What is life? Catching up with Paul Nurse from the Francis Crick Institute

 

Sir Paul Nurse, Director of the Francis Crick Institute in London, UK is a Nobel Prize winning geneticist and cell biologist whose research is recognised worldwide, particularly for his contributions to cell biology and cancer research.

In this insightful interview with our sister publication, Research Features, Nurse discusses the institute’s creative ‘bottom up’ approach to research, his presidency of the Royal Society, science communication, and how he stays grounded despite a staggeringly successful career.

Read more in Research Features: doi.org/10.26904/RF-150-5477109273

Visit the Francis Crick Institute’s website: crick.ac.uk

 

Image Source: Adobe Stock Images / Knssr

 

 

Transcript 

Hello, I’m Todd. Welcome to ResearchPod.

20 years is a long time in science. From the leaps in visualistions of planets and black holes, to the invention of ever smaller, ever smarter gadgets, a lot has changed since 2001. And, at the same time, so have the institutes in which we conduct specialised scientific research.

As he accepted his Nobel Prize for medicine in 2001, Sir Paul Nurse shared his optimism that biology was on the edge of a new paradigm of discovery. Today, he speaks with us about just how much of that has come to fruition.

From the start of his career in cell biology, through being the first director and CEO of the Francis Crick Institute upon its inception in 2010, this insightful interview with our sister publication, Research Features, covers Nurse’s creative ‘bottom up’ approach to research, his time as president of the world renowned Royal Society, science communication, and staying grounded in the face of success.

Todd: Would you be able to tell me a little bit more about what it was like sort of growing up coming from a working class background and what it’s like sort of achieving what you have?

Paul: Well, yes, I was brought up in North West London in Wembley. I was brought up by my grandparents. She was a cleaner, actually, and my grandfather worked in Heinz in the baked bean production line. So this was a pretty working class background. You know, I was brought up talking to, if you like, sort of ordinary people. And I was more academic than my siblings and so on, and so I went to a grammar school, but I was always at home talking to more normal people you find on the streets. I think that has influenced my ability to, or I don’t know about ability exactly, but it’s influenced the way I sort of think about talking to people.

Todd: Yeah, yeah. As you’ve sort of come further in your career, has it been more difficult to sort of hold on to those roots?

Paul: I do not think it has actually. I think I’ve always been fairly grounded and my own family are always grounding me anyway, in case I get above myself. So I think I’ve got quite a lot of checks and balances and it’s persisted.

Todd: You said that you’re in your research institute at the moment. What sort of projects, if you’re able to disclose, what sort of projects are you working on at the moment?

Paul: Well, the Francis Crick Institute is a little unusual compared with the majority of research institutes. It’s very large, in fact.

Paul: About 1,500 researchers here in biomedical research in the middle of London. We’re independent, funded by major biomedical research funders, but we do things a bit differently. And what we’re trying to do here is actually put together things that work in other places I’ve, you know, like a magpie, picked up things and served my colleagues from different places and put them all together. And one of them is strangely not to have, and this is a bit unusual, top-down programs and projects. So most institutes saying, well, we’re going to follow five big themes and so on, and then they search for people who work within those themes. And what I’ve noticed over the years is that ahead, people who are only saying mostly the absolute obvious. And a much more creative way to go ahead with it, which is what we do here, is to have very open searches in a very broad approach, and actually focus on hiring people who are very interesting, and who will pursue novel things. And that way actually build up the projects and programs bottom up rather than top down. Now of course in the end you get the focus on different areas and so on because people get attracted so we do end up having foci if you like in certain areas but what’s interesting about it is it is largely not set by leadership top down but by particularly early career group leaders, because we tend to have a focus on getting younger researchers. And it’s set by the next generation of research leaders. And that is a really effective way of producing the highest quality research. And it’s one that often those who administrate research funding don’t fully appreciate because you make very interesting discoveries. And then what we do is we try and capture things that might have applications and translational opportunities. And the themes develop from that. But we have a very effective capturing mechanism, but we don’t control very much what’s happening on the ground. And that’s a bit of an anathema, if you like, to those who are more controlling. And we’re anarchic, in fact.

