The Central Dogma and the Weismann Barrier: Does Genetic Information Flow Both Ways? Denis Noble Interview

For a century, the belief was that genetic information built organisms, never the other way around. A new paper by Denis Noble definitively proves otherwise. The paper is called “Central Dogma or Central Debate.” In this interview, Denis explains the revolution that is going on in genetics.

Interview Transcription

Perry Marshall: Hello! This is Perry Marshall and I’m here with Denis Noble. It’s a real privilege to have Denis here. Denis is one of the most eminent scientists in the UK.

He is on the Evolution 2.0 judging panel for the prize, and he organized a very very important meeting at the Royal Society in 2016 which was probably the most revolutionary evolution meeting certainly in the last couple of decades if not longer.

I was there, and I kind of felt like Forrest Gump witnessing history when it was happening there, and I wanted to get Denis on the line here because he’s published a very interesting paper in Physiology Science Journal called “Central Dogma or Central Debate”.

We’ll probably talk about that paper a little bit today, but I wanted to introduce you to Denis and have him share his thoughts with you and just a little bit more about Denis.

Denis is known around the world as being the guy who figured out the cardiac rhythm which made pacemakers possible, and he was the first human to model a human organ on a computer which he did on punch cards at University College London in the basement of a lab in 1960.

I just think it’s pretty interesting he’s also a very active musician and he founded something called Voices from Oxford which is a video interview series that Oxford University has. He’s been a professor at Oxford for pretty much all of his career so very distinguished scientist, very important voice in the new evolution that’s happening now. So Denis, welcome. I’m glad to have you here today.

Denis Noble: Thank you very much, Perry. My ears are already ringing, or my face is blushing, whichever you want to say but thanks for that introduction.

Perry Marshall: I am not – very much not – an evolutionary biologist, and you’re not an evolutionary biologist either. You’re a physiologist but what I can observe as an entrepreneur, as a consultant, is that almost all reformations of industries come from the outside.

Martin Luther was not a Catholic priest, and Bill Gates was not a mainframe computer guy. Larry and Sergei, who started Google, were not search engine guys, and the guy who started Federal Express was not a shipping industry guy.

You can go on a long list of revolutions that have happened in various fields and it’s almost always the outsiders who say “Hey, wait a minute… you know we’re really missing something here…” You’re a physiologist and, for a very long time, you have felt “Hey, guys, we are missing something here. There are things here that you’re saying are true that I know cannot possibly be true because I’m a physiologist.” Denis, I would like you to, however you wish, take us inside the mind and the skin and the shoes of a physiologist and help us understand well what is a physiologist. Maybe not everybody exactly knows and just kind of tell us how you kind of stumbled into this. It’s not like you started out with a plan but tell me about that Denis.

Denis Noble: Absolutely right, Perry. The way in which I got on to the issue goes back to a period during the 1980s when we were working out the more complete details than I could do in 1960 of how the heart pacemaker works.

We found something quite extraordinary which is that it seems initially to be unnecessarily complicated. In fact, I remember people asking that kind of question as I lectured on what we were finding one mechanism after another but the point made was ‘but you only need one of these’.

Then, we did a very interesting experiment both in terms of using a drug to do the actual experiment on the heart but also to run the computer model which was this. Take one of those mechanisms out.

On a computer model, you could do that easily, you could do it with a drug to knock out a particular mechanism. We did that with a mechanism that was contributing 80% of the functionality. It made only a 15% difference to the frequency of the heart if you take it out.

To an engineer like you and to a physiologist because in a sense, a physiologist is an engineer of the body.

A physiologist like me that said the following, first if you do gene knockouts you do not necessarily get a good quantitative estimate of the function.  The difference between 15% and 80% is, for biologists, that’s pretty big, pretty bad. The story doesn’t end there because actually the pacemaker of the heart is backed up as we would say in a number of ways, not just 2.

So I then thought about that, and I asked myself the question if you can’t actually relate genes to function by doing knockouts what are we doing?

I’m not saying that knockouts never reveal function; of course, you get spectacular cases where with rare genetic diseases a particular change will make a disastrous consequence of the person.

Generally, what have people found with all the genome-wide association studies that are going on now?

There are so many genes involved exactly as in the cardiac pacemaker but what is happening is that nature has created robustness. So you have so many mechanisms involved that you have to ask the question why are they involved?

