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Paul Nurse (The Francis Crick Institute)

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#36 — Today’s guest on The Microscopists is Nobel Laureate Sir Paul Nurse, Chief Executive and Director of The Francis Crick Institute in London. Paul’s early career used microscopic screening to identify temperature-sensitive cell-cycle mutants in fission yeast. This work led to the identification of the cell division cycle 2 gene (cdc2), which encodes a kinase critical for cell cycle progression. It was for this work that he was awarded the 2001 Nobel Prize in Physiology or Medicine alongside Tim Hunt and Leland Hartwell.

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This is an automated transcript and may not be 100% accurate.

Intro/Outro (00:02):
Welcome to The Microscopists, a Bitesize Bio podcast hosted by Peter O’Toole, sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O’Toole (00:14):
Today on The Microscopists I’m joined by Sir Paul Nurse, director of the Francis Crick Institute, former president of the Royal Society, former president of the Rockerfeller over in New York and Nobel prize winner in 2001 in physiology or medicine. This is an amazing interview. Enjoy. Hi, I’m Peter O’Toole from the University of York and on The Microscopists today, I’m joined by Sir Paul Nurse from the Francis Crick Institute. Paul, how are you today?

Paul Nurse (00:52):
I’m okay. Peter do call me Paul.

Peter O’Toole (00:54):
Yeah. Thank you very much, Paul. Actually I director of the Francis Crick Institute, former president of the Royal Society, Nobel winner in 2001 in physiology or medicine, former president president, I think wasn’t it of the Rockefeller that’s a pretty long list. And I think even over 60 honorary degrees.

Paul Nurse (01:15):
Yes. Yes. All of that’s true. It sounds if I can’t keep a job, though, with all the different jobs on here, <laugh>

Peter O’Toole (01:24):
Ah, dear, excuse me. That, that is quite a, quite a CV, which Jobs’s been your favorite.

Paul Nurse (01:34):
I liked the Royal Society cause it was very wide in the experience and what you had to do. I liked the Crick cause I started it a fresh and so could craft it in a way that I’d light and I liked Rockefeller University in New York because it was so different because it was in New York. So I think that’s my top three.

Peter O’Toole (01:56):
Okay. And what was it obviously the American culture can be very different to the UK science culture. Did you try and bring some of that back with you or, or did you leave that behind and accept the UK way of work in that mindset? Well,

Paul Nurse (02:11):
It is a very interesting question, Peter, because actually I took something to Rockefeller from here and I brought something back from the US back to the UK. So I it was, it worked in directions. I learned something from the us. It made me think more about the importance of the individual scientist who tends to be the center of attention in the US. It’s a more of a personality cult, which I wasn’t so keen on, but I did more fully recognize that it is important to re remember always and to support the fact that you do have excellent people and they do need to be looked after, but what goes, what’s less good in that US system is much less in my view of a feeling of community and working together, which we have in Europe and the UK in particular. And so I in, I put into the Rockefeller a bit more working together and not just rescue it, not just sort of worshiping the hero scientists. And I brought back this notion that individual scientists can be very special and have to be recognized as such.

Peter O’Toole (03:32):
So I think I first met you when you were at the Research Institute before, before Crick itself. When did you have the idea of setting up the whole new Crick Institute?

