Sir Paul Nurse on cells and life

Amy Barrett: Hello and welcome to the Everything You Wanted to Know about podcast from the team behind BBC Science Focus magazine. I'm Amy Barrett, editorial assistant at BBC Science Focus. For this series, we've sourced questions from Google, our listeners, and the Science Focus team to put to experts and help you understand key ideas in science in short, 30 minute episodes.

Today I'm joined by geneticist Sir Paul Nurse, the director of the Francis Crick Institute in London and one of the recipients of the 2001 Nobel Prise in Physiology or Medicine, which he shared with Leland Hartwell and Timothy Hunt. Paul has recently published a book that helps readers understand biology, called What is life? He's going to share some of the concepts from the book with us today.

So let's dive straight in with the big question. What is biology?

Sir Paul Nurse: Well, my book, and it does tackle biology, so it is relevant to your question, is really exploring how do we define life, what is life? And really that's the central subject of biology. And what I wanted to do here was to try and identify principles by which one could understand what is different between something that's living and something that's not living. And this is something that perhaps biologists don't think quite enough about.

You know, physicists are always having grand ideas and they have lots of books and so on about grand ideas. We biologists tend to be a little bit more mundane in some ways. We like to describe things, you know, like how many species are in a habitat or how many hairs there might be on a beetle's leg. I'm a molecular biologist, so I sequence genes. And so this is a lot of details and that's what we tend to sort of gravitate towards.

But actually, there are some really grand ideas in biology, which I describe at least some of them, and they can lead to principles to understanding how life works. So it's a rather short book and it's aimed at just the ordinary lay-reader to try and deal with those those topics.

AB: So for someone who perhaps hasn't encountered biology for a long time, what key aspects do they need to know about it to feel like they've got a grip on what life is?

PN: Well, what I do in the book is describe five of what I call the great ideas of biology. And they are the cell, which is the basic unit of life. We're all made of cells. And in fact, there are some living things which are only one cell. And so that's a very important idea.

A second one is the gene, which is the basis of heredity. That is why when we have different generations, we look a bit like our mother and father, and a plant looks like the plants that got together to make that plant, and that is heredity. And the basis of that is genes. So I talk about genes as the basis of heredity.

Then probably the greatest idea in biology, which is that evolution by natural selection. Charles Darwin's great idea, because that leads to the living things having purpose. It's a very clever idea. They have purpose. You know, they grow, they maintain themselves, they reproduce themselves. And based on, in fact, the cell, the gene you can through natural selection, living organisms can acquire that purpose. And how do they do it?

Well, that's the two next ideas, they do it because they are chemical machines, fantastically sophisticated chemical machines who which is the basis of their growth and how they can copy themselves and so on. And it's all connected together because they are also informational machines. So all the different bits of the chemistry talk to other bits of the chemistry and that leads to them behaving as a whole. That is the whole organism. That is five ideas. And then I generate principles from that to try and say what I think life is.

AB: So it seems like the cell is very fundamental in our understanding of what life is. Can you tell me what are cells?

PN: Well, cells are the basic unit of life in two meanings of the word unit of life. They're the basic structural unit, by which I mean every living thing that we know on this planet is built of cells. And we have about, I think, three trillion cells. If I've got that number wrong, all you have to remember is it's a lot of them and it's a basic structural unit. But it's also more than that. It's also the basic functional unit.

Now, what do I mean by that? What I mean is that it functions as life. It has the properties of life that some living things. I'm a researcher and I work on yeast, which is only made of a single cell. And so all the characteristics of life are seen there in that single cell. Others, like ourselves, for example, are made up of, as I've said, of a large number of cells. But one thing, if you're not interested in cells with what I've said, always remember that you were once a single cell when you were at the very conception when the sperm from your father entered the egg of your mother, you were a single cell.

And so there's very good reasons for you to be interested and everybody else to be interested in cells.

AB: And how big or how small can cells be?

PN: Well, they can be very small. If we take bacteria, for example, which are one of the smallest forms of life, they are only one or two micrometres long and micrometre is a millionth of a metre. So that's absolutely tiny. If we take my yeast so that I study, it's 10 micrometres. So it's still very, very tiny.

But some cells can be really quite big. If you take a hen's egg, and when you look at the yolk in there, that is a single cell, which then will then-

AB: Really?

PN: Absolutely. And it will undergo repeated divisions and eventually make a little chicken. But that's a single cell and that's very large. Or if we take one of your nerve cells that can spread from that can extend from your spine right down your leg, that could be half a metre or even a metre long. So cells vary in size over a thousand fold or more. So they are amazingly diverse.

