Paul Nurse, Robyn Williams

What is Life?

The question has been asked before, famously by Nobel Prize-winning physicist Erwin Schrödinger in 1944. Now biologist Paul Nurse has addressed the question in his book, What is Life? He describes the wonder of the cell, where thousands of chemical reactions take place at a microscopic scale, all coordinated by the instructions contained in DNA. So what are essential qualities of life? It is an ability to change. A living thing is an entity that is subject to natural selection and can evolve. It needs a gene or a genome of genes and changes and adapts to the environment. The purpose is to survive and reproduce.

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  1. shinichi Post author

    Robyn Williams: Our next superstar has only one Nobel, but he has also been president of the Royal Society of London. Sir Paul Nurse is the first director of the renowned Francis Crick Institute in London and, like Crick, is obsessed by ‘What is Life?’, the title of his delightful first book.

    My first question, Paul, is the unlikely nature of life, one’s own personal life. I just assume you had a gilded path going through the universities, but now I read in your book that in fact you hardly managed to get in because you’d failed French a few times. What happened?

    Paul Nurse: Well, you know, I didn’t come from an academic family, it was a rather normal working-class family, so nobody else in my family stayed (brothers, sisters) beyond 15. So I wasn’t used to books and examinations, to be quite honest with you. I got more used to it as I went through school.

    But one enormous failing that I had then and I still have is my inability to master any foreign language, including Australian English, which has completely escaped me. And at the time, which was the late ’60s, to get into any university in the United Kingdom, you needed to have a number of different what were called O-levels, that’s an examination you take at the age of 15, 16. And one of the requirements was a foreign language.

    And I did three languages at school, I did ancient Latin, ancient Greek, and French. I was so bad at Latin and Greek they wouldn’t even let me sit the examinations, and when it came to French, I managed a world record of failing it six times, twice a year for three years, and never actually passed it. So this meant that I couldn’t go to university, and I worked as a technician in a brewery for a year until some enlightened Professor of Genetics called John Jinks in the University of Birmingham wrote to me and said, ‘I quite liked your A-level grades,’ which is the next examination up, ‘would you like to come and see us so that we could perhaps talk about this French problem you had?’ Up I went to Birmingham, and he fixed it, he got me into university.

    However, the university senate let me in but said I had to do a foreign language for a year at university, so I had to do French. And I remember this so well because I was given the most junior lecturer in the French department and I remember the meeting as if it was yesterday. He sat down with me, a class of one (this couldn’t possibly happen today, by the way, what I’m about to tell you), and he said to me, ‘Paul, you don’t want to be here and I don’t want to be here, so what we’re going to do is a deal. At the end of this year you have to pass an examination, it will be 400 words of scientific French to translate into English. About half the words will be English anyway. I’m going to allow you to take any book you like into the examination and that includes a dictionary, and all you have to do is look up each word and put it approximately in the right order and I will pass you, albeit at a low grade, and that means I don’t think we ever need to meet again.’

    Robyn Williams: And a few years later, extraordinarily, you had to give a speech in French, having got the Legion d’Honneur.

    Paul Nurse: That’s exactly what happened, I got a Legion d’Honneur about ten years ago, no 20 years ago now actually, and indeed I got it from the French ambassador in London, I didn’t go over to Paris, I couldn’t go over then, and I gave of course a thank-you speech in the most dreadful French that you could imagine.

    Robyn Williams: The book is a delight to read, and it’s about one of the most important questions there is—what is life? —and something that was discussed in Dublin…

    Paul Nurse: 1943, lectures. Book, 1944.

    Robyn Williams: Erwin Schrödinger who asked the question brilliantly as a physicist. You’ve tackled it. Why did you want to ask that question and answer it in a book?

    Paul Nurse: Well, firstly that book, the Erwin Schrödinger book, had quite a lot of influence on me, even when I was a schoolboy, which is when I first read it. Getting the clarity of a physicist, looking at the somewhat messiness of biology…I mean, biology is a bit messy, but getting that clarity was really illuminating for me. And Schrödinger focused on perhaps one aspect of life, hereditary essentially, inventing this term ‘code script’ and saying life had to have a code script. And I thought it was worth having another go at it, but in a similar sort of way to Schrödinger, so a small book, a short walk, rather concisely written in fact, and not only draw on the last 70 years but actually push back further into some of the great ideas of biology which have been around for quite a long time, so that was one reason.

