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Good evening. My name is Charles Godfrey, I am director of the Oxford Martin School,

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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.

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Jim Martin was a computer and information scientist who wrote Prescient presciently about the challenges faced by humanity in the 21st century,

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both natural challenges and challenges associated with technology.

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Jim, with an enormous generosity in doubt, the Oxford Martin School with a challenge to the university to do major work to address the

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major challenges that mankind's humanity will face over the coming over the coming decades.

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It's a great delight that we retain a close contact with the Martin family.

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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.

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So our speaker this afternoon is Sir Paul nurse, Paul nurse.

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And Paul is one of the UK's most distinguished scientists.

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He's a geneticist, a cell biologist whose work on the cell cycle, the proteins that can control the cell cycle,

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led to him being awarded with Leland Hartwell and Tim Nurse, the 2001 Nobel Prise.

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This work is of fundamental importance, fundamental basic science importance because the mechanisms are conserved all the way from yeast up to humans.

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And because of that, it is a great medical significance as well, especially around cancer.

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Paul is not only a scientist but an extraordinary science leader.

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And if I stood here and said everything he has done over the last 20 years, there'd be no time for his lectures.

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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.

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He's been president of the Rockefeller of Rockefeller University in New York.

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He's been president of the Royal Society.

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And he was one of the people who conceived of the extraordinary Francis Crick Institute at King's Cross in London.

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And as Anne is its first director and chief executive, Paul is on a huge number of things in government,

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including the review that led to the restructuring of the research councils and the creation of UK Airai.

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On television and radio, Paul is a fabulous and might I say sometimes slightly wicked performer,

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a doughty defender, both a good science and the importance of supporting science.

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Tonight, Paul is going to tell us what is life. Paul.

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Well, thank you, Charles, for that introduction and thank you all for coming.

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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,

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a long time ago. A pleasure also to meet Lillian Lillian Martin.

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Can I just tell you, it's a wonderful school.

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The Martin School taking on big problems and putting together interdisciplinary approaches to solve them.

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So thank you. And your family is enabling that and allowing it to happen.

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So I'm going to talk about, well, what is for me one of the most fundamental questions in biology,

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perhaps the most fundamental, really, which is what is life?

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It's only three words. It's very easy to ask that question, but actually it's not so easy to answer it.

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There's a bewildering diversity of life on our planet all around us.

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There are bacteria, fungi, plants, animals.

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And, of course, our cells, human beings, living organisms found on earth are physical entities that maintain themselves,

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grow self, organise, reproduce, making more copies of themselves.

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But what is it which links these different life forms all together?

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For example, what do we have in common with this yellow brimstone butterfly behind me here?

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I like insects. I should say I particularly fond of beetles.

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Somebody said that before. In actual fact, I'm particularly from the beetles.

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But I thought in the Sheldonian a brimstone yellow would be more appropriate.

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And you'll see it flitting about your gardens in a couple of weeks time.

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It's a harbinger of spring and it's going to flit about my lecture a bit as well.

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And I'll refer to a couple of times. So what links this butterfly with us?

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In short, what are the core principles that underlie life now?

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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?

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It was written by the famous physicist Erwin scrutiniser in 1944.

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His book was influential, if somewhat incomprehensible.

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We all read it. I did 50 years ago.

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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.

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I will quote a cut of one or two passages from it.

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However, now my approach to the same question that Schrodinger asked here is to consider some of the important ideas of biology.

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I'll describe where they came from. Explain what they are.

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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.

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But they stood the test of time. And I want to pull on those ideas to develop these principles that are fundamental to life.

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I should also say at the beginning, the biologists don't often talk about fundamental principles.

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This is this talk about an all the time. Of course. But biologists tend to like to describe details.

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You know, we sequence genes and ecologists will count how many species there are in a habitat.

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We like making lists. But actually, from what we know about biology, there are principles.

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And I want to try and develop them as we go along.

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Now, the first idea I'm going to talk about is a simple one.

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It's the idea, the concept of the cell. So is the basic structural and functional unit of life.

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I call it here, life's atom. They were discovered here in Oxford.

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If you go down to the high street, you'll find a plaque recording this.

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They were discovered by Robert Hooke, one of the founders of the Royal Society.

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A polymath of many were then an architect designing churches in London, an artisan,

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an experimentalist, inventor of Hooke's law, which we all had to learn involving Springs at school.

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But he also discovered and describe cells.

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And this is the picture on your right here.

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Sorry, your left. You're using this microscope which he constructed, or one like this.

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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.

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And what he saw were neat arrays of boxes. He called themselves after the Latin word cellar for small cubicle.

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It's shown here in this drawing published in sixteen sixty five in a popular book at the time called Micrograph.

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Here I put on the other side there the yellow one, which is a scanning electron microscope picture of the same sorts of material.

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So these are the first cells. The basic unit of life.

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Few years later, a rather humble Dutch Draper, Anthony von Môn Hook working in Delft in the Netherlands, scraped between his teeth.

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Put it under a single lens microscope, which was actually a very good one and discovered single celled life.

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What we now know as a bacteria. Mm hmm.

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Let me. Good. This is a pitch from Loan Hook.

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He sent this picture to the Royal Society in the 60s, 70s or 16 80s.

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It's rather charming. If you look at the figure B, C, D up there, obviously under the microscope,

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these bacteria don't just A, loop the loop swimming about under the microscope.

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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.

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And you'd rather proud of his dental hygiene and felt disturbed at finding his little animals living in his teeth.

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He was a close neighbour in Delph to the painter Vermeer and Vermeer.

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Unusually for an artist, actually, both then and now painted pictures of scientists.

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He did two pictures and he only has about 14 genre. And this is the one in the loo.

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I'm getting better at it. This is the one in the Louvre called the Astronomer.

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I like to think that this might have been stimulated by low input.

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There's no evidence for this, of course. Pure speculation, although when Vermeer died alone, Hook was appointed as his executor.

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So it's very likely that they did know each other anyway.

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Let's imagine it could be loan hook. The discoverer of single celled life.

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Now, over the next two centuries, it became clear that all living organisms consisted either of a single cell or a collection of cells.

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And this led to the early 19th century.

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It took two centuries really to sort all this out.

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It's quite difficult to examine living material under a microscope, particularly animal material, over the next two centuries.

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It became clear that cells were everywhere. And Theodore Schwarm, German zoologist here in 1839,

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summarised all this up when he concluded that all organisms are composed of essentially like parts, namely of cells.

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There were many who contributed to this. He was one of the better publicists.

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So we tend to give him a SLIDIN. Schwarm QLogic was a botanist.

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The credit for that. But it has to be said, he would just better publicist, probably.

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But as well as cells being the basic structural unit of life,

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which is how we generally talked about it at school, they are also the basic functional unit of life.

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And as was argued by another German scientist, pathologist, this time Rudolf Burkhoff, who in 1858,

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some 30 years later wrote that every animal we see up there appears as the thumb of vital units,

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each of which bears in itself but complete characteristics of life.

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What that means is, is that cells are living organisms and then cells, they they are alive.

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They bear the characteristics of life. And he also argued the all cells come from cells on this cellular, a cellular.

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In Latin, that was important, too,

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because at the time it was thought that maybe living cells just arose spontaneously in some way that wasn't fully understood.

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And indicating that all cells were derived from pre-existing cells, my cell division was rather fundamental.

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If you think carefully about it, it means that there's a stream of connexion between cell generations through a process

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of cell division that stretches back through the development of all living things,

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including ourselves,

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but also extends eventually back into deep time during the evolution of life on this planet connected through repetitive cell division.

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Now, I hope I've convinced you that sells are interesting, but if you are still doubting it, I'll show you this.

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This is an egg being fertilised by a sperm.

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And perhaps I should remind you that every one of us once looked like this.

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We will all once a single cell, we have all been derived from a single cell.

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And if you're not interested anymore. There is a door over there.

