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 Leen, the Netherlands,

too long. This is Leen, 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.

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

Dawkins. Extraordinary book, The Selfish Gene. It's a fabulous story.

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.

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

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

cell. Neither automatically follow from the DNA alone.

Instead of viewing evolution as a blind, meaningless and bottomup mechanism of nature, Noble argues for biological relativity.

>> Oh, that's it. Yes, exactly. I

formulated that as a principle of biological relativity is 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 the 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 bio semiotics. We will touch upon that.

semiotics. We will touch upon that.

>> Yes.

>> But maybe good for audience for people who do not know you. You're a pioneering physiologist and ameritus 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

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 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 now at that time

the embryo is nothing more than a ball of cells that's remarkable a tube form s 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.

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 autoc catalytic 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

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?

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

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

selfexite 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-exitation already. The word self it implies that

already. The word self it implies that there's some form of agency which when I say that of course is is is already a bit sinful. I I think in evolutionary

bit sinful. I I think in evolutionary biology to you not allowed to think that way.

>> Yeah.

>> In 1958 >> you call that also in your book or it's known as the teological 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

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 Rosalyn 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

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

>> exactly. So you need nothing more than that. Now,

that. Now, >> which is what Shreddinger had predicted, right? Shreddinger.

right? Shreddinger.

>> It was actually Shreddinger 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.

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

anyway. Caves and goblins and goodness knows what. Yes. So it's all to us as

knows what. Yes. So it's all to us as children very exciting to see that. But

what Shreddinger said in his book, well maybe life does that. It just replicates like

a crystal. And that has continued

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 ex 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

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

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 Shreddinger 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 nucleide. The moment the cell knows

nucleide. The moment the cell knows there are no errors anymore, we can now divide. How how does the cell know that

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

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

that. I don't know that they do. I think

they would have won a Nobel Prize if they had found out. Let's let 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

single cell. Um, we can insert certain um I found this in this 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

>> 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

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

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

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 correct correction on a cell level

that's to me that is very is pretty convincing what puzzles me is this question of agency that the 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 soul 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,

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 Shering 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 meiosin 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 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 >> the organ. You say it it works both ways. So these passengers it has to.

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.

been established. Right.

>> It's been established that is necessarily true. Yes. Because that's

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

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

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

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 service 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. Yesdeed

and that of course relates back to metaphysics what our foundation is about. It was the work of Michael Evan

about. It was the work of Michael Evan 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

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. 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

heat, sound. That's the way our ears work. All the various receptor processes

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

happening. And so they're able to detect. For example, in Michael Evans

detect. For example, in Michael Evans 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 pilia on the surface of the cell to swim in the environment to see where they can find food. They're already an organism.

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 Leven's work is the insight 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

>> Yeah. Yeah. are doing.

>> 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

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.

>> Yeah. But it does doesn't he sort of his work point to a 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

bodies. But what does it normally experience? The immune system comes and

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 it really interests me that when talking about Michael Evan 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 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.

>> 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

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 neodyarwinism is dead.

>> Yes.

>> True Darwinism is far from dead.

Exactly. So

>> tell me about what what is true Darwinism? True Darwinism includes

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 Lamarian 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

neodyarwinism 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 pee hen 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 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. M

>> beehen. M >> and then a bit later in the same book he writes the pee hen 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.

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

>> 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 speeded evolution up.

Ah, that's what Darwin realized. There

has to be other processes that shortcircuit 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

too long. Let me give an example back to the human genome sequencing in 2001.

What that showed was a comparison between 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

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

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

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. 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

it consciously. But to come back to Darwin, we're now back to the peacock displaying its beautiful

feathers for the pehen to appreciate, convince it to mate.

He wrote that 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 zenobots of Mike Leven

system. Those zenobots of Mike Leven have got agency which they have generated from that situation which they suddenly find they're no longer part of the frog's

skin.

>> Yeah. and they create the agency to look around with their silia 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

anyway. Um 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. How did it know to do

that? I don't think we fully know the

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 the just the 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 you do not necessarily have to account for everything in a material

way. But

way. But >> Right. Well, I'm not sure it's quite so

>> 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

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 zenobots 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

molecular level. But interestingly the most constrained level is the molecular level.

That's the level at which no choice can be made. H

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 is 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

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

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

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

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

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

level up. Micro things within cells and then cells constraining those and then tissues conraining 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

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

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.

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

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 photo receptors 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 co 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

selfexitation >> yes of as the universe as a selfexited 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

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.

Absolarity 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,

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.

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% of them have been shown to be

very small. If you understand what I've

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.

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

this. You're getting help from the system that enables this to occur relatively easily. So that difference

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 repo

repository. Now it's a long name for

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. 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. M

>> 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 was 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 is 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 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.

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

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 some stage or another admit when you've got the wrong metaphysics.

And believe me, 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.

>> Yeah. being the only process by which evolution occurs. And I think we have to

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

explain. Worse still, it's failed to deliver the health care that we thought genomics alone would be able to deliver.

That's serious.

>> And and that indeed is very serious. and

and also I'd say on a cultural level it also have implications on how people leave 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.

>> Yeah.