Todd: Is that in part any sort of response to your sort of working across various institutions throughout your career?

Paul: It really is. I’ve worked in places which are more directed. I’ve worked at modern universities who have to be directed because they have to teach across disciplines. So they’ll say we’re missing a cell biologist or a geneticist, so we have to search in a certain area. But research institutes don’t have to be constrained that way. And so we can behave differently to universities. And because we are large, it means if you’re a small institute, you have to be more focused as well, because you need to have some critical mass there. If you’re large, we can change wherever we go, because we’ve got enough critical masses in a variety of areas. So for this model to work, you have to be large, which is one reason I set it up. way, merging pre-existing institutes.

Todd: I did read that you did have a bit of opposition when you were starting the CLIC Institute as well.

Paul: Almost nobody was in favour of it. In fact, in the institutes that I merged together, that isn’t completely true. There were three institutes and two were completely against it and one was half against it. I was sort of used to that sort of response because people don’t like change and scientists particularly don’t like gloomy about things. And the reality is it all disappeared within almost months of getting into the building. And so unlike most mergers, which are complicated in different cultures and people’s fighting, we’ve had none of it. It’s absolutely worked extremely well. So it’s all done. But you’re right, a lot of opposition. And also a lot of opposition from other institutions and universities who were very jealous And what they constantly didn’t realise is that we didn’t get any new money, we just took money from old institutes and put it together. And so they were constantly on social media complaining about this, that and another, and telling me it wouldn’t work and I’d never attract anybody to come here and it was in central London and it should be somewhere else and all of this. And I’m afraid they’ve been shown to be completely wrong in every score. I mean, we have reduced obligations with teaching. We do have other obligations. For example, I think I mentioned, we put a focus on early career group leaders who will be higher when they’re not that experienced. And so the senior group leaders here have to be deeply involved in looking after them. And also, we pay huge attention to the recruitment. And more so than my experience, because I’ve worked in universities and other institutes half my life. So for example, with these open searches, we get 400 to 500 applicants for a group leader position. I mean, this is 10 times more than you get in, it’s the same with our graduate students, we get 1500 graduate applications for 30 slots, that’s 40 to one.

null: And I mean, this

Paul: lot of work to do to get through those things. So there is more things to do than maybe immediately meets the eye. And the other thing about being a researcher here is you’re under constant sort of surveillance because it is a privilege to be here. And we heavily review people. I mean, really stringently every five, six years. And if you don’t pass that, we do ask people to move on. Again, what’s different, I put money aside to help them move on. And that’s almost unheard of. So because the early career people who come here only come for a fixed term. It’s a career term really, 12 years in total. But then we help them move somewhere else.

null: So this is something else that’s completely different. Most institutions, they’ve got something to be excellent, they hang on to them.

Paul: Our idea is that we train them. We completely agree to being a successful leader, and then we export them around the country, around the world, that will set up networks.

Todd: So all of these things are different from conventional institutions. I did also hear, read somewhere about your, you use the term guilt to refer to independent scientific discovery or research, perhaps a certain amount in guilt in sort of pursuing your own, however well-driven, whether it’s from intuition or from sort of very empirical sort of followings, sort of following that creativity. Could you perhaps elaborate on that a little bit?

Paul: I can. This was quite an important for me personally. I often talk about it, but it’s quite important to me. When I was young, just finishing my PhD, I thought, what should I do? And I sort of got to a place in my head, I suppose, that I wanted to be a researcher. If I was a very good researcher, but not an excellent one, if I can make that distinction, then I ought to try and do something that more clearly was likely to be useful for humankind. I mean, you know, work on a disease like malaria or whatever, because human suffering is something that you wouldn’t feel guilty about and which we would be able to feel, well, that’s worthwhile. But if I thought I was really close to the top of the tree, then I felt that I should have the freedom to pursue what I’m interested in on the grounds that you could make a higher level discovery that could influence many things. But that meant two things. I had to hold myself to a high standard. and not think that I’m entitled to this. And if I feel that I have slipped from that state, if I can put it that way, then I should change the way I operate, that’s one thing, because otherwise I’d have guilt there. And the second, which is even sort of slightly odder, I did find out fairly early in my life, in my 30s, when I was head of a department in Oxford, for example, that I was quite good at running things. And then I sort of got this new thing in my head, which was, I’ll spend some of my time running things, which is my donation back to society. And in exchange for that, I have freedom to pursue what I think is interesting.

null: And that’s how I’ve run it for the last 30, 40 years.

