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

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.

The mathematics of it all tells us that something needs to influence it. Yes. To move faster. It's that otherwise it would take far too long. This is Leiden, the Netherlands, where I attended a lecture by Professor Dennis Noble, who argues that biology has to break free from dogmatic thinking. A dogma in science. Come on. But it's not a joke. It's one of the most important errors ever made in science.

Noble is known for his cheerful yet fierce attack on the central dogma in biology. The idea that organisms are fully covered by genes, which got popularized by Richard Dawkins. Extraordinary book, The Selfish Gene. It's a fabulous story. It's just completely different from what actually happens in biology.

We're here to celebrate the completion of the first survey of the entire human genome. 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. This is the most important, most wondrous map ever produced by humankind. It's an assumption that everything flows according to DNA self-replicating. That simplistic analysis has failed to explain what we need to explain. Where does the instruction come from that the heart receives to do its beating? There's none.

Noble developed the first mathematically based model of cardiac cells and one of his key insights was that there is no mass or clock or oscillator to be found in our genome. Instead, there seems to be agency on a cellular level to account for our heartbeat. Purposiveness, agency, as we would like to call it today, is central to understanding any living system. The body as a whole can tell the genome what to do. So what I'm saying is that both replication is dependent on the living cell and the function of the proteins is dependent on the living cell. Neither automatically follow from the DNA alone.

Instead of viewing evolution as a blind, meaningless, and bottom-up mechanism of nature, Noble argues for biological relativity. Oh, that's it. Yes, exactly. I formulated that as a principle of biological relativity. It's two-way causation. We have such a strong tendency on we want to plot agency somewhere. Exactly. And and and your image makes that difficult, right? Because it's impossible. There's no way. It's everywhere and it's nowhere. Is that a way? It's everywhere and nowhere. Is the yin and yang and that the essence of us is out there.

A very warm welcome to the Asencia Foundation's YouTube channel. I have the honor of sitting down in Leiden with Professor Dennis Noble. A very warm welcome. Great pleasure to come and talk about whatever you want me to talk about. That's amazing. I just uh heard you present here at a conference about biosemiotics. We will touch upon that. Yes. But maybe good for audience for people who do not know you. You're a pioneering physiologist and emeritus professor at Oxford and in the 1960s you built the first computational model of a living heart cell and you've spent basically a lifetime showing how organisms aren't just driven by genes but by dynamic networks across different skills. And in your latest book that you wrote with your brother, brother Raymond Noble, Living System, that I really enjoyed reading, you summarize all your arguments against the popular reductionist idea of the the selfish gene. So nice to touch upon all of that. And good to know that our audience watching is interested in philosophy and metaphysics, but I think your work in a brilliant way will bring us to those topics. I think it's Yes, I understand where you're going. Yes, maybe good to start with the beginning of life. How does our life really start? What causes our very first heartbeat?

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 centimeter 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 multicellular 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. Now, at that time, the embryo is nothing more than a ball of cells. That's remarkable. A tube form, which pumps peristaltically is the word we use, but it means the tube itself has a wave of contraction forcing the fluid around that tiny ball of cells. But at that time, there is no nervous system. And that's important because each of our muscles in our body, like our arms, legs, head, and so on, is moved by instructions from the nervous system to do what I'm now doing. Where does the instruction come from that the heart receives to do its beating? There's none.

And 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. Now, nowadays we talk about autocatalytic reactions. It's a long word, but it just means that something self-propels itself. But we didn't have that idea way back in 1958. So they stopped me with one absolutely fundamental question. They looked at my equations and they said, "Where, Mr. Noble, in your equations, is the oscillator?" You see, their mindset was, if he's going to produce this, there must be something that forces the system to do this. Whereas actually, the question was, nothing does. So how does it happen? How could a system excite itself? And they were not really persuaded, but they did say, "Okay, you've convinced us you've got a problem. We don't know how you're going to solve it, but we will give you some time on the computer." And well, it worked. I got a paper in Nature, one of the top science journals, showing that indeed it self-excites. There is 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.

Yeah. And this is so there's a lot in here for people who are not are new to these terms. Self-excitation. Already the word self, it implies that there's some form of agency. Which when I say that, of course, is is already a bit sinful. I I think in evolutionary biology, you're not allowed to think that way. Yeah. In 1958. You call that also in your book, or it's known as the teleological sin. Maybe indeed it is. That's right. You were not allowed to think like that. Um, 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, 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. I've come to realize that after another 40 years of work before I actually retired from my position at Oxford University and became what's called an emeritus professor. But that was my freedom. I could at last ask myself the audacious question, was that really true?

Francis Crick is one of the greatest molecular biologists ever, ever, together with Jim Watson and Wilkins in London. And we have to remember also Rosalind Franklin, who actually did the experiment to get that X-ray picture of DNA as a double helix. Yeah. And to show that that's exactly what it is. And that was brilliant. And I don't challenge any of that. I think all of that is brilliant molecular level discovery. But he then went on to formulate it as a dogma. He called it the central dogma of biology, which is that we can relate everything back to genes, everything back to DNA. That that codes. Exactly. So you need nothing more than that. Now, which is what Schrödinger had predicted, right? Schrödinger. It was actually Schrödinger who formulated that idea way back in 1942 when he wrote a book called What is Life? Yeah. 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. Students in school often take a saturated salt solution, let it evaporate slowly, and you watch the crystals forming at the bottom of the solution. It's fascinating. It looks like magic. Yeah. It looks like magic. The crystals, lovely. The children love crystals anyway. Caves and goblins and goodness knows what. Yes. So it's all to us as children, very exciting to see that. But what Schrödinger said in his book, well, maybe life does that. It just replicates like a crystal. 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. It's a fabulous story. It's just completely different from what actually happens in biology.