They’re there to make the system robust, to make it safe just as you have a double control system on an aircraft but then you move further on, you see you ask the question ‘does that mean that the control networks, lying if you like above the genome, are really dictating what the genome does and I think that’s the right way round to think about it but once you start going down that road you start questioning the very basis of all gene-centric theories of evolution notably including the selfish gene itself.

Perry Marshall: Let me feedback to you what you said in engineer language.  So I have a digital watch here.

It’s analog hands but its electronics inside and it’s got a quartz crystal and the crystal vibrates and a little circuit divides up the vibrations and sets the pulse of the watch and so the second hand ticks each second and what I think you are saying is that people initially said well I just figured the heart has a little quartz crystal, so to speak, and then it gets subdivided and then the heart beats and then oh my goodness it turns out there’s another quartz crystal and another one and then another one.

When I take out one of them I don’t get an 80% change I only get a 15% change, so they’re actually redundant; but, furthermore, what you begin to suspect was that there was a mutual almost circular relationship between the mechanisms and the genes that code for it, not a one way. It wasn’t just gene to quartz crystal it was each affects the other. Am I correct?

Denis Noble: Yes and moreover, for quite a long time, the network which is producing the rhythm can function whether or not the genome is there.

Perry Marshall: Wait a minute. Okay, so you can take out the genome?

Denis Noble: Yes. The genome is required only when the cell wants to make more protein. That’s an absolutely crucial point.

This applies generally, there are mechanisms in the body that enable us to know or the body to know when it hasn’t got enough calcium transporter protein or muscle contracting protein and it goes and tells the genome to do so.

You see the direction of causality I think we have got it usually the wrong way round. It’s actually the networks and the cell and the tissues and the organs that tell the genome how much to make of each protein.

Now that leads on to a very clear understanding of why a liver cell, heart cell, a bone cell and so on are all very different in terms of the proteins that they contain, but they use exactly the same genome. What’s telling the genome to make a bone cell, a liver cell, a heart cell is the cell itself. So the causality is that way round.

Perry Marshall:  What you’re describing is a complete total conceptual change from the way most people have been talking about genes and evolution for a hundred years.

Denis Noble:  Well, certainly since Weismann came up about a hundred and thirty years ago with the idea of his barrier that is there was no connection between the soma changes; that is the body changes and the so-called germline that is the sperm and egg.

So it really goes way back and that incidentally, of course, was the foundation of what’s called the modern synthesis which is the standard theory of evolution.

So challenging that and challenging, in particular, the misconception that the central dogma of molecular biology which is that you go from genes to that is DNA to RNA to protein but never the other way round; challenging that is to challenge the very basis of the modern synthesis of evolutionary biology. I think it is fundamental it’s not just a minor change; it’s a major one.

Perry Marshall:  When I began investigating evolution I concluded, yes, evolution did happen, but there’s no way the normal explanation could possibly be correct.

I came to that conclusion as an engineer because what they were telling me in biology I had never encountered in engineering school, and most people following that line of reasoning would have just become some flavor of creationist but I said no I think there’s something more going on here and what I found was we know that actually the cells change the genes.

Can you give a couple of examples of where we have clearly documented that the cell modifies the genome and it’s not just the genome building the cell? I think we have to be very clear about this otherwise we can’t move forward

Denis Noble: Absolutely. Of course, the classic example of that is the immune system.

You see we can resist an absolutely fantastic number of different invaders viruses, bacteria and other foreign bodies invading our body because we have the ability to make vastly more keys to fit the lock. Imagine the invaders a bit like a lock, you’ve got to get a key to it because it would neutralize it.

We can make many more of those than could ever have been put into the genome as sequences. How do we do it? The organism effectively has a feedback mechanism which operates when a foreign body arrives which it has not met before, and it says to the genome please mutate at a very high speed.

Now don’t mutate everywhere that would be disastrous. It does so in a pinpoint fashion. It goes straight for the variable bit of the protein that it has to make in order to fit that lock and then it creates absolutely millions of different new keys.

It finds one that works and it says to those cells reproduce, and the rest die.  We already have an example of that mechanism.

Moreover, if you ask the question what’s happening to those bacteria that are now evolving very quickly to resist antibiotics they’ve got the same mechanism. We call it hyper mutation that is the cell effectively or a population of cells because it is obviously not a single cell that does that.

It’s a population of cells, in the case of bacteria, a tissue or organ of the body in the case of the immune system in the case of our bodies that says to the genome, please do the following.