    But the second was just to tackle a really interesting problem that probably most people don’t think about too much. And in particular if you go to a bookshop and look at popular books, the physicists are always taking on great ideas, relativity and quantum mechanics and so on, and you always feel sort of good reading their books. Us biologists seem to get deep into particulars and specifics and we are always looking about how it might help us cure some disease or something or other. And I felt, well, biology has its great ideas too, and maybe we should let everybody know what they are as well. So that was the second objective. Biologists do think about problems and this is where we’ve got to.

    Robyn Williams: You quote in the book Sydney Brenner who is talking about the question of what is science. So you’ve got: maths is the art of perfection, physics is the art of the optimal, biology because of evolution is the art of the satisfactory, what works. Beautiful. May I ask you first about the five chapters you have there. The first one really is about the cell. We talk about the cell, this tiny box we think of in which a couple of things go on, but what you demonstrate so extraordinarily is how busy it is and how many thousands of activities are going on all at once. If you take a yeast cell, yeast is your creature, how many things are going on in a cell of yeast, all those chemical reactions and the enzymes working?

    Paul Nurse: Well, you know, the cell is the first chapter and it’s the basic unit of life. I sometimes call it life’s atom, because just like the atom is one of the fundamental units of matter, of course we now though there’s lots within it but it is a very fundamental unit, we biologists think of the cell as the fundamental unit of life, by which I mean it’s really the smallest entity that we can be pretty confident is living.

    And so if you’re interested in ‘what is life’, and in some sense I’ve studied that all my life using the simple yeast cell, as you’ve already hinted at, if you are interested in those problems I always think it’s best to go to the simplest possible situation, the single cell, and a simple version of it, of which yeast is an example, is the best way to start. But though simple, still absolutely extraordinary, and that is reflected in a second chapter which I called ‘Life as Chemistry’, because within this tiny space, and it really is tiny, if you take a yeast cell it’s about 10 micrometres long, that’s 10 millionths of a metre long. If you look into a yeast, there are thousands of chemical reactions going on simultaneously in that tiny space, very, very efficiently, producing all the components needed for the cell, breaking down the components that are no longer needed, and all coordinated one with another, which reflects another chapter which is ‘Life as Information’, because that can only happen if there is management of the information so that all of these different chemical reactions are completely coordinated. So, thousands of very diverse chemistries going on, and also coordinated, all in this absolutely tiny space. Isn’t it absolutely marvellous?

    Robyn Williams: It’s marvellous but also boggling because you’re looking for something very simple that says the answer is, here is the…as Paul Davies wrote in his book The Demon in the Machine, there’s a demon in there somewhere that makes it all happen. I’m reminded of my heart, for example, and you think there’s a kind of cell there, a mission control. It turns out all the cells separately are working together somehow. There is a coordination that goes on which we call life. When it comes to the bigger body, especially if we’ve got multicellular things, you’ve got the growth, these genes are being switched on and off in a way that makes the body grow, and as an aside you mentioned Alan Turing in your book who did all sorts of things we know about, but one thing that lots of people forget is he did the maths of how you develop growth stage by stage. What did Turing actually do?

    Paul Nurse: Well, just before I get to Alan Turing’s work, which is indeed amazing, just to comment on Paul Davies’ book which I also recommend to your listeners, he quotes me a number of times in it because his book is also about information, he focuses on that aspect, how it’s important in life, and that’s something I’ve been thinking about for decades actually, and he’s done a very nice exposition of it. I just wanted to say that.

    Robyn Williams: Yes, that is the demon in the machine, information, yes.

    Paul Nurse: That’s the demon in the machine, and the demon is how it all works together and that’s all to do with information. Alan Turing, total genius, we think about him as the origin of computing, but he was a mathematician that thought about the real world, and he was particularly interested in one of the wonders of the biological world, which is how you generate organisation, form, in for example an embryo. So an embryo, if it’s an insect, a head, a thorax, an abdomen, and you have structure in that form.

    We actually have structure in a cell as well. So it also has the same ability to organise itself. And what was so clever about Turing’s model was this. When you think of very small components, a ribosome would be an example, it also has a structure, but it’s a structure that’s very easy to understand because all the different components, the molecules in a ribosome are all fitted together like a jigsaw, and so it is very easy to see how you get a complex structure if you put Lego together, jigsaw Lego metaphors, and you will get a structure. But of course a living thing has a form over a much bigger scale, and secondly it has this wonderful property of being able to adopt to different scales.

    So if you were to take, for example, an embryo of an insect which was twice as long as another embryo, they would still make almost perfect embryos, so they have the ability to divide up space in exactly the right way, even if that space is a very different scale. And a ribosome can never, never do that, that’s impossible.

