Denis Noble: "Neo-Darwinism Is Dead" | We Need A Biology Beyond Genes

In 1958, when asked by examiners where the oscillator was in his equations for cardiac rhythm, Noble realized the question itself was wrong; the heart beats not because something external forces it, but because it self-excites—a fundamental property he later showed is universal in living systems.

“I was faced in 1958 when I started graduate study at University College London with that extraordinary fact. Nobody knew how it could be that a muscle could excite itself to be rhythmic.”

Darwin recognized in his 1871 writings that the peacock intentionally displays its feathers to convince the peahen to mate, demonstrating that Darwin attributed agency and intention to animals—a view later erased by neo-Darwinism's commitment to blind, purposeless mechanisms.

“he thought, well, it's trying to tell that pen, I want to mate with you. But then he realized, but wait a minute, that means the peacock intends to do. He writes that he says in his book in 1871, the peacock consciously tries to convince the beehen.”

Schizophrenia correlates more strongly with poverty within communities than with any identifiable genetic markers, and the correlation is likely due to social causes (poverty, family stress) not genetic causation, yet this is often attributed to genes.

“what does explain that kind of problem? Schizophrenia is a very good example actually because what we found is that it's much more to do with poverty within communities which is why it's familial why it goes down through the generations like this biggest circle in your image it's the biggest circle there in that diagram exactly and that is vastly more important than the gene sequence the correlation but remember the difference between correlation or association and causation”

Michael Levin's xenobots (reprogrammed frog skin cells) self-organize when isolated and begin using cilia to swim and search for food, demonstrating agency and goal-directed behavior arising from cellular networks without centralized instruction.

“You can take cells from the skin of a frog, isolate them from their environment, which is the frog skin, which is a very complex organ... we're no longer connected. There's just a little bunch of us, maybe five cells, but we've got to feed. What do they start doing? They start using their little wavy pilia on the surface of the cell to swim in the environment to see where they can find food. They're already an organism.”

The reductionist central dogma of biology is a metaphysical assumption disguised as science; changing how biology is conceived will require acknowledging that the central dogma is a form of metaphysics, not empirical fact.

“the central dogger is a for central dogma, which is one of the problems in what I'm describing in standard biology. That is a form of metaphysics. It's an assumption that everything flows according to DNA self-replicating and simple selection by does the organism die or not. being the only process by which evolution occurs. And I think we have to come to the conclusion that that simplistic analysis has failed to explain what we need to explain.”

Cells communicate their organismal identity to each other via exosomes and extracellular vesicles (tiny packets of information exchanged between cells), which carry signals that maintain organismal integrity; when this communication breaks down, cells become rogue and may become cancerous.

“cells have to forget themselves in a sense right they they function in sort of uh in favor of the whole organism and a cancer cell stops doing that it no longer is part of the organism and we know how cells communicate to tell themselves that they're part of the same tissue these are called the microsomes or the exosomes or the extracellular visicles. These are tiny packets of cell information and cells are exchanging these all the time.”

By 1992, Noble's research identified 55 proteins involved in heart rhythm generation, but blocking the one known to contribute 80% of the electric current caused only a 10% change in heart rate, demonstrating that association (80%) is distinct from causation (10%), a pattern repeated in 90% of genomic associations.

“By then I'd found not just five protein mechanisms involved in heart rhythm but at least 55 or maybe 555. I mean these are vast networks of gene products, the proteins, RNAs and so on. And what we found was that you can knock a key one out that was known by our experiments to contribute 80% of the electric current causing that pacemaker potential to develop and therefore causing the heart rhythm. You can block that and only a 10% change in frequency occurs.”

The genome cannot self-replicate without a living cell because the human genome is 3 billion base pairs long, and chemical self-replication occurs with an error rate of approximately 1 in 10,000 base pairs, producing 300,000 errors per replication—any cell replicating with this error rate would die.

“The problem is that our genomes are three billion base pairs long. Divide by 10,000, you'll have 300,000 errors approximately. Any cell that reproduced with that degree of error would not live.”

70% of proteins formed from the DNA sequence can be folded in many different ways; protein function is determined by environment and context (the same protein can act as an enzyme in the cytoplasm or as a transporter in a lipid membrane), not solely by DNA sequence.

“It codes for the protein sequence. The amino acid sequence in the protein. 70% of the proteins formed that way can be folded in many different ways.”

The body has multiple, redundant mechanisms to achieve the same function, ensuring robustness and survival; if organisms did not have such backup systems, they could not survive environmental changes.