We now know as physiologists exactly how that can work too because we can show the mechanisms by which an event right up at the surface of the cell can be transmitted all the way down into the nucleus where the genome is and to target that in a specific way in the case of the immune system to say please mutate this bit very rapidly, in the case of the bacteria doing the same thing to each genome knowing it’s got defined as a population a solution to the challenge of a new antibiotic.

Perry Marshall: Is it the case that that cell can now transmit the immunity to its progeny?

Denis Noble:  Yes exactly, because that’s why in the case of the immune system that’s precisely why the body tells those cells to reproduce. It tells the rest to die in a specific process which we happen to call apoptosis, but that’s just a nice Greek word which means in effect kill yourself.

Perry Marshall:  Yeah right.

Denis Noble:  It’s remarkable, and it’s so effective because you see as I said at the beginning of this part of our discussion, the total number of new challenging invaders that we could encounter is vastly greater than could ever be encoded by our genome. Now the obvious question about that is this.

Could that be passed on to subsequent generations in case of the immune system? The answer is no. Each generation has to start off with its immune system with a number of different locks and keys that it’s already got and then as it were learn again.

In that case, that is not passed on but many other things are passed on and what we discovered is that there are many particles in the sperm line and in the egg line which enable what we call paternal and maternal effects to be transmitted down through the generations.

Again as a physiologist, we will find this very straight forward. I tell you bury in my field of physiology internationally I find very little opposition to the ideas that I’m expressing. Everything I’ve told you that in this little discussion would be regarded by most physiologists as damned obvious. What’s the argument about?

Perry Marshall:  But it’s met with hostility by evolutionary biologists.

Denis Noble: In a curious way and I still don’t really understand this I mean I’ve got here you see the issue of the Royal Society Journal: New Trends In Evolutionary Biology.

For many evolutionary biologists, what you might call standard evolutionary biology was like a red rag to a bull. They didn’t like it. I just looked on the internet before our discussion, and I find new trends in cardiology comes out every year.

In physiology, we discuss new trends all the time. We welcome the new trends. So what is going on and I think what is going on is very interesting. The problem I think is that so much is at stake in relation to the arguments in evolution it’s an area which is hotly disputed not just by scientists but also by the general public as we well know particularly in the United States.

It’s a very hot area, and big reputations are at stake. I feel that what is going on is that people are shifting the goal post to avoid having to admit that some major assumptions in the original theory as it was formulated to give us the modern synthesis having that being shown to be wrong simply.

First one, the fact that it is possible for what we call changes in the body during life to be passed on to subsequent generations that’s being now shown in many different species including the human.

Point two, could it be the case that what we now call the central dogma of molecular biology which is the point I made earlier on. The DNA creates an RNA that creates a protein missed only one way. Could that now be, in defense of Weismann’s barrier, the original idea that the germ line was carrying something which was not influenced by the rest of the body. The answer is there’s no way in which that could be the case.

Just a bit technical for a moment but I’m trying to keep this simple. If only represented a molecule let’s say a bit of DNA as the size of my fist here, I’m in Oxford in England, the edge of the cell that contains that molecule that DNA would be way up in Scotland that’s about eight hundred miles away.

That’s the difference of scale that we’re dealing with. Now the Weismann barrier is about a cell, a central dogma is about a molecule, and there’s no way in which those can be the same. Now what I found….

Perry Marshall:  Can I just try to maybe clarify what you just said? So the central dogma in its most simplest form says you have a strand of DNA and it gets transcribed into a protein and proteins don’t turn back into strands of DNA. That’s the simplest version of what that says.

Denis Noble:  It’s a molecular coding mechanism.

Perry Marshall: And you agree with that. That is true? Proteins don’t get turned back into DNA. However, there’s a higher level architecture question which is, Is DNA edited or re arranged by the cell? Yes or no?

Weismann said absolutely not. It only goes one way. You start with the genes and you build an organism and what you start to discover in the 1980s  and what has now become abundantly clear is genes are absolutely edited and changed by cells and in some cases not just your skin or your heart or your liver cells, genomes get changed, but it can actually go to the sperm and egg.

Denis Noble:  Yeah that’s right. Also just to clarify that in case we got some good molecular biologist listening to this who would want to say Hey wait a minute.

What do you mean by being changed? A variety of ways I now know. One of those, of course, is the mechanism by which the genome that is those sequences in the DNA can be mocked. We call that epigenetic change. There are other mechanisms too, but I don’t want to complicate this. One will do.

Those marks can go down through the germ line, and that means that it’s possible for changes that occurred during the organism’s lifetime to be transmitted down through the germ line.

