and contextuality–are a far distance more puzzling.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 56.

“What is really bizarre, looking back, is that from 1927 on, there had existed a realist version of quantum mechanics…. It [a stunningly simple idea for an alternative] is simply to posit that there are both waves and particles. What gets created and detected, what gets counted, is a particle. Meanwhile, a wave flows through the experiment. The wave guides the particle. The result of this guidance is that the particle goes to where the wave is high.

“Faced with a choice of which way to go around an obstacle, such as in the double slit experiment, the wave goes both ways. The particle goes through only one slit around only one side, but where it goes once it gets through is guided by the wave, and shows the influence of both paths.

“This obvious solution to the challenge of the wave-particle duality was thought up by Louis de Broglie. He worked it out in detail and called it the pilot wave theory. De Broglie presented his theory at a famous conference held in Brussels in 1927….

“The core of pilot wave theory was de Broglie’s idea that the electron is actually two entities, one particle-like and one wave-like. The particle is always located some particular place and always follows some particular path. Meanwhile, the wave flows through space, taking simultaneously all the possible paths or routes through the experiment. The wave then directs the particle where to go, and that piloting will be based on conditions along all the paths. Even though the particle must take one route or another, which route it takes is influenced by the wave, which flows through all routes.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. pp. 97-8.

“But it didn’t take long for Bohm to invent a realist completion of quantum mechanics [in 1952]. What he did was, basically, to reinvent de Broglie’s forgotten pilot wave theory.

“There is, it should be mentioned, a difference between de Broglie’s and Bohm’s theories, in that Bohm chose a different law for the guidance equation by which the wave guides the particle….

“In Bohm’s theory, the law that guides the particle is a version of Newton’s law of motion: it describes how a particle accelerates in response to a force. What is new is that there is a force which guides the particle to move to where the wave function is largest.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 109.

“… de Broglie had understood from the beginning that his particles would move in ways that violate basic principles of Newtonian physics, such as the principle of inertia and the conservation of momenta. This was necessary if light quanta could bend their trajectories to diffract around obstacles. De Broglie’s and Bohm’s guidance equations resulted in trajectories that diffracted and refracted, but there was a price to pay, which was apparent violations of basic principles.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 111.

“It is easy to say that Bohm failed, and that his greatest achievements by far were his early contributions to quantum physics. At the same time, he explored a road that few of us have had the courage or the vision to even take one step toward, in spite of the obvious fact that the greatest dangers we face as a species can be tied to the utter incoherence of human culture, a break that has its roots in the incommensurability of scientific and spiritual understandings of the world.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 116.

“The pilot wave theory explains everything that ordinary quantum mechanics does, without the awkwardness of Rule 2. The wave function evolves always according to Rule 1, so it never jumps or collapses. What is new [from Bohm] is that there is a particle that moves according to its own law, guided by the wave function. Together the two laws give an entirely realist description of quantum phenomena.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 116.

“It would be more compelling if the modifications we make to quantum mechanics are motivated by a problem besides the measurement problem, such as the problem of quantum gravity. This brings us to the work of Roger Penrose.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 133.

“Penrose is a realist, but he makes an unusual move for a realist on quantum theory. Rather than ascribing reality to both waves and particles, or inventing new ‘hidden variables,’ Penrose takes reality to consist of the wave function alone. This leads him to take up the suggestion by Pearle and others that the collapse of the wave function during a measurement is a real physical process. The sudden change of the wave function is not, as some hold, due to an update in our knowledge of where the particle is; it is a genuine physical process.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 139.

“Pilot wave theory and the collapse models [e.g. Penrose] have given us options for quantum physicists who want to be realists. The differences are striking, but so are the similarities.

“One option is to believe there are both waves and particles; this leads to pilot wave theory….

“The collapse models avoid all these objections. There are only waves, so there is no doubled ontology and no issue with reciprocation….

“Both approaches agree on two key lessons: the wave function is an aspect of reality, and there is a tension with relativity theory. These are vital clues for the future of physics.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 142.

“The philospher Imre Lakatos recommended investing in research programs that are progressive, by which he meant that they are rapidly developing and have the potential to lead to a breakthrough. A progressive research program is also one that is open to future developments and surprises, in contrast to programs which assume the basic principles and phenomena are understood.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 175.