“the body has many ways of making the same function happen. If it didn't, it wouldn't survive. It's robust.”

Aristotle distinguished between causation by form (constraint imposed by boundary conditions) and causation by physical interaction (particles colliding); both are necessary to understand living systems.

“That's a distinction that goes way back to Aristotle. He was the first as far as we know to distinguish between causation by form which is the constraint by the boundary conditions of any system and constraint by the physical interaction knocking into each other sliding over each other or whatever it might be that molecules take part in. You need both.”

People taught that 'my genes made me do this' are given a disempowering mindset that reduces responsibility and agency; research shows better outcomes when people are encouraged to recognize their own agency and capacity to change, even when genetics are involved.

“If you really believe that you can't help it. My genes made me do this. That is actually the defense that somebody once produced in an American court... I pulled the trigger, but I was not responsible.”

The central dogma of molecular biology—the idea that DNA determines protein, which determines function, which determines organism—is fundamentally flawed because it ignores feedback from higher levels of organization (cells, tissues, organs) back to genes.

“Francis Crick... formulated what he called the central dogma of molecular biology which is a very simple idea that from a sequence in our genes you generate a protein. The protein then forms a structure which is determined by the sequence and finally that produces the function of the body. So everything could be predicted from what happens at the level of DNA. That is impossible.”

McClintock published a paper stating that 'the genome is an organ of the cell,' meaning the cell controls the genome, not the reverse—directly contradicting the central dogma's claim that the genome controls the cell.

“She published a paper saying, you know, this gives a totally different picture of life. The genome is an organ of the cell. What she meant was the cell controls the genome. What was I describing earlier in this discussion? Precisely how it does that the body as a whole can tell the genome what to do.”

Errors in genome replication and genetic variation are not mere defects but sources of adaptive innovation; cells and organisms use errors as information to respond to environmental challenges; the immune system exemplifies this: antibody genes are deliberately mutated, generating variation from which effective antibodies are selected.

“you cannot describe that as anything other than the order arising out of disorder without the disorder you wouldn't be able to have learning The AI people know that too. Alan Turing, the first person to write about artificial intelligence in 1950 said it very clearly. You need to have an element of randomness to have any learning at all.”

DNA cannot replicate itself with sufficient accuracy without living cell machinery; when DNA in a test dish without cellular machinery was tested, it replicated with roughly one error per 10,000 base pairs, but the human genome contains 3 billion base pairs, meaning such accuracy would result in approximately 300,000 errors per cell division—an amount that would be fatal.

“chemists actually checked if you unravel the DNA in a dish without a cell, how does it replicate? And it does...the accuracy...it's about one error in something like 10,000 pairs...The problem is that our genomes are three billion base pairs long. Divide by 10,000, you'll have 300,000 errors approximately. Any cell that reproduced with that degree of error would not live.”

Royal Society secretary Henry Oldenberg refused to publish Spinoza's 'Ethics' because of suspicion of Spinoza's theology, a lost opportunity that would have integrated philosophical and scientific thought earlier and prevented the mind-body dualism that has plagued science.

“the then secretary Henry Oldenberg who himself was from the Netherlands incidentally he was suspicious of Spinosa's theology and couldn't feel that he could take the decision to publish his ethics which is one of his greatest philosophical achievements”

A 2023 University College London study published in the British Medical Journal Medicine analyzed National Health Service genomic and disease data and found that polygenic risk scores—the sum of all genetic association scores for disease—have very weak predictive power, correctly predicting disease in some cases but incorrectly predicting disease in many others, at a level that would not meet regulatory standards for pharmaceutical approval.

“a very large team that did it led by a man called Hin Garani...they did was to say, okay, all the association scores are fairly small, but if we add them all together, we get what might possibly be the cause...Do they predict the diseases those people suffered from? Very simple question. And the answer in the conclusion of their paper, the correlation is very weak.”

Young scientists who question the central dogma or propose alternative frameworks face barriers in funding and publication; Noble has formed a network of young researchers around the world exploring non-reductionist biology despite institutional headwinds.

“What can we do to swim within this environment in which you can't even get funding if you want to do that? Tragic. Yeah. And I've examined thesis where people have been clearly knocking against the dogma of the times. I've tried therefore to give encouragement to those people by forming a group”

A 2023 study published in the British Medical Journal at University College London tested whether combined genomic association scores predict disease in a large NHS population database; the correlation was very weak, and the predictions were no better than random chance by pharmaceutical regulatory standards.