So that’s just one example of the kind of process that I’m referring to. It’s not that the cell has a sort of cell version of CRISPR; this new technology that enables you to cut and paste DNA which is being used to extraordinarily important effects in modern biology.

But it is the case that the cell can through its experience include information in what goes down through the germ line that enables it to be the case that the DNA code in itself is not enough.

Perry Marshall: So you wrote a book called Biological Relativity, and you wrote this paper that in the physiology journal that you tease out these distinctions between the Weismann Barrier, the central dogma and you’ve pointed out that from a system level point of view this is a complete conceptual shift in how evolution works. It’s radical.

This is as different as Catholic and Protestant, or it’s as different as Newtonian Mechanics versus Quantum Mechanics. You can’t just say Oh well you know that was always there and we just didn’t talk about it enough. It’s a complete reversal.

Denis Noble:  It is a reversal. That’s right. It’s not just a minor modification. I think there’s a way of explaining that to your listeners and watchers. If we transcribed on a keyboard what we are just saying we would use a Qwerty keyboard.

The important thing to note is that it wouldn’t matter if we used a different keyboard. The point I’m making is when I type my paper out on a keyboard whatever keyboard; a Qwerty one, a French one whatever. It is not the case that the qwerty keyboard is responsible for what is typed.

In a similar way, the cell is responsible for interpreting the genome and that code between the DNA and the protein which is a very exciting discovery; no question about that, it is absolutely fundamental. I’m not challenging that at all. But it no more determines life than the Qwerty keyboard would determine what I would write if I write down what we’re just discussing.

Perry Marshall: You are introducing the idea of the cell as an agent of its own evolution.

Denis Noble:  And organisms as agents of their own evolution precisely and of course that smacks of another forbidden word which is Lamarck but don’t worry too much about that. It’s another respect in which the agency is at higher levels than the gene.

I would go further and say DNA on its own cannot have any agency which is a passive molecule. If I took the DNA out of one of your cells and I put it in a Petri dish with as many nutrients as you like.

Give it Glucose, give it goodness knows what to keep it happy. For ten thousand years it would do absolutely zilch. So the agency has to be at a higher level, and again I come back to what engineers and physiologists readily understand. The agency process lies in those interacting clever networks, not in a bunch of molecules.

It lies in what we would call the software and of course, you need a hardware that’s good enough for that software to be able to be implemented but clearly, the intelligence lies in the cleverness of those networks.

Perry Marshall: I think we’ve probably explained the basic science adequately so tell me about the family dynamic, the politics, the profession.

You wanted to organize this meeting at the Royal Society, and you’re a fellow of the Royal Society, and you are a very eminent scientist, and you have some clout. So what happened when you tried to do that?

Denis Noble:  First of all, I just wrote to the president; it was actually both the Royal Society and the British Academy. The British Academies of Humanities and Social Sciences. The Royal Society is what we call the hard sciences.

 I don’t know whether that distinction is; actually, I find that Humanity is pretty hard, but that’s a whole another conversation. Anyway, the fact is that what I did was very simply to write to the president of both of those societies and say that I thought that the implications of some of the new trends in evolutionary biology were of much greater importance than just in biology.

It relates to economics. You know the equations that people use in economics, they are the same equations.

The price equation and things like that are used in evolutionary biology. It relates to economics for another reason too which is that a lot of economic theory centers on things like selfishness and cooperation and what’s the balance between the two.

If you start to question some of the basis of, for example, selfish gene theory then my goodness yes you have implications way outside of the realm of biology. So that’s why I wrote to both the president of the British Academy and the President of the Royal Society.

They simply responded saying it sounds like a good idea. Put it to our committee. In each case, committees passed it. No problem at all. They got to the point of advertising the meeting which occurred towards the beginning of 2016, and that was the point at which a large number of evolutionary biologists said that this didn’t sound like a good idea at all.  

I think the intent there was clearly to stop the meeting or to get it transformed in one way or another. Probably they had not really thought through the care and carefulness with which I had worked with four other collaborators in putting the meeting together with consultation widely around the world to try to produce a good program.

Moreover, we tried to produce a balanced program because we actually invited several of the orthodox if you might want to call them that evolutionary biologists to talk. Only one of our original invitees actually agreed initially.

We had to appeal to the Royal Society to try to convince more than one to come. Now, what did they do at the meeting itself? What they said in effect was well we’ve known this for a long time.