Paul Nurse (03:45):
It was, I, I remember it cuz it didn’t go anywhere. It was around 2000. I was then just essentially formed Cancer Research UK merging two research charities, the old ICRF and the old CRC. And we had in the ICRF and then CRUK a couple of institutes, the buildings of which were really quite old, one in Lincolns and field in central London put up in the 1950s, a second one in South Mims, Claire hall put up in 1970s, early eighties, but rather jerry built and they were both looking very tired and South Mims was a bit isolated. And then the MRC had an Institute, National Institute of Medical Research on top of a Mill Hill in London. And that’s a 1940s building and was also very tired. So everybody was a bit worried about the real estate. And I had the idea which was mad of putting all three together in the millennium dome, which you may remember, nobody knew what to do with after the 2000. And I went round saying, should we think about this or moving to Greenwich? And quite rightly I was told, this is barking mad and we shouldn’t do it. And as indeed it was cause how on earth could you turn the millennium dome into a sensible Institute? You’d just have to erase it and start again. And so it was forgotten quite rightly until 2007 when I was working in New York in Rockefeller and Keith Peters who was acting head of the National Institute of Medical Research phoned me and this idea rose up again of putting the institutes together because the MRC had got the idea that they should close Mill Hill a significantly reduce its size and move it into UCL as a Translational Institute. And this wasn’t such a brilliant, I idea really because all the researchers, most of them in Mill Hill were not doing translational clinical work. It would’ve meant half to three quarters losing their jobs anyway. So it would’ve been a very sour transition and the space they were moving into was an old hospital and probably not fit for purpose. So that then led to the idea, could we find another site and Keith had identified the site, which is where we are. Just north of the British library. It belonged to the British library and was a government um land. And I ended up going to see Gordon Brown who was then the Prime Minister and asking for the site for the budding consortium that involved the MRC, CRUK, where there was a lot of support from the chief executives there. Um and also from UCL who were involved because of the previous plan and this worked, we were given the site with a lot of money, 75 million, but half the price that it was probably worth. And that was really the birth of the curriculum about 2008. And it took a lot of work to get everybody on board. I wanted not just UCL, but the two other great London Universities, Imperial and King’s college to be involved. And that took a year or two of negotiation because not everybody was happy with that change. I also wanted the Wellcome involved. So we had the three main funders of biomedical research and they came in at a lower level than the other two, but eventually we came in with six founders, three universities and three funders and started the serious planning about 2010, when I moved back to the UK to become president of the Royal Society. And it’s a lot of work and only came to full fruition when we moved into the building in 2017, with all the people here in the first months of 2017. So we’ve been going about four to five years.

Peter O’Toole (07:48):
I say, so I, I, it’s an awesome project. I think it’s an inspiring building. I love visiting it. It, it is brilliant. I think the idea of bringing it all all together, it’s utterly brilliant too. If you could change anything, would you change anything about it?

Paul Nurse (08:07):
Well, I think the, the most difficult thing, it, it, and it probably would’ve been most difficult. Whatever we’d have done was getting six different organizations working together. There is actually a power in that because if one of the organizations gets a bit difficult, which of course can happen in these situations, you have others at the senior level that can provide corrective action. And so there is a certain resilience as a con consequence of that, but getting six organizations to work together means they’ve all to agree on something. And that can be quite difficult. The three universities in particular universities have government structures, which are often where authority and power is devolved out further down the organization. So you might agree something with the vice chancellor and then you talk to a departmental head and they just say, well, that wasn’t agreed with me and you have to go back again. Or if you agree that with those two, then you want to do something with students, you’ll go to the office of, of students. And they say, well, that wasn’t agreed with me. And you spend a lot of time running around trying to get things to work that is gradually getting better. As as everybody gets used to the idea that they got, they all have to work together and we solve many of the problems, but that was probably the biggest difficulty. And you asked, what would I change? I couldn’t change anything. I just wish that had been a bit of an easier passage,

Peter O’Toole (09:35):
Easier ride. So is the building big enough?