“The important experiment that was done at University College London two years ago published in 2023 in the British Medical Journal Medicine... led by a man called Hin Garani... if we add them all together, we get what might possibly be the cause... Together, they function to create a situation in which somebody at sometime has a heart attack or develops a cancer... Do they predict the diseases those people suffered from? Very simple question. And the answer in the conclusion of their paper, the correlation is very weak.”

The Royal Society was originally called 'Philosophical Transactions' because in the 17th century no distinction was made between philosophy and science; this historical erasure of philosophy from science is problematic.

“the then secretary Henry Oldenberg... he was suspicious of Spinosa's theology and couldn't feel that he could take the decision to publish his ethics which is one of his greatest [1:10:40] philosophical achievements but that's what would have happened had oldenberg agreed to take spinosa's work and publish it in what are they called the philosophical transactions of the royal society that's a scientific journal is still called the philosophical transaction because nobody in those days distinguished between a philosopher and a scientist people understood you have to do both.”

The 2001 human genome sequence comparison showed that proteins evolved multiple functions by transferring and recombining entire domains of genetic sequence from one gene to another—a mechanism forbidden by the central dogma—and Barbara McClintock discovered in the 1930s-50s that corn plants under environmental stress actively move genes between chromosomes, a process she called 'jumping genes.'

“figure 42 of that paper...showed that they had evolved by transferring whole domains of sequence from one gene to another. It's forbidden by the central dogma. Now that had actually been discovered nearly a hundred years ago by a very famous American geneticist called Barbara Mcccleintok. She showed...that suddenly the corn starts to do exactly that. It juggles its genes. It actually moves genes from one chromosome to another.”

Charles Darwin in 1868 postulated that cells communicate with each other to transmit body characteristics to germ cells, a Lamarckian idea that was dismissed but has been validated by discovery of the particles (exosomes) that Darwin postulated but could not observe with 19th-century microscopes.

“The curious thing is that idea goes back to Charles Darwin 1868. He didn't see and couldn't with the microscopes of the day the particles that he postulated, but he knew that cells had to communicate to each other because he thought that we could communicate body characteristics to the germ cells, the future egg and sperm. That's a Lamarian idea.”

A muscle like the heart can excite itself rhythmically without external instruction from the nervous system through autocatalytic (self-propagating) processes, which Noble demonstrated mathematically in 1958 and published in Nature.

“In a biological system there is always the possibility that it might generate an automatic cycling process...a fundamental process that must have been operating at the very origin of life, the ability to self-excite and to continue doing so indefinitely.”

Darwin's concept of sexual selection involves intentionality and agency—the peacock 'consciously tries to convince the peahen' to mate, and the peahen actively selects—a dimension of evolution that neo-Darwinism rejects but which Darwin explicitly described in his 1871 book.

“What is that magnificent peacock doing when it opens up its wings...He thought, well, it's trying to tell that peen, I want to mate with you. But then he realized, but wait a minute, that means the peacock intends to do...He writes...in his book in 1871, the peacock consciously tries to convince the peehen.”

Alan Turing said in 1950 that artificial intelligence requires an element of randomness to have any learning at all; this principle applies equally to biological intelligence and was already recognized at the birth of AI research.

“Alan Turing, the first person to write about artificial intelligence in 1950 said it very clearly. You need to have an element of randomness to have any learning at all. He said that way back in 1950.”

Biological systems are robust and exhibit redundancy—they have evolved multiple independent pathways for accomplishing critical functions—which is why organisms survive even when individual genetic mechanisms are disrupted, but this redundancy also means weak genetic associations in population studies do not reflect causal importance.

“the body has many ways of making the same function happen. If it didn't, it wouldn't survive. It's robust...Would we trust flying in aircraft if they didn't have backup systems...the pilot is the key backup. But before that there is backup in the system.”

The belief that genes determine behavior and criminality has real social harms: historical example is Nazi eugenics ideology that justified killing 6 million people based on the false belief that genomes could be 'bad' and determine criminal or undesirable behavior.

“if you ask the question, what motivated the killing of 6 million people during the Second World War? 6 million gypsies, Jews, and other strange in the view then of the ruling organization, the Nazi organization within Germany. What was the justification for killing them? It was that their genomes were bad. There are no criteria that can be usefully used from the genome alone to identify criminality.”

The belief in genetic determinism undermines human agency and psychological resilience; people who believe 'my genes made me do this' adopt a passive, hopeless mindset and are less likely to change behavior or improve circumstances, whereas people who recognize agency are more motivated and resilient.