You produced the question of can an organism, be it a plant or an animal or a human alter its genome?

Barbara McClintock showed that over 80 years ago working on Indian corn and watching how the chromosomes changed as the corn was challenged in its environment.

Jumping genes as they were called and the ability of cells to signal to their genomes what I was discussing earlier on about bacteria signaling to their genomes, our immune system signaling to our genome to rearrange the genome; that’s been known for a long time.

Of course, it has, but the point is that it is fundamentally incompatible with the central thesis which is there is just random variation in the genome followed by natural selection, and that is all that is necessary.

I will say this, Perry, there are many evolutionary biologists whom I respect that have understood that there are major changes that occurred. Many of them now while claiming to be standard orthodoxy evolutionary biologists will say okay yes we accept the inheritance of acquired characteristics.

My goodness I’m fine if they do I don’t have any quarrel with that obviously but that was the key difference between Darwin and Weismann. When Weismann introduced his barrier, he says so in his 1883 lecture reproduced in a book published by the Oxford University Press at that time. Translated from German into English he says Darwin included Lamarck’s idea.

My idea is that we can get rid of it. So it was an intention to get rid of that. If you change the goal posts and you redefine theory to be something different from what it was originally I think it’s much more honest to say that we changed. My goodness, what is shameful about that? Nothing.

Perry Marshall: If I can just speak to that I think there’s a very subtle thing that is going on here which is the old evolutionary theory that Weismann espoused was very friendly and simpatico to a reductionist view of the world and to making it sound as though we have this all figured out when in fact really if you look at how evolution works the universe becomes much more amazing than you ever conceived it to be before.

It shows that there’s vast regions that we just have no idea how this stuff works. I personally would love to know what you think. My opinion is we understand about five percent of how evolution actually works in detail. Would you have a number that you would throw out like how much you think we… I’m just curious.

Denis Noble:  The tough news is that evolution occurs normally over such a long timescale that any of our experiments have difficulty coping with that in any organisms, arguably the most tiniest of organisms which of course is why much of the work has been done on extremism organisms like bacteria or the fruit fly and so on.

I wouldn’t be able to put a percentage on, but I think we’ve got a long way to go. I would agree with that. I think the difficulty is not so much identifying what the mechanisms are in addition to the standard one of random variation in the genome and then some action between the results of those random variations.

There are so many other mechanisms that occur including incidentally one that I’m very keen on which is that the variation is not just the cause of differences between different organisms in the progeny on which natural selection can then act, it is also something which is used by organisms to create novelty. Now, come back to agency, why have we got agency?

I don’t know if that’s the right way to put the question but if we have agency that’s extremely important because that is what enables us to be creative whether it is as scientists, as writers of literature, as musicians, whatever it might be. You can’t have a Beethoven without there being the possibility of doing something completely new from what anybody else had done previously.

You don’t have an Einstein if you stick with the idea that there can be no novelty but how do you get novelty? You get novelty in exactly the same way, in an analogous way that the immune system gets the novelty. It’s got a new challenge. It needs a new key to that new lock, and it goes down into the stochastic level of the molecular processes and asks for the wheel to be turned very rapidly and to produce the onset. I think that’s what organisms do generally.

There is the agency that is what partly drives evolution. So it’s interesting to ask the question as you did what percentage do we yet know.

I think you’re right, it’s small, but there’s a huge amount that we’re going to have to look into, in the future as we work out how the different mechanisms that could be involved have interacted with each other. That even includes the study of the icon of Darwin’s evolutionary theory; the birds and the tortoises in the Galapagos islands.

The birds have been studied, and the interesting thing is that there are many epigenetic changes; that’s those changes that have to do with changing the genome with genome marks as there are genetic changes. The people who’ve studied that simply come to the conclusion that probably both processes, the epigenetic and the genetic have occurred together.

One naturally leads to changes in the other. These processes therefore interact, and we are very far from understanding all the details of how they interact. Incidentally, for young scientists listening to this, it’s an area to get into.

The founding of biology is here that’s where it is, and the frontier lies not in making more discoveries at the molecular biological level though my goodness we do need those. I’m not against the molecular biological discoveries. They have been fantastic.

It’s largely going to be at the level of understanding those networks of interactions that lie above the genome and which give organisms agency and therefore the ability to choose and the implications of that for history, for literature, for economics, for I don’t know; you name the area of human interest. It’s everywhere.