Paul Nurse (09:38):
I don’t think it can get very much bigger than what it is and still operate in the way that we operate. I mean, that is an interesting question. I, I wanted it to be big so that we could be truly multidisciplinary and wouldn’t have to focus on a particular area. If you take a, imagine how most institutes arise, they, they, this is very big. We have, you know, up to 1500 scientists here. Okay. So this is large around a hundred groups in total, 120 groups. And if you have a typical Institute, it’ll be, let’s say an Institute for Stem Cell. Okay. Yeah. It’ll probably be 10 groups with about a hundred people, 120 people. Now, the problem there is that it can only be a Stem Cell Institute because you need a critical math there to get it to work. And the, it runs the danger of becoming static because it’s okay for five years, 10 years, it may no longer be quite what you is cutting edge in different directions. Come 30 years. It’s probably redundant and and no longer, completely relevant. I’m not mocking stem cells. I’m only giving it as a a no, I know. I know. And what I wanted with the Crick was the ability to essentially hire across the board, anybody who was interesting and excellent, and let the, let the program, the programmatic focus be driven bottom up rather than top down, which is what happens if you have a Stem Cell Institute. Now this is alien to particularly research funding. The administrators, as they always want to say, we’re gonna solve this problem. It’s top down and you’re gonna, and then you come back and say, we need to solve these four problems. I need groups in this and so on. And it’s generally decisions being made by elderly scientists and committees, which are mostly rather obvious and certainly not cutting edge. My philosophy was to make it bigger enough that we could hire very widely and let the agenda in terms of programmatic activity, get driven bottom up, which is much more likely to be in front of the curve than behind the curve, but it is a different way of working compared with most ways that these sorts of things are set up. And that’s also been a difficult message to communicate because people, the, the leadership of different funding organizations and so on can come here and say, well, you know, this isn’t operating the way that we’re used to. And they keep trying to evaluate us on something that we are not. And one of the reasons it’s worked is exactly this structure by the way,

Peter O’Toole (12:18):
Which is no, I’m a big, big fan, big supporter of that type of structure as well, because it does give that nimbleness that flexibility to grow and expand and contract as the trends of science change. You know, as you say, they will burn themselves out to a degree. And then resurrect suddenly a new technology opens it back up again or something else. It’s we,

Paul Nurse (12:38):
A resurrection Institute, we constantly are rejuvenating. And because the second thing I didn’t mention is that we had a shift of demographic to more junior early career group leaders. We take them for a career period of 12 years, and then we help them move somewhere else. Now there’s a couple of reasons for doing it. Giving people giving people a a, a 10, 12 year period is quite a lot of stability, quite a lot of commitment to them. You know, most of the fellowships people get a five years and they’re already worrying about what they’re gonna do after three years. And there’s no situation for boldness in what you do when we hire somebody, we back them. And we back them for 12 years. We review them to check that things are sort of okay, but our commitment is to them and they come, they’re ambitious. They don’t worry about the fact that, that they can’t stay because they are ambitious and, and realize it’s a career stage and they have a good support during that period. Then we help them go somewhere else, help them. We’ll give them money to start up to go somewhere else. This is unheard of.

Peter O’Toole (13:45):
Oh, I didn’t know that.

Paul Nurse (13:46):
Yes. Yeah, no, of course it is. And the notion was a lot, of course it is. I mean, that is how it is. Yep. And the reason we do that is that so, you know, when they stop funding will say, well, we can fund you for another year or two, you spend half your time in one place or whatever. And we tailor it to what they, they want. And then you see, we support the U the research endeavor, particularly in the UK, but of course, some people go other places, and this is the way which is also different to an Institute. So if you work in most institutes or for that matter, universities, people hang on to their best people like grim death. They don’t want them to go because I’ve gotta satisfy the Ref or the next Q, who are we say, you spent 10, 12 years. You’re brilliant. You’ve done well. As many we hope will, we’ll help you go somewhere else. And seed and populate institutions, universities around the country, as well as around the world, that sets up a network, something else completely different from the way most places would work.

Peter O’Toole (14:47):
Which of course, as you said earlier, though, that also means that you can always remain nimble and you can always be changing and resurrecting because as people go away with their excellence, you bring in where the latest fact, otherwise you do get stuck. Exactly. The staff that you have,

Paul Nurse (15:02):
Sorry to interrupt. You put those two things together and you have a very agile structure where you turn over maybe two thirds or three quarters, your staff every 10 to 12 years, or maybe even less. And you rejuvenate with new people with new interests that follow the new areas that emerging and the people you export are in established areas can set those up in other research institutions. So a different model from how nearly anywhere else works.