“I think that a person who thinks like a criminal might, I can't help it. It's my genes. has got the wrong mindset to survive in society...The mindset is I can lay back because there's nothing I can do about it. That is the very opposite of what somebody should be trying to do. The best way of bringing up somebody who feels like that is to encourage them. Well, actually, you do have agency.”

In Oriental philosophy, 'anatman' (Sanskrit: 'no-self') is the concept that there is no fixed, essential self—a view that accords with Noble's claim that the self is a relational process dependent on communication and cultural context rather than something intrinsic to the individual.

“the oriental philosophers have a word for this. They call it an atman. Atman is Sanskrit for the self. An is no. So it's no self. There isn't one.”

Descartes' concept of mind (res cogitans) as separate from body (res extensa) emerged in the context of 17th-century fascination with automata—mechanical toys in aristocratic gardens that used hydraulics to mimic living motion; Descartes reasoned that if bodies could be mechanical, there must be something (mind/soul) that makes humans different.

“he was impressed, as many were amongst educated people at the time, with extraordinary things, constructions that had been made in the gardens of the rich. Effectively, robots had been created from tiny tubes that were making them move...using early water computers if you like causing mechanical toys to behave like robots even making sounds”

The placebo effect is evidence that mind/consciousness affects physical body states; but if materialism is true and mind is 'merely' brain state, the placebo effect should not exist; therefore the existence of placebo effect suggests that materialism is incomplete or wrong as a metaphysical framework.

“if you want to do that within that still that materialist reductionist framework, you have to close your eyes because then a doctor would have to say we cannot account for the placebo effect because I basically deny the existence of your free will or mind. Indeed. Uh but we know from studies that it does work.”

Without the concepts of philosophy and metaphysics, scientists cannot distinguish between association (correlation) and causation—showing that philosophy is essential to science, contrary to the reductionist claim that science needs no philosophy.

“If you think that you won't even know how to distinguish between association between one thing happening, another thing happening and the causation that enables that to happen...comes out of my own work on the heart.”

Alan Turing stated in 1950 that any system capable of learning must have an element of randomness; modern AI systems that rely solely on weights and optimization cannot learn without incorporating stochasticity.

“Alan Turing, the first person to write about artificial intelligence in 1950 said it very clearly. You need to have an element of randomness to have any learning at all. He said that way back in 1950.”

Signals from the cell surface (in 'Paris') to the nucleus (in 'Leiden') occur within seconds when calcium enters protein channels, triggering a biochemical reaction that places a messenger on molecular motors that walk along microtubules to deliver genetic instructions.

“How can a cell that on a molecular scale is enormous... the cell surface for that single cell would be over there in Paris... the nucleus here in Leiden, then the cell surface... hundreds of miles and kilometers away. And yet within seconds a signal comes from way over there in Paris to the nucleus here in Leiden and tells the genome please do the following.”

Living cells repair DNA errors using approximately seven cut-and-paste enzymes that travel along the DNA molecule, locate errors, remove incorrect nucleotides, and insert correct ones; the cell does not allow division until all errors are corrected, but the mechanism by which the cell knows replication is complete is unknown.

“Even more extraordinary, the living cell does not allow itself to divide and distribute the DNA to the two daughter cells until that has happened. How does it know that?”

The placebo effect demonstrates that the mind can produce measurable changes in the body, which contradicts strict materialism that denies the causal efficacy of consciousness.

“if you want to do that within that still that materialist reductionist framework, you have to close your eyes because then a doctor would have to say we cannot account for the placebo effect because I basically deny the existence of your free will or mind. Indeed. Uh but we know from studies that it does work.”

In the 1960s-70s, Neo-Darwinism became the dominant paradigm in evolutionary biology, suppressing alternative views (like those of Barbara McClintock on genetic reorganization and of physiologists like Noble on cellular agency) that did not fit the reductionist framework.

“I was taught as a student by people at University College London who were very much part of the reductionist as we call it strategy in biology because just previously two years before Francis Crick had formulated what he called the central dogma of molecular biology”

In 1966, Dennis Noble examined Richard Dawkins' doctoral thesis, and they have remained intellectual friends for over 50 years despite deep disagreements; this long relationship was acknowledged when they debated three years ago (ca. 2021) at a UK festival organized by the Institute of Art and Ideas.