You're you're now even being polite, I think. Well, I've spent the last 20 years of my work working out precisely what I've just said is true. Yeah. First of all, the idea that something replicates itself. True, crystals do that. You don't need a tele-crystal to do it. As soon as the amount of water has evaporated off, that makes it impossible to hold those molecules in solution, they will enter into the right place within the crystal. That happens. And of course, it's automatic. And when you think of the genetic material, DNA, it is a little bit like a crystal in the sense that each of our nucleotides will attract its pair. They're linked together, A T C G in pairs, and they like to be together. That's a chemical fact. We don't need to. We use the word like, but it doesn't mean quite what we're saying when we like somebody, but it is a bit like because they pair together. Okay, that's pure chemistry. And about a dozen years ago, chemists actually checked if you unravel the DNA in a dish without a cell, how does it replicate? And it does. M. And the titles of their papers are interesting. One of them refers to the efficiency of self-replication chemically, and the other with a very similar title for RNA. One did DNA, the other RNA. And they measured the accuracy. And that's the key. It's about one error in something like 10,000 pairs of these CGs, A's and T's. Yeah. Which sounds pretty accurate to me. It's pretty good. And that's why the title of the paper is efficient replication. Yeah. 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. It would be in effect fated to to die. And of course, the rest of the population of cells would use the energy and the components. So it can't be how it's done. But what actually happens would have utterly surprised Schrödinger, who formulated this idea in the first place. What actually happens is that under the guidance of a living cell, around seven enzymes, these are proteins that cause a reaction to occur. In this case, the reactions are to cut the DNA and to paste a new nucleotide in. So they're called cut and paste enzymes. And they literally creep along this extraordinarily long thread, which is the DNA, locate where the errors are, take out the nucleotide that's wrong, and put the right one in. It's utterly extraordinary. 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? I don't think we know yet. We don't know. If how do those enzymes know where when they encounter an error? Ah, well, no, they can. That we do know. You see, you're back to the double helix formation. Yeah. You can check what is in the other thread that's now unraveled, but it's still there. Okay. So you get the information that there's an error from that, and you know then that you've got to replace that nucleotide. The moment the cell knows there are no errors anymore, we can now divide. How, how does the cell know that moment? That that's the bit we don't know. See, I don't think anybody at the moment. I'm not an immunologist, so may not be able to know everything, but let's um make a guess. Somehow the cell as a whole has got to be ready to start the division process. That's when the membranes actually fold in on each other. And two cells appear. And the DNA has also got to be separated, sometimes mixed together if it's sperm and egg, exactly what happens. But I don't think at the molecular level we know exactly how a cell can be said to know the time has come to divide. But it won't do so until that is the case. If it does do so, the two daughter cells will be fated to die. So they will they will never be used. But biochemically speaking, we do not know of a way where it could be coded. I don't think we do. No. I'm talking from my knowledge. Yeah. Whether somebody else already knows that, I don't know that they do. I think they would have won a Nobel Prize if they had found out.

Let's for people watching uh who are more uh interested in genes and have always been sort of taught this more classical story that most of us think of when we hear about that it is all in our genes. So just to provoke you a little bit, we have Dolly the sheep, I mean, a clone from a single single cell. Um, we can insert certain um I found this in this example of a green fluorescent protein from a jellyfish into a mouse that then starts glowing. Yeah. Um, there are all these these wonderful examples of how it does seem like genes are the code of life and of okay, the cell might be sort of the computer we need to sort of compute it, but the genes, it it surely looks like the genes are the code of life. Professor Noble. So, yes, sorry. I know that's what people tell me, you see, and I say, "Well, wait a minute. If the genome cannot self-replicate, which I've just demonstrated, that's yeah, you're in trouble because you need life in order to make that happen." So already you're in a situation in which a very important function of genes, which is to replicate, to go to the next generation, depends upon the living cell. Think that through first of all. Second, another problem which we've not yet discussed. 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. This has been brought out quite recently. The degree to which protein folding, which is how it works chemically, because that's how it, for example, the protein that grabs a virus formed by the immune system has a particular shape which is designed, I use that word advisedly because I think it is is designed to fit that virus. And that is not determined solely by the genome, partially by because that's how the immune system generates a new grabbing protein that enables that particular virus to be grabbed. That's why it takes us about a week to become naturally immune to, for example, the COVID uh during the COVID pandemic. But if you ask the question, are proteins automatically folding according to their structure? The answer is no. They 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, meaning something that speeds reaction up that's necessary for our generating energy. And at the same time, if it happens to find itself within a lipid membrane, one of the membranes of the cells, it can be a transporter. It can be both, either, just depending on the circumstances. Now, why can it do that? One of the great successes of the human genome project when it was first announced in 2001 with a big paper in Nature. There's a figure in that paper which shows the evolution according to the species in which they were investigating of the way in which proteins have generated additional functions by adding a new functional bit of amino acid sequence to their structure. That's gone on over the billions of years of evolution. Proteins have evolved to have multiple functions, but which they serve is dependent on the living cell. So what I'm saying is that both replication is dependent on the living cell and the function of the proteins is dependent on the living cell. Neither automatically follow from the DNA alone. So I'm very happy to have that question. Yeah. And be told that surely it's just automatic that the genome specifies. I now lecture worldwide on genes are not the blueprint for life. I was asked, in fact, to write an article for Nature last year.