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You know, cells are generally considered to be the simplest entities which exhibit the characteristics of life.

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I will talk a little more about that later. But this means understanding self is key to understanding life.

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So they will figure out several times quite prominently in the rest of my talk.

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So what can we learn about cells that is relevant to understanding life?

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This is a modern picture of a cell. Well, first, let's take the obvious.

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Cells are bounded physical entities. They are separate from their environment.

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They're surrounded by a semi-permeable lipid membrane which separates them from their surroundings, but allows communication with those surroundings.

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This, for example, allows nutrient chemicals in the environment to become concentrated in the cell.

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So there a physical entity in communication. But separate from the environment.

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This means this separation, that order can be built up in cells at the expense of increasing disorder outside cells.

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In this way, life does not contravene the second law of thermodynamics, which states the universe as a whole moves towards increasing this order.

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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,

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life is solve the problem. It doesn't contravene this law of physics.

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It worries Schrodinger a bit, as you can see in this quote here.

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This is the first quote up here.

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And organisms astonishing gift of controlling a stream of order on itself and thus escaping the decay into atomic chaos.

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It's quite sort of exaggerated, of course, in its language,

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but what it implies is that that life avoids the problem of the second law of thermodynamics.

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And he was very, very concerned about that.

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But it found the fact that it's bounded deals with that issue.

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He was astonished that life could escape that decay into atomic chaos, as he said here.

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And he proposed that a way of solving this of the chromosomes, which will come to in a moment.

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It could be explained in some terms of a code script which was passed on through the generations.

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And that is linked to the second idea. I'd like to discuss with you.

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And that is the gene which explains the mysterious phenomenon of inheritance.

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The idea here is, of course, that the gene is the basis of heredity.

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It had its origins with the work of an Augustinian monk, Griego Mendel, abbot of Bruno Brno Monastery in the now the Czech Republic.

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I was there a couple of weeks ago. This is Griego.

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I call him the Gardening Monk because he did a lot of experiments with plants crossing different

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plants with different characteristics to look at how those characteristics were inherited.

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He had quite good facilities there. I'll show you a picture of the monastery in a moment.

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But what Mendel did was to experiment with maybe half a dozen different plant species,

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but then decided to focus on one where he seemed to be able to make sense of what he was observing.

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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,

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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.

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And you could call it cheating in a way. Could you just focus on what you can make central?

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But if you don't do that, then you can never make sense of the complexity that we're looking at.

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So he found pea plants good that have different characteristics.

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We analyse the outcomes of thousands of the progeny produced in these crosses.

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Publishing his work in 1865. I first visited his monastery in 1981 wasn't so easy to go then.

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It was the height of the Cold War. And what you see here is his garden.

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It now looks much better when I visited a few weeks ago and he had a greenhouse which was even bigger.

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I am astonished that amongst Guss, a Casteen monastery should have invested so much time in indulging a monks curiosity,

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which is essentially what was happening. They were like a little research council really funding research.

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Except he didn't have to write grants and he didn't have to think about impact factors.

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He simply was studying the crosses to see what he could learn from them.

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He crossed paths of a varied characteristics, including plants of different height, different flower colours, different seed shapes.

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You see some examples up there. Now, he was trained as a physicist.

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He never got a degree in. He was in Vienna. I'm not sure he was good at examinations.

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But he was good at science. But he took something from physics, which was a respect for consultation,

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a respect for theory, which was rather lacking in biologists of the of the time.

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And this meant that he was very quantitative in his approach.

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He was very careful about how he counted and classified the different characteristics

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and only focussed on those characteristics where he could make clear distinction.

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And what began to emerge out of these crosses, which had not been noticed by others who were doing similar experiments with simple ratios.

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Many of us at school would have learnt the ratio had been taught.

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The ratio of three to one, for example. I won't go into it, but this eventually led these simple ratios to mentalism.

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The notion that heredity is based on indivisible particles or factors which are inherited through the germ cells,

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like the pollen and abuse in these plants, or sperm and eggs in animals.

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And these indivisible components,

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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.

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After Mendel could Mendel's work was ignored. Actually, he he became abbot of the monastery.

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He got into a fight with the government about taxation and drifted off from counting his plants.

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And he published his his his his work.

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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.

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But he published there in Darwin. Charles Darwin, who even had a copy of it, though he never cut.

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He never read it, by the way. Darwin. Charles Darwin also observed three to one ratios in Cross' with snapdragons.

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But he just recorded it more like a naturalist.

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He didn't try to think about it, didn't have good enough data to be sure that that ratio was absolutely clear.

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And he didn't try to interpret it.

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Now, some years after Mendel, around 25, 30 years, these factors were found to be linked to the chromosomes which were discovered in.

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In dividing cells. Let me give you an example. This is a picture from the late 19th century from an onion root tip.

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Showing chromosomes appearing when cells divided.

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I think the nice one. This one here where you can see these threads separating.

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I like this particularly because I first saw cells and I first saw chromosomes in an onion tipped squash just like this.

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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.

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Now, these Mendelian factors are, of course, what we now call genes and genes.

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Well, one of the most important discoveries of the 20th century and I want to say a little

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bit about those discoveries because it's important for developing our principles.

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In the 1940s, Oswald Avery in Rockefeller University, New York, which Charles mentioned by, worked him for seven or eight years.

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He showed that genes were made of deoxyribonucleic acid or DNA.

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It was contentious at the time. Many didn't believe it was published in nineteen forty four.

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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.

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And he said his name was Matt. Matt McCarty.

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And I looked at him and I said, you're not the McCarty who was on Oswald Avery's paper in nineteen forty four.

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And he said, Yes, I am that Makati. He was 91 and still coming in to the university.

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Anyway, this was not an idea that was rapidly agreed with his own colleagues at Rockefeller amongst his fiercest cricket critics,

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by the way, typical of academics, what we expect from my academic colleagues.

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But he would certainly not immediately accepted, however, come 10 years later.

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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,

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the experimentalists, Rosalind Franklin, Ryan Gosling, Maurice Williams, Wilkins, and in Cambridge, Francis Crick and Jim Watson.

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Crick and Watson famously proposed the structure based on the other experimental evidence of the double helix.

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That could explain heredity through the linear sequence of bases, the making up the DNA and the pairing between these complementary bases.

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You can see here the base adenine if pairing with thymine, grinding with scientists thing.

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Now, this is a double helix, which is this structure allows it to be replicated.

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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,

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if you untwist that and separate the rungs and then you use that pairing to make a new copy,

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just as you see here, you get a precise copying of the genetic material.

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And will very familiar with this.

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It's copied during the process of cell reproduction, the cell cycle, which I spent my life studying and accounts, of course, for heredity.

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It explains Schrodinger's code script, which I mentioned.

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It explains the permanence of the gene between generations that bothered Schrodinger because DNA is precisely copied or almost precisely copy,

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which are returned to every time a cell divides.

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Also, the sequence of bases which encode the information is tucked inside the double strand.

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It's kept in the middle of the DNA polymer. Crick went on with others then to propose what we call the central dogma.

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What is the central dogma? Such a terrible name, Rudy Dogma.

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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.

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And that's REIBER nucleic acid.

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This acts as a messenger from the DNA located in the nucleus where the chromosomes are to the cytoplasm where the proteins are made.

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The proteins being the structure of the proteins being encoded by the DNA sequence.

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The sequence of the messenger RNA determines the structure of those proteins.

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And this led in the 50s to the conclusion 60s to the conclusion that there's one gene for each protein.

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The initial work which was done in a fungus, actually with one gene for each enzyme.

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These discoveries made in the 20th century, mostly the second half, laid the foundations of what we now call molecular biology.

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And they are critical to understanding life. Central to it is the genetic code.

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Heredity is in a four letter code made at the four bases.

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And one thing to emphasise here, this way of storing information is the same as linear sequences in a book which you read.

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That's a linear sequence in my talk. I'm talking to you in linear sentences or in bytes in a computer.