“what my dear friends within the reductionist camp in biology because I I've been friendly with Richard Dawkins for over 50 years now. Examined his thesis back in 1966. That's true. Yes. Exactly. So when we debated three years ago in the big festival in England organized by the Institute of Art and Ideas, he started the whole debate or discussion as we called it with you know that man over there was my thesis examiner.”

Erwin Schrödinger predicted in 1942 (in 'What Is Life?') that life might work like self-replicating crystals because crystals were the only things known in that era that could replicate themselves, and this idea became the basis for the central dogma despite being a crude analogy.

“It was actually Shreddinger who formulated that idea way back in 1942 when he wrote a book called what is life? And as a physicist, he was after all one of the formulators of the wave equation in quantum mechanics, he realized that the only thing that we knew in those days that could replicate itself was a crystal.”

The first heartbeat in a human embryo occurs at approximately 28 days when the embryo is about one-third of a centimeter in size, before any nervous system develops, driven by the heart tissue's intrinsic self-excitation rather than neural instruction.

“The first heartbeat in an animal as complicated as us occurs after about 28 days of an embryo. The embryo at that time is no more than perhaps a third of a cimeter in size embedded in the mother's womb. It has to start that early because oxygen and CO2 can diffuse over relatively tiny distances a few microns. So as soon as the multisellular organism has become that size at which it becomes impossible for oxygen to diffuse to the center CO2 to diffuse out without a circulation that's when the heart is needed.”

Spinoza wrote that a tiny worm living in the bloodstream would perceive the motion of blood particles but would not understand the purpose of circulation—a metaphor for the difficulty of understanding wholes from parts.

“Spinoza wrote in Latin... 'Seriously plulum conceive if you wish a tiny worm living in the blood and it will perceive how the individual particles of blood move around within the blood but it would have no idea what the purpose of the circulation is.'”

Self-excitation—the ability of a biological system to generate automatic cycling processes indefinitely without external instruction—is a fundamental biological principle that must have operated at the origin of life itself.

“In a biological system always the possibility that it might generate an automatic cycling process. In another sense, what I was showing was a fundamental process that must have been operating at the very origin of life, the ability to self-excite and to continue doing so indefinitely.”

Biological relativity is the principle that two-way causation operates at all levels of organization: nothing exists in isolation; every component exists in relation to and constrains other components; this applies across scales from molecular to social levels and explains how higher-level organization constrains lower-level molecular behavior.

“I formulated that as a principle of biological relativity. It sounds like a long word, but all the word relativity means...is two-way causation is that nothing exists in of its own. It's already always relative to what it can interact with.”

There is a crucial distinction between association (correlation) and causation in biology: in Noble's heart rhythm research, blocking a protein mechanism that contributes 80% of electrical current to the heart's pacemaker potential causes only a 10% change in heart rate, showing that association strength (80%) bears no relationship to causal contribution (10%).

“I'd found not just five protein mechanisms involved in heart rhythm but at least 55 or maybe 555...You can knock a key one out that was known by our experiments to contribute 80% of the electric current...You can block that and only a 10% change in frequency occurs. What it tells you is there's a difference between association 10% and causation 80%.”

The self is not a 'thing' located in the brain but a 'process' that emerges from communication and interaction with other beings; feral children who grow up without human interaction do not develop human minds even though they have human brains, showing that selfhood requires social interaction and cultural context.

“We define who we are by interacting with other beings. The little bit of evidence we have on feral children...they don't behave like a human...They have not acquired the cultural environment in which we as babies grow up within our families...there isn't a human there. There's the form of a human, but it hasn't got the mind of a human.”

Organisms live at the interface between order and chaos (disorder); they control lower-level disorder (stochasticity, randomness, errors) to generate higher-level order; without this harnessing of randomness, learning and evolution would be impossible.

“life lives on that boundary between order and chaos between order and disorder...harnessing...the control of disorder at lower levels of organization in our bodies to produce the order that we see...using stochasticity to produce the order that enables us to live.”

Darwin himself (1859 onward) recognized that organisms communicate characteristics acquired in life to the next generation through the germ cells (egg and sperm), which is a Lamarckian idea that has been scientifically validated within the last 20+ years.

“The curious thing is that idea goes back to Charles Darwin 1868. He didn't see and couldn't with the microscopes of the day the particles that he postulated, but he knew that cells had to communicate to each other because he thought that we could communicate body characteristics to the germ cells, the future egg and sperm. That's a Lamarian idea. But the point I'm making is that the idea that cells tell each other, I'm part of this tissue. I think they're doing that all the time and that's what produces the integrity that's normally there.”

