Good evening. My name is Charles Godfrey, I am director of the Oxford Martin School,
and it's my great pleasure to welcome you to the Fifth James Martin Lecture, a lecture in which we commemorate the memory of James Martin.
Jim Martin was a computer and information scientist who wrote Prescient presciently about the challenges faced by humanity in the 21st century,
both natural challenges and challenges associated with technology.
Jim, with an enormous generosity in doubt, the Oxford Martin School with a challenge to the university to do major work to address the
major challenges that mankind's humanity will face over the coming over the coming decades.
It's a great delight that we retain a close contact with the Martin family.
And I'm really pleased to say that Jim's wife, Lillian and Lillian's daughter Jay Wrong are in the audience with us this evening.
So our speaker this afternoon is Sir Paul nurse, Paul nurse.
And Paul is one of the UK's most distinguished scientists.
He's a geneticist, a cell biologist whose work on the cell cycle, the proteins that can control the cell cycle,
led to him being awarded with Leland Hartwell and Tim Nurse, the 2001 Nobel Prise.
This work is of fundamental importance, fundamental basic science importance because the mechanisms are conserved all the way from yeast up to humans.
And because of that, it is a great medical significance as well, especially around cancer.
Paul is not only a scientist but an extraordinary science leader.
And if I stood here and said everything he has done over the last 20 years, there'd be no time for his lectures.
I'm just gonna mention a few things beginning slightly parochially. He was a chair in the 1980s, I think, of our Department of microbiology here.
He's been president of the Rockefeller of Rockefeller University in New York.
He's been president of the Royal Society.
And he was one of the people who conceived of the extraordinary Francis Crick Institute at King's Cross in London.
And as Anne is its first director and chief executive, Paul is on a huge number of things in government,
including the review that led to the restructuring of the research councils and the creation of UK Airai.
On television and radio, Paul is a fabulous and might I say sometimes slightly wicked performer,
a doughty defender, both a good science and the importance of supporting science.
Tonight, Paul is going to tell us what is life. Paul.
Well, thank you, Charles, for that introduction and thank you all for coming.
It's a complete honour to speak in the Sheldonian and also to speak back at the university where I spent five years is true in the 1980s,
a long time ago. A pleasure also to meet Lillian Lillian Martin.
Can I just tell you, it's a wonderful school.
The Martin School taking on big problems and putting together interdisciplinary approaches to solve them.
So thank you. And your family is enabling that and allowing it to happen.
So I'm going to talk about, well, what is for me one of the most fundamental questions in biology,
perhaps the most fundamental, really, which is what is life?
It's only three words. It's very easy to ask that question, but actually it's not so easy to answer it.
There's a bewildering diversity of life on our planet all around us.
There are bacteria, fungi, plants, animals.
And, of course, our cells, human beings, living organisms found on earth are physical entities that maintain themselves,
grow self, organise, reproduce, making more copies of themselves.
But what is it which links these different life forms all together?
For example, what do we have in common with this yellow brimstone butterfly behind me here?
I like insects. I should say I particularly fond of beetles.
Somebody said that before. In actual fact, I'm particularly from the beetles.
But I thought in the Sheldonian a brimstone yellow would be more appropriate.
And you'll see it flitting about your gardens in a couple of weeks time.
It's a harbinger of spring and it's going to flit about my lecture a bit as well.
And I'll refer to a couple of times. So what links this butterfly with us?
In short, what are the core principles that underlie life now?
I'm not the first to ask this question. Of course, I should have here the first title page of a book also called What is Life?
It was written by the famous physicist Erwin scrutiniser in 1944.
His book was influential, if somewhat incomprehensible.
We all read it. I did 50 years ago.
I will quote from it. But I think we remember it in a different way from what it actually is, to be quite honest with you, anyway.
I will quote a cut of one or two passages from it.
However, now my approach to the same question that Schrodinger asked here is to consider some of the important ideas of biology.
I'll describe where they came from. Explain what they are.
None of these ideas are particularly new. I hope I'll be able to explain them to you in perhaps a new sort of way.
But they stood the test of time. And I want to pull on those ideas to develop these principles that are fundamental to life.
I should also say at the beginning, the biologists don't often talk about fundamental principles.
This is this talk about an all the time. Of course. But biologists tend to like to describe details.
You know, we sequence genes and ecologists will count how many species there are in a habitat.
We like making lists. But actually, from what we know about biology, there are principles.
And I want to try and develop them as we go along.
Now, the first idea I'm going to talk about is a simple one.
It's the idea, the concept of the cell. So is the basic structural and functional unit of life.
I call it here, life's atom. They were discovered here in Oxford.
If you go down to the high street, you'll find a plaque recording this.
They were discovered by Robert Hooke, one of the founders of the Royal Society.
A polymath of many were then an architect designing churches in London, an artisan,
an experimentalist, inventor of Hooke's law, which we all had to learn involving Springs at school.
But he also discovered and describe cells.
And this is the picture on your right here.
Sorry, your left. You're using this microscope which he constructed, or one like this.
And what he did is he used a razor to cut slivers of of cork plant cork, then examine them under a microscope like this.
And what he saw were neat arrays of boxes. He called themselves after the Latin word cellar for small cubicle.
It's shown here in this drawing published in sixteen sixty five in a popular book at the time called Micrograph.
Here I put on the other side there the yellow one, which is a scanning electron microscope picture of the same sorts of material.
So these are the first cells. The basic unit of life.
Few years later, a rather humble Dutch Draper, Anthony von Môn Hook working in Delft in the Netherlands, scraped between his teeth.
Put it under a single lens microscope, which was actually a very good one and discovered single celled life.
What we now know as a bacteria. Mm hmm.
Let me. Good. This is a pitch from Loan Hook.
He sent this picture to the Royal Society in the 60s, 70s or 16 80s.
It's rather charming. If you look at the figure B, C, D up there, obviously under the microscope,
these bacteria don't just A, loop the loop swimming about under the microscope.
It was a bit disturbed by this discovery of these little animals, which he called Animal Cool's, because he found them between his teeth.
And you'd rather proud of his dental hygiene and felt disturbed at finding his little animals living in his teeth.
He was a close neighbour in Delph to the painter Vermeer and Vermeer.
Unusually for an artist, actually, both then and now painted pictures of scientists.
He did two pictures and he only has about 14 genre. And this is the one in the loo.
I'm getting better at it. This is the one in the Louvre called the Astronomer.
I like to think that this might have been stimulated by low input.
There's no evidence for this, of course. Pure speculation, although when Vermeer died alone, Hook was appointed as his executor.