AB: And you've mentioned that cells can divide. How do they do that?

PN: Well, that's critical because if you have a cell, it can maintain itself and it can grow. But the critical thing for life is that after it's grown for a while, it can divide into two and produce two new cells. And those two new cells behave just like the original single cell.

And that's because they contain all the genes that they inherited from the mother cell. So you have a mother cell, two daughters cells and lots of- they contain the similar amounts of genes that you have there. And so it is actually central to life that you can reproduce because if you can't reproduce, you don't go anywhere, really.

I mean, and so it's absolutely core for life. How did it occur? Well, it occurred through a process that actually I study it called the cell cycle. And what it means is it's the cycle by which cells reproduce themselves. And critical for that is back to genes again are two processes.

One process where you copy all the genes. So instead of having one copy, you have two. And then towards the end of the cell cycle, those two copies are separated into the newly divided cells. And every cell cycle, every reproductive cycle has to have those two processes working. And I spent almost my entire life trying to understand what controls those processes and why they occur in such a regular way.

AB: So how does a cell know when it's time to to divide?

PN: You know, that's a really good question. And 40 years on, I'm still not quite sure of the answer, to be quite honest. And I'm just hoping I'll have a few more years left so that I can actually crack it. I know roughly what is important for most cells, and it's actually you can state the problem, rather simply.

Cells grow to a certain size. Double the size of the original so often, and then they divide, so somehow the cell knows how big it is. It measures how big it is. This is sort of acting as a whole. I mentioned that a bit earlier. It's acting as a whole. It knows how big it is.

And it says to itself, if it could speak, now it's time to divide. And it goes through the process of division and all the genes that have been copied earlier segregate, separate into the two newly divided cells. So the question you ask mostly reduces to how the cells know how big they are. And that's something I'm really interested in.

I have to say, and I don't know quite the answer. I've got some ideas. But what that information, when you get that information, how big you are, you then have to activate the chemistry that leads to the reproductive process and that works through of a key molecule. I'm not going to talk too much about molecules because it gets a bit complicated, but it's a key molecule. And I do want to mention this one called cycling dependent kinase. It's an enzyme.

And that enzyme triggers all the events that are needed for the cell to reproduce it self. And my lab discovered it together with one or two other labs. So we discovered it quite a few years ago. I discovered it in yeast and then showed that the exactly the same process and the same enzyme works in human beings and everything in between yeast and human beings.

So that was my Eureka moment. Very got very excited about that. And the way we showed that was a rather it's an experiment that everybody thought just couldn't possibly work. I took a yeast cell which is defective in the gene that makes this enzyme. It's a gene we called CDC 2, but you don't have to remember that CDC 2.

And what we did is we sprinkled human genes on the yeast cells. It wasn't quite like that, but that's essentially what happened, sprinkled them on the cells. And the theory was this. If humans had DNA that encoded the same gene or same type of gene, I should say, then if a cell took it up, it could rescue a defective yeast gene, if you see what I mean.

So I use the yeast strain that is defective in this gene and it couldn't divide at high temperature. It divides well at low temperature, but not at high temperature. And simply what we did and when I mean, we it was Melanie Lee who was a collaborator of mine in the lab, who did most of the experiments and what she did, sprinkle the genes on to this defective strain that couldn't divide and looked for a human gene that would make it divide.

And we found it. I mean, nobody believed that could possibly work because you imagine yeast and humans diverged in evolutionary terms one point five billion years ago. That's one thousand five hundred million years ago. And it's amazing.

What it means is that we could take, despite the immense amount of time, it still works. It still works. And that's why we could conclude that everything we see, a living thing that we can see, like fungi or plants and animals turn out to have the same control that was discovered by that experiment.

AB: That's amazing. And so that enzyme itself must have been quite fundamental in the early stages of life on Earth.

PN: Well, it is fundamental for most of life that we can see. It is different in very simple forms of life. Bacteria, for example, they don't have that enzyme. So it was somehow I'll call, I'll say invented, it wasn't invented, but it came about some time between one point five billion years ago and two billion years ago.

But life on this planet has been going for about three and a half billion years. So for the first couple of billion years, it didn't work in bacteria like this. But once it was invented one point five, two billion years ago, it inhabited all the living things we can say except bacteria.

AB: That's amazing, and you mentioned the word gene quite a bit. Can you just tell me what is it?