2024, I think. Also, the point in your conversation to relate back what you told earlier that it needs error correction on a cell level. That to me, that is very is pretty convincing. What puzzles me is this question of agency. That the the I'm just thinking, okay, so the the the cell wants something. The cell has purpose. The cell. Would you go along with terms like that terminology like that? Yes, I think you have to because in the end, you have to use terms that mean what we say. In this case, what we are saying is we do not know how the cell generates the intelligence it clearly has, but that it has it is obvious. It doesn't divide until it knows that the genome has been accurately replicated. And the current microbiology, physics, even cannot give us a mechanism here. Not not at the detail of the molecular biology. No. But what we can say is that that process clearly exists. So without working out exactly in detail how it happens, we can be certain that it is there. Now, we do get some parts of the pathways. Physiologists now do the following kind of experiment. How can a cell that on a molecular scale is enormous? If I represent a single nucleotide in one of my genes as the size of my fist, and this here in Leiden was the center of it, the nucleus, then the cell surface for that single cell would be over there in Paris, quite a distance, 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." Now, how do we know that? We know that because physiologists have been able to follow what happens when calcium enters another kind of protein channel at its cell surface way back there in Paris. And underneath the membrane, the calcium rises to a higher concentration. That triggers a biochemical reaction. We don't need to go through the fine molecular details of that, but that puts a messenger on a motor. Believe it or not, there are motors that walk along tubes in a cell. There are tube trains. I've seen those images. It's crazy. It's literally a motor on these two wheels. Yeah. They they literally walk. Yeah. Messaging. If somebody had told this to Schrödinger way back in 1940, could he have even? Oh, come on. No, this is not possible. But it is. 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 myosin, which is a muscle protein, and more actin, which is another muscle protein. That's how they do it. And so that dogma or what's it called, the the the whole idea that it's only one chain of causation from genome to RNA to proteins and then the and then then the organism or the the organ. You say it it works both ways. So these passengers, it has to. Okay. It has to. That's right. There has to be feedback from the higher level of. Now, wait for it. I'm going to use. It has to. But it has been it's this has been established. Right. It's been established that is necessarily true. Yes. Because that's how the immune system works. But if you ask the question, do we know the full molecular details? No. We know about those tram lines going all the way from Paris to Leiden. Yeah. Yeah. In our metaphor, for a moment. Yeah. But if you ask the question, what exactly is the structure that is the messenger in that case for, let's say, telling the muscle proteins to make more protein? Well, the muscle gene coding for those proteins to make more of those proteins. Well, we'd probably know that the messenger is probably an RNA. That is another kind of nucleotide sequence, possibly existed before DNA. But let's not worry about that technical detail. We can probably guess it would be one of those. There are many RNAs. The the genome in fact produces more RNAs than it produces proteins. Yeah. That's difficult too. Those should be called genes, too. But don't we don't because that's not the way our discoveries occurred. Anyway, however one puts all of that, yes, you can make good guesses as to what would be going down as messengers on that little tubulin going from the cell surface to the nucleus to tell it what to do. But in every single case, we won't know the precise molecular details. That's for people to work out in the future. Yeah.

But but your work, what I find astonishing is that or or just very nice to see how science operates that to be science operates on the questions we permit permit ourselves, right? Yes, indeed. And that of course relates back to metaphysics, what our foundation is about. It was the work of Michael Levin, who's been inspired by your work to think, hey, wait a minute, if it's not all coded in the genome, and interested in bioelectric fields, who has now been able in the lab to show by influencing bioelectric fields that basically influencing the messenger in Paris that I want this. And what he wants is like a different organ, even. Indeed. So yes. And which is crazy, right? It I'm just curious what your thoughts here on his work, how it relates to your thinking. Yes, well, first of all, it's absolutely phenomenal what he's showing. 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. Incidentally, we ought to often think of skin as well, just what makes us look beautiful if we are or handsome if we're not. Laughter. You hope. But anyway, it's not. It's extraordinarily sensitive. But I'm just doing this at the moment to feel what I'm feeling. Extraordinarily sensitive structure to heat, sound. That's the way our ears work. All the various receptor processes occur at the surface. And cell surfaces too have got ways of detecting what is happening. And so they're able to detect. For example, in Michael Levin's work, 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 cilia on the surface of the cell to swim in the environment to see where they can find food. They're already an organism. Wow. Together, together. Now that brings me to cancer. So I think one of the big implications of Mike Levin's work is the insight cancer is an organism within the organism. It's a group of cells that have done what his xenobots, as he calls them, his frog skin robots, yeah, yeah, 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 xenobots of Mike Levin. 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. Yeah.

But it does, doesn't he sort of his work point to a like a paradigm shift in treating cancer? Namely, that we can tell those cells, tell those cells to stop by influencing bioelectric fields? If we can, that's what the immune system tries to do, of course. The immune system has a huge role to play. 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. Now you've got a problem. How does it know what to kill and what not to kill? If it's ramped up too much, you get autoimmune disease. There's a fine balance between giving the immune system too much power, in which case it will kill the body itself. Yeah. And giving it enough power to detect all of those defective cells and kill them. That's very characteristic of living systems that they have to make those very difficult decisions, a balance of what what what degree of power do you give? Yeah.

Philosophically, it it really interests me that when talking about Michael Levin, thinking about his work. Yes. I also had a moment, thoughts. Cells have to forget, forgive, sorry, forget, sorry, 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 vesicles. These are tiny packets of cell information. And cells are exchanging these all the time. 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 Lamarckian 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. But when it goes wrong, of course, it produces a cancer.