Paul: So guilt, you’re clever to have picked it up. It came in two versions, the guilt about what I worked on and the guilt freedom I have. But one thing I think I really want to emphasise, that word entitlement, I do find that some researchers feel almost entitled, that they ought to be, they ought to be supported. And I actually think it’s a privilege to be supported.

Todd: Yeah, and there’s so many people out there doing such great research, and it’s so competitive. Did that derive from schooling?

Paul: I think it derives actually somewhere coming from my working class background where we weren’t very wealthy. I was supported by my grandparents. You know, everybody else left school at 15, 16, and then made money to support the family. And I did not. I went to school till I was 17, 18, then university. So I think it has, that sort of ethos came from That’s where I felt I had a privileged situation. And maybe not everybody in my research sort of feels that. They feel entitled that they should be supported and so on. Whereas I just feel privileged.

Todd: Do you think there’s any sort of communication or barrier in universities with sort of working class students connecting with academics?

Paul: I think there is, you know, some difficulties but, you know, my personal experience is now 50 years ago and things have changed dramatically but my school wanted me to apply to go to Cambridge or to Oxford and I visited and did think about it but there were two reasons I didn’t. One is I could never pass O-level French so I didn’t manage to tick the boxes that you’ve had. I failed it six times so I wasn’t, I didn’t try.

Paul: I was just absolutely hopeless at it. you needed to have one in a foreign language to go to any university. Actually I failed to get into a university for a year and I worked as a technician in a brewery. The fact that I couldn’t get to university affected me with this, but when I visited, particularly Cambridge because I’m shown around the college and so on, I did feel a bit like a fish out of water. I wasn’t too bad because I’m reasonably confident and articulate, but I did I ended up going to Birmingham, who did let me in, which was a more down-to-earth sort of university, and that was a bit easier for me. But even so, in my year, there were very few who came from a working-class background. I think that has improved very significantly in the last half century. I’m not saying it’s not still there, but I think it’s significantly improved.

Todd: In almost all of your interviews you are, just like in your response just then, you’re very historically and philosophically minded. And the phrase that you used in the interview was, biology may be on the edge of a new paradigm of discovery. How has the field sort of changed in your lifetime and perhaps where do you see it going?

Paul: Well, what I was referring to, I think, was two things. One is the increasing appreciation that biological understanding, and I think I’m focusing more on how cells and organisms work rather than ecosystems and so on, so that part of biology, has always focused on the chemistry of life and to some extent the physics of life. And I felt 20 years ago, and actually for 20 years before that, that in addition to the chemistry, it was clear that biology was an informational science too, that you only understand life when you understand how information is being processed by chemical machines and physical machines, which we have to understand how they work, but we have to have a focus more on information processing. And so I’ve always thought about that. At the time, earlier in my career, I thought a lot about the logic of how different components are connected together and increasingly, you know, machine learning and other thinking around artificial intelligence. where that type of thinking can be combined with the chemistry and the physics to generate a better understanding of life and how it works. That’s what I was primarily thinking about to say we were on the edge. There was another aspect to it, which was It reflects the fact I’m a cell biologist, so I study cells, and we’re all made up of billions of cells, of course. And the cell is the simplest entity that we can, without reservation, say is living. And I also felt that by understanding a cell and how it works, we will get insight into how life works. And so that’s the second element of it. But to do that, it had to be both information as well as chemistry.

Todd: And I suppose you do explain that very, very well as well in your fairly recent book, What is Life? The Five Great Ideas in Biology. And I’d just like to say that when I read it from the perspective of someone that doesn’t necessarily have a background in biology, I found it really, really interesting and very accessible. Was that the sort of aim for the work to engage people who may not have a science background in the wonders of biology, you could say.