So it's very likely that they did know each other anyway.
Let's imagine it could be loan hook. The discoverer of single celled life.
Now, over the next two centuries, it became clear that all living organisms consisted either of a single cell or a collection of cells.
And this led to the early 19th century.
It took two centuries really to sort all this out.
It's quite difficult to examine living material under a microscope, particularly animal material, over the next two centuries.
It became clear that cells were everywhere. And Theodore Schwarm, German zoologist here in 1839,
summarised all this up when he concluded that all organisms are composed of essentially like parts, namely of cells.
There were many who contributed to this. He was one of the better publicists.
So we tend to give him a SLIDIN. Schwarm QLogic was a botanist.
The credit for that. But it has to be said, he would just better publicist, probably.
But as well as cells being the basic structural unit of life,
which is how we generally talked about it at school, they are also the basic functional unit of life.
And as was argued by another German scientist, pathologist, this time Rudolf Burkhoff, who in 1858,
some 30 years later wrote that every animal we see up there appears as the thumb of vital units,
each of which bears in itself but complete characteristics of life.
What that means is, is that cells are living organisms and then cells, they they are alive.
They bear the characteristics of life. And he also argued the all cells come from cells on this cellular, a cellular.
In Latin, that was important, too,
because at the time it was thought that maybe living cells just arose spontaneously in some way that wasn't fully understood.
And indicating that all cells were derived from pre-existing cells, my cell division was rather fundamental.
If you think carefully about it, it means that there's a stream of connexion between cell generations through a process
of cell division that stretches back through the development of all living things,
including ourselves,
but also extends eventually back into deep time during the evolution of life on this planet connected through repetitive cell division.
Now, I hope I've convinced you that sells are interesting, but if you are still doubting it, I'll show you this.
This is an egg being fertilised by a sperm.
And perhaps I should remind you that every one of us once looked like this.
We will all once a single cell, we have all been derived from a single cell.
And if you're not interested anymore. There is a door over there.
You know, cells are generally considered to be the simplest entities which exhibit the characteristics of life.
I will talk a little more about that later. But this means understanding self is key to understanding life.
So they will figure out several times quite prominently in the rest of my talk.
So what can we learn about cells that is relevant to understanding life?
This is a modern picture of a cell. Well, first, let's take the obvious.
Cells are bounded physical entities. They are separate from their environment.
They're surrounded by a semi-permeable lipid membrane which separates them from their surroundings, but allows communication with those surroundings.
This, for example, allows nutrient chemicals in the environment to become concentrated in the cell.
So there a physical entity in communication. But separate from the environment.
This means this separation, that order can be built up in cells at the expense of increasing disorder outside cells.
In this way, life does not contravene the second law of thermodynamics, which states the universe as a whole moves towards increasing this order.
I mentioned this because when physicists think about life and they get very worried about this and there is no need for them to worry,
life is solve the problem. It doesn't contravene this law of physics.
It worries Schrodinger a bit, as you can see in this quote here.
This is the first quote up here.
And organisms astonishing gift of controlling a stream of order on itself and thus escaping the decay into atomic chaos.
It's quite sort of exaggerated, of course, in its language,
but what it implies is that that life avoids the problem of the second law of thermodynamics.
And he was very, very concerned about that.
But it found the fact that it's bounded deals with that issue.
He was astonished that life could escape that decay into atomic chaos, as he said here.
And he proposed that a way of solving this of the chromosomes, which will come to in a moment.
It could be explained in some terms of a code script which was passed on through the generations.
And that is linked to the second idea. I'd like to discuss with you.
And that is the gene which explains the mysterious phenomenon of inheritance.
The idea here is, of course, that the gene is the basis of heredity.
It had its origins with the work of an Augustinian monk, Griego Mendel, abbot of Bruno Brno Monastery in the now the Czech Republic.
I was there a couple of weeks ago. This is Griego.
I call him the Gardening Monk because he did a lot of experiments with plants crossing different
plants with different characteristics to look at how those characteristics were inherited.
He had quite good facilities there. I'll show you a picture of the monastery in a moment.
But what Mendel did was to experiment with maybe half a dozen different plant species,
but then decided to focus on one where he seemed to be able to make sense of what he was observing.
I mention this because biology is complex, and if you're to make sense of the complexity, it helps greatly if you study biological material,
which actually you can make sense of, because having made sense of it, you can perhaps apply those ideas and principles to more complex situations.
And you could call it cheating in a way. Could you just focus on what you can make central?
But if you don't do that, then you can never make sense of the complexity that we're looking at.
So he found pea plants good that have different characteristics.
We analyse the outcomes of thousands of the progeny produced in these crosses.
Publishing his work in 1865. I first visited his monastery in 1981 wasn't so easy to go then.
It was the height of the Cold War. And what you see here is his garden.
It now looks much better when I visited a few weeks ago and he had a greenhouse which was even bigger.
I am astonished that amongst Guss, a Casteen monastery should have invested so much time in indulging a monks curiosity,
which is essentially what was happening. They were like a little research council really funding research.
Except he didn't have to write grants and he didn't have to think about impact factors.
He simply was studying the crosses to see what he could learn from them.
He crossed paths of a varied characteristics, including plants of different height, different flower colours, different seed shapes.
You see some examples up there. Now, he was trained as a physicist.
He never got a degree in. He was in Vienna. I'm not sure he was good at examinations.
But he was good at science. But he took something from physics, which was a respect for consultation,
a respect for theory, which was rather lacking in biologists of the of the time.
And this meant that he was very quantitative in his approach.
He was very careful about how he counted and classified the different characteristics
and only focussed on those characteristics where he could make clear distinction.
And what began to emerge out of these crosses, which had not been noticed by others who were doing similar experiments with simple ratios.
Many of us at school would have learnt the ratio had been taught.
The ratio of three to one, for example. I won't go into it, but this eventually led these simple ratios to mentalism.
The notion that heredity is based on indivisible particles or factors which are inherited through the germ cells,
like the pollen and abuse in these plants, or sperm and eggs in animals.
And these indivisible components,
another example of just like the cell is like the structural functional unit of life and that and this was the the unit of heredity, these factors.
After Mendel could Mendel's work was ignored. Actually, he he became abbot of the monastery.
He got into a fight with the government about taxation and drifted off from counting his plants.
And he published his his his his work.
It was actually published in a decent journal. I'm not sure what the impact factor was, but I'm sure it was moderately good.
But he published there in Darwin. Charles Darwin, who even had a copy of it, though he never cut.