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They aren't all linear ways of storing information.

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It means that this linear digital storage of information was invented by life probably three billion years before the computer age.

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We are. We learnt it. If we only know where to look for life.

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Well, the nature and function of the gene is an introduction to the next two ideas.

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I'm going to talk about life as chemistry and then life as information.

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How does chemical activity and physical forces bring about life?

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Because life is wonderful.

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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.

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They this idea that the functioning of living organisms is can be understood in terms of

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chemical activity and physical force is an idea that can be traced back to French chemists.

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The initial work was done by Lavoisier just before the French Revolution.

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Unfortunately, his research was cut short because he met the guillotine being a tax collector for the ancient regime.

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A great pity because he was well on his way to sorting this out.

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But then it was handed on 50 years later or more to Louis Pasteur, who we know as the father of chemistry.

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But shown here in this some heroic painting, not as good as the Vermeer painting, in my view, but still a painting.

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And he was carrying out experiments. Would you believe, on sugarbeet fermentation in the north of France?

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It was before he was famous and it led to the concept that life can be understood in terms of chemistry.

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What was he doing? Well, he was working in the north of France where Sugarbeet was being used to make alcohol.

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And the industrialists who were doing that were worried because many of their fermentations failed.

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And instead of making alcohol, they made acid.

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And he, by just looking at the fermentation, demonstrated that for the successful production of alcohol,

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you needed to have a yeast in that a single cell microbe east.

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And if you weren't yeast there, it would work. If there wasn't yeast there and there was bacteria, for example,

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then the fermentation made acid and he concluded that it was the yeast that was critical.

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Now, that was an applied project, totally apply project.

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He was working. He was helping industry, but he went on from helping industry to making a fundamental proposal.

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What he concluded more generally was that fermentation was a physiological act yielding products for the cell.

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In other words, chemical reactions are an expression of the life of a cell.

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What he was arguing was like chemistry.

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And let me, as an aside, just say that sometimes we argue a lot in our profession about the differences between discovery,

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basic research, translational research, applied research, they are much closer than is sometimes thought.

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Same principles apply, same curiosity apply. They do work in different ways.

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In the case of pasta with what I just described to you, they will complete the mingled.

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So Pasteur Pasteur proposed like his chemistry.

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But it is very elaborate and special chemistry. And I want to just describe that briefly.

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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.

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We've already met carbon polymers because they make up nucleic acids, DNA and RNA.

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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.

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I want to remind you that carbon is central to life.

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But it had its origins in the centres of dying stars where it's made carbon comes from dying stars.

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We literally have our origins in the stars.

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Now, the substances from yeast that Pasteur with working on are proteins that act as enzymes and enzymes catalyse chemical reactions.

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They make chemical reactions go faster. Proteins are polymers of amino acids based on carbon and nitrogen.

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The carbon atoms form part of the backbone to that polymer,

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and they can also link to chemically different side chains of the amino acids is a little bit of a protein backbone.

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And what I want you to see is the the atoms NCD and the nitrogen see for carbon aren't providing a backbone.

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But then if you look that you see you have side chains and some of them are constant and oxygen and hydrogen, for example,

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others which are down here, as are very and they vary according to the different amino acids that are found in the protein.

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Now, these different amino acid side chains are chemically very different.

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And this is a very important sum of positively charged.

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Someone negatively charged, some repel water. Some are big, some small.

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There's 20 different amino acids that make up proteins.

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There's only four different nucleotides that make her nucleic acids.

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And we'll come back to that when I talk a bit more about principles.

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Here are some examples of the different amino acids and their different potential for different chemistry being positively chaffer,

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lysine or negatively charged like a spa state.

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This result in a wide variety of chemistry that can produce elaborate structures

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which have the ability to carry out many and varied different chemical reactions.

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And this contrast with DNA, which is stable, is not chemical diverse.

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In fact, it's chemically rather dull, which is why Avery's colleagues at Rockefeller oppose his idea.

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It just wasn't interesting. Chemistry. Protein do have interesting chemistry.

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Now, the change of amino acids making up these protein polymers can fold up in many ways to make complex molecular structure.

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Here we have a protein.

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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.

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And this generates a three dimensional molecular structure that is derived from a one dimensional chain,

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which in turn is derived from a one dimensional chain, a linear information device.

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And I empathise. So here we have a three dimensional structure. Now,

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these very structures combine with very chemistries is the reason why we and all living things can undertake a

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wide diversity of chemical reactions because of the huge variety of enzymes that can be that can be produced.

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And they produce these chemical machines, a huge variety of chemicals that are needed for us to operate, for life, to operate.

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They make new molecules. They break them down, they recycle them.

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They generate molecular assembly, they make polymers, nucleic acid, protein, lipid carbohydrate, all mostly done by these chemically devised proteins.

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They can also do physical work. They can make motors which carry cargoes around the cell on protein based trackways.

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They can act in hybrid ways, combining chemistry and physics.

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Capturing energy from sunlight, often breaking down sugars to produce energy rich chemicals that drive all the activity that cells need to operate.

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Now, what does this mean? It means that the thousands of chemical reactions being carried out simultaneously

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and close to each other in living cells are put up here just a fraction.

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Each of these dots is a chemical reaction that the biochemistry biologists in the room will know.

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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.

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And all these reactions, all of which require somewhat different micro environments to work, are going on simultaneously all the time in all cells.

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At this moment in your body all the time. How is that possible?

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It's only achieved by compartmentation.

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And this compartmentation is brought about by the surfaces and folds of the enzymes themselves by complexes of enzyme.

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Acting together and by membrane bounded organelles.

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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.

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I'd like you to think of them as actually organised compartments,

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organised micro chemical compartments that allow hundreds, if not thousands of chemical reactions to occur simultaneously.

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Because without that compartmentation, that could not work.

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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

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generating the different chemical microenvironments required for the elaborate chemistry of life to take place.

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Now, that allows the chemistry to take place. But remember, the cell and all life has to operate as a whole.

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And that means that these different chemistries have to talk to each other.

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If they're not talking to each other, then they cannot behave and act as a whole.

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And that talking to each other is communication transfer of information, which leads to my next idea.

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If life as information. And life information is reflecting the fact that living things are complex systems.

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That we need in those complex systems control for it to work properly together.

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And that leads in turn to purpose,

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the purpose that you see something happening which has a higher purpose than what the chemistry itself is providing.

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Surprisingly, the idea of life is a complex system was first argued by the philosopher Emmanuel Kant.

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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.

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The 30 pages of his book on moral philosophy,

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which talked about life as a complex system in eighteen hundred and two and no because picked up on it now.

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Now we talk about system biology and so on. And I don't think most know it had its origins 200 years ago.

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Now the operation of a complex system requires management of information.

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It's only possible by managing information, by having properly controls.

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And I operative and I can give two examples to illustrate this.

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The first is to return to DNA. You remember this, the double helix.

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Now, the structure of DNA is iconic. It's beautiful. Although I get tired every time I go into a biological research institute.

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You immediately see a double helix. So when I put up the crick, I said, I don't mind.

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What are we put in there? As long as it looks nothing like a double helix.

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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,

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in fact, a digital information storage device. It's written, as I've already said to you, in the linear script of four letters.

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This linear polymer DNA is ideal for storing information and the encoding bases being turned inside are protected from chemical change.

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And as I've already explained, but I wish to emphasise and therefore repeat, this information can be turned into chemical action,

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but can do work by encoding the chemical activity of the proteins, as I've explained to you.

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For me, this is absolutely wonderful. It's a wonderful characteristic of life.

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The carbon based polymers have both abilities to encode information in one dimensional,

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stable linear structures and to carry out chemical and physical work in three dimensional, chemically active structures.

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And it's worth pondering. I was taught this at school university everywhere, but some owners of realised this in recent years.

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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.

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Now, to understand what I'm saying here, I'm going to go to manmade machines and you may be like me.