Paul: It was. It’s not always a completely easy read because it’s quite dense in some ways. I mean, I try to lighten it up with stories of my own sort of scientific life. But as some of my friends and my family who have read it say, you know, if you miss out a few sentences, you can miss the argument. It is pretty condensed.

null: It’s a short book, but it’s pretty condensed.

Paul: But I can tell you something that drove me. I wanted to write something that would still be correct, largely, 30 years, 40 years, 50 years from now. And what I’ve noticed in many popular science books, they either didn’t take on really the big problem, and I think what is life is a big problem, question but also they tended to be always trying to look over the horizon at the next discoveries and quite often that got out of date extremely quickly as they didn’t go anywhere and I got really aware of this when I was asked about 10 years ago to make a commentary on the BBC Horizon series and which had been running for 40-50 years and they selected 10 films for me to look at which they were proud of. And when I looked at them, I realised that most of it was no longer actually considered to be correct. And I thought, maybe there’s a tendency in science communications, and of course, you’re more of an expert about these things, to be always wanting to say something exciting over the horizon. And quite often, you get it wrong, and it just disappears. So in some ways, my book is boring. No, I think I say it in an interesting way and connect things that perhaps many people haven’t connected. I also try and give some explanation where the ideas came from, which curiously in biology are often very old.

null: I mean, it’s not that everything’s been done in the last 10 years. I mean, some of the basic principles are two, three, 400 years old.

Paul: And so that was something else that drove me. So I’ve written a book. It isn’t trying to predict the future. I want it, I would like my grandchildren or great-grandchildren to read it and think, this is still probably right.

Todd: Would you be able to sort of go into what it was like working with the Royal Society, as the President of the Royal Society for your time?

Paul: Yes, yes, so the Royal, when I was asked to be President of the Royal Society, I mean, That was probably the, in some respects, the peak of my career. I mean, when I started being a scientist, I thought, if I was really, really lucky, I might get elected to the Royal Society. I had no dreams of getting a Nobel Prize and so on. But the Nobel Prize and being President of the Royal Society, which many would say is the greatest science academy in the world, really, even today, was a huge privilege, honour. What I tried to do there was to make it more open to the public and to participate in public debate. The problem with a venerable body like the Royal Society is the leadership is petrified they’re going to make a mistake and the reputation of the institution is damaged and this results in sometimes timid relevant in the real world, you have to engage with the world, engage with issues that are important to the world, and accept that sometimes you won’t get it completely right. And I was prepared to do that. And at the time I was president, 13, 14 years ago, when they appointed me, the climate change debate was raging, really. And there was a very well-funded and rather anti-climate change sort of movement, were really not looking properly at the science. And although the science wasn’t absolutely clear, it was much clearer than they were claiming. You know, this was particularly from the right wing in America, but also scientists, a few scientists, but mostly commentators in the UK. So I felt we should take them on publicly, which I did, And they really attacked me with a lot of abuse, personal abuse, because they were using, essentially, they didn’t like climate change. They didn’t like it politically. I mean, because you have to have sort of regulations and it’s a sort of movement from the right, essentially. And so they used political tricks to try and undermine the Royal Society and me as president. And so that could be a bit stressful, to be quite honest. But I’m glad I did it, and I tried to do it beyond, of course, climate change, because I’m not a climate change scientist, though one of my daughters now does work in climate change. That was something, getting more engaged with the public and taking on issues that I thought were important to society.

Todd: And would you say that would be sort of your main, your greatest achievement as the president of the Royal Society, sort of taking on battling issues like this?

Paul: Scattling, I think it was. I mean, I did a number of sort of minor things. I changed the charter of the Royal Society, which hadn’t been changed since 1666, I don’t think. And as a consequence, you can imagine it had some rather strange things in it. So I did change it, which was another example, I suppose, of not just being so hidebound that you wouldn’t take things on. So I did quite a few of those sorts of smaller things, but it was making science relevant to society as a whole.

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