“John Wheeler put it like this:

“It from bit symbolizes the idea that every item of the physical world has at bottom–at a very deep bottom, in most instances–an immaterial source and explanation; that what we call reality arises in the last analysis from the posing of yes-no questions and the registering of equipment-evoked responses; in short, that all things physical are information-theoretic in origin and this is a participatory universe.

“The first time you hear this kind of view expressed, you may not be sure the speaker means it. But he does. Here is another, briefer quote: ‘Physics gives rise to observer-participancy; observer-participancy gives rise to information; information gives rise to physics.’” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 188; subquotes: Wheeler, John Archibald. 1989. “Information, Physics, Quantum: The Search for Links. In: Kobayashi, Shunichi et al (eds). Proceedings of the 3rd International Symposium: Foundations of Quantum Mechanics in the Light of New Technology, Tokyo. Tokyo: Physical Society of Japan; Wheeler, J.A. Quoted in Davies, Paul. 2006. “The Goldilocks Enigma. NY: Houghton Mifflin. p. 281.

“Rovelli’s proposal [of a thought experiment that sets up Schroedinger’s cat as nested series of boxes where a woman named Sarah outside the box containing the cat and Geiger counter is in her own box around the prior box so that when she, starting out in the classical state, opens the box she becomes a superposition of herself with the Geiger counter and the cat from our point of view while to her the cat is either alive or dead] is that these are all equally correct, partial descriptions of the world. All are part of the truth. Each gives a valid description of a part of the world, defined by a boundary. Is Sarah truly in a superposition, or does she definitely see and hear a live cat? Rovelli would like to not have to choose between these. He insists that a description of physical events and processes is always made with respect to some particular way of drawing the boundary between quantum and classical. He posits that all ways of drawing the boundary are equally valid and all are part of the total description.

“Simply put, Rovelli would say that it is true, from Sarah’s point of view, that the cat is alive, and it also true, from my point of view, that Sarah is entangled in a superposition of ‘seeing dead cat’ and ‘seeing live cat’….

“If relational quantum theory [Rovelli’s concept] had a slogan, it would be ‘Many partial viewpoints define a single universe’….

“Rovelli wants to call his view realism, but it means something different from naive realism, as I have used the term so far….

“Rovelli denies that that kind of naive realism is possible in our quantum world, so he proposes we adopt his radically different version of realism, according to which what is real is always defined relative to a split of the world that defines an observer.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. pp. 196, 197, 198; reference: Rovelli, Carlo. 1996. “Relational Quantum Mechanics.” International Journal of Theoretical Physics. 35(8):1637-78. arXiv:quant-ph/9609002.

“Several writers, beginning with Heisenberg and including my teacher Abner Shimony, have proposed that the world of the possible has to be included as part of reality–because in quantum physics the possible influences the future of the actual.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 199.

“Here is a way we might develop the view that the possible is part of the real. Bring in time, and let us take the view that the present moment and the flow or passage of moments are real and fundamental….

“The past consists of those events which were once present and real. They no longer exist, although their properties can be captured and remembered in presently existing structures.

“The future is not real. Moreover, the future is slightly open, in the sense that rare novel events with novel properties may happen every once in a while. But if for a moment we ignore that possibility, then there does exist in the present a finite set of possible next steps, which are possible next events and their properties.

“Given the present state of the world, not everything can happen in the next time step. Those events that might be next Kauffman calls the adjacent possible. The possible near-future events that make up the adjacent possible are not yet real, but they define and constrain what might be real.

“The adjacent possible of Schroedinger’s cat includes a live cat and a dead cat. It does not include a brontosaurus or an alien dog. So the elements of the adjacent possible have properties, even if the law of the excluded middle does not apply to them. As objects with properties, there are facts of the matter about them. This is the sense in which we may say that a small part of the possible may be considered real.

“This starts to make sense. Not everything that is possible is real. But a small part of the possible has definite properties that justify assigning it to a new category of the real and possible.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. pp. 200-201.

“The lesson I draw from these theories [universe as information, relational quantum theory, past’s having an influence on the future] is that to extend quantum mechanics to a theory of the whole universe, we have to choose between space and time. Only one can be fundamental. If we insist on being realists about space … then time and causation are illusions, emergent only at the level of a coarse approximation to the true timeless description. Or we can choose to be realists about time and causation. Then … we have to believe that space is an illusion.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 204.