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I sort of understand most machines that were made before nineteen hundred and

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increasingly less and less machines that were made after nineteen hundred.

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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.

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And it had a beautiful governor. This is a governor. What does this do.

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It was invented by James Watt in the 18th century. And as the engine goes fast, that spindle goes fast.

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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.

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The board go back in and it puts more steam in and the engine goes up again.

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It's a homeostatic mechanism designed to maintain a constant speed of the steam engine.

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It manmade is designed to do this purpose, and that's what it does.

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It's essentially a negative feedback loop up there, which is shown in the context of a magic bullet pathway in a cell.

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Just imagine that you have three chemicals, A being turned into B being turned into C by different enzymes, a C accumulate.

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Imagine it inhibits the enzyme that the catalyses is going to be.

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Then if you get too much C, it will switch off its production. It will drop and it will maintain homeostasis negative feedback.

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And that is something that is used frequently in living cells.

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It was well demonstrated by brilliant pair of French geneticists, France Soir Jacobe and Jacques Momo.

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I had the privilege of spending some time with Jakob earlier in my life who worked all of this after studying the.

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Regulation of sugar metabolism and bacteria simply by genetics, abstract thinking and brilliant models of how it might work.

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Other control modules, and I'm going to call them modules, for example, lead to a positive feedback loop.

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That means as sea accumulates, it activates the A to be enzyme.

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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.

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Now, many such feedbacks and controlled modules operate in cells.

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They maintain homeostasis that generates switches, timers, toggles, oscillators, translating the chemistry into informational modules.

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So you're going from chemistry now to managing information and they can be linked

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together to generate more elaborate routines and informational management.

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I want to put this up as a metaphor for this.

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This is a transistor radio and some wit has put these red and yellow labels, which are genes involved in cancer.

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Actually,

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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.

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Must be said, though, a better metaphor rather than hardware is Dennis Braze proposal that it's wetware.

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Why does he say wetware? What he means is these components are all hard wired together.

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So you can't change the basic structure. You can change the inputs and outputs and you can get regulation.

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But wetware connects the different components by diffusion through liquid.

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And that means you can rewire the hardware for different purposes.

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And that's something I suspect we haven't yet thought quite enough about.

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But it certainly has the potential to increase the versatility of these control modules.

397
00:47:25,010 --> 00:47:34,280
Now, the management of life chemistry by information allows the behaviour of the complex system to act as a whole.

398
00:47:34,280 --> 00:47:41,660
And that means it can act with overall purpose, such as reproducing a cell, making a butterfly.

399
00:47:41,660 --> 00:47:46,490
Maintaining ourselves. So key here is life, its chemistry, life.

400
00:47:46,490 --> 00:48:00,210
As information now for centuries, generating purposeful behaviours in living things was thought to require a designer, a divine creator.

401
00:48:00,210 --> 00:48:04,260
It took evolution by natural selection to change this.

402
00:48:04,260 --> 00:48:12,810
And that's going to be the final idea that I'm going to discuss with you before trying to pull it together now.

403
00:48:12,810 --> 00:48:18,360
Evolution by natural selection, how living things come apart.

404
00:48:18,360 --> 00:48:22,440
Now, this beautiful idea. And it is a beautiful idea.

405
00:48:22,440 --> 00:48:28,560
Probably the most beautiful idea in biology, mainly due to Charles Darwin.

406
00:48:28,560 --> 00:48:34,590
The idea has two parts, actually. The first is that life evolves over time.

407
00:48:34,590 --> 00:48:42,900
The second is that a major mechanism for that, evolving for evolution is natural selection.

408
00:48:42,900 --> 00:48:48,400
Now that life evolves was not really Charles Darwin's discovery.

409
00:48:48,400 --> 00:48:54,990
It had been around quite, quite a lot before that.

410
00:48:54,990 --> 00:49:00,330
Mm hmm. Not back. Yes.

411
00:49:00,330 --> 00:49:07,410
We have Charles here on your right. And this is his grandfather, Erasmus Darwin.

412
00:49:07,410 --> 00:49:19,440
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.

413
00:49:19,440 --> 00:49:26,610
But actually, he was a very good biologist. And Charles, his own grandfather, Erasmus.

414
00:49:26,610 --> 00:49:34,980
Now Erasmus with a colourful character. He's he was a scientist, a doctor, a poet.

415
00:49:34,980 --> 00:49:44,730
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.

416
00:49:44,730 --> 00:49:49,050
He wrote a quite a famous book called All the Loves of Plants,

417
00:49:49,050 --> 00:49:55,980
which is all about plants fertilising each other, couched in sort of classical illusions.

418
00:49:55,980 --> 00:50:01,230
He was a Republican. He was asked to be George, the third physician, which he refused to do.

419
00:50:01,230 --> 00:50:09,450
He was a proponent of women's education. He was had a terrible stutter, was a great conversationalist.

420
00:50:09,450 --> 00:50:12,810
He also argued for the evolution of life.

421
00:50:12,810 --> 00:50:21,750
And he suggested that simple formulas life like molluscs found in a scherrer could evolve into complex animals.

422
00:50:21,750 --> 00:50:29,040
And so he had a motto on his coach which said everything from shelves.

423
00:50:29,040 --> 00:50:34,470
Now, he lived in Litchfield at the time and he was in the cathedral close.

424
00:50:34,470 --> 00:50:44,180
And the dean of Litchfield didn't like this very much and began to preach against him and his wealthy, his wealthy patients.

425
00:50:44,180 --> 00:50:49,380
And because he was also quite an idealist. He didn't charge his poorer patients.

426
00:50:49,380 --> 00:51:01,380
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.

427
00:51:01,380 --> 00:51:10,440
Anyway, read about Erasmus. Really interesting. Charles with actually rather more moderate sort of individual compared with his grandfather.

428
00:51:10,440 --> 00:51:18,750
Now, the evolution of life that life changes implies there's a tree of life that living organisms are related.

429
00:51:18,750 --> 00:51:24,060
If life only arose once and only survived once on the planet, it seems likely,

430
00:51:24,060 --> 00:51:31,320
given the conserved chemistry encoding that we find then all life on earth is related.

431
00:51:31,320 --> 00:51:41,970
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.

432
00:51:41,970 --> 00:51:46,080
He wasn't quite sure whether life originated more than once.

433
00:51:46,080 --> 00:51:51,240
Look at the bottom eight hour. He was a bit, um. You didn't quite know about it.

434
00:51:51,240 --> 00:51:54,420
But here we see a clear tree of life.

435
00:51:54,420 --> 00:52:04,650
He gathered evidence in favour of this during his trip round the world in the Beagle, and he proposed a mechanism, natural selection.

436
00:52:04,650 --> 00:52:14,490
Now, briefly, what is natural selection? It's based on the fact that populations of a species of a living organism exhibit very Asians.

437
00:52:14,490 --> 00:52:25,800
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.

438
00:52:25,800 --> 00:52:32,580
If these variants then influence characteristics that can make these organisms more successful,

439
00:52:32,580 --> 00:52:41,160
then in principle they will reproduce more and that particular genetic variant would spread through the population over time.

440
00:52:41,160 --> 00:52:47,850
Such variations will accumulate and lead to sufficient changes in that population such that the individuals

441
00:52:47,850 --> 00:52:54,300
will no longer be able to breed with examples from the original population leading to a new species.

442
00:52:54,300 --> 00:53:05,190
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.

443
00:53:05,190 --> 00:53:10,260
And I like to think I didn't invent this. I'm afraid I study, but it's a great metaphor.

444
00:53:10,260 --> 00:53:16,150
So some some finches had evolved to crack nuts.

445
00:53:16,150 --> 00:53:23,220
Others to think insects under bark and are what we have here of pliers that basically have

446
00:53:23,220 --> 00:53:32,130
the same structure but are designed to do different things like strip wires or wrench things.

447
00:53:32,130 --> 00:53:41,190
And these were intelligent design and these were designed by natural selection.