Peter O’Toole (15:32):
So obviously the closest model I can think is EMBL where, where you go have a nine year position and, and then go on having made your name, establish yourself. You take that off with you. What about the core facilities there? Because I presume they’re not under the same 12 year contract or, or am I wrong? Well,

Paul Nurse (15:50):
First of all, EMBL, I should say I I’m chair of the scientific advisory committee at EMBL and I’ve sat for 18 years on and off on the advisory committee. So I should have said, I stole that part of the idea completely from EMBL. The only difference being that I extended it somewhat. Cause I noticed that EMBL, it was still a little bit on the short side and the, the 12 year a period is, is a better one. Now our technical cause is another feature, which is found in very good institutes where you have good high quality centralizes cores I mean, let’s take my like microscopy something that might be of interest to you. Of course. They what you have there is high quality centralized instruments, which are looked after who people know what they’re doing. And if you now map that out across we’ve got 18 such technical cores in all sorts of areas, it means I come in here with limited technical skills in a lot of these areas, but it’s extremely easy for me to get to support and to be to do experiments that involve those technical cores. So they are critical, but now you ask the question, well, what about continuity in those cores, well, one thing I didn’t say about the group leaders is we don’t turn over everybody. Yep. We have, and we don’t, I don’t know what the sweet spot is, but say two thirds, three quarters, early career group leaders. And we have one third quarter on rolling tenure. Like I am every five years at, at the moment and we provide continuity and stability. Our job is also to help support the early career group leaders. And if we now turn to the STP’s there’s some similarities. We do have senior people running them. We also have teams in there and we’re training those and already exporting them to run their own cores in other institutions. So it’s part of the Crick’s wish to support the whole UK biomedical research endeavor through training and export

Peter O’Toole (17:57):
Try. Yeah. I don’t think we’ve imported anyone yet from your labs. I think we’ve, we’ve had a student come through to your labs, but we haven’t, but we’ll get them back one day. Maybe that’s the best way to think about it. So on the technician here you are, as we said earlier, stellar career, but you at one point were a technician in lab as well.

Paul Nurse (18:16):
I was because I couldn’t get into university. This is now a long time ago, cause look at the color of my hair. But in the late sixties or mid to late sixties you needed to what was called matriculate to get into inner university and the matriculation required a set of O levels, which are a bit similar to GCSEs today. And you needed to have certain categories of those examinations, an examination you’d sit when you were 16, usually to make sure that you had a, a, a sort of general education, so you’d need English, maths and and a foreign language, which was my problem. And what happened to me is I had actually pretty good A levels. I sat in one year early. So by 17 I had very good A levels that would’ve get me into any university in the UK, but I didn’t have an O level in a foreign language. And I kept failing my any attempts to do it. My school, I did Latin, Greek and French. I was appalling at Latin and Greek and they wouldn’t even let me sit the examination. And I managed to sit French O level six times and fail it six times, which is, think a world record for failures. And this meant I couldn’t get a place in any university. So I was offered conditional offers to everywhere I applied to, which were some of the greatest universities the land, Oxbridge for example. And it was all conditional, no level fringe, which I failed to get. So I, I was, I had to, I left school 17 and I worked as a technician, not knowing what to do. And I worked in a offshoot of the Guinness brewery in Park Royal, which is in west London no longer a brewery there. Um but there was then, and they had a startup company in biotech, what we would call biotech today. And I spent a year there right next to the brewery. And I assumed that I would have a the a career as a technician. But actually the University of Birmingham, which is where I am up going looked at. I don’t know what the head of department of genetics was looking at, but he was looking at some of the students they’d rejected and came across me and asked to see me. This is the head of department to see a failed undergraduate. His name was Professor Jinks. And I went up on my motorbike from London to Birmingham. He spent an hour interviewing me. I spent half a day looking around the department being interviewed. And they at the end of it said, we’d like you to come here and we’ll fix his O level French i’ll, take it to Senate and get a clearance Senate. It cleared me, but you know what they said? They said, we’ll let you come, but you’ll have to sit a foreign language in, well, first year at university. So I was allowed in, but I had to do French now at a very low level O level. This is university. Yep. They gave me, this is impossible to happen today. What the story I’m going to tell you. They gave me the most junior lecturer in the department and we met in the October the beginning of the term, maybe September. And I remember that it’s a very entertaining conversation. He said, Paul, you don’t want to be here. And I don’t want to be here. He said you, I got to give you an examination at the end of this year. And it’ll be an examination of translating scientific French into English. About a third of the words will be English anyway, because it’s scientific French. I’m allowed to let you take any books into the into the exam. But I think are appropriate and I’ll allowed take a dictionary into that examination. And as long as you put the words in the right order, as according to the work, I will pass you not well, but I will pass you. And I don’t think we need to meet again now. Oh, wow. So I even got outta that one too. Couldn’t happen today though? I’m sure.