He never read it, by the way. Darwin. Charles Darwin also observed three to one ratios in Cross' with snapdragons.
But he just recorded it more like a naturalist.
He didn't try to think about it, didn't have good enough data to be sure that that ratio was absolutely clear.
And he didn't try to interpret it.
Now, some years after Mendel, around 25, 30 years, these factors were found to be linked to the chromosomes which were discovered in.
In dividing cells. Let me give you an example. This is a picture from the late 19th century from an onion root tip.
Showing chromosomes appearing when cells divided.
I think the nice one. This one here where you can see these threads separating.
I like this particularly because I first saw cells and I first saw chromosomes in an onion tipped squash just like this.
When I was 12 or 30 at school. And so it looked exactly like that, except it was in colour rather than black and white.
Now, these Mendelian factors are, of course, what we now call genes and genes.
Well, one of the most important discoveries of the 20th century and I want to say a little
bit about those discoveries because it's important for developing our principles.
In the 1940s, Oswald Avery in Rockefeller University, New York, which Charles mentioned by, worked him for seven or eight years.
He showed that genes were made of deoxyribonucleic acid or DNA.
It was contentious at the time. Many didn't believe it was published in nineteen forty four.
And I when I went to Rockefeller, they had a cocktail party to welcome me, and this little old man came up to me and shook my hand to welcome me.
And he said his name was Matt. Matt McCarty.
And I looked at him and I said, you're not the McCarty who was on Oswald Avery's paper in nineteen forty four.
And he said, Yes, I am that Makati. He was 91 and still coming in to the university.
Anyway, this was not an idea that was rapidly agreed with his own colleagues at Rockefeller amongst his fiercest cricket critics,
by the way, typical of academics, what we expect from my academic colleagues.
But he would certainly not immediately accepted, however, come 10 years later.
The next major step, which are all very familiar with, is the structure of DNA is a double helix was determine involved a number of people in London,
the experimentalists, Rosalind Franklin, Ryan Gosling, Maurice Williams, Wilkins, and in Cambridge, Francis Crick and Jim Watson.
Crick and Watson famously proposed the structure based on the other experimental evidence of the double helix.
That could explain heredity through the linear sequence of bases, the making up the DNA and the pairing between these complementary bases.
You can see here the base adenine if pairing with thymine, grinding with scientists thing.
Now, this is a double helix, which is this structure allows it to be replicated.
If you think of a double helix as like a twisted ladder and then the rungs of that ladder are the paired bases, then if you, um,
if you untwist that and separate the rungs and then you use that pairing to make a new copy,
just as you see here, you get a precise copying of the genetic material.
And will very familiar with this.
It's copied during the process of cell reproduction, the cell cycle, which I spent my life studying and accounts, of course, for heredity.
It explains Schrodinger's code script, which I mentioned.
It explains the permanence of the gene between generations that bothered Schrodinger because DNA is precisely copied or almost precisely copy,
which are returned to every time a cell divides.
Also, the sequence of bases which encode the information is tucked inside the double strand.
It's kept in the middle of the DNA polymer. Crick went on with others then to propose what we call the central dogma.
What is the central dogma? Such a terrible name, Rudy Dogma.
I hated it. But it's what we all know it is. It describes how the sequence of bases making up of a gene is copied from the DNA to RNA.
And that's REIBER nucleic acid.
This acts as a messenger from the DNA located in the nucleus where the chromosomes are to the cytoplasm where the proteins are made.
The proteins being the structure of the proteins being encoded by the DNA sequence.
The sequence of the messenger RNA determines the structure of those proteins.
And this led in the 50s to the conclusion 60s to the conclusion that there's one gene for each protein.
The initial work which was done in a fungus, actually with one gene for each enzyme.
These discoveries made in the 20th century, mostly the second half, laid the foundations of what we now call molecular biology.
And they are critical to understanding life. Central to it is the genetic code.
Heredity is in a four letter code made at the four bases.
And one thing to emphasise here, this way of storing information is the same as linear sequences in a book which you read.
That's a linear sequence in my talk. I'm talking to you in linear sentences or in bytes in a computer.
They aren't all linear ways of storing information.
It means that this linear digital storage of information was invented by life probably three billion years before the computer age.
We are. We learnt it. If we only know where to look for life.
Well, the nature and function of the gene is an introduction to the next two ideas.
I'm going to talk about life as chemistry and then life as information.
How does chemical activity and physical forces bring about life?
Because life is wonderful.
And yet it's based on chemistry and physics, and this is why vitalism, the idea that there was some special spark was so prevalent.
They this idea that the functioning of living organisms is can be understood in terms of
chemical activity and physical force is an idea that can be traced back to French chemists.
The initial work was done by Lavoisier just before the French Revolution.
Unfortunately, his research was cut short because he met the guillotine being a tax collector for the ancient regime.
A great pity because he was well on his way to sorting this out.
But then it was handed on 50 years later or more to Louis Pasteur, who we know as the father of chemistry.
But shown here in this some heroic painting, not as good as the Vermeer painting, in my view, but still a painting.
And he was carrying out experiments. Would you believe, on sugarbeet fermentation in the north of France?
It was before he was famous and it led to the concept that life can be understood in terms of chemistry.
What was he doing? Well, he was working in the north of France where Sugarbeet was being used to make alcohol.
And the industrialists who were doing that were worried because many of their fermentations failed.
And instead of making alcohol, they made acid.
And he, by just looking at the fermentation, demonstrated that for the successful production of alcohol,
you needed to have a yeast in that a single cell microbe east.
And if you weren't yeast there, it would work. If there wasn't yeast there and there was bacteria, for example,
then the fermentation made acid and he concluded that it was the yeast that was critical.
Now, that was an applied project, totally apply project.
He was working. He was helping industry, but he went on from helping industry to making a fundamental proposal.
What he concluded more generally was that fermentation was a physiological act yielding products for the cell.
In other words, chemical reactions are an expression of the life of a cell.
What he was arguing was like chemistry.
And let me, as an aside, just say that sometimes we argue a lot in our profession about the differences between discovery,
basic research, translational research, applied research, they are much closer than is sometimes thought.
Same principles apply, same curiosity apply. They do work in different ways.
In the case of pasta with what I just described to you, they will complete the mingled.
So Pasteur Pasteur proposed like his chemistry.
But it is very elaborate and special chemistry. And I want to just describe that briefly.
The first point you should be aware of that it is based on carbon polymers and this is going to be important links with other things I've said.
We've already met carbon polymers because they make up nucleic acids, DNA and RNA.