448
00:53:41,190 --> 00:53:50,690
This was the. This the fact that these are intelligently designed and these, of course,

449
00:53:50,690 --> 00:54:00,160
divine without an intelligent designer is the reason why Darwin is still contentious, because it it removes the need for a divine creator.

450
00:54:00,160 --> 00:54:04,860
Now, I'm going to push this a little further for natural selection to take place.

451
00:54:04,860 --> 00:54:15,630
Three things are needed. Reproduction, a hereditary system and a hereditary system which exhibits variability upon which selection can work.

452
00:54:15,630 --> 00:54:20,760
Let me show you how this can work on the ideas of simply the cell and the gene.

453
00:54:20,760 --> 00:54:24,750
Imagine a single celled life form with a brown coat.

454
00:54:24,750 --> 00:54:33,210
Imagine the brown coat is encoded by the DNA. Imagine there's a mutation which results in the brown coat becoming a red coat.

455
00:54:33,210 --> 00:54:37,230
And imagine the red coat better than ones with brown coats.

456
00:54:37,230 --> 00:54:39,660
Perhaps they can't be eaten so easily.

457
00:54:39,660 --> 00:54:49,650
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.

458
00:54:49,650 --> 00:54:57,360
These three ideas are all closely linked and can give rise to the variety of life.

459
00:54:57,360 --> 00:55:06,210
This is an important idea. So much so that the 20th century geneticist Herman Miller used it to define life.

460
00:55:06,210 --> 00:55:11,790
And that's going to be the starting point for the principles that are now going to draw together.

461
00:55:11,790 --> 00:55:20,520
He defined life as living. Things have properties which allow them to undergo natural selection and therefore to evolve.

462
00:55:20,520 --> 00:55:25,620
So he simply took Darwin's definition and turned it into a definition of life.

463
00:55:25,620 --> 00:55:31,740
And this definition is one ongoing to use in the final part.

464
00:55:31,740 --> 00:55:37,830
Talking about the principles. But first, I want to say goodbye to Darwin when he was an old man.

465
00:55:37,830 --> 00:55:41,990
You have to. This is the last sentence in the Origin of Species.

466
00:55:41,990 --> 00:55:44,550
Was this planet of gone cycling on?

467
00:55:44,550 --> 00:55:55,350
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.

468
00:55:55,350 --> 00:56:05,640
I wish I could write papers, right. The editors who of course would scrap it out and said far, you know, superfluous, superfluous.

469
00:56:05,640 --> 00:56:12,810
Also note that he's linking himself to Isaac Newton and that biology can have laws just like physics.

470
00:56:12,810 --> 00:56:14,910
And I'm going to turn to core principles,

471
00:56:14,910 --> 00:56:25,680
but I want to have two minutes on viruses because viruses are always troubling when well, actually very troubling at the moment.

472
00:56:25,680 --> 00:56:31,440
But viruses are also troubling conceptually in what?

473
00:56:31,440 --> 00:56:38,910
And by thinking about them, I think it will clarify us how we should think about life, not viruses.

474
00:56:38,910 --> 00:56:46,320
This is a bacteria phage which infects bacteria, actually have a nucleic acid genome, DNA or RNA.

475
00:56:46,320 --> 00:56:54,690
They have genes important for the virus. They undergo evolution by natural selection, which is why influenza changes each year.

476
00:56:54,690 --> 00:57:04,350
So pass Mullers tests, but they can only reproduce when they're inside the cells of other host living organisms.

477
00:57:04,350 --> 00:57:09,930
And they do so by hijacking the cells molecular machinery to copy itself.

478
00:57:09,930 --> 00:57:14,040
This means a virus cannot operate separately from its host.

479
00:57:14,040 --> 00:57:20,700
The cellular environment of its host is completely dependent upon another living entity.

480
00:57:20,700 --> 00:57:25,970
So the question is, are they alive or are they not alive?

481
00:57:25,970 --> 00:57:34,380
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,

482
00:57:34,380 --> 00:57:41,400
completely dependent also on other living beings, which is something in this debate that we don't often consider.

483
00:57:41,400 --> 00:57:52,530
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.

484
00:57:52,530 --> 00:57:58,050
We can't make certain amino acids. We must obtain them from other living organisms.

485
00:57:58,050 --> 00:58:04,700
Even Frade. Living microbes like yeast are dependent upon molecules usually made by other low living organisms.

486
00:58:04,700 --> 00:58:11,100
ALBE, albeit simple ones like glucose and ammonia plants, are more independent.

487
00:58:11,100 --> 00:58:20,970
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.

488
00:58:20,970 --> 00:58:25,350
Perhaps the most free living organism are the cyanobacteria.

489
00:58:25,350 --> 00:58:34,890
Single celled microbes that can capture carbon and nitrogen from the atmosphere and work on the energy from light.

490
00:58:34,890 --> 00:58:39,510
Now I mention all of this so you can see that's a great spectrum of living

491
00:58:39,510 --> 00:58:46,120
organisms from the viruses through to plants with a wide range in before in.

492
00:58:46,120 --> 00:58:51,690
And these all have very dependencies on other life forms.

493
00:58:51,690 --> 00:58:59,490
In the case of the virus, the dependency is very strong. While it's in other organisms, that dependency can be weak.

494
00:58:59,490 --> 00:59:06,910
But I argue that these different my forms are all alive because they all can evolve by natural selection.

495
00:59:06,910 --> 00:59:10,580
If you don't like that explanation, I'll give you another one for viruses.

496
00:59:10,580 --> 00:59:15,610
They're dead when they're outside the cell and they're alive when they're inside the cell.

497
00:59:15,610 --> 00:59:19,210
So that's another solution to the conundrum.

498
00:59:19,210 --> 00:59:29,560
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.

499
00:59:29,560 --> 00:59:34,240
The tree of life and also through these deep relationships and interdependencies

500
00:59:34,240 --> 00:59:40,300
and interactions that I've just very briefly summarised now with this in hand,

501
00:59:40,300 --> 00:59:50,200
a big breath. I'm about to finish. We're going to have a few principles which reflect what we've said now.

502
00:59:50,200 --> 00:59:55,630
I said that explaining these ideas will help us establish principles.

503
00:59:55,630 --> 01:00:02,650
Let me summarise where I think we've got to. I'll start by reminding you what living organisms do.

504
01:00:02,650 --> 01:00:08,090
They maintain themselves, they grow. They self organise. They reproduce. They have heredity.

505
01:00:08,090 --> 01:00:11,660
So this is what they do at school.

506
01:00:11,660 --> 01:00:16,270
Well, we just taught what they do. But we're going to try and go a bit further from that.

507
01:00:16,270 --> 01:00:22,820
This is all brought about by evolution, by natural selection, central principle for life.

508
01:00:22,820 --> 01:00:27,280
But I think is important is the one by Muller that I just explained to you.

509
01:00:27,280 --> 01:00:31,720
Living things are entities that can undergo evolution by natural selection.

510
01:00:31,720 --> 01:00:36,790
Once you have that, then you can evolve diversity and you do evolve purpose.

511
01:00:36,790 --> 01:00:43,840
You get things at work. They acquire purpose. They are entities that build, maintain and reproduce themselves.

512
01:00:43,840 --> 01:00:47,620
Living things evolve because they have the following attributes.

513
01:00:47,620 --> 01:00:56,230
They are also bounded, separate physical entities based on the self as the basic structural and functional unit of life.

514
01:00:56,230 --> 01:01:05,260
They have a hereditary system which determines how the entity functions that is copied every time the entity reproduces.

515
01:01:05,260 --> 01:01:14,740
The copying is precise but exhibits variation variation that natural selection can work on it with absolutely precise and DNA was never damaged.

516
01:01:14,740 --> 01:01:26,660
We'd have no evolution. So the balance. Life is based on polymer carbon, polymer chemistry.