Peter O’Toole (22:27):
Good, good old Birmingham. So I I’m a Brumy by nature.

Paul Nurse (22:32):
Oh, right. Well, I’m been, I’ve been constantly thankful for, for Birmingham and Birmingham University in particular.

Peter O’Toole (22:41):
CT’s changed a lot since then as well though. So it’s mind you that, that was back in the seventies, wasn’t it? I think for sixties

Paul Nurse (22:49):
67, I went there. Yeah.

Peter O’Toole (22:52):
Wow. <laugh> so so for the technicians you know, you obviously appreciate the technical role, but you’ve also set up stable and supported the technical careers and the importance technicians in research which I think is greatly appreciated. And I think you saw that over at Rockerfeller well. And, and Allison North says hello by the way. Okay. But I, I think it’s tremendous to support and the need of core facilities, that expertise. And as you said, bringing in, you can come in Crick and you got all that expertise at hand, just going back to the Crick itself, how stressful was it? How stressful is it still? Cuz actually now it’s up and running. It doesn’t stop. Does it?

Paul Nurse (23:34):
It doesn’t stop. I mean at the beginning, we, at the beginning we had to merge three research institutes and one research administration, which was in a different place altogether. And these were all different cultures. So that was a pretty, I mean, mergers often fail because of things of that sort and, and this one worked, we had to transfer all the equipment and so on, we didn’t get new equipment in the building. We just transferred what we had. We had to move, move in many thousands, oh, I mean 130,000, I think mouse cages in here for example and everything all the freezes and so on, this was a major logistical exercise now to do it. The MRC who, of course, one of the bodies strongly proposed that we should use project managers. And I was a bit dubious. I didn’t think that was necessary. Really. I was totally wrong as I’m so often am by the way. And we, but I did put it in place and the, the project managers were incredibly important because they’re used to this sort of thing, whereas where I’d be an amateur isn’t. I mean, I got some common sense, but you know, that that was not enough. And so we did move in here and move in here fast. And the majority of scientists were up and running within weeks which was quite an achievement, not quite all. We had a few things that didn’t work so well. So that was a lot of work. Then we had to set up the recruitment, which when I told you was completely open, that isn’t how the founding institutes had generally wor worked. So put together a, a, a, a massive search committee to cross all areas worked with the research director I have here, Richard Treisman, who was from one of the institutes. Uh Jim Smith was involved too for a bit, but they went off to the Wellcome and just setting up that recruitment because we would have, for every position, we advertise 300 applicants. I mean, just, just completely unbelievable. Our graduate program is like that. We get 1500 applicants each year of potential PhD students for 40 posts, 40 places. So it’s nearly 40 to one. I it’s, I’ve never seen anywhere in America or anywhere else with that, with those numbers. So what am I saying? There were a lot of new practices that had to be put in place. We made lots of mistakes and we had to get through them, but now we’re running smoothly. You could say the workload is a little a, a, a little reduced, cause it’s not all change, but you now mustn’t get complacent. You, you, you’ve gotta keep keep maintaining the drive and the standards that you’re trying to apply. And it is a bit exhausting cause you just have to keep going. Otherwise once you lose that drive and enthusiasm, it ceases to be quite so special as I think it it probably is now, as it happens this last year, I’ve been involved in the major five year review of our whole Institute. Cause we’ve been going, it’s a third major review I’ve had already, I mean, they do review me an awful lot. Yeah. This review was, was very heavy, 5,000 pages we had to produce for our three funders and I mean excessive in my view, but that’s what we did. It’s gone very well. So I’m very pleased with that. We’ve got the maximum scores for the Institute overall. So and I’m awaiting the outcome. In fact, it’s very day, I’m waiting to get the the formal outcome of that. I’ve got the informal one. And but that’s another, if you said stress it’s carrying on cause all of these things just keep going all the time.