You seem to be uh wanting to rehabilitate the true Darwin. I mean, I just heard you say in a presentation that you said neo-Darwinism is dead. Yes. Laughter. True Darwinism is far from dead. Exactly. So tell me about what what is true Darwinism? True Darwinism includes natural selection, which of course is his original great contribution together with Alfred Russell Wallace. They did that together in 1858. And in 1859, Darwin published his famous book, The Origin of Species. But nearly 10 years later, he knew that there was something missing because even in The Origin of Species, he explains that the body communicates change to the future egg and sperm. That's the Lamarckian idea, which is that characteristics developed in us can be transmitted down to future generations. Physiologists have found that for at least 20 years now. So we've been in conflict, in a sense, with standard neo-Darwinism for that period of time. Now I come to what Darwin did. He not only thought there may be communication between cells in the body, but he also thought, well, wait a minute. What is that magnificent peacock doing when it opens up its wings and the peahen sees what is it, 40 or 50 eyes staring at it with great translucent fluorescent coloring? He thought, well, it's trying to tell that peahen, "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 peahen. And then a bit later in the same book, he writes, "The peahen can do it too." Of course, in a different way. She's not spreading enormous um beauty. Yeah. As the male does. It depends. Some species have it that way round. The males carry the beauty and the females don't. In us, it's the other way round. And people watching will just think, I mean, like just like a surface understanding of of evolution that has been just like the trial and error of nature ending up with a beautiful um. Exactly. So well, if you give evolution as natural selection enough time, but that may be 30 billion years longer than the existence of the universe. Something has to speed evolution up. Ah, that's what Darwin realized. There has to be other processes that short-circuit the extremely slow process of random change in the genome. Ah, can we can we sort of account for that mathematically for this point that that ma the mathematics of it all tells us that something needs to in something needs to influence it? Yes. To move faster. It's that otherwise it would take far too long.

Let me give an example back to the human genome sequencing in 2001. What that showed was a comparison between the human genome and the genome of a yeast cell, that's a single-cell organism, fly, worm, through to the mouse, and then human. At that time, 2001, we had last had the genomes of all of those. They did a very simple thing in figure 42 of that paper. They represented the proteins that arose. Well, they were particular proteins. They're called transcription factors, but don't worry about the detail. They took particular types of protein and 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 McClintock. 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. She didn't know about DNA in those days. This is way back in the 1930s, 1940s. 1950s is when we got to know about DNA. And she was eventually awarded the Nobel Prize in 1983. And 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. Now, we don't necessarily do it consciously. But to come back to Darwin, we're now back to the peacock displaying its beautiful feathers for the peahen to appreciate, convince it to mate. He wrote that the peacock was intending to do that. He had the concept of agency. He didn't use the word agency. But what is intention? It's precisely that. I think that a very big mistake has been made since the central dogma was formulated way back in 1956. And that's the idea that purposiveness, agency, as we would like to call it today, is central to understanding any living system. Those xenobots of Mike Levin have got agency, which they have generated from that situation, which suddenly find they're no longer part of the frog's skin. Yeah. And they create the agency to look around with their cilia, swimming away to try and find food. I think therefore agency is something that is fundamental to any living system. How do we explain it? Good question. I don't think we have the evidence yet to say in detail how that happens. Yeah. But that it happens. We can't doubt any more than we can doubt whether the immune system knew, in inverted commas, for the moment anyway. Um, the immune system during the COVID pandemic knew that it had to find new immunoglobulins and told its cells, "Mutate, please make new immunoglobulins," and then selected out of those the few that succeeded, asked them to reproduce. How did it know to do that? I don't think we fully know the answer to that yet. But do we need to know in order to know that it did it? No. We know already. Just as I know that you are an agent, and I'm an agent, and he over there is an agent. Yeah. So there's a difference. This gets on to philosophy, doesn't it? Because there is a difference between admitting that something exists and that something has been explained. Yeah. And it's the purpose of science to try and explain. Indeed. If you assume that our our physical universe, matter, the the just the chemistry of life is all there is, you would need a mechanism. Whereas if you say it there might be an immaterial processes or whatever, you you do not necessarily have to account for everything in a material way. But Right. Well, I'm not sure it's quite so simple as that, but you it's getting there. Yes. There's a difference between knowing that something happens because you see the evidence for it. Yeah. In the intentionality of the peacock, for example, or the whatever it is you're investigating, those xenobots going shooting off and trying to live. The the difference between that and having explained how exactly it does it. Because once you get on to the question of how exactly it does it, you're into the question of levels of organization. Because at what level is all of that integrated? That's what led me to the idea that we have to see systems all the way up and down, all the way up to the body as a whole, and even to the social context in which the body exists, and down to the molecular level. But interestingly, the most constrained level is the molecular level. That's the level at which no choice can be made. H. You can say, in a sense, that a nucleotide chooses to be associated with T rather than G if it's an A. But in fact, it's determined chemically. Once you've got the energy of interaction between those nucleotides, there's nothing they can do other than to do what they do. Yeah. So that is inevitably the most constrained level. As you go up the levels, you get to increasing openness to forms of structure that are open to what the environment is doing. And once you do that, it becomes no longer a matter of chemistry. It becomes a matter of the organization at higher levels of organization. I formulated that as a principle of biological relativity. It sounds like a long word, but all the word relativity means, and even in Einstein, this is what it means, is two-way causation. Is that nothing exists in in of its own. It's already always relative to what it can interact with. Yeah. Matter doesn't exist without a space that it deforms in general relativity to be the space within which the matter moves in the first place. Yeah. I mean, it's two ways all the time. So relativity just means that it's always a relational situation between two parts of a system. And well, you can give it all sorts of names. You can say it's special. That's part of Einstein. It's what leads to his ideas about the speed of light movement through the universe. You can say it's general, which is his ideas about the general properties of the universe. And you could say it's biological because it's the structure of the way in which there's organization within biology to do exactly the same thing. The molecular level being constrained by the next level up. Micro things within cells, and then cells constraining those, and then tissues constraining cells. Organs constraining the tissues. Finally, the organism as a whole constraining itself, and then the social level constraining the organism. So it's all constraints all the way up. Yeah.