    And he did it by a very clever and very simple model where you have chemicals that react to each other but they are diffusing, and they are diffusing at different rates. That leads to structure within the medium in which they are diffusing, and you can simulate this in a bowl of water and mix certain chemicals together and they diffuse away and they make structures. And he used this as an analogy, more of a metaphor for how living form occurs. We still don’t know how living form properly occurs, but there is no doubt that this model of Alan Turing is going to play a role in it, and it’s one of the most interesting parts, this aspect of developmental biology that I can think of.

    Robyn Williams: One wonders what made him think of it, having won the war and having worked out how computers can operate, suddenly he turns to biology as the great challenge.

    Paul Nurse: Well, I don’t know of course that he…unfortunately a tragic figure in many ways, he committed suicide in the early ’50s when I was only three or four years of age. Do you know, my answer would be he had a really intense curiosity about the world and what’s in that world, and he applied what he was good at, the maths, to thinking about that problem, and he came up with something very new. I think it was curiosity that drove him.

    Robyn Williams: Yes, the essential thing. Those examples you give, the cell, the gene, evolution we hinted at, chemistry and information, and you put those together, and the whole point of the book is to ask what is absolutely essential in terms of qualities and the first one you mention is the ability to evolve. You must have the capacity to change, not just sit there forever. You must be open to the environment so that the information can come in and you can respond to it.

    Paul Nurse: It is. I’d like to think that this was my idea, but of course it isn’t, I stole it from geneticists in the past, and it is a definition of life. It’s actually a very complete definition, but a living thing can be defined as an entity which can evolve by natural selection. To be able to evolve by natural selection you have to have a gene or a genome made up of genes and those genes have to make components which alter how the living thing works, and then the living thing is subject to selection because it needs to compete with other living things or work in a different environment, and only those living things which have a gene combination that is more effective actually survive. And so what happens is that gradually the living thing changes and becomes adapted to the conditions under which it is living.

    And what that leads to, and this is the clever trick about it really, what it leads to is the acquisition of purpose, and that isn’t so easy to do. You get purpose which is to survive more effectively, to reproduce more effectively, and behaving as a whole. And that’s why it’s so critical to thinking about life because normally you can only get purpose by design, that is by somebody creating something. A carpenter or a sculptor might create something out of wood, and so you have the design or the very famous metaphor where a watch is found on a path. This is from around 1800, a watch is found on the path, somebody looks at it and sees that it is a mechanism which has purpose and that is therefore evidence that somebody designed it, and that was used as a way of explaining how life came about because it was designed and designed by a creator.

    Robyn Williams: The blind watchmaker, yes.

    Paul Nurse: That’s exactly right, the blind watchmaker, a very famous book, built on this nice story of 1800. And so it’s a central idea to thinking about life. But you then have to explain how life works to be able to get that to all operate, and that’s why I said it is a beautiful start but you don’t actually know quite what life is that allows it to form.

    Robyn Williams: Yes, indeed. And it’s got to be bounded, in other words it’s got to be back in those cells, it’s got to be somehow finite, and we can think of single-cell creatures, we can think of ourselves. But then of course there are the viruses. Are they half alive, depending whether they are in you or out?

    Paul Nurse: Well, I’m glad you brought up viruses, I bring up viruses towards the end of the book because these are always what trip us over when you try to think about what life is, because a virus does evolve by natural selection, so it satisfies that particular criterion, but it can only live in another organism. So we are all living with coronavirus in our societies, but if it were to be in us, then it would invade our cells, and it has a genome, a genome made of RNA, and it undergoes evolution by natural selection when it’s in our bodies, when it’s reproducing itself and growing, and then then it goes and infects another individual. And the reason why it has always been a question of ‘is it alive or is it not alive’ is of course its utter dependency on another living form.

    Well, in my book I make two observations which might help. One is actually all living things are mostly dependent on other living organisms to a greater or lesser extent. As human beings there are certain chemicals we can’t make and we rely on microbes to make them for us. Everything we eat or most things that we eat are made by other living things, plants and animals, for example, and you can go right through the different living kingdoms, and what is revealed by that is how interactive all life is, one with another.

    So, although viruses are extreme, the principle of being dependent upon other life forms and interacting with other life forms is not simply found in viruses, it’s found in other life forms as well, so that’s one way of thinking about it.

    The second one, which is really tongue in cheek, is actually to answer and to say it is both alive and it is dead. It’s alive when it’s inside cells and growing and reproducing, and when it is simply a chemical substance outside the body it’s dead. And so that’s another answer you could have; it’s both alive and it’s not alive.