>> It's according to what science tells us, right? I pulled the trigger, but I was

right? I pulled the trigger, but I was not responsible.

>> Yeah.

>> At that time, people thought they'd identified, believe it or not, genes that cause criminality.

There are no such genes.

>> This is Skinner ulcerite 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 other

War? 6 million gypsies, Jews, and other strange in the view then of the ruling organization, the Nazi organization

within Germany. What was the

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

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.

>> Yeah.

>> The mindset is I can lay back because there's nothing I can do about it.

>> Yeah.

>> That is the very opposite of what somebody should be trying to do.

>> Yeah.

>> 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.

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

children. Let us educate our children because we're the only species that can do this."

do this." Where does that idea come from? Can you

believe it is Daycart?

It's the philosopher back there three or 400 years ago who said animals are autom.

But then he realized, well, women mean I'm not.

>> So there must be something the self that causes me, the soul, he used as the word, of course, the soul, the self,

whatever. Um, that enables me to control

whatever. Um, that enables me to control this body, which otherwise would be a mechanical automaton. Of course, he was

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 1660 area >> 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

real. Without that, you can very easily sink into what I would call an almost depressive view of life.

>> I can't help it.

>> Yeah. 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.

>> Yeah. And you, as you just said, you critique Decart um many many philosophers do. Um uh to what

philosophers do. Um uh to what philosopher do you feel uh more aligned?

I think you you mentioned Spinoza's thinking for instance >> actually. So Spininoza is extraordinary.

>> actually. So Spininoza 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.

>> Yeah.

>> And he wrote in Latin I can even reproduce part of it. 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.

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,

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. M and he would say, wouldn't

life. M and he would say, wouldn't Spinoza say that this cut that Deart 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 in light.

>> 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

philosophy. The two in those days were not thought of to be a separate um set of activity. But there he was

of activity. But there he was excommunicating 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 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 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.

>> 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 we 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 watch maker 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

anywhere. It's it's definitively what living things do.

>> Yes. Could you explain a bit on this sort of metaphysics which you are proposing? Actually, that's not the

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 is connected with almost every other part which is why he chose the clustm 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 perused.

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.

>> Yeah.

>> 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

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

philosophy. It doesn't make sense to ascribe a self to the brain alone.

And I there there I lay my case that is my metaphysics in relation to the nature of the self.

>> Yeah, I can follow you and that it is a process. It reminds me of of what Alan

process. It reminds me of of what Alan Watts would say that we shouldn't talk about a tree but about treeing the process ofdeed which is >> the process of being a tree. Yes.

Exactly. So

>> and that knows a community because it roots do that.

>> What fascinates me though but this is like purely speculation. And I I'll ask you to speculate here is if we see it all as a self- excited thing, the

universe that 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

Yes. between order and disorder. That's

the way I put it in a book called the language of symmetry.

>> Yeah, >> there is a book 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. So give it a boost.

>> It exists. The language of symmetry is a book. I'm not the sole author. It was

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

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

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 and to for people to understand that that notion of harvesting stoasticity.

It would be that through for instance errors being made in the genome um an antibbody can be presented that the cell knows I need this one right so

it it is out of these errors that you see this is what I need >> indeed so >> 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.

>> Yeah. 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

machines. They're harnessing all of that information.

>> But of course, and you write uh you have a very interesting story, a love story in your latest book about that that >> we could of course conceive of machines that have random number generators in

them. So wouldn't we then have sort of

them. So wouldn't we then have sort of that stoasticity you're talking about?

>> Yes. our story of the um poor girl who is not really a human. Her brain is a silicon chip

uh system.

Um 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

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

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

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

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

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

yet. I know now coming just back from filming at a conference where a lot was presented about microtubules and quantum effects in microtubles. So we're talking about the highway we discussed earlier

from Paris to Leiden commuting communicating stuff to our genome >> and it now seems very likely and we are on the brink of experimentally

um 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 >> by Stuart Hammer.

>> 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

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 Amarof and Penrose even though they've published together

but I think we should ask at the very source in each case Stuart have his reasons as a neurologist uh and knowing about microtubules and

those tram lines all the way from Paris to here um 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 it's quantum gravity and

general relativity as developed by Einstein? Can we find a way of bringing

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 that there's no meaning in life no purpose >> indeed. Yes.

>> 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 Penner 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 be have put sort of aside and

>> I think this is a resolution then that we can make with the great

cultural tradition s 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 welldeserved 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 Trouador poetry.

>> Wow.

>> The medieval poetry of the Trouidors, including Arno, Danielle, Jeafrey, Rudell, um, Lami,

K.

It's fantastic poetry.

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 and the system all makes sense but only in his language which is not

French it's oxyto and he makes a stick ver 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.

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

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 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.

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

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

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.

>> 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 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 uh doing what

they're doing. M

they're doing. M >> 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 shephering people around and so on. But I discovered of course they

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

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?

>> Yeah.

>> 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 and breaking out from a paradigm which has had its day in science and 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

achieve something. It gives them purpose. They're people looking for what

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

them. But you know who else used to say that? The Jesuits used to always 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.

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,

conversation. If you have any questions, you can leave them below and we will make sure to put links to all we reference to and work of Dennis Noble in the description below. Thank you for

watching.