517
01:01:26,660 --> 01:01:33,440
This is the basis of the lipid membranes that surround cells that can generate order and organisation.

518
01:01:33,440 --> 01:01:41,780
The carbon polymers that make up DNA and RNA, the proteins that make enzymes and all the chemistry we need for life.

519
01:01:41,780 --> 01:01:45,740
Polymer based chemistry gives rise to digital information devices,

520
01:01:45,740 --> 01:01:53,450
storing information in linear change that can be translated into chemical and physical devices and machines.

521
01:01:53,450 --> 01:01:58,400
Integrating all these functions requires the management of information.

522
01:01:58,400 --> 01:02:04,070
Inputs are gathered from within and from outside the cell process stored and then

523
01:02:04,070 --> 01:02:09,740
instructs cells and organisms behave in ways that allow them to maintain themselves,

524
01:02:09,740 --> 01:02:17,900
grow and to reproduce. Now, should we ever encounter life elsewhere in this universe?

525
01:02:17,900 --> 01:02:22,310
I suspect it will be based on rather similar principles.

526
01:02:22,310 --> 01:02:27,710
The details may be different. It could involve different chemistries, perhaps not based on carbon.

527
01:02:27,710 --> 01:02:35,780
However, in my opinion, for it to readily serve the need for both term information storage and diverse chemistry,

528
01:02:35,780 --> 01:02:42,410
I think polymers are likely to be involved. Life forms will require energy sources.

529
01:02:42,410 --> 01:02:51,890
This energy could come from the nuclear reactions within stars, light and heat or geothermal energy within planets circling stars.

530
01:02:51,890 --> 01:03:00,030
But to return to our planet, this is the only corner of the universe where we know for certain life exists.

531
01:03:00,030 --> 01:03:03,780
The life that we are part of is extraordinary on Earth.

532
01:03:03,780 --> 01:03:07,770
It surprises us. It has bewildering diversity.

533
01:03:07,770 --> 01:03:17,200
Scientists are making sense of it, and that understanding makes a fundamental contribution to our culture and to our civilisation.

534
01:03:17,200 --> 01:03:21,540
I want to emphasise that it contributes to our civilisation.

535
01:03:21,540 --> 01:03:32,730
Biology shows that all life, including ourselves, is related to each other, is deeply connected to all of our life.

536
01:03:32,730 --> 01:03:38,100
We share much with this yellow, brimstone butterfly.

537
01:03:38,100 --> 01:03:48,450
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.

538
01:03:48,450 --> 01:03:58,650
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.

539
01:03:58,650 --> 01:04:04,830
Some close, some more distant. We need to care about it.

540
01:04:04,830 --> 01:04:09,540
We need to care for it and to do that. We need to understand it.

541
01:04:09,540 --> 01:04:34,170
And that's what I'm trying to do in this lecture. So thank you very much.

542
01:04:34,170 --> 01:04:39,120
So let me begin by thanking Paul for a really stimulating lecture.

543
01:04:39,120 --> 01:04:45,540
We now have a little bit of time for question and answer. I need to remind you that we're being filmed.

544
01:04:45,540 --> 01:04:51,330
So if you are not meant to be here, then perhaps don't ask a question.

545
01:04:51,330 --> 01:04:57,660
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,

546
01:04:57,660 --> 01:05:03,910
the people in the upper gallery, we won't be able to get a microphone to you.

547
01:05:03,910 --> 01:05:09,220
And so if you can begin to wave and perhaps a first person can go there while we're doing that,

548
01:05:09,220 --> 01:05:13,290
I'm going to take Prerogative Chairman's property up and ask the first question.

549
01:05:13,290 --> 01:05:18,750
And Paul, you talked about the language of the genes that is written in four letters.

550
01:05:18,750 --> 01:05:24,180
And of course, we're just coming to the threshold where we're going to be able to change that if we

551
01:05:24,180 --> 01:05:32,100
want to increase the cavalry in the sense and to do things within synthetic biology.

552
01:05:32,100 --> 01:05:38,820
I wanted to ask you the degree to which you're excited about that, nervous about that,

553
01:05:38,820 --> 01:05:45,420
and what it might be able to do in terms of new science and producing new things and also whether

554
01:05:45,420 --> 01:05:53,850
it might give any insights into the questions that you so clearly outlined in your talk?

555
01:05:53,850 --> 01:05:58,140
Well, I think the people doing this are absolutely brilliant.

556
01:05:58,140 --> 01:06:06,960
I mean, for those and maybe not familiar with it, it's the ability to construct what are called orthogonal codes,

557
01:06:06,960 --> 01:06:17,430
which actually allow living devices to be made that don't depend on the details.

558
01:06:17,430 --> 01:06:21,360
It's the same principles as we talk about. But the same details.

559
01:06:21,360 --> 01:06:34,410
And so this may have the potential to broaden the ability of living things, to do different sorts of things, in particular different chemistries,

560
01:06:34,410 --> 01:06:42,060
which is where synthetic biology has been discussed, that producing organisms that might do more useful things.

561
01:06:42,060 --> 01:06:47,880
I have a feeling it's not going to be quite as useful as it's sometimes argued,

562
01:06:47,880 --> 01:06:54,360
and that just may mean I'm just too old and white haired and not imaginative enough.

563
01:06:54,360 --> 01:06:59,100
I think it's brilliant work and we should do it. And it may work to produce new things.

564
01:06:59,100 --> 01:07:01,380
I think it will produce some new things.

565
01:07:01,380 --> 01:07:09,930
But I think we have yet to explore the extraordinary diversity that Mike is capable of simply by manipulating what we have already.

566
01:07:09,930 --> 01:07:14,460
So I, I don't see it yet as the big shift that some do.

567
01:07:14,460 --> 01:07:20,820
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,

568
01:07:20,820 --> 01:07:26,580
are doing wonderful work, which I couldn't have imagined 20 years ago.

569
01:07:26,580 --> 01:07:32,330
Thank you. Do we have a question? Go ahead. Thank you.

570
01:07:32,330 --> 01:07:38,810
In your view, can information be stored exterior to DNA?

571
01:07:38,810 --> 01:07:43,160
But within the organism? And secondly, briefly, if I may.

572
01:07:43,160 --> 01:07:48,950
Are you satisfied that we can define easily precisely what the organism itself is?

573
01:07:48,950 --> 01:07:59,210
Thank you. What was the second part again? Can we define satisfactorily exactly what the organism itself is?

574
01:07:59,210 --> 01:08:07,580
Well, I think you could imagine information being stored in different sorts of ways.

575
01:08:07,580 --> 01:08:16,430
Indeed, many around 1950 thought it was encoded in protein structure, for example.

576
01:08:16,430 --> 01:08:20,660
And in a sense, there is information that is stored there.

577
01:08:20,660 --> 01:08:31,430
I personally think, and I argue quite strongly that for versatility and for ease of operation that it's stored,

578
01:08:31,430 --> 01:08:36,360
it'll be stored most readily in linear form. And we see that everywhere.

579
01:08:36,360 --> 01:08:39,380
You know, as I said, I'm speaking in linear form.

580
01:08:39,380 --> 01:08:48,170
But you could design and indeed, the synthetic biology approach is to design different and different ways of doing it.

581
01:08:48,170 --> 01:08:53,290
So I could conceive of it being different DNA. You we have store in RNA, for example.

582
01:08:53,290 --> 01:09:01,130
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.

583
01:09:01,130 --> 01:09:10,370
But we have that in the mitochondria, which was probably a a captured microbe from one thousand five hundred million years ago that persisted.

584
01:09:10,370 --> 01:09:13,640
So we do have different hereditary systems.

585
01:09:13,640 --> 01:09:21,020
Now, the second question I still didn't quite catch, which I think was to do with definition of an organism.

586
01:09:21,020 --> 01:09:27,590
Well, the way I tried to define an organism was not a dictionary style definition.