I I I printed out this one from your. Oh, that's it. Yes, exactly. In fact, in fact, you can no longer arrange it quite right because it's no longer correct to arrange it as levels like that up and down. It's better to think of it as radiating circles of interaction. Yeah. Because I think once you move to the social level, which is the level where you've got to have meaning-making, you are outside the standard causation between the levels of physical processes. Yeah. And of course, the the big question in thinking about we have such a strong tendency on we want to plot agency somewhere. Exactly. And and and your image makes that difficult, right? Because it's impossible. There's no way. It's everywhere and it's nowhere. Is that it's everywhere and nowhere. Yeah. And you know, this is an insight of oriental philosophy for a long time. What is the yin and yang? It is actually the same idea that each molecular element interacts with other molecular elements in a two-way interaction. The way we detect some of the most invisible particles in the universe, the neutrinos, is to look for the very rare event when a neutrino interacts with another particle. That's how the physicists do it. They build huge underwater caverns of underground, I mean, caverns of water in which to watch this happen. It's so rare. There's dark matter postulated to exist. We're getting into metaphysics now. There's dark matter postulated to exist that we can't see. Physicists already having to at least consider. There might be things we can never detect. There might be matter that we can never detect. But that depends upon first having the concept that all that we can detect is always two-way. Because what do we mean by detect it? We mean we can see it. How do we see it? Because our photoreceptors enable us to see something happening that says that exists. Yeah. And of course, dark matter won't do that because it doesn't enable our receptors to be excited. But look, there are many things like that. There are wavelengths we can't see. Yeah. But many of those wavelengths are seen by a fish or by the squid or the octopus. We can't say with certainty that what we see is all there is. There's a thought. We're trapped in our own our our images, our cognition, our models of the world. Yes.

Hearing you talk also, I've mentioned it maybe too often on this channel, but I'm just fascinated by the work of of of John Wheeler, the the physicist, that this image of relating back to how we started our conversation, that self-excitation. Yes. Of as the universe as a self-excited circuit. Indeed. I think that must be true. It seems to me very improbable that it's just in this part of the universe that something quite phenomenal has happened which is leading to and has led to the existence of you and me and all the rest of humanity and the octopus and the squid and the and so on and so forth. That seems to me to be exceedingly implausible. 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. Yeah. And 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." Absurdity amongst the audience at this idea that these two people on opposite sides of the of the debate were one student and examiner. Anyway, that's all true. But to come back to the point, what people like Richard will do, and others also in the camp of thinking that things can be represented extremely simply without any philosophy at all. Science has not to do with philosophy, nothing. That's what Richard says. Now, my reply to that is very simple. 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. Now, why do I say that comes out of my own work on the heart? 30 years after presenting my work for the first time internationally, actually here in Leiden at a big congress in 1962. So we're fast forwarding to 1992. By then, I'd found not just five protein mechanisms involved in heart rhythm, but at least 55, or maybe 555. Are huge. 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. What it tells you is there's a difference between association, 10%, and causation, 80%. Now, unfortunately, nearly all the associations in genomics, 90-odd percent of them, have been shown to be very small. If you understand what I've just said about the heartbeat, and you extend that to all the other functions in the body, we know why. That is, that the body has many ways of making the same function happen. If it didn't, it wouldn't survive. It's robust. Yeah. It's redundant or survival. Exactly. So, would we trust flying in aircraft if they didn't have backup systems to get kicked in? If the control mechanism has been compromised? Yeah. No. And in the end, of course, the pilot is the key backup. But before that, there is backup in the system to ensure that it will continue to fly, land safely, and so on. So we're used actually in our ordinary living day, every time we fly, every time we drive a a car, for that matter, because cars are modern computers now. Yeah. They are. They are. So you're no longer struggling to turn this. You're getting help from the system that enables this to occur relatively easily. So that difference between association and causation is absolutely universal across biology.

Now I come to the important experiment that was done at University College London two years ago, published in 2023 in the British Medical Journal Medicine. And what they did was to take all the genomic information being stored in the National Health Service in England in what is called the polygenic repository. Now, it's a long name for what is actually very simple. All your genome sequences are there, and all the diseases you later suffered from are also there because the life histories of those people, you can't identify them. So nobody is identifiable from all of this, but you can do statistics on it. And that's precisely what the University College London team did. It's quite a large team that did it, led by a man called Hin Garani. And what 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." That's the hypothesis. It's the cause. Yeah. Together, they function to create a situation in which somebody at sometime has a heart attack or develops a cancer. Both of them possibly fatal. So they pushed those scores into a computation. 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. In effect, what they were saying is, by the same standards that determine whether we accept regulatory wise a new drug proposed by a pharmaceutical company, accept it or not, that is, does it work without too many side effects? There are too many.

Side effects. What you find is that occasionally you predict correctly, but equally, there are a number of occasions where you predict the wrong way from those scores. That's tragic.

We were led to believe in 1999, when the whole thing was about to be announced as the first sequencing of the human genome, that within 10 years, that was the prediction by the leaders in the United States of the human genome project, within 10 years, we'd be able to cure your cancer. Has not happened. And you see what my kind of physiology has done is to explain why that's the. That's why I want to get this across publicly, that there's a big problem here.

I think that means that it's going to be necessary to change tack 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. What the biggest textbook of evolutionary biology in the United Kingdom and in America, for that matter, because it's both, um, Futuma's textbook called "Just Evolution," omits which is anything to do with agency. Nothing must be accepted as having a purpose. Well, I don't understand that. I used to understand it about 40, 50 years ago. But in the last 20, 30 years, I've come to the view, no, look, you have to, at some stage or another, admit when you've got the wrong metaphysics. And believe me, the central dogma, the 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. Worse still, it's failed to deliver the healthcare that we thought genomics alone would be able to deliver. That's serious.