Perry Marshall: Denis, you gave a talk in Oxford to a bunch of students, and you raised the question of what if someone committed a murder and his defense attorney used the selfish gene as a defense? Could you elaborate because I don’t want to steal your thunder? Could you tell me what you said?

Denis Noble: You are really welcome to steal the thunder. What I did was to pretend to be as it were, on the one hand, a judge judging this and also to be the criminals or what do we call? The suspects yes. That’s right.

I was also pretending to be the suspect’s lawyer, so I was playing two parts in the talk. What I was saying was, your honor; here in England, we call the judge your honor. My client says he doesn’t think he really did this murder.

He doesn’t challenge the fact that he did it in the sense that yes he used the gun that killed the person that was murdered but it wasn’t him doing it because his nervous system was created by his genetic system which means that he wasn’t responsible.

We both know of course that no court of law anywhere in the world would accept that as a defense.  Now the question why?

Actually, there was a court in the United States that did accept it for reducing the sentence. It did not actually reverse the sentence, but it was used. I found this out after I gave this talk. Now there are two reasons why we would never accept that as a defense. The first is that society would fall apart if we did.

None of us are responsible for our actions, and that is not the way to create a working society, but the much more important point and the deep point is that we are active agents. We are responsible, and there can be no way in which our genes or our nerves made us do what we do. Now that gets into some very deep issues of biology and is overlapped with philosophy, but I think we can perhaps leave it there. That was the speech I made exactly.

Perry Marshall: This gives you an idea of what’s at stake because there’s a whole posse of scientists and public figures like Sam Harris or Susan Blackmore, I think Richard Dawkins although I’m not sure who believe; well Richard Dawkins said we are lumbering robots powered by our genes. I think that is a very disempowering view.

In fact, it’s contrary to the axioms of every society in every civilization and I would just say look just because you can’t explain agency doesn’t mean it doesn’t exist, and personally I view organisms and animals and humans as they’re free to a degree to make choices and this is why evolution happens.

It’s because we live in a universe of free choices and I think it’s really interesting to watch materialists try to carry this all the way to the extent. I listened to an interview with Susan Blackmore and Jordan Peterson, and she was saying no I don’t really have choices I’m just a product of my biology, and he said to her well if I were to treat you that way you would really resent it. You know people want to be treated as though they have choices.

Denis Noble: You can also do a demonstration in another very simple way, and in fact, Richard Dawkins himself showed this.

He took a Shakespearian quote from As You Like It and it’s simply the phrase, it’s 28 letters long: “Me thinks it is like a weasel”. Now he asked a question, a very interesting question; how long would a monkey on a typewriter take to produce that phrase, just that 28 letters by chance. It’s more than the whole, the billions of years of the existence of the universe.

Then he went, and I think spoilt his argument because he started to produce programs that would somehow get there much more quickly. We don’t need to go into the detail of that. He was right with the first thing, and that’s what he should have stuck with which is that it’s impossible.

What standard evolutionary biologists would say well yes but it is possible if it is just incremental. But there’s a major difficulty with that, and I pointed this out in another article recently which we called “Was the watchmaker blind?” to deliberately raise that question.

The problem is simply this that if you think you could get there incrementally for example by holding every letter that the monkey got right and as it were making the keyboard stick at that point, of course, you get there much more quickly.

In fact, Richard calculated that it would take only about 40 generations typing away to get there but who is providing the information that tells the system it is getting closer to the goal. That is the problem.

Now I think there is something that he’s getting there and it’s you and me and it’s the other organisms. We have as you say agency, and they are therefore capable, for example of choosing their mates. What does that do? Why do women look beautiful to men? Why do men look handsome to women?

It’s because we chose them that way and we bred with them that way, and that’s why they end up being as they are. It’s so damn simple. Darwin immediately wrote a whole book on sexual selection. It’s the organisms that do the selecting.  My genes don’t do that selection; my genes didn’t love Susan, my wife. I did.

Perry Marshall:  When we introduce agency to evolution, it completely changes everything.

Denis Noble: I absolutely agree. I think this is the fault line. Reductionists don’t like agency because it’s very difficult for them. What you have to then admit is that the causation comes from a high level.

That, of course, is putting it simply. It’s the whole idea of biological relativity that causation can come from any level within the organism. Again, engineers don’t have any difficulty with that.

It isn’t your Mac or your PC that does everything you make them do it is you who types away on the Qwerty keyboard and whatever it might be to create the functionality and the great novelty that is in your computer.