587
01:09:27,590 --> 01:09:37,400
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,

588
01:09:37,400 --> 01:09:42,170
which I hinted that is to say what organisms do.

589
01:09:42,170 --> 01:09:51,020
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.

590
01:09:51,020 --> 01:09:56,900
I think you have to deliver that programme that gets you into chemistry and information.

591
01:09:56,900 --> 01:10:01,430
And I think that you need something to do it in which gets us into cells.

592
01:10:01,430 --> 01:10:11,870
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.

593
01:10:11,870 --> 01:10:19,500
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.

594
01:10:19,500 --> 01:10:24,250
Thank you. I think someone has a microphone up there. Yeah.

595
01:10:24,250 --> 01:10:28,520
Hello. You way. Hello. Where are you? I can't see you right up there.

596
01:10:28,520 --> 01:10:35,580
Hello. Hi. So all of the properties that you ascribed to life,

597
01:10:35,580 --> 01:10:40,950
one could imagine a computer programme being written that displayed all those properties like you can.

598
01:10:40,950 --> 01:10:46,890
You can make evolving computer programmes fairly easily.

599
01:10:46,890 --> 01:10:52,580
Would you consider computer programmes that have all those properties to be a form of life?

600
01:10:52,580 --> 01:10:57,450
Or do you think that the subject, like the physical substrate matters?

601
01:10:57,450 --> 01:11:02,280
Or is it more of like a structural property?

602
01:11:02,280 --> 01:11:07,290
Well, you're quite right. We have programmes that evolved by natural selection.

603
01:11:07,290 --> 01:11:15,030
So some people have argued that in some sense this might represent life.

604
01:11:15,030 --> 01:11:25,980
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.

605
01:11:25,980 --> 01:11:33,690
Now, in the tense of a computer programme, it is also reliant on another life form just to go back to interdependency.

606
01:11:33,690 --> 01:11:40,980
In this case, a human being that creates the computer programme but also creates the hardware in which it works.

607
01:11:40,980 --> 01:11:50,910
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,

608
01:11:50,910 --> 01:11:58,650
is it is not a physical, independent entity which is doing it itself.

609
01:11:58,650 --> 01:12:02,610
It is working within a medium, as you fully I know you fully understand.

610
01:12:02,610 --> 01:12:13,680
And within that medium, it is it's evolving in terms of its language is evolving, but it is not a physical, independent entity.

611
01:12:13,680 --> 01:12:20,070
I would argue, but that's certainly the point you make is is made and cogently.

612
01:12:20,070 --> 01:12:27,120
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.

613
01:12:27,120 --> 01:12:31,930
Computer programmes that dead. A question here.

614
01:12:31,930 --> 01:12:40,240
Hand up. I loved your repeated use of purposeful on purpose.

615
01:12:40,240 --> 01:12:49,460
And that's a very rich concept that can be used to mean children downward causation as opposed to a bottom up reductionism.

616
01:12:49,460 --> 01:12:53,870
Yeah. Albeit with the need to address the challenge of over determination.

617
01:12:53,870 --> 01:13:00,700
Yep. All the way through to the general purposes that one can find and choose and determine.

618
01:13:00,700 --> 01:13:06,150
And I wondered how you were using it and how you see a continuum all the way through to us.

619
01:13:06,150 --> 01:13:11,210
Who suddenly feels as if we're biological beings who can choose purposes yet?

620
01:13:11,210 --> 01:13:15,880
No. So that's an insightful question.

621
01:13:15,880 --> 01:13:21,850
We think we behave with purpose all the time. Sometimes our purposes seem utterly trivial.

622
01:13:21,850 --> 01:13:27,850
And that should not divert us in some ways from the sort of purpose I'm talking here.

623
01:13:27,850 --> 01:13:31,190
Monarch Jacques Monod, who I mentioned, coined a term for it.

624
01:13:31,190 --> 01:13:35,090
He call it a fancy term. So we didn't get confused with purpose.

625
01:13:35,090 --> 01:13:47,920
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.

626
01:13:47,920 --> 01:13:58,960
But I want to explore a bit more of what you were saying about levels, because purpose is occurs at different levels and purpose.

627
01:13:58,960 --> 01:14:05,290
That is behaviour of the system as a whole. Lift you from chemistry into biology.

628
01:14:05,290 --> 01:14:11,830
And a chemical reaction is not life replication of DNA that we can do in a test tube.

629
01:14:11,830 --> 01:14:16,460
Isn't life, but the purposeful behaviour of a cell is.

630
01:14:16,460 --> 01:14:21,340
And somewhere in there is a transition from chemistry to biology.

631
01:14:21,340 --> 01:14:28,450
And I think that's something that is worth thinking about because I'm not quite sure where that transition occurs.

632
01:14:28,450 --> 01:14:32,680
But there's something else to do with these different levels, which I think is interesting.

633
01:14:32,680 --> 01:14:38,290
I mentioned life is information now at different levels of life,

634
01:14:38,290 --> 01:14:47,800
from molecular assemblies to cells to organs to organism to populations to ecosystems are all

635
01:14:47,800 --> 01:14:57,580
complex systems subject to similar laws when they are reduced to the management of information.

636
01:14:57,580 --> 01:15:03,340
And what I happen to think is that what we may learn in terms of the management of

637
01:15:03,340 --> 01:15:09,430
information at the level of molecules will turn out to be relevant in an ecosystem.

638
01:15:09,430 --> 01:15:20,200
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.

639
01:15:20,200 --> 01:15:26,560
When we teach it and not have molecular biologists and botanists and zoologists or whatever,

640
01:15:26,560 --> 01:15:31,480
which we we we're reversing a bit now, but with a real problem.

641
01:15:31,480 --> 01:15:35,420
So I think the unifying way of thinking about this is the management.

642
01:15:35,420 --> 01:15:40,180
The information at different levels isn't quite the question you asked for.

643
01:15:40,180 --> 01:15:44,440
I'm glad to be able to make that point, too. That's very helpful.

644
01:15:44,440 --> 01:15:49,940
Thank you. Thank you. Lady in the striped jersey.

645
01:15:49,940 --> 01:16:00,820
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.

646
01:16:00,820 --> 01:16:04,430
Oh, yes. And it was called you correct me if I'm wrong.

647
01:16:04,430 --> 01:16:11,680
Four great ideas. And by the way, the cell. DNA, you're telling me I gave the same.

648
01:16:11,680 --> 01:16:19,130
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?

649
01:16:19,130 --> 01:16:25,790
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.

650
01:16:25,790 --> 01:16:30,930
But I wonder if you could just summarise what.

651
01:16:30,930 --> 01:16:34,640
People like me, the first part was all completely new.

652
01:16:34,640 --> 01:16:43,490
What the key factors that weren't there in your remains, lectures, information and the linearity and the folding?

653
01:16:43,490 --> 01:16:46,670
Well, I. I'm embarrassed.

654
01:16:46,670 --> 01:16:53,310
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.

655
01:16:53,310 --> 01:16:58,190
I had to come again. You're quite right that it was.

656
01:16:58,190 --> 01:17:07,520
That was a precursor to this. But it evolved by natural selection to to take on a more important problem.

657
01:17:07,520 --> 01:17:16,420
I was interested then in just identifying some of the ideas of biology in a way to generalise about phenomena which which,

658
01:17:16,420 --> 01:17:20,240
as I said at the very beginning, as biologists are rather reluctant to do.

659
01:17:20,240 --> 01:17:27,830
But what I realised over the years in thinking about it is that this is a way of thinking about what life is.

660
01:17:27,830 --> 01:17:33,290
And it also made me think more carefully about the things that you brought up.

661
01:17:33,290 --> 01:17:38,470
You know, going, you know, that linear code, the turning it into Three-Dimensional Action,

662
01:17:38,470 --> 01:17:44,030
you know, chemical inertness, but storing information to chemical activity.

663
01:17:44,030 --> 01:17:48,770
None of that was there. Information wasn't there. I didn't have Mullers definition there.