And we're now going to consider them in how they make up proteins. Before going there, though, just to sort of keep you excited.
I want to remind you that carbon is central to life.
But it had its origins in the centres of dying stars where it's made carbon comes from dying stars.
We literally have our origins in the stars.
Now, the substances from yeast that Pasteur with working on are proteins that act as enzymes and enzymes catalyse chemical reactions.
They make chemical reactions go faster. Proteins are polymers of amino acids based on carbon and nitrogen.
The carbon atoms form part of the backbone to that polymer,
and they can also link to chemically different side chains of the amino acids is a little bit of a protein backbone.
And what I want you to see is the the atoms NCD and the nitrogen see for carbon aren't providing a backbone.
But then if you look that you see you have side chains and some of them are constant and oxygen and hydrogen, for example,
others which are down here, as are very and they vary according to the different amino acids that are found in the protein.
Now, these different amino acid side chains are chemically very different.
And this is a very important sum of positively charged.
Someone negatively charged, some repel water. Some are big, some small.
There's 20 different amino acids that make up proteins.
There's only four different nucleotides that make her nucleic acids.
And we'll come back to that when I talk a bit more about principles.
Here are some examples of the different amino acids and their different potential for different chemistry being positively chaffer,
lysine or negatively charged like a spa state.
This result in a wide variety of chemistry that can produce elaborate structures
which have the ability to carry out many and varied different chemical reactions.
And this contrast with DNA, which is stable, is not chemical diverse.
In fact, it's chemically rather dull, which is why Avery's colleagues at Rockefeller oppose his idea.
It just wasn't interesting. Chemistry. Protein do have interesting chemistry.
Now, the change of amino acids making up these protein polymers can fold up in many ways to make complex molecular structure.
Here we have a protein.
It's got a couple of hundred different amino acids and it's starting to fold to make connexions between different amino acid residues that make it up.
And this generates a three dimensional molecular structure that is derived from a one dimensional chain,
which in turn is derived from a one dimensional chain, a linear information device.
And I empathise. So here we have a three dimensional structure. Now,
these very structures combine with very chemistries is the reason why we and all living things can undertake a
wide diversity of chemical reactions because of the huge variety of enzymes that can be that can be produced.
And they produce these chemical machines, a huge variety of chemicals that are needed for us to operate, for life, to operate.
They make new molecules. They break them down, they recycle them.
They generate molecular assembly, they make polymers, nucleic acid, protein, lipid carbohydrate, all mostly done by these chemically devised proteins.
They can also do physical work. They can make motors which carry cargoes around the cell on protein based trackways.
They can act in hybrid ways, combining chemistry and physics.
Capturing energy from sunlight, often breaking down sugars to produce energy rich chemicals that drive all the activity that cells need to operate.
Now, what does this mean? It means that the thousands of chemical reactions being carried out simultaneously
and close to each other in living cells are put up here just a fraction.
Each of these dots is a chemical reaction that the biochemistry biologists in the room will know.
This is in the middle. Here is the Krebs cycle. There are hundreds of reactions going on on this limited part of of life metabolism.
And all these reactions, all of which require somewhat different micro environments to work, are going on simultaneously all the time in all cells.
At this moment in your body all the time. How is that possible?
It's only achieved by compartmentation.
And this compartmentation is brought about by the surfaces and folds of the enzymes themselves by complexes of enzyme.
Acting together and by membrane bounded organelles.
Which we can see in the cell. Now, I wanted to emphasise that because when you look at the cell, you think, oh, these are bits that make up the cell.
I'd like you to think of them as actually organised compartments,
organised micro chemical compartments that allow hundreds, if not thousands of chemical reactions to occur simultaneously.
Because without that compartmentation, that could not work.
It's Keema ties here in this one, which is a polygraphing Scientific American where you can see some of the compartments that are actually there
generating the different chemical microenvironments required for the elaborate chemistry of life to take place.
Now, that allows the chemistry to take place. But remember, the cell and all life has to operate as a whole.
And that means that these different chemistries have to talk to each other.
If they're not talking to each other, then they cannot behave and act as a whole.
And that talking to each other is communication transfer of information, which leads to my next idea.
If life as information. And life information is reflecting the fact that living things are complex systems.
That we need in those complex systems control for it to work properly together.
And that leads in turn to purpose,
the purpose that you see something happening which has a higher purpose than what the chemistry itself is providing.
Surprisingly, the idea of life is a complex system was first argued by the philosopher Emmanuel Kant.
I, I was taught this when I was at the University of Sussex and I didn't believe the person who told me is true.
The 30 pages of his book on moral philosophy,
which talked about life as a complex system in eighteen hundred and two and no because picked up on it now.
Now we talk about system biology and so on. And I don't think most know it had its origins 200 years ago.
Now the operation of a complex system requires management of information.
It's only possible by managing information, by having properly controls.
And I operative and I can give two examples to illustrate this.
The first is to return to DNA. You remember this, the double helix.
Now, the structure of DNA is iconic. It's beautiful. Although I get tired every time I go into a biological research institute.
You immediately see a double helix. So when I put up the crick, I said, I don't mind.
What are we put in there? As long as it looks nothing like a double helix.
Now it's beautiful, but it's real beauty lies in the fact that it only makes sense when it's realised that this molecule is,
in fact, a digital information storage device. It's written, as I've already said to you, in the linear script of four letters.
This linear polymer DNA is ideal for storing information and the encoding bases being turned inside are protected from chemical change.
And as I've already explained, but I wish to emphasise and therefore repeat, this information can be turned into chemical action,
but can do work by encoding the chemical activity of the proteins, as I've explained to you.
For me, this is absolutely wonderful. It's a wonderful characteristic of life.
The carbon based polymers have both abilities to encode information in one dimensional,
stable linear structures and to carry out chemical and physical work in three dimensional, chemically active structures.
And it's worth pondering. I was taught this at school university everywhere, but some owners of realised this in recent years.
Second example I want to discuss is regulation that is making complex systems in living organisms act as a whole to be able to behave in with purpose.
Now, to understand what I'm saying here, I'm going to go to manmade machines and you may be like me.
I sort of understand most machines that were made before nineteen hundred and
increasingly less and less machines that were made after nineteen hundred.
This is a picture I took on a steam boat in New Zealand, I think, and the boat was built in eighteen ninety six or something like that.
And it had a beautiful governor. This is a governor. What does this do.
It was invented by James Watt in the 18th century. And as the engine goes fast, that spindle goes fast.