So in a similar way, it’s not difficult to understand that it’s the higher level of the organisms that will determine what they do and that’s what we’re talking about. That is agency.

Perry Marshall:  And you bring up computers which brings us right to the doorstep of the biggest question in AI which is agency, right?

Right now, algorithms are just algorithms I mean even Siri and Alexa are as dumb as a box of rocks. You only have to talk to them for five minutes to figure that out. Yet what would happen if they had agency? AI and evolution are converging together.

Denis Noble: I would make the following prediction for it being possible which is that the AI people would have to reproduce what organisms do when they harness stochasticity. What do we do?

Again use the immune system as the model but then if you can transfer that to all aspects of organism and human behavior. What it does, just to repeat, is to go down to the stochastic level and turn the wheel of chance to produce trillions of possible solutions to, in case of the immune system, how you produce a new antibody to deal with an invader. What do we do when we’ve got a problem, just thinking of human choice when we’re dealing with a difficult issue we say better sleep on that.  

What I think is going on is that we are then climbing down into the stochastic level wherever that might be, a neural discharge, in cellular activity, whatever it might be and then we have some sort of a filter which is the rationality filter, does it fit or not.

It’s like the immune system asking is this key good to deal with this particular lock. It is the same kind of thing, I think the AI people will have to put in that kind of very clever use of stochasticity then I begin to believe that they might create intelligent forms which are silicon rather than protein.

Perry Marshall:  I agree. So here you are in Oxford, and you did the Royal Society meeting, you’ve published “Was the Watchmaker Blind? Or Was She One-Eyed?” which was a very interesting paper.

You are challenging the Weismann barrier, and you’ve been reaching out to colleagues all around the world and in England. So what’s going on in these conversations that you’re having, and you’re wanting to debate the issues. What going on?

Denis Noble:  Very willing indeed. I’ll tell you what I think is going on within my own church if I might call it that. The physiologists, the bio-chemists, the pathologists and the whole of the medical science community – the great majority of what I’m saying you know they might say “well Denis you’re putting it in a funny way. I’m not used to that because that isn’t what I read in my text books well that’s true”.  But they generally won’t disagree with what I’m saying. So there’s a whole swathe of biological and physical science and mathematical scientists out there. I go and lecture to Congresses all around the world in a whole range of such disciplines.

The only time that I find any degree of resistance to what I’m saying is when I have a bunch of zoologists who’ve been taught the classical theory and then they will say well professor Noble what new discovery have you made in evolutionary biology which is a very nice challenge to be given because I then go through the story that I went through with you. I say well I looked at the question of would a knockout tell you what the gene does, and then I say just think that through.

Once you’ve challenged whether there is a clear, simple relationship between the genes and the organism’s function, you’re undoing the basis of saying that it’s all down there in the genome.

Once you start questioning that, you find if you search enough, you will question much else beside, but that’s the only kind of community within which I find a serious resistance to what I’m saying, but there is another thing I want to add.

I put out the challenge to debate with me; it’s not been replied to. Nobody has taken the trouble from the standard evolutionary biologists to review the new book that’s now out for nearly two years in, for example, the New York review of books, the London review of books. However, you want to put a serious analysis.

What is going on is interesting, it’s as though there’s a kind of silence out there. I don’t know where they are. It’s serious because although I can’t name names, I have been through the process of interacting with an organization that wanted to arrange a debate with me. Four major Neo-Darwinists in turn turned it down for a variety of reasons. I don’t really think they’ve got an answer.

If on the internet as you’ll find very easily by searching, you’ll have a simple misunderstanding like that the Weismann barrier which remember is about the germ line cells is now embodied in the central dogma of molecular biology which remember is something about coding at the molecular level.  

If somebody can say that and think that that justifies the original theory based on Weismann and then on these modern interpretations then they’ve got a big problem because there’s absolutely no way in which the Weismann barrier can be embodied by the central dogma of molecular biology. I’m not challenging the central dogma I think it’s actually correct as a coding mechanism but coming back to the point I made about the qwerty keyboard.

That keyboard which is the CGAT code which then gets typed away as it were by that molecular mechanisms in the cell to produce this protein or that protein no more determines life than the qwerty keyboard determine what I wrote in my articles. It’s very simple actually. There’s nothing complex about the idea at all. So why people won’t come out and debate it, I really don’t know.

Perry Marshall:  It seems pretty clear to me that when you realize that the cell in the organism control the changes of DNA and that it’s not just random and it’s not just selection, then a whole bunch of books, a whole bunch of scientific papers and a whole bunch of careers become obsolete overnight. To just come right out and say it. Isn’t that true Denis?