And indeed, that is very serious. And also, I'd say on a cultural level, it also have implications on how people live their lives. Right? If I think so, for very good reason, which has been demonstrated too. 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. It's according to what science tells us, right? I pulled the trigger, but I was not responsible. At that time, people thought they'd identified, believe it or not, genes that cause criminality. There are no such genes.

This is Skinner, ultra-behaviorism. I'm afraid so. It is all of that. But worse than that, if you ask the question, what motivated the killing of 6 million people during the Second World War? 6 million gypsies, Jews, and others 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. Just as there are no genes within your gene sequence or mine or anybody else's that will determine whether or not we're going to be schizophrenic.

To take another example, 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. The association is there. It's in the families. But the reason for that is a social reason.

And we have to admit that, I think now, to tackle that problem, you're going to have to give rise to treatment that recognizes agency. Because I think the 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.

You can. And 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? It's Descartes. It's the philosopher back there, three or 400 years ago, who said animals are automatons. But then he realized, well, women mean I'm not. So there must be something, the self, that causes me, the soul, he used the word, of course, the soul, the self, whatever. Um, that enables me to control this body, which otherwise would be a mechanical automaton. Of course, 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.

I didn't know that. The fluidics. They were using early water computers, if you like, causing mechanical toys to behave like robots, even making sounds. I mean, it's quite extraordinary what happened during that period in the mid-1660s. I think artists now doing that with. There's a Dutch artist. Yes, exactly. That's wonderful. So I think it is actually terribly important socially, culturally, to let people realize that agency is real. Without that, you can very easily sink into what I would call an almost depressive view of life. "I can't help it."

And what we see now, I guess, 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. Sorry, I cannot give you, but just do it because it's. But the moment you open up and be and are scientific about it, you have to sort of question your metaphysics.

Well, yes. Well, any good doctor knows the placebo effect is important. And you, as you just said, you critique Descartes. Many, many philosophers do. Uh, to what philosopher do you feel more aligned? I think you mentioned Spinoza's thinking, for instance. Actually. So Spinoza is extraordinary. He was incidentally Jewish in origin and must originally have come from the Spanish, um, environment, Toledo or wherever it was in Spain. And he was in Amsterdam eventually, um, as Benedictus de Spinoza, and he entered into correspondence with the early secretary of the Royal Society in England, which is the National Academy of Science.

And he wrote in Latin. I can even reproduce part of it. "Si plerumque concipere," 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. It was a beautiful statement of the difficulty of proceeding from one level of organization, the particulate in this case. We didn't know about molecules, but the particulate to the general form. But 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. Without both, you can't even begin to get solutions to any of the equations of life.

And he would say, wouldn't Spinoza say that this cut that Descartes made, he, to him, was a unity, that the whole of nature is an expression of of the divine. Indeed he did. Yes. His theology, which has got him, he got him expelled from the synagogue in Amsterdam, just down the road from here, inlight. Yeah. Yeah. Yeah. I mean, it's extraordinary, isn't it? There was a man over there in Amsterdam who thought very deeply about science, philosophy. The two, in those days, were not thought of to be a separate, um, set of activity. But there he was, excommunicated from his own community and thinking still about what on earth is divine. Just extraordinary. Um, it was a sad fact that the Royal Society never accepted to publish what he sent because, well, to come to the point, there, the then secretary, Henry Oldenburg, who himself was from the Netherlands, incidentally, he was suspicious of Spinoza's theology and couldn't feel that he could take the decision to publish his ethics, which is one of his greatest philosophical achievements. But that's what would have happened had Oldenburg agreed to take Spinoza's work and publish it in, what are they called, the Philosophical Transactions of the Royal Society? That's a scientific journal. It's still called the Philosophical Transactions because nobody in those days distinguished between a philosopher and a scientist. People understood you have to do both.

It's just interesting how this dualism, our mind-matter divide, way of thinking still influences us. It does. That's right. It's so hard for us to conceive of that as being one. I think models like these start helping that we say we cannot locate it somewhere. It's everywhere and nowhere, as you, your biological relativity, as you call it. But you do write stuff. For instance, in your latest book, there's a sentence where you say, between brackets, "The watchmaker may be blind." So you're talking about the universe as a whole, I suppose, but she like it's she feels her way in the process of change and intention does not come from anywhere. It's it's definitively what living things do.

Could you explain a bit on this sort of metaphysics which you are proposing? Actually, that's not the first book in which I elaborated this particular metaphysics. That was in fact "The Music of Life," way back in 2006. And it's worth going back to that because I was trying to ask myself the question, was Crick, back to Francis Crick, I'm afraid, was he correct in thinking that if he took the cluster out of my brain, the cluster is a tiny part of the brain which has the property that it's connected with almost every other part, which is why he chose the cluster, have something that connects with everything else, and perhaps there you've got the neurological form of the self, me? So Dennis Noble is there. So I thought, wait a minute, if I've got a pot here and I take that bit of my brain out, forget all the technical difficulties in doing this, and I keep the bit of tissue that I've taken out beautifully preserved. Is it going to be me? You keep it alive. That is easily done because even slices of brain tissue can be made to continue living. So is it me? Well, first of all, I can't even talk to it. That's a big difficulty. I can't even communicate with it. Now we come to another aspect of the self, which is it depends upon that communication. We define who we are by interacting with other beings. The little bit of evidence we have on feral children, there aren't many, but of the few authenticated cases one can take, they don't behave like a human.

These are children who grew up amongst animals or amongst dogs, whatever it might be, monkeys that have adopted them. Very rare that this happens. But what you find is that they don't behave humanlike anymore. They have not acquired the cultural environment in which we as babies grow up within our families. And I think you have to say there isn't a human there. There's the form of a human, but it hasn't got the mind of a human. But that tells a lot about the nature of the self. Again, 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.