The balls are centrifugal force. They lift up this valve here and that regulates the steam going into the engine and that slows the engine down.
The board go back in and it puts more steam in and the engine goes up again.
It's a homeostatic mechanism designed to maintain a constant speed of the steam engine.
It manmade is designed to do this purpose, and that's what it does.
It's essentially a negative feedback loop up there, which is shown in the context of a magic bullet pathway in a cell.
Just imagine that you have three chemicals, A being turned into B being turned into C by different enzymes, a C accumulate.
Imagine it inhibits the enzyme that the catalyses is going to be.
Then if you get too much C, it will switch off its production. It will drop and it will maintain homeostasis negative feedback.
And that is something that is used frequently in living cells.
It was well demonstrated by brilliant pair of French geneticists, France Soir Jacobe and Jacques Momo.
I had the privilege of spending some time with Jakob earlier in my life who worked all of this after studying the.
Regulation of sugar metabolism and bacteria simply by genetics, abstract thinking and brilliant models of how it might work.
Other control modules, and I'm going to call them modules, for example, lead to a positive feedback loop.
That means as sea accumulates, it activates the A to be enzyme.
And so you get more of C. And what this is, is like a switch. Once you start going, you rapidly go from one state to another.
Now, many such feedbacks and controlled modules operate in cells.
They maintain homeostasis that generates switches, timers, toggles, oscillators, translating the chemistry into informational modules.
So you're going from chemistry now to managing information and they can be linked
together to generate more elaborate routines and informational management.
I want to put this up as a metaphor for this.
This is a transistor radio and some wit has put these red and yellow labels, which are genes involved in cancer.
Actually,
just to show that the network that we have designed in a radio or a smartphone or whatever has similarities to the network that we see in in life.
Must be said, though, a better metaphor rather than hardware is Dennis Braze proposal that it's wetware.
Why does he say wetware? What he means is these components are all hard wired together.
So you can't change the basic structure. You can change the inputs and outputs and you can get regulation.
But wetware connects the different components by diffusion through liquid.
And that means you can rewire the hardware for different purposes.
And that's something I suspect we haven't yet thought quite enough about.
But it certainly has the potential to increase the versatility of these control modules.
Now, the management of life chemistry by information allows the behaviour of the complex system to act as a whole.
And that means it can act with overall purpose, such as reproducing a cell, making a butterfly.
Maintaining ourselves. So key here is life, its chemistry, life.
As information now for centuries, generating purposeful behaviours in living things was thought to require a designer, a divine creator.
It took evolution by natural selection to change this.
And that's going to be the final idea that I'm going to discuss with you before trying to pull it together now.
Evolution by natural selection, how living things come apart.
Now, this beautiful idea. And it is a beautiful idea.
Probably the most beautiful idea in biology, mainly due to Charles Darwin.
The idea has two parts, actually. The first is that life evolves over time.
The second is that a major mechanism for that, evolving for evolution is natural selection.
Now that life evolves was not really Charles Darwin's discovery.
It had been around quite, quite a lot before that.
Mm hmm. Not back. Yes.
We have Charles here on your right. And this is his grandfather, Erasmus Darwin.
And this idea that life evolves was discussed for 50, 60 years before Charles by Lamarque Sean Bhatti's Lamarque, who gets rather a bad press today.
But actually, he was a very good biologist. And Charles, his own grandfather, Erasmus.
Now Erasmus with a colourful character. He's he was a scientist, a doctor, a poet.
He wrote most of his research up in poems. I've got I collect books and I've got a number of 18th century books all written in poetry.
He wrote a quite a famous book called All the Loves of Plants,
which is all about plants fertilising each other, couched in sort of classical illusions.
He was a Republican. He was asked to be George, the third physician, which he refused to do.
He was a proponent of women's education. He was had a terrible stutter, was a great conversationalist.
He also argued for the evolution of life.
And he suggested that simple formulas life like molluscs found in a scherrer could evolve into complex animals.
And so he had a motto on his coach which said everything from shelves.
Now, he lived in Litchfield at the time and he was in the cathedral close.
And the dean of Litchfield didn't like this very much and began to preach against him and his wealthy, his wealthy patients.
And because he was also quite an idealist. He didn't charge his poorer patients.
His income depended on his wealthy ones. And because he was getting a disrespectful reputation, he had to paint out his motto from his coach.
Anyway, read about Erasmus. Really interesting. Charles with actually rather more moderate sort of individual compared with his grandfather.
Now, the evolution of life that life changes implies there's a tree of life that living organisms are related.
If life only arose once and only survived once on the planet, it seems likely,
given the conserved chemistry encoding that we find then all life on earth is related.
This is captured in the only illustration in Darwin's Origin of Species, published in 1859, which is where he illustrated the Tree of Life.
He wasn't quite sure whether life originated more than once.
Look at the bottom eight hour. He was a bit, um. You didn't quite know about it.
But here we see a clear tree of life.
He gathered evidence in favour of this during his trip round the world in the Beagle, and he proposed a mechanism, natural selection.
Now, briefly, what is natural selection? It's based on the fact that populations of a species of a living organism exhibit very Asians.
And if these are caused by inheritable genetic changes, which can be caused when the DNA is not copy precisely, or DNA is damaged by external causes.
If these variants then influence characteristics that can make these organisms more successful,
then in principle they will reproduce more and that particular genetic variant would spread through the population over time.
Such variations will accumulate and lead to sufficient changes in that population such that the individuals
will no longer be able to breed with examples from the original population leading to a new species.
Accounting for the title of his book, The Origin of Species. Darwin concluded this in part by his studies of finches in the Galapagos for those.
And I like to think I didn't invent this. I'm afraid I study, but it's a great metaphor.
So some some finches had evolved to crack nuts.
Others to think insects under bark and are what we have here of pliers that basically have
the same structure but are designed to do different things like strip wires or wrench things.
And these were intelligent design and these were designed by natural selection.
This was the. This the fact that these are intelligently designed and these, of course,
divine without an intelligent designer is the reason why Darwin is still contentious, because it it removes the need for a divine creator.
Now, I'm going to push this a little further for natural selection to take place.
Three things are needed. Reproduction, a hereditary system and a hereditary system which exhibits variability upon which selection can work.
Let me show you how this can work on the ideas of simply the cell and the gene.
Imagine a single celled life form with a brown coat.
Imagine the brown coat is encoded by the DNA. Imagine there's a mutation which results in the brown coat becoming a red coat.
And imagine the red coat better than ones with brown coats.
Perhaps they can't be eaten so easily.