Peter O’Toole (27:27):
What do you do to de-stress? What do you do at home? What, what, what’s your hobbies? Mm,

Paul Nurse (27:34):
Well, I’ve had several hobbies. One of, two of them, I I’m sort of doing less. I, I used to be not a mountain climber, but certainly a mountain walker. So in, I worked in Edinburgh for seven years, did a lot of mountain walking there and the Lake District as well. And so on, haven’t done that so much in recent years, perhaps more exotically I’m a pilot and fly both glider and airplanes. GL I’m a, I’ve been a glider pilot since I was 16, actually. So for, for a very, very long time, I still do flying gliders, but not so often these days and flown in Scotland, in east Anglia, in Oxfordshire, but also in the Alps in the Pyrenees as well. So mountain soaring. So that’s one thing I do to relax. Cause I can tell you when you’re up there flying only 10 meters away from a rock face, you are not thinking about the Crick. I can tell you that. And the other thing I did when I was in America, I, I had a pilot’s license, but in America I got an endorsement as a, a, as a sort of a Bush pilot. So I used to fly old aircraft by planes, open cockpit, buy plane, or what a Bush pilot planes, the sort that you land in clearings in forests and so on. And I learned how to do that, which is a very interesting way of flying, which nothing like normal landing on runways. You you’re you’re, you’ve gotta have it very, very finely tuned cause otherwise it’s, it, it can be can be dangerous. So I use that to relax myself

Peter O’Toole (29:21):
That, that that’s, I’ve not had anyone have that hobby to date. Sure you have. So just, just some quick five questions. Yep. Mac or PC person.

Paul Nurse (29:32):
I’m a Mac appalling

Peter O’Toole (29:34):
<Laugh> okay. Are you an early bird or a night early

Paul Nurse (29:38):
Bird by far.

Peter O’Toole (29:40):
Okay. tea or coffee,

Paul Nurse (29:44):
Tea,

Peter O’Toole (29:46):
Beer or wine?

Paul Nurse (29:50):
Actually both, but I know more about beer than wine, but I drink both

Peter O’Toole (29:54):
Red or white wine.

Paul Nurse (29:57):
Depend on the time of the evening, white at the beginning, red later,

Peter O’Toole (30:02):
This sounds like a long evening that you could, you can be having with the, the beer to the white, to the red. I’m

Paul Nurse (30:07):
Afraid. It’s true. There are often long evenings of that sort.

Peter O’Toole (30:11):
Did you have a favorite beer?

Paul Nurse (30:14):
I I do have some favorite beer actually. I, when I was in Norwich where I worked I liked Adnams, which is a, a south wald south. Oh, I see. You’re a beer person.

Peter O’Toole (30:26):
No, I I, 10 years in Essex and we, we love Norfolk and Suffolk, so

Paul Nurse (30:31):
Yes. And I have to say this cause my, one of my daughter’s partner is a Theakston and was part of the Theakston family that ran the Theakston beer in Masham. And actually his father runs Black Sheep because they had the FA the, the family had a bit of a split and had two breweries. And so I have to sell like Black Sheep too.

Peter O’Toole (30:52):
[Inaudible] is actually one of my favorites. So, and from Yorkshire that that’s only the right thing to do, I think at that point yes. What’s your favorite food?

Paul Nurse (31:03):
You know, I’m not a sophisticate in food when people ask me what I’m cooking. I often say cornflakes, cause I am, don’t do anything. I am living in Birmingham and as a student with no money, I learned a lot about Indian food. And so I’m, I’m, I’m pretty good on Indian food dish. I have to say.

Peter O’Toole (31:25):
Yeah. So obviously home of the Balti in Birmingham,

Paul Nurse (31:29):
Well, of course is a bit of a invention in this in this country. I mean, it’s not

Peter O’Toole (31:35):
Birmingham I think was yeah, Birmingham.

Paul Nurse (31:37):
That’s what I was gonna say

Peter O’Toole (31:40):
What about God, take me off track. Now. What about any foods you don’t like, go to a conference and take you out for dinner and they it’s a set menu