“The problem with skipping the stage of principles and hypotheses and going right to models is that we can lose our way. It’s easy to get trapped in a microscopic focus while trying to work out the details of those models….

“Einstein expressed this lesson by insisting that we distinguish two kinds of theories. Principle theories are those that embody general principles. They restrict what is possible, but they don’t suffice for the details. Those are supplied by the second kind of theory, which he called constitutive theories. These describe particular particles or specific forces that nature may or may not contain. Special relativity and thermodynamics are principle theories. Dirac’s theory of the electron and Maxwell’s theory of electromagnetism are constitutive theories.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. pp. 226, 227.

“1. Background independence.”

“A physical theory should not depend on structures which are fixed and which do not evolve dynamically in interaction with other quantities.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 229.

“2. Space and time are relational.

“Background-independent theories speak to us about nature through relational observables.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 232.

“3. Principle of causal completeness.

“It is never the case that the chain of causes traces back to something outside the universe.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 232.

“4. Principle of reciprocity.

“This principle states that if an object, A, acts on a second object, B, then B must also act back on A.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 232.

“5. Principle of the identity of indiscernibles.

“This states that any two objects that have exactly the same properties are in fact the same object.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 233.

“Putting them in order, we have five closely related principles:

“1. The principle of background independence
“2. The principle that space and time are relational
“3. The principle of causal completeness
“4.The principle of reciprocity
“5. The principle of the identity of indiscernibles” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 233.

“Leibniz believed we could uncover a rational explanation for every apparent choice God might seem to have made in the creation of the universe. He spoke of the state in which this understanding would be achieved as one of having ‘sufficient reason.’ His principle of sufficient reason states that the universe can be completely understood.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 234.

“Leibniz posited that the actual universe is distinguished from many possible universes by ‘having as much perfection as possible.’ If we strip this of its poetic or allegorical meaning, what Leibniz is doing is positing that there is some observable quantity which is larger in the real universe than in all the other possible universes.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 243.

“I believe that quantum mechanics is incomplete and aim to construct a realist theory according to the principles of temporal relationalism, which can stand as a simultaneous completion of quantum mechanics and general relativity. I have hopes that this theory will not only resolve the puzzles in the foundations of quantum theory, but will lead to the discovery of the right quantum theory of gravity, as well as address mysteries in cosmology and particle physics coming from the universe’s apparent freedom to choose both laws and initial conditions.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 253.

“Symmetries are properties of fixed backgrounds, and the occurrence of a symmetry in a theory is a clear sign that that theory is background dependent. A symmetry is an operation that translates or rotates the system we are studying, with respect to the background, which is left unchanged. Symmetries characterize a system that has been isolated from a larger universe, and arise from what is ignored in that isolation.” Smolin, Lee. 2019. Einstein’s Unfinished Revolution: The Search for What Lies Beyond the Quantum. NY: Penguin Press. p. 264.

“Overall, it can be said that work on photosynthetic organism [sic] has provided substantial evidence of quantum effects at room temperature, something that was considered virtually unthinkable not so long ago. There is considerable evidence the coherence demonstrated in these biological systems is capable of enhancing the efficiency of photosynthetic units, such as the FMO complex. This enhancement may only be by a few per cent, but this may confer significant survival advantage to certain species which live in low-light conditions, such as green sulphur bacteria or algae.” Goh, Bey Hing, Eng Siang Tong & Priyia Pusparajah. 2020. “Quantum Biology: Does quantum physics hold the key to revolutionize medicine?” Progress in Drug Discovery & Biomedical Science. 3(1):1-22. doi: 10.36877/pddbs.a0000130. p. 16.

“Based on the existing literature, it is evident that nature has been able to evolve mechanisms and structures by which to harness quantum mechanics to aid processes necessary to life in ways that were highly unexpected based on the initial findings of quantum physics where these behaviours were thought to only occur under very tightly controlled environmental conditions. From what has been discovered, it seems likely that we have only just begun to unearth the tip of the iceberg in terms of how quantum phenomena play a role in living organisms….” Goh, Bey Hing, Eng Siang Tong & Priyia Pusparajah. 2020. “Quantum Biology: Does quantum physics hold the key to revolutionize medicine?” Progress in Drug Discovery & Biomedical Science. 3(1):1-22. doi: 10.36877/pddbs.a0000130. p. 19.