Then what you can see is by combining the idea of the gene and the idea of the cell, you automatically get evolution by natural selection.
These three ideas are all closely linked and can give rise to the variety of life.
This is an important idea. So much so that the 20th century geneticist Herman Miller used it to define life.
And that's going to be the starting point for the principles that are now going to draw together.
He defined life as living. Things have properties which allow them to undergo natural selection and therefore to evolve.
So he simply took Darwin's definition and turned it into a definition of life.
And this definition is one ongoing to use in the final part.
Talking about the principles. But first, I want to say goodbye to Darwin when he was an old man.
You have to. This is the last sentence in the Origin of Species.
Was this planet of gone cycling on?
According to the fixed law of gravity, from so simple a beginning, endless forms, most beautiful and most wonderful have been and are being evolved.
I wish I could write papers, right. The editors who of course would scrap it out and said far, you know, superfluous, superfluous.
Also note that he's linking himself to Isaac Newton and that biology can have laws just like physics.
And I'm going to turn to core principles,
but I want to have two minutes on viruses because viruses are always troubling when well, actually very troubling at the moment.
But viruses are also troubling conceptually in what?
And by thinking about them, I think it will clarify us how we should think about life, not viruses.
This is a bacteria phage which infects bacteria, actually have a nucleic acid genome, DNA or RNA.
They have genes important for the virus. They undergo evolution by natural selection, which is why influenza changes each year.
So pass Mullers tests, but they can only reproduce when they're inside the cells of other host living organisms.
And they do so by hijacking the cells molecular machinery to copy itself.
This means a virus cannot operate separately from its host.
The cellular environment of its host is completely dependent upon another living entity.
So the question is, are they alive or are they not alive?
Now, I am thinking about this. I think it is important to remember that other forms of life are also to a greater or lesser extent,
completely dependent also on other living beings, which is something in this debate that we don't often consider.
Many parasites live on or inside the cells of bodies or animals, plants or fungi, although their dependency is less total than for a virus ourselves.
We can't make certain amino acids. We must obtain them from other living organisms.
Even Frade. Living microbes like yeast are dependent upon molecules usually made by other low living organisms.
ALBE, albeit simple ones like glucose and ammonia plants, are more independent.
They use the energy of the sun to make biomolecules. But even plants rely on bacteria found in their roots to capture nitrogen from the atmosphere.
Perhaps the most free living organism are the cyanobacteria.
Single celled microbes that can capture carbon and nitrogen from the atmosphere and work on the energy from light.
Now I mention all of this so you can see that's a great spectrum of living
organisms from the viruses through to plants with a wide range in before in.
And these all have very dependencies on other life forms.
In the case of the virus, the dependency is very strong. While it's in other organisms, that dependency can be weak.
But I argue that these different my forms are all alive because they all can evolve by natural selection.
If you don't like that explanation, I'll give you another one for viruses.
They're dead when they're outside the cell and they're alive when they're inside the cell.
So that's another solution to the conundrum.
Now, the conclusion I want to draw from this is that life on earth is fundamentally connected, both through being related as a result of evolution.
The tree of life and also through these deep relationships and interdependencies
and interactions that I've just very briefly summarised now with this in hand,
a big breath. I'm about to finish. We're going to have a few principles which reflect what we've said now.
I said that explaining these ideas will help us establish principles.
Let me summarise where I think we've got to. I'll start by reminding you what living organisms do.
They maintain themselves, they grow. They self organise. They reproduce. They have heredity.
So this is what they do at school.
Well, we just taught what they do. But we're going to try and go a bit further from that.
This is all brought about by evolution, by natural selection, central principle for life.
But I think is important is the one by Muller that I just explained to you.
Living things are entities that can undergo evolution by natural selection.
Once you have that, then you can evolve diversity and you do evolve purpose.
You get things at work. They acquire purpose. They are entities that build, maintain and reproduce themselves.
Living things evolve because they have the following attributes.
They are also bounded, separate physical entities based on the self as the basic structural and functional unit of life.
They have a hereditary system which determines how the entity functions that is copied every time the entity reproduces.
The copying is precise but exhibits variation variation that natural selection can work on it with absolutely precise and DNA was never damaged.
We'd have no evolution. So the balance. Life is based on polymer carbon, polymer chemistry.
This is the basis of the lipid membranes that surround cells that can generate order and organisation.
The carbon polymers that make up DNA and RNA, the proteins that make enzymes and all the chemistry we need for life.
Polymer based chemistry gives rise to digital information devices,
storing information in linear change that can be translated into chemical and physical devices and machines.
Integrating all these functions requires the management of information.
Inputs are gathered from within and from outside the cell process stored and then
instructs cells and organisms behave in ways that allow them to maintain themselves,
grow and to reproduce. Now, should we ever encounter life elsewhere in this universe?
I suspect it will be based on rather similar principles.
The details may be different. It could involve different chemistries, perhaps not based on carbon.
However, in my opinion, for it to readily serve the need for both term information storage and diverse chemistry,
I think polymers are likely to be involved. Life forms will require energy sources.
This energy could come from the nuclear reactions within stars, light and heat or geothermal energy within planets circling stars.
But to return to our planet, this is the only corner of the universe where we know for certain life exists.
The life that we are part of is extraordinary on Earth.
It surprises us. It has bewildering diversity.
Scientists are making sense of it, and that understanding makes a fundamental contribution to our culture and to our civilisation.
I want to emphasise that it contributes to our civilisation.
Biology shows that all life, including ourselves, is related to each other, is deeply connected to all of our life.
We share much with this yellow, brimstone butterfly.
Now, as far as we know, we are the only lifeforms who can see this, the connectivity and can reflect upon what it might mean.
In my view, this means that as human, have a special responsibility for life on this planet made up as it is by our relatives.
Some close, some more distant. We need to care about it.
We need to care for it and to do that. We need to understand it.
And that's what I'm trying to do in this lecture. So thank you very much.
So let me begin by thanking Paul for a really stimulating lecture.
We now have a little bit of time for question and answer. I need to remind you that we're being filmed.
So if you are not meant to be here, then perhaps don't ask a question.
When you do ask a question, if you could wait for the microphone to get to you so I can go into the recording and I'm really sorry,
the people in the upper gallery, we won't be able to get a microphone to you.
And so if you can begin to wave and perhaps a first person can go there while we're doing that,
I'm going to take Prerogative Chairman's property up and ask the first question.
And Paul, you talked about the language of the genes that is written in four letters.