Richard Dawkins himself acknowledges we can 'frustrate our selfish genes' through education, but this creates a paradox: if genes are truly selfish masters, how can we override them? The answer: genes are tools of the organism, not masters—Dawkins' own statement contradicts genetic determinism.

“Richard Dawkins says this too. We can frustrate our selfish genes. He writes, 'I have to ask myself the question, how does that work?' Well, he said, 'So, we can educate our children. Let us educate our children because we're the only species that can do this.'”

Quantum mechanics and general relativity remain fundamentally incomprehensible or mathematically incompletely formulated; Roger Penrose stated that 'we don't even understand quantum mechanics,' suggesting we may need to accept limits to what science can explain.

“I've actually discussed this with Roger Penrose... what he said in that discussion because I put to him the question directly. Do you think that quantum mechanical processes... Do you think that's the basis of consciousness? No. No, it's worse than that... He said, we don't even understand quantum mechanics.”

To solve major biological problems (cancer treatment, disease prediction, aging), biology must abandon reductionism and accept that agency, purposiveness, and multi-level organization are real features of life, not eliminable by better physics.

“I think that means that it's going to be necessary to change tac in the way in which biology is conceived and the way in which it is done. And that is going to include accepting the existence of quite a lot of things that the usually reductionist analysis denies even exists.”

The Human Genome Project's promise in 1999 that genomic knowledge would enable cancer cure within 10 years has completely failed to materialize, indicating a fundamental error in the assumption that genetic knowledge alone can explain or treat disease.

“We were led to believe in 1999 when the whole thing was about to be announced as the first sequencing of the human genome...within 10 years we'd be able to cure your cancer has not happened”

Young scientists today face funding barriers when they try to pursue research questions that challenge reductionist orthodoxy; Noble mentors young scientists globally and helps them navigate this barrier by encouraging them that challenging paradigms is legitimate despite institutional pressure.

“What can we do to swim within this environment in which you can't even get funding if you want to do that? Tragic...I've examined thesis where people have been clearly knocking against the dogma of the times. I've tried therefore to give encouragement to those people by forming a group and they meet from time to time.”

Rogue cancer cells exist in our bodies all the time because cell division sometimes fails to complete error-correction before dividing, creating defective cells; normally the immune system kills these cells, but a fine balance must be maintained between immune power (which can cause autoimmune disease if too strong) and tolerance.

“my concept of cancer is that can there are potentially cancerous cells all the time because come back to that cell division occasionally does go wrong and it starts to divide before the accurate replication has been completed when that happens you get a defective cell. Often that will just die of its own accord, but sometimes it will survive. That will be happening all the time in the sense that a cancer is a rogue cell. Rogue cells exist all the time in our bodies. But what does it normally experience? The immune system comes and kills it.”

Evolution requires processes faster than random mutation because natural selection alone would take approximately 30 billion years longer than the universe has existed to produce the complexity we observe.

“Something has to speed evolution up. And that's what Darwin realized. There has to be other processes that short circuit the extremely slow process of random change in the genome.”

Francis Crick's central dogma of molecular biology—that DNA sequences determine protein sequences, which determine structure, which determines biological function—is incorrect because it omits the role of the living cell in controlling both DNA replication and protein function.

“from a sequence in our genes you generate a protein. The protein then forms a structure which is determined by the sequence and finally that produces the function of the body. So everything could be predicted from what happens at the level of DNA. That is impossible.”

Michael Levin's xenobots (reconstructed frog skin cells) demonstrate cellular agency: when isolated from their normal frog skin environment, these cells reorganize themselves into new multicellular structures, develop novel behaviors (using cilia to swim and seek food), and pursue survival goals—showing that cells possess intrinsic purposiveness independent of developmental context.

“You can take cells from the skin of a frog, isolate them from their environment, which is the frog skin...There's just a little bunch of us, maybe five cells, but we've got to feed. What do they start doing? They start using their little wavy pilia on the surface of the cell to swim in the environment to see where they can find food. They're already an organism.”

Neo-Darwinism is fundamentally incorrect and should be replaced with 'true Darwinism,' which combines natural selection with recognition of agency, intention, and Lamarckian transmission of acquired characteristics—mechanisms that Darwin himself described but that modern synthesis evolutionary theory explicitly excludes.

“True Darwinism includes natural selection...together with Alfred Russell Wallace...But nearly 10 years later, he knew that there was something missing...he explains that the body communicates change to the future egg and sperm. That's the Lamarian idea...Physiologists have found that for at least 20 years now. So we've been in conflict in a sense with standard neodyarwinism for that period of time.”