Yes, I should have done that. So that gene is the base. It's my second idea in the book, actually. And the genes are the basis of heredity. They are the key for inheritance. So I can't see what colour eyes you have, but they will be controlled by by genes. I have blue eyes and there will be a certain combination of genes that give blue eyes.

So many of the characteristics that we have and every living thing has are determined by genes interacting with the environment as well. I mean, affected by what you eat and how you live and all those sorts of things. But genes are absolutely crucial.

Now, what are they made of? Well, this was a very important discovery. They're made of a chemical. The chemical is DNA. That's an acronym for deoxyribonucleic acid. But let's just call it DNA because it's much easier to say.

And this was discovered in the 1940s, 1944, 45. It was discovered in a research institute I used to work in. I used to be president of it in New York, but not in 1945 it must be said - much later. And that was shown by the researcher working there - a collection of researchers there that DNA was the basis of genes. But how did they do that? A little bit. They used a sort of similar thinking to how I just described finding the CDC 2 gene.

What they did is they took a bacteria that was harmless, didn't cause disease, and they took a similar bacteria which did cause the disease, and they extracted different chemicals from the one that did cause disease. And again, sort of sprinkled it on to the cells a little bit like we did 50 years later.

And they found that if they sprinkle DNA onto the cells that weren't virulent, that didn't cause disease, then they could transform them into cells that did cause the disease. So they came to the conclusion that DNA must be the basis of heredity and that was in the mid-1940s.

And then the second experiment, which most people are more familiar with, is the one that was done in England, actually, and that was based on the structure of DNA. And that's based on experiments done by Rosalind Franklin and Maurice Wilkins in London who did the, looked at the structure of DNA. And it was interpreted in Cambridge by Jim Watson and Francis Crick.

And that led to the very famous double helix structure, which is the basis of DNA. A double helix structure means is this is like a ladder which is twisted, twisted ladder, and the sides of the ladder are connected by the rungs of the ladder and the sides are made up of four chemical bases and they have names. I'm going to just give the letters so we don't have to remember them, AGC and T. And what's clever about these chemicals is that if you have A on one side of the ladder, that can only connect to a T on the other side of the ladder through the rungs.

So you have A connected T and you have G connected to C. And what this means is that if you now pull the rungs to break the rungs and pull those ladder apart, you'll have A, for example, down one side and A will connect with T, and so on on the other side. So you can make a precise copy of the original DNA model. Isn't that a clever idea?

So the combination of knowing it was DNA was important and then getting the structure really revealed the basis of heredity in the gene. So that's why it's such an important idea.

AB: And so the DNA of every living thing only has those A, G, C and T?

PN: Absolutely right. Every living thing. And that includes bacteria, even though they are more primitive. So it's even older. And it's likely that that emerged very soon after life appeared on the planet. And we are talking three and a half billion years ago when life. First, it can be what we say is we can see what looked like fossils, fossil bacteria, which are three and a half billion years old.

AB: Wow, containing DNA?

PN: Yeah, well, we don't know if they contain DNA, so we do get at that. But since every living thing on the planet, we do know what contains DNA, we're making the assumption that one did as well.

AB: Hmm. And so genes that we have, do we all have the same number of genes?

PN: We, that is all human beings, have very similar numbers. It's 22,000 that we have. The genome, human genome was sequenced nearly 20 years ago. Now, actually, it's still not absolutely complete, but we know a lot more about it than we did 20 years ago. And there's 22,000.

Now my lab organised the sequencing - back to my yeast - of the yeast I worked on a bit before the human genome sequenced. So it's a bit older. It's much easier to do yeast than humans. So we got it completely done over 20 years ago and we showed it only has five thousand genes. So so we have 22,000, yeast has 5,000, but some organisms have many more genes than we do. Some plants have 50,000 genes. There's probably even more.

So, having a large number of genes doesn't mean you're intelligent. It just means you have the ability maybe to be intelligent. And so different living things have a wide range of different numbers of genes.

AB: That's it for us today. In the next episode, Paul and I will pick up where we left off to continue talking genes and DNA. He will reveal how these are key to understanding the evolution of life on Earth and even explore some of the possibilities for life outside our planet. If you've enjoyed this episode and will be listening to the next one, why not subscribe to be notified when it's released? For more easy to understand explanations of key scientific concepts, visit sciencefocus.com, or pick up the latest issue of BBC Science Focus magazine.

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Sir Paul Nurse on cells and life

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