664
01:17:48,770 --> 01:17:53,810
I didn't hadn't read it then. So but you're right. It was built on that.

665
01:17:53,810 --> 01:17:59,480
I'm writing a book on it's actually a simple book. I mean, I think it's simple and it will come out.

666
01:17:59,480 --> 01:18:06,840
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.

667
01:18:06,840 --> 01:18:12,610
That's a fine question that are purely the embodiment of urban shredding and oxer today,

668
01:18:12,610 --> 01:18:21,800
as Tim Palmer, the physicist, is going to ask the next question. And I betrayed Betray my ignorance.

669
01:18:21,800 --> 01:18:26,990
But probably the last. I think the last time I read a book about DNA popular book, I have to say was.

670
01:18:26,990 --> 01:18:31,610
Was about 20 years ago. I remember the phrase junk DNA.

671
01:18:31,610 --> 01:18:35,510
98 percent or something. Sidney Brenner was the only Brando.

672
01:18:35,510 --> 01:18:42,170
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.

673
01:18:42,170 --> 01:18:49,970
What's the thinking today? Is it. Is it still this junk DNA or does every piece play a vital role?

674
01:18:49,970 --> 01:18:59,780
Well, you're quite right. Junk DNA was, I think, invented by Sidney, if I remember rightly, who had a witty way with words.

675
01:18:59,780 --> 01:19:04,370
He which meant that in this case it was would be slightly exaggerated.

676
01:19:04,370 --> 01:19:09,860
But what he was pointing out was that we had genes that encoded things, the proteins.

677
01:19:09,860 --> 01:19:14,090
And then in organisms like ourselves, we had big gaps in between.

678
01:19:14,090 --> 01:19:20,810
And they didn't seem to do anything. Now, in yeast, which you may remember is what I've devoted my life to.

679
01:19:20,810 --> 01:19:27,140
Poor, pathetic person. I am you. We don't have big chunks of DNA in between genes.

680
01:19:27,140 --> 01:19:32,720
It's very gene rich in more complex organisms like ourselves.

681
01:19:32,720 --> 01:19:35,960
There's lots of DNA in between.

682
01:19:35,960 --> 01:19:45,350
And that DNA is increasingly being revealed as having roles primarily in regulating the genes are found embedded within it,

683
01:19:45,350 --> 01:19:55,310
and that it has the potential to give a richer set of behaviours than if you don't have it.

684
01:19:55,310 --> 01:19:58,580
Now, I'll say something else for which I have no evidence.

685
01:19:58,580 --> 01:20:06,950
But it might be relevant to it that if you have an organism like yeast, which is trying to divide as rapidly as possible,

686
01:20:06,950 --> 01:20:12,530
then it doesn't want to be replicating lots and lots of DNA that isn't doing very much.

687
01:20:12,530 --> 01:20:17,720
And so it's managed to get along fine by getting rid of that DNA.

688
01:20:17,720 --> 01:20:23,930
And I think Sydney therefore called it junk. We are rather more complicated in the East.

689
01:20:23,930 --> 01:20:33,980
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.

690
01:20:33,980 --> 01:20:37,700
So we haven't got a copy of the DNA. And so.

691
01:20:37,700 --> 01:20:45,770
So having all that junk DNA definitely increases the ability to regulate it in more complex and interesting ways.

692
01:20:45,770 --> 01:20:51,590
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.

693
01:20:51,590 --> 01:20:59,920
But to understand how all this works, we need to think about the junk as well as the genes, because it isn't junk.

694
01:20:59,920 --> 01:21:15,150
Thank you. There's a question in the back there, there's the chat with the blue t shirt.

695
01:21:15,150 --> 01:21:23,900
Yeah, so the the image you put up there up the butterfly together with your discussion about information and biological systems.

696
01:21:23,900 --> 01:21:26,630
And it brings up the idea of chaos theory.

697
01:21:26,630 --> 01:21:40,520
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,

698
01:21:40,520 --> 01:21:49,310
but laws that are of a complexity that lead to chaotic systems that at a certain level of detail we cannot possibly understand?

699
01:21:49,310 --> 01:21:56,450
Well, I ponder on this, actually. And I'm beginning to think I'm too old.

700
01:21:56,450 --> 01:22:03,350
I'm not going to see through. Because I think you're right.

701
01:22:03,350 --> 01:22:09,860
And how can I. How can I put this? I'll put it like this.

702
01:22:09,860 --> 01:22:16,580
If we look at physics pre nineteen hundred, Newtonian physics not completely divided in that way.

703
01:22:16,580 --> 01:22:22,100
It is a common sense world where the operation of balls hitting each other.

704
01:22:22,100 --> 01:22:29,180
And so then we have Einsteins relativity in nineteen hundred and five.

705
01:22:29,180 --> 01:22:41,570
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.

706
01:22:41,570 --> 01:22:44,990
I buy them. I read them. You understand it.

707
01:22:44,990 --> 01:22:55,010
You close the book. And then it drifts away. And it drifts away because it isn't really part of a completely commonsense world.

708
01:22:55,010 --> 01:23:01,790
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.

709
01:23:01,790 --> 01:23:12,350
And so on and Heisenberg and and so on with the structure of matter and urine analysis and wonderland world,

710
01:23:12,350 --> 01:23:17,240
you know, where, you know, things can be alive and dead at the same time.

711
01:23:17,240 --> 01:23:22,250
You know, cats can be showing off. Cat is alive and dead simultaneously.

712
01:23:22,250 --> 01:23:26,600
And so this is a very strange world. Now, why do I use that as a metaphor?

713
01:23:26,600 --> 01:23:32,750
Well, that may be due to the fact that in physics you're looking at the very small and

714
01:23:32,750 --> 01:23:38,240
you're looking at the very big and the live moves out of our common sense world.

715
01:23:38,240 --> 01:23:43,610
Now, biology is infinitely complex. It's very, very complicated.

716
01:23:43,610 --> 01:23:50,900
You know, people go on, I'm going to sidetracks forgive me, but I you know, people worry about reproducibility in biology.

717
01:23:50,900 --> 01:23:55,010
And then the next thing that the newspapers say, it's all fraudulent.

718
01:23:55,010 --> 01:24:04,490
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.

719
01:24:04,490 --> 01:24:10,790
And that is because we're dealing with great complexity and we don't understand that complexity.

720
01:24:10,790 --> 01:24:19,310
And I sometimes wonder whether the complexity is going to take us into a different world of the sort you were just not describing,

721
01:24:19,310 --> 01:24:23,360
but on the edge or where are normal common sense principles?

722
01:24:23,360 --> 01:24:26,150
Let's call it. Don't actually apply.

723
01:24:26,150 --> 01:24:36,680
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.

724
01:24:36,680 --> 01:24:40,760
And when I said I'd like to see that time, because I think that will come.

725
01:24:40,760 --> 01:24:48,290
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.

726
01:24:48,290 --> 01:24:57,050
Now, you ask the question, is there a limit? I sort of think we're going to understand how cells work.

727
01:24:57,050 --> 01:25:02,210
I'm not so sure that we're going to understand how consciousness works.

728
01:25:02,210 --> 01:25:09,380
Certainly not in a straightforward way as a cell. So there may be a limit there that I struggle with.

729
01:25:09,380 --> 01:25:15,110
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.

730
01:25:15,110 --> 01:25:19,970
But I think we'll understand. So it may take us to a strange world.

731
01:25:19,970 --> 01:25:24,790
I think you want to reply. Is that right? You looked as if you were.

732
01:25:24,790 --> 01:25:33,130
I think that's a very satisfying answer. Thank you. Well, on that note, I think we have to bring proceedings to a close.

733
01:25:33,130 --> 01:25:37,330
Paul, when you said biology and doing experiments is bloody difficult.

734
01:25:37,330 --> 01:25:45,160
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.

735
01:25:45,160 --> 01:26:05,374
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.