Artificial intelligence, regardless of processing power, cannot replicate human behavior because it cannot harness stochasticity (randomness) in the way biological systems do; specifically, AI operates only on past information (what is written about or recorded) while humans can do things they've never done before and don't yet know what they will do in the future.

“The AI can only work on the basis of what's written about me or what I've written. So if even I can't say with any certainty what I shall be saying in two years time, how on earth can an AI system determine that I will do X? It won't...as organisms we have that...knowledge that we can actually do that. I can say I don't know what I'm going to do in two years time and live with that and know that it's up to me to find out”

Nature itself took three billion years to solve the problem of creating water-based computational systems (biological life); creating artificial life using water-based computers rather than silicon would require either emulating that evolutionary process or discovering the principles that biological evolution discovered, which remains beyond current technology.

“he seems to think I'm rather pretty and nice. Well, honey, the problem is that I don't know how to make computers out of water. Nature did that. It took three billion years to do it. And I have no idea how to copy that.”

Francis Crick's central dogma formulated the one-way causation from DNA to proteins to function, but this followed Schrödinger's 1942 hypothesis in 'What is Life?' that life might replicate like a crystal; the 70-year-old dogma has persisted through Crick's influence and Richard Dawkins' 'The Selfish Gene' popularization.

“It was actually Shreddinger who formulated that idea way back in 1942 when he wrote a book called what is life?... And that has continued all the way down the 70 years or so since as a kind of dogma reinforced by what Crick did in his central dogma, but made into a popularization by Richard Dawkins and his extraordinary book, The Selfish Gene.”

The essence of the self is not inside us but out there in our social relationships and cultural expressions—poetry, drama, music, dance; these are not ephemeral but fundamental to human nature.

“the essence of us is out there in our social relationships. We're back into culture. What is that? It's the culture and it's there for the poetry, the drama and the music and all the other the dance.”

The immune system generates new antibodies to viral threats by directing cells to mutate their immunoglobulin genes, selecting successful variants, and reproducing them—a process showing cellular agency and intentionality in response to environmental challenges.

“the immune system during the COVID pandemic knew that it had to find new imunoglobulins and told its cells mutate please make new imunoglobulins and then selected out of those the few that succeeded asked them to reproduce.”

Cancer can be understood as rogue cells exhibiting agency similar to Levin's xenobots—searching for survival strategies—which is why cancer cells adapt to radiation and chemotherapy by finding new genetic survival mechanisms, making cancer difficult to control.

“cancer is an organism within the organism. It's a group of cells that have done what his zenobots, as he calls them, his frog skin robots are doing. It looks for its own way of surviving. And actually, the more we invade it with radiation or with chemotherapy, the more it will find ways of escaping all of that, which is why we manage to push cancer back for a few years, but very often, not always, thank goodness, but very often, it just starts to come back again. And the reason for that is exactly what happens in those Zenobots of Mike Levan. They start radiating their way of changing their genes to look for ways of surviving even better. That's what a cancer does. It's why it's so difficult to control.”

Francis Crick searched for the neural substrate of consciousness in the claustrum (a brain region with widespread connections) assuming consciousness would be localized; but consciousness (the self) is not a thing located in a part of the brain but a process involving whole-organism and social context.

“Francis Crick...took the cluster out of my brain the cluster is a tiny part of the brain which has the property that is connected with almost every other part...perhaps there you've got the neurological form of the self, me...if I take my body alone and it never had any communication with other humans, I would not have a human self.”

Quantum mechanical processes (like wave function collapse) are sometimes proposed as the basis of consciousness, but Roger Penrose argues 'it's worse than that'—we don't even understand quantum mechanics itself, so we cannot use it to explain consciousness; attempting to ground consciousness in poorly-understood quantum effects is circular reasoning.

“Do you think that quantum mechanical processes like the collapse of a wave function...is the basis of consciousness? No. No, it's worse than that. I looked at him. Okay, how is it even worse? He said, we don't even understand quantum mechanics. That explains why we can't compute it. If we can't even compute quantum mechanics, how can we use quantum mechanics to compute us?”

Richard Dawkins said 'We can frustrate our selfish genes' and argued for education as the mechanism by which humans can transcend genetic determination; this acknowledgment of education comes from Descartes' insight that the soul/self can control the body.