    Robyn Williams: Well, may I say that your book is a triumph, it gets these ideas together and it connects them and it tells the story right through. The one thing that you don’t explain, having provided what we talked about before, information as being the demon, something vastly important, which then goes through everything, but the information, is it in other things as well, the non-living things, and is it intrinsic to materials, to physics, to everything that is around us that, given half a chance, it could become living, and yet we have no signs outside the Earth of there being any life at all. So is it intrinsic in the molecules or not?

    Paul Nurse: Well, it is intrinsic in molecules. I mean, this is an interesting issue that you’ve brought up, because I do make a speculation which is to do with an aspect of information, that is the storage of information in heredity. And information is stored in most living things, in deoxyribonucleic acid, in DNA, the double helix. In some it’s in RNA, a related nucleic acid. And this information is stored in a linear way. And what is really striking about this, and I’m not sure we actually emphasise it enough, is that information stored in a linear way is a very common motif. We thought we invented it in computing 50 years ago with lots of zeros and ones, and of course it does encode information, but life invented it about 3 billion years ago because when you take a piece of DNA, what is it, it’s really a collection of letters which you can read as words, as sentences and paragraphs, all of which are conveying information, and it’s digitally encoded in a linear form.

    Then, if you think about it, what happens in life is you have long-term storage in very stable DNA, which actually is a rather boring chemical, it doesn’t do very much, but it turns into something else through a process of transcription and translation, where the code that is in the DNA is translated into a protein, and a protein is also made up of a linear molecule or polymer, a macromolecule, and instead of this being made up of nucleotide bases, as it is in DNA, it’s made up of amino acids. Now, amino acids are much more interesting chemically than bases. Bases are very similar, they don’t have much differences in the chemistry, they can’t do very much. Amino acids, on the other hand, the ones used in life, have really a great variety. Some of them are big, some of them are small, some of them like water, some of them don’t, some are negatively charged, some are positively charged, and they are also in a string which is set up by the string of nucleotides found in DNA, and that has properties that means that the proteins will fold up in a particular way and make a three-dimensional structure, and within that three-dimensional structure the different chemistries of the different amino acids are organised very precisely in space to bring about chemical work.

    So now you have a very interesting concept here, you have long-term storage in a polymer, in DNA, which is chemically mostly inert, and that is translated into proteins which are chemically very diverse and very lively and do all the work in the cell. So the information is turned into work, into chemical work, and that isn’t found in non-living…to go back to your original question, it’s not found in non-living objects but is absolutely core and central to life on our planet. And I make one more speculation, I’m so impressed by this, what life has built on here, that I’m going to speculate that should we ever find life anywhere else in the universe, and I’m sure there is life elsewhere in the universe, by the way, I mean, I can’t say I’m sure, but I suspect strongly…

    Robyn Williams: You just did!

    Paul Nurse: I did, and I’m correcting myself. It’s early in the morning here, I’m just a bit too excited! I think it will be based on polymer chemistry. It may not be the same chemistry, carbon-based for example, but I think it will be polymer chemistry because it both stores information and turns it into chemical work, and that’s central for evolution by natural selection.

    Robyn Williams: Final question; what you describe is so elegant and wonderful as a process, but also still so complicated. We’ve got 3.5 billion years during which that can all happen to produce what we see around us, but one person was so unsure of this. Francis Crick said there is a fair chance that life actually landed from outer space called panspermia, and it kind of picked up what it was doing when it landed. Did you ever argue with him about that?

    Paul Nurse: I had a conversation with him once about it. The reason he argued that was because planet Earth was formed may be 4.2-, 4.3 billion years ago, it had to cool down before you could get life as we know it, and that took a couple of hundred million years. And then we start seeing very early fossils at around 3.3-, 3.5 billion years ago. Some of the oldest are found in Australia of course, and that meant life had to have emerged within actually 200-, 300-, 400 million years. Now, that is a bit of a surprise since it did take to about a billion years ago, so it did take about 2.5 billion years to go from a primitive single-celled life form to multicellular life, which seems a much easier thing to do than to get life in the first place. So I think his reasoning was that was just too short and it was easier to imagine that it came on a comet or somewhere.

    However, I do think it is really a copout for the origin of life because you then have to imagine how did it end up on a comet and where did it come from? But it does give you more time to actually do it. So I think panspermia, we always have to think it’s possible, but I would prefer just to say it happened here and let’s see how it might have happened. That is the origin of life.

    Robyn Williams: Thank you very much Paul, it’s good to talk to you again.

    Paul Nurse: Very good, very nice to talk to you indeed.


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