Denis Noble:  I think it is, but it is a bit more insidious than that because, of course, nobody’s career is actually going to collapse.

Many of the evolutionary biologists are actually doing damn good work it’s just they interpret it within a theoretical structure that I think is faulty. They’ll continue to do their epigenetics and continue to do their field work and so on.

That’s fine, but I think the insidious thing is that it teaches through the standard teaching process, a theory which I think has got things upside down. That’s the problem, and that’s a mindset. It’s not so much as it were are the facts of epigenetics different? Of course, they are not.

Are the facts of genome reorganization in response to challenge any different? All the way from Barbara McClintock to modern studies on hyper mutation, of course, they’re not. Those scientific facts are still the same. It’s just the way in which you view it but why is that important?

We come back to the other thing we were discussing earlier on. It’s important in economics; it’s important in ethics, it’s important in legal processes, it’s important in almost every walk of life because once you’ve accepted the determinist reductionist agenda, you have a very different view of the nature of humanity.

That is what is at stake; it’s the nature of humanity and of course of monkeys, cats, dogs, paramecium, and of viruses.

Perry Marshall:  I think it’s very disempowering to say that I am a lumbering robot controlled by my genes.

It is very empowering to say you are an individual with agency and choice and furthermore your eating choices, your exercising choices, your moral choices, all of these things actually in some maybe small way, they even affect your children and your grandchildren genetically so at every crossroads in life you better make the right decision. I think that’s tremendously empowering.

Denis Noble: Yes. Absolutely right. Imagine a pregnant mother with a child as it was slowly growing in the womb who realizes that what she eats, what else she does, how much exercise she takes and so on will all have an influence on the health of that child in the future and the health of the children of that child and so on.

There are beautiful studies of that. We call these the maternal effect in physiology. Nobody in the world of physiology even questions whether those occur. It’s just that it’s not normally seen in the context of evolution.

They should be, and you are right. It’s empowering, and I think that’s another reason why I find in addition to the communities that I spoke about, the medical science communities, the computer science communities and so on where I lecture and get very little resistance there’s another area, and that is the humanities.

I talk a lot with people in the humanities and people who are interested in evolution from a humanities perspective. They also don’t seriously challenge the great majority of what I’m saying.

Perry Marshall: Well, I want to commend you for your work. I think it’s very important that you’re doing this.  

As far as I can tell, you’re the most credentialed scientist who is challenging the orthodox view and people have been challenging this view for a long time but what seems to be the case was nobody could really get away with in ad hominem attack on you or say that you didn’t know what you were talking about or that you were a lousy scientist where other people they can get away with saying that but they couldn’t say that about you so it seems that if nothing else you’ve gotten them to quiet down quite a bit.

Denis Noble: They’ve had to go quiet because I don’t think they know how to answer the basic argument.

I would put out a very simple challenge, anybody reading the little article, it’s only three pages long, so you don’t spend a long time reading it which is Central dogma or Central debate.

Anybody reading that who thinks there is something wrong in it, I would love to debate with them. There is the challenge.  

Perry Marshall: Fantastic. I’ll just personally invite Richard Dawkins, Jerry Coyne, Daniel Dennett or anybody in that crowd. Denis would be happy to debate with you folks, and I’m sure Denis can arrange for the debate to be held in a perfectly large venue with crowds and cameras and everything and Denis I know you. I know that if you’re wrong about anything you’d welcome to be called out on it so you could be corrected.

Denis Noble:  Exactly. If I’m wrong, I’ll just change my mind. You know some really brilliant people change their minds.

John Eccles who got the Nobel Prize for his work on the nervous system changed his mind critically about the role of synapses.

You can go through a large number of people who through the observations they made came to the conclusion they were wrong. If I’m wrong, I’d love to be shown to be wrong. That’s the way science advances.

Perry Marshall: Excellent. I’d like to encourage our listeners and viewers to check out Denis’s book Dance to the Tune of Life: Biological Relativity, look at his lectures on YouTube. There’s one on the Evolution2 site that’s really wonderful.

Take a look at some of these papers; we’ll include links to them. Denis thank you for being a champion of self-corrective science and in truth-telling and thanks for organizing the Royal Society meeting.  Thanks for helping me the way that you help me and I hope everyone will lend a listening ear.

Denis Noble:  Right. Perry, it was great talking to you.

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