And of course, we're just coming to the threshold where we're going to be able to change that if we
want to increase the cavalry in the sense and to do things within synthetic biology.
I wanted to ask you the degree to which you're excited about that, nervous about that,
and what it might be able to do in terms of new science and producing new things and also whether
it might give any insights into the questions that you so clearly outlined in your talk?
Well, I think the people doing this are absolutely brilliant.
I mean, for those and maybe not familiar with it, it's the ability to construct what are called orthogonal codes,
which actually allow living devices to be made that don't depend on the details.
It's the same principles as we talk about. But the same details.
And so this may have the potential to broaden the ability of living things, to do different sorts of things, in particular different chemistries,
which is where synthetic biology has been discussed, that producing organisms that might do more useful things.
I have a feeling it's not going to be quite as useful as it's sometimes argued,
and that just may mean I'm just too old and white haired and not imaginative enough.
I think it's brilliant work and we should do it. And it may work to produce new things.
I think it will produce some new things.
But I think we have yet to explore the extraordinary diversity that Mike is capable of simply by manipulating what we have already.
So I, I don't see it yet as the big shift that some do.
But I think it will add something to that. And what is absolutely sure certain is the people who have done it are absolutely brilliant,
are doing wonderful work, which I couldn't have imagined 20 years ago.
Thank you. Do we have a question? Go ahead. Thank you.
In your view, can information be stored exterior to DNA?
But within the organism? And secondly, briefly, if I may.
Are you satisfied that we can define easily precisely what the organism itself is?
Thank you. What was the second part again? Can we define satisfactorily exactly what the organism itself is?
Well, I think you could imagine information being stored in different sorts of ways.
Indeed, many around 1950 thought it was encoded in protein structure, for example.
And in a sense, there is information that is stored there.
I personally think, and I argue quite strongly that for versatility and for ease of operation that it's stored,
it'll be stored most readily in linear form. And we see that everywhere.
You know, as I said, I'm speaking in linear form.
But you could design and indeed, the synthetic biology approach is to design different and different ways of doing it.
So I could conceive of it being different DNA. You we have store in RNA, for example.
It's still in nucleic acid. But it's a different molecule. We have information stored outside the nucleus, which is not what you were saying.
But we have that in the mitochondria, which was probably a a captured microbe from one thousand five hundred million years ago that persisted.
So we do have different hereditary systems.
Now, the second question I still didn't quite catch, which I think was to do with definition of an organism.
Well, the way I tried to define an organism was not a dictionary style definition.
It was to share principles. I think we should think about that approach isn't quite the same as the way that we define organisms at school,
which I hinted that is to say what organisms do.
It was to try and dig deeper as to what the principles are. I think Mullers definition of evolution by natural selection is a very unifying one.
I think you have to deliver that programme that gets you into chemistry and information.
And I think that you need something to do it in which gets us into cells.
I think once we've sort of taken all that on board, I think we have a reasonable a reasonable basis for thinking about what organisms are.
But I agree it's not a dictionary definition. The Oxford English Dictionary would have a page on it if from if we had to take this on.
Thank you. I think someone has a microphone up there. Yeah.
Hello. You way. Hello. Where are you? I can't see you right up there.
Hello. Hi. So all of the properties that you ascribed to life,
one could imagine a computer programme being written that displayed all those properties like you can.
You can make evolving computer programmes fairly easily.
Would you consider computer programmes that have all those properties to be a form of life?
Or do you think that the subject, like the physical substrate matters?
Or is it more of like a structural property?
Well, you're quite right. We have programmes that evolved by natural selection.
So some people have argued that in some sense this might represent life.
I did sort of anticipating the question. I did sort of stress at several stages that we needed a physical entity that could do it itself.
Now, in the tense of a computer programme, it is also reliant on another life form just to go back to interdependency.
In this case, a human being that creates the computer programme but also creates the hardware in which it works.
So the way I sort of push a computer programme to one side, although fully acknowledging that it has some of the characteristics that I describe,
is it is not a physical, independent entity which is doing it itself.
It is working within a medium, as you fully I know you fully understand.
And within that medium, it is it's evolving in terms of its language is evolving, but it is not a physical, independent entity.
I would argue, but that's certainly the point you make is is made and cogently.
And we have to think about that, just like we have to think about viruses. But for me, me, I'm including viruses of alive.
Computer programmes that dead. A question here.
Hand up. I loved your repeated use of purposeful on purpose.
And that's a very rich concept that can be used to mean children downward causation as opposed to a bottom up reductionism.
Yeah. Albeit with the need to address the challenge of over determination.
Yep. All the way through to the general purposes that one can find and choose and determine.
And I wondered how you were using it and how you see a continuum all the way through to us.
Who suddenly feels as if we're biological beings who can choose purposes yet?
No. So that's an insightful question.
We think we behave with purpose all the time. Sometimes our purposes seem utterly trivial.
And that should not divert us in some ways from the sort of purpose I'm talking here.
Monarch Jacques Monod, who I mentioned, coined a term for it.
He call it a fancy term. So we didn't get confused with purpose.
He called it Teeley Anomic, which is purpose in the sphere of biology rather than human behaviour, so that it's to make some distinction there.
But I want to explore a bit more of what you were saying about levels, because purpose is occurs at different levels and purpose.
That is behaviour of the system as a whole. Lift you from chemistry into biology.
And a chemical reaction is not life replication of DNA that we can do in a test tube.
Isn't life, but the purposeful behaviour of a cell is.
And somewhere in there is a transition from chemistry to biology.
And I think that's something that is worth thinking about because I'm not quite sure where that transition occurs.
But there's something else to do with these different levels, which I think is interesting.
I mentioned life is information now at different levels of life,
from molecular assemblies to cells to organs to organism to populations to ecosystems are all
complex systems subject to similar laws when they are reduced to the management of information.
And what I happen to think is that what we may learn in terms of the management of
information at the level of molecules will turn out to be relevant in an ecosystem.
And what we learn in an ecosystem will be relevant to the behaviour of molecules, which is why I think we have to focus on biology as a whole system.
When we teach it and not have molecular biologists and botanists and zoologists or whatever,
which we we we're reversing a bit now, but with a real problem.
So I think the unifying way of thinking about this is the management.
The information at different levels isn't quite the question you asked for.
I'm glad to be able to make that point, too. That's very helpful.
Thank you. Thank you. Lady in the striped jersey.
Hello. It it feels like yesterday, but it was actually a few years ago you gave a wonderful lecture in this room, I think it was the Remains lecture.
Oh, yes. And it was called you correct me if I'm wrong.