Now, I think that's strictly true. If I take my body alone and it never had any communication with other humans, I would not have a human self. I would develop whatever self was appropriate to the being that I had become within the community in which I had grown up, if I had the luck to have grown up at all. But that means, I think, that the self is a process rather than a thing. I state that in "The Music of Life," long before writing "Understanding Living Systems." So what Ry and I are stating there in "Understanding Living Systems" is a a simpler explanation of the same point because we don't need to put it in the form of an oriental system of thought. Even within our own system of philosophy, it doesn't make sense to ascribe a self to the brain alone. And I, there, I lay my case. That is my metaphysics in relation to the nature of the self.

I can follow you and that it is a process. It reminds me of what Alan Watts would say, that we shouldn't talk about a tree, but about treeing, the process of being a tree. Yes. Exactly. So and that knows a community because its roots do that.

What fascinates me though, but this is like purely speculation. And I'll ask you to speculate here, is if we see it all as a self-excited thing, the universe, that sort of gets itself into this process. You write that it's that interface between order and chaos. Yes, indeed. And you write interesting things like, "Nature creates problems." If there wouldn't be, well, how do you put it? If there wouldn't be life, there wouldn't be problems. So it is nature that creates this dichotomy, then starts playing with it, and somehow at this boundary is utterly fascinating.

Absolutely. I think life lives on that boundary between order and chaos, between, yes, between order and disorder. That's the way I put it in a book called "The Language of Symmetry." There is a book. It hasn't sold many copies because most people find it terribly difficult to understand. We'll put it down in the descriptions for people, they can give it a boost. It exists. "The Language of Symmetry" is a book. I'm not the sole author. It was done with a philosopher called Benedict Ratagan and also a popular science writer. But our idea comes from the harnessing, as I call it, the control of disorder at lower levels of organization in our bodies to produce the order that we see that is us. If we are ordered, and most of us are, thank goodness. So we we do that all the time, using stochasticity to produce the order that enables us to live. So I don't buy the idea that we're just the random variation in our genes giving us a phenotype. That's a long word for being us, the properties we have, that we're just that we are in control of what the genes do in our bodies, if we understand the ways in which we can exercise that control.

And to for people to understand that that notion of harvesting stochasticity, it would be that through, for instance, errors being made in the genome, an antibody can be presented that the cell knows, "I need this one." Right? So it is out of these errors that you see, this is what I need. Indeed. Then that error becomes the solution. Indeed. So and an error becomes the solution. And 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. He said that way back in 1950.

And now the machines, AIs, rely for a great part, I think, on our, uh, randomness, the human input on these machines. They're harnessing all of that information. But of course, and you write, you have a very interesting story, a love story in your latest book about that. We could of course conceive of machines that have random number generators in them. So wouldn't we then have sort of that stochasticity you're talking about? Yes. Our story of the, um, poor girl who is not really a human. Her brain is a silicon chip system. It imagines her saying eventually, "Oh dear, I don't understand my boyfriend. He asked me, 'What's my purpose in life?' Well, I think my purpose in life is to make him happy, and I do. But he doesn't seem to think that's enough. And a few days ago, we had an argument about it. He even hit me across the face just to stop me smiling because I used to just smile every time he got upset with me. It worked beautifully until that day yesterday. And so I asked myself, what is the difference between me, a robot inside a human body, and a girl? Am I like a doll to him? Oh dear. I go back to my maker and I say, 'Look, I've risen and encountered a major problem. Could I not be made of water like him?' And my creator says to me, 'Well, honey,' he calls me that, 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. So you better just go away and put up with being as you are.' Oh, dear. Poor Julie. She has just to put up with being as she is, and she can't find a purpose in life." Now, that's the story. Of course, it's made up. It's just imagining a situation. But I think it's an interesting challenge to the artificial intelligence people working away as they are now and producing exceedingly impressive responses of AI to all kinds of questions that we may ask it. But I, I find it difficult to imagine that that alone will, without harnessing the stochasticity in an ordered way, I find it difficult to imagine how that will produce behavior like a human. But it will be increasingly difficult to tell the difference because ultimately, if people asked, "What is my purpose?" I would say, "It is to acquire understanding of living systems." That's my subject. But do I know what I'm going to end up with in, say, two years' time? No, I don't. Otherwise, I would already know it now. 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.

But you see, as organisms, we have that. I would like to say 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." And I don't know yet.

I very, I love that sort of thinking of of water-based AI and and water computers. I think it's just very interesting. Well, it's not impossible, but it did take nature three billion years to do it.

We haven't discussed quantum mechanics yet. I know, now coming just back from filming at a conference where a lot was presented about microtubules and quantum effects in microtubules. So we're talking about the highway we discussed earlier from Paris to Leiden, communicating stuff to our genome. And it now seems very likely, and we are on the brink of experimentally establishing it, that quantum effects play a role there. I'm just super curious what you think this would imply and how it informs your work and thinking.

I've actually discussed this with Roger Penrose, who is said to be the origin of this idea, together with Stuart Hameroff. Exactly. Yeah. Now, Roger's answer was very simple. It's not just that. I have a five-minute recording of my discussion with him. And what he said in that discussion, because I put to him the question directly, "Do you think that quantum mechanical processes like the collapse of a wave function and all the various terms that people use to try to describe quantum mechanical behavior, do you think that's 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?" Now, looks to me as though there is a disagreement there between Hameroff and Penrose, even though they've published together. But I think we should ask at the very source in each case. Stuart has his reasons as a neurologist, uh, and knowing about microtubules and those tram lines all the way from Paris to here, that I think also one needs to ask Roger himself. And he says quite clearly, no, I think it's not quite like that. It is worse than that because we don't even understand quantum mechanics. Now, that is a sort of statement that I like. I think part of the problem in science is that we too readily think we must understand it all. It may be we have to live with the fact that we can't.