“Richard Dawkins says this too. We can frustrate our selfish genes. He writes, 'I have to ask myself the question, how does that work?' Well, he said, 'So, we can educate our children. Let us educate our children because we're the only species that can do this.' Where does that idea come from? Can you believe it is Daycart?”

Richard Dawkins' 'The Selfish Gene' is 'a fabulous story'—it's compelling narrative—but it is 'completely different from what actually happens in biology'; it oversimplifies biological causation and has become a cultural narrative that influences how people understand themselves and behave.

“The Selfish Gene. It's a fabulous story. It's just completely different from what actually happens in biology.”

Approximately 70% of proteins formed from genetic sequences can fold in multiple different ways, and which configuration a protein adopts depends on the cellular environment, not solely on the DNA sequence; the same protein can function as an enzyme in the cell fluid or as a transporter in a lipid membrane, depending on its location.

“70% of the proteins formed that way can be folded in many different ways...proteins fold according to their environment. You can even show that the same protein can be present in the fluid of the cell and act as a simple enzyme...and at the same time if it happens to find itself within a lipid membrane...it can be a transporter...it can be both either just depending on the circumstances.”

Baruch Spinoza proposed that all of nature is a unified whole (God/nature) and rejected Descartes' mind-body dualism; his correspondence with the Royal Society included the argument that a worm living in blood could perceive individual blood particles but would not understand circulation's purpose—illustrating the problem of understanding higher-level organization from lower-level perspective.

“Spininoza...he was in Amsterdam eventually...he entered into correspondence with the early secretary of the Royal Society...he wrote in Latin...Seriously plulum conceive if you wish a tiny worm living in the blood and it will perceive how the individual particles of blood move around within the blood but it would have no idea what the purpose of the circulation is.”

Medieval Troubadour poetry (specifically Arnaut Daniel's invention of the sestina) demonstrates that artistic form can be mathematically organized while maintaining emotional and romantic meaning; this shows that meaning-making is compatible with mathematical structure and precision—relevant to bridging science and humanities.

“medieval poetry of the Trouidors...Arno, Danielle...He invented the cestino which is the way of arranging the rhyming words in a sixline stanza to have a different order in each of the six verses according to a mathematical formula...it's the beginning of Dante writing the purgatorio the inferno and the paradiso of the divine comedy.”

When exercising, muscles send messages via these molecular tube-trains to the nucleus instructing the genome to make more myosin (muscle protein) and actin (another muscle protein); this bidirectional causation—body commanding genome—contradicts the central dogma's one-way flow.

“When I exercise, I'm telling my muscle cells, please make more protein. How do they do that? They send a message along those tube lines to tell the DNA in the right place in the nucleus to make more meiosin which is a muscle protein and more actin which is another muscle protein.”

We cannot verify metaphysical claims about the universe beyond observable bounds; once reasoning crosses from physics to metaphysics, we must accept limits—but this does not invalidate metaphysical inquiry, which complements science.

“But what else has happened elsewhere in the universe is very difficult of course to know. We can speculate but that's where we pass across the boundary to metaphysics rather than physics.”

Barbara McClintock discovered in the 1930s-1950s that corn under environmental stress (drought) rearranges its genes—moving genes from one chromosome to another—a process she could visualize under the microscope and which contradicts the central dogma's assumption of static genomes.

“It had actually been discovered nearly a hundred years ago by a very famous American geneticist called Barbara Mcccleintok. She showed looking at corn growing in conditions of drought and any other factors that influenced its environment, putting it under stress that suddenly the corn starts to do exactly that. It juggles its genes. It actually moves genes from one chromosome to another. She could see all of that under a microscope watching the chromosomes.”

Spinoza (17th-century philosopher) proposed that nature is a unified whole expressing the divine, rejecting Descartes' mind-body dualism, but was excommunicated from the Amsterdam synagogue for this theology.

“Spinoza is extraordinary. He was incidentally Jewish in origin and must originally have come from the Spanish um environment uh Toledo or wherever it was in Spain. and he was in Amsterdam eventually um as Benedict Espinosa and he entered into correspondence with the early secretary of the Royal Society in England which is the National Academy of Science.”

Descartes proposed that the body is a mechanical automaton controlled by an immaterial soul, an idea inspired by the 17th-century water-powered mechanical devices (early water computers, robotic toys) being constructed in wealthy gardens.

“He was impressed, as many were amongst educated people at the time, with extraordinary things, constructions that had been made in the gardens of the rich. Effectively, robots had been created from tiny tubes that were making them move in particular ways... they were using early water computers if you like causing mechanical toys to behave like robots even making sounds”