Four great ideas. And by the way, the cell. DNA, you're telling me I gave the same.
No. I thought you were going to give the same lecture, but then you did and you'll remind me what you're going, right?
Yes. And then he went and I think there's a fear. And most of what you were told that today was a fifth was the fifth.
But I wonder if you could just summarise what.
People like me, the first part was all completely new.
What the key factors that weren't there in your remains, lectures, information and the linearity and the folding?
Well, I. I'm embarrassed.
You were present at the Reman his lecture, because I was rather hoping nobody would be here so that it wouldn't look as if I was giving good.
I had to come again. You're quite right that it was.
That was a precursor to this. But it evolved by natural selection to to take on a more important problem.
I was interested then in just identifying some of the ideas of biology in a way to generalise about phenomena which which,
as I said at the very beginning, as biologists are rather reluctant to do.
But what I realised over the years in thinking about it is that this is a way of thinking about what life is.
And it also made me think more carefully about the things that you brought up.
You know, going, you know, that linear code, the turning it into Three-Dimensional Action,
you know, chemical inertness, but storing information to chemical activity.
None of that was there. Information wasn't there. I didn't have Mullers definition there.
I didn't hadn't read it then. So but you're right. It was built on that.
I'm writing a book on it's actually a simple book. I mean, I think it's simple and it will come out.
So you it's all laid out there. And I say more things than I said tonight, but I still have a brimstone yellow in it.
That's a fine question that are purely the embodiment of urban shredding and oxer today,
as Tim Palmer, the physicist, is going to ask the next question. And I betrayed Betray my ignorance.
But probably the last. I think the last time I read a book about DNA popular book, I have to say was.
Was about 20 years ago. I remember the phrase junk DNA.
98 percent or something. Sidney Brenner was the only Brando.
I just wondered what it was. It struck me that was an odd thing to happen, that so much of our structure was somehow irrelevant.
What's the thinking today? Is it. Is it still this junk DNA or does every piece play a vital role?
Well, you're quite right. Junk DNA was, I think, invented by Sidney, if I remember rightly, who had a witty way with words.
He which meant that in this case it was would be slightly exaggerated.
But what he was pointing out was that we had genes that encoded things, the proteins.
And then in organisms like ourselves, we had big gaps in between.
And they didn't seem to do anything. Now, in yeast, which you may remember is what I've devoted my life to.
Poor, pathetic person. I am you. We don't have big chunks of DNA in between genes.
It's very gene rich in more complex organisms like ourselves.
There's lots of DNA in between.
And that DNA is increasingly being revealed as having roles primarily in regulating the genes are found embedded within it,
and that it has the potential to give a richer set of behaviours than if you don't have it.
Now, I'll say something else for which I have no evidence.
But it might be relevant to it that if you have an organism like yeast, which is trying to divide as rapidly as possible,
then it doesn't want to be replicating lots and lots of DNA that isn't doing very much.
And so it's managed to get along fine by getting rid of that DNA.
And I think Sydney therefore called it junk. We are rather more complicated in the East.
Believe it or not. And we can exploit everything about DNA and the stuff in between because we don't care too much about how fast ourselves divide.
So we haven't got a copy of the DNA. And so.
So having all that junk DNA definitely increases the ability to regulate it in more complex and interesting ways.
And I think it would be fair to say that we don't yet understand it well enough to have a whole picture of it.
But to understand how all this works, we need to think about the junk as well as the genes, because it isn't junk.
Thank you. There's a question in the back there, there's the chat with the blue t shirt.
Yeah, so the the image you put up there up the butterfly together with your discussion about information and biological systems.
And it brings up the idea of chaos theory.
And I was wondering, do you think that there are intrinsic limits to how much biology we can understand that is put in place by deterministic laws,
but laws that are of a complexity that lead to chaotic systems that at a certain level of detail we cannot possibly understand?
Well, I ponder on this, actually. And I'm beginning to think I'm too old.
I'm not going to see through. Because I think you're right.
And how can I. How can I put this? I'll put it like this.
If we look at physics pre nineteen hundred, Newtonian physics not completely divided in that way.
It is a common sense world where the operation of balls hitting each other.
And so then we have Einsteins relativity in nineteen hundred and five.
And it's a bit strange. You know, if you go to Blackwells and there'll be quite a few popular books on relativity and you buy them list.
I buy them. I read them. You understand it.
You close the book. And then it drifts away. And it drifts away because it isn't really part of a completely commonsense world.
It's beautiful, very beautiful, but it's not part of a common sense world. And if you get over that, you end up with Schrodinger et al.
And so on and Heisenberg and and so on with the structure of matter and urine analysis and wonderland world,
you know, where, you know, things can be alive and dead at the same time.
You know, cats can be showing off. Cat is alive and dead simultaneously.
And so this is a very strange world. Now, why do I use that as a metaphor?
Well, that may be due to the fact that in physics you're looking at the very small and
you're looking at the very big and the live moves out of our common sense world.
Now, biology is infinitely complex. It's very, very complicated.
You know, people go on, I'm going to sidetracks forgive me, but I you know, people worry about reproducibility in biology.
And then the next thing that the newspapers say, it's all fraudulent.
They don't realise how bloody difficult it is, how varied biological material is and how difficult it is to get experiments to work all the time.
And that is because we're dealing with great complexity and we don't understand that complexity.
And I sometimes wonder whether the complexity is going to take us into a different world of the sort you were just not describing,
but on the edge or where are normal common sense principles?
Let's call it. Don't actually apply.
And that and that we're going to need help from scientists to thinking more abstract ways like the physicists to work our way through it.
And when I said I'd like to see that time, because I think that will come.
But I have a feeling it can be beyond my lifetime. So I think we're going to go into a strange, a strange world in biology.
Now, you ask the question, is there a limit? I sort of think we're going to understand how cells work.
I'm not so sure that we're going to understand how consciousness works.
Certainly not in a straightforward way as a cell. So there may be a limit there that I struggle with.
And for sure, we're going to need the help with the humanities and all sorts of other areas to be able to deal with it.
But I think we'll understand. So it may take us to a strange world.
I think you want to reply. Is that right? You looked as if you were.
I think that's a very satisfying answer. Thank you. Well, on that note, I think we have to bring proceedings to a close.
Paul, when you said biology and doing experiments is bloody difficult.
I could see all experimentalists in the audience when a Nobel PRISE winner says that makes all the rest of us feel so much better.
This has been such a funny evening. Thanks so much for coming along. And please, everyone, join me in thanking Paul for a superb lecture.