Actually, the discussion today in our meeting here in Leiden led to discussion of that particular point between order and disorder in the universe. Can we have a good resolution? Or in the case of quantum mechanics and its quantum gravity and general relativity as developed by Einstein, can we find a way of bringing the two together? Well, it's worth asking the question, do we need to? Or should we just simply live with the fact that there are limits to what we can understand? I actually come to that view myself, that the best, for the time being at least, way to think about it is that this is beyond what we can know. So let's live with that and get on with it.

I like that approach. I think I think what's happening with quantum is that culturally, uh, people have so long lived, had difficulty with what science tells us, seemingly tells us, there's no meaning in life, no purpose. Indeed. Yes. And then we grasp on to this, this new science that tells us things like non-locality and entanglement, which seem to be compatible with religious ideas. So we want to grasp it as a mechanism, but still forget that it's still a model of reality. And as Roger Penrose said, there's a fundamental debate about what it all means. But to me, it points to sort of this that society at large is just, just so dearly wants meaning back, which science seems to have put sort of aside. And I think this is a resolution then that we can make with the great cultural traditions of humanity, in the stories we write, in the poetry we write, in the music we write, with all of those forms of the humanities, I think we can come to a well-deserved mutual understanding that yes, there are processes beyond what science can analyze in the way in which it is traditionally used.

I happen to be a musician as well. What instrument do you play? I play guitar, but more importantly, I sing the Troubadour poetry. Wow. The medieval poetry of the Troubadours, including Arnaut Daniel, Jaufre Rudel, um, Lami, K. It's fantastic poetry. He invented the sestina, which is the way of arranging the rhyming words in a six-line stanza to have a different order in each of the six verses according to a mathematical formula. And the system all makes sense, but only in his language, which is not French, it's Occitan. And he makes a strict verse become the tool with which eventually he unites with his lover when they can ascend to paradise because only in paradise can they actually have that joy, as what his song says. And that is the beginning of Dante writing the Purgatorio, the Inferno, and the Paradiso of the Divine Comedy. Look, I think there is a need for a laying down of the weapons with which science has quarreled with the humanities. We need to bring a resolution to that. And I think that kind of resolution is perfectly possible because once science accepts that there is a concept of agency which doesn't depend on some ghostly thing determining what we do, does not depend on supposing that there's something inside us that is the essence of us, and that 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. I forgot about dance. That would be my.

It's very nice to think there could be a resolution of that because it's been a standoff for absolutely enormous number of decades between the obvious fact to the humanities that we can be creative, and the science is giving the impression that all of that is a bit ephemeral and doesn't have any real existence. It's time to resolve that, and I think that is resolvable. We may not be able to resolve our concepts of the universe, but I think we can resolve this argument.

I couldn't agree more. No longer an argument. I couldn't agree more. And we're trying to do our best, uh, by by making this plea for different metaphysics, and you do it in a different approach in systems thinking in biology.

And as a final question, but you already sang to us. So that already to me was my question would be like, on a personal level, if you speak to young people who are, uh, find it difficult to find their way in life, or people in distress, and you write "Dancing to the Tune of Life." What is your advice on how to dance to the tune of life on a personal level?

Well, I do this all the time. I have a small group of young people working with me. Not working in my team in Oxford. I'm not creating a team anymore. No, there are people dotted around the world and I've accumulated who are looking for precisely that. How, given that they are also thinking very similarly to me, and that's why they've come to me for advice. What can we do to swim within this environment in which you can't even get funding if you want to do that? Tragic. And I've examined theses 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. I just, what do I do? I animate the group to some degree, but they do so too because, in the end, they enjoy doing what they're doing. Um, I also accumulate people. When I went to Santiago de Chile earlier this year, in January, to take part in their Congress Futuro, the Congress of the Future, I gave a talk on genes and not the blueprint for life, which is exactly the nature paper that I published last year, very short paper, so anybody can read it very quickly. I was given around five young people who have been selected for the congress to help with shepherding people around and so on. But I discovered, of course, they were well-selected people from within the school systems in Santiago with tremendous inspirational to me sense of their wanting to find their purpose in life. I've continued to mentor two or three of those to help them negotiate what to them are huge hurdles. How do we, in a tiny part of the world, in Chile, for example, manage to have opportunity to go to major universities, for example? But that requires that people get encouragement to think, "You might be able to do it. If you really want to try and do it, why not have a go?" So my way of doing it is is to try and inspire young people to think, "Well, what is being opened up here? Breaking out from a paradigm which has had its day in science for many years now is to encourage them to think that actually the world is their oyster. The world is the place where they can achieve something." It gives them purpose. They're people looking for what they can possibly do.

I love it. So give me somebody aged about 16 or 17, and I enjoy mentoring them. But you know who else used to say that? The Jesuits used to always say, "Give me a child, I'll bring it up, and it will remain in my religion for the rest of life." It's cultural transference, isn't it? Yeah. From generation to generation. I'm trying to create an environment in which, certainly, I don't tell people what religion they should have. I've no interest in that at all. Um, but at the same time, to for them to respect all the traditions of mankind and think that somehow we can manage to negotiate through all of those controversies that have fueled war after war after war and come to a better resolution in the future. That's what I'd love to see.

I think that's a beautiful way to end this discussion, or conversation, I should say. Thank you very much. Thank you very much. Thank you very much. Really enjoyable discussion too. I enjoyed it very much. Thank you. Thank you very much for watching our conversation. If you have any questions, you can leave them below, and we will make sure to put links to all we referenced to and work of Dennis Noble in the description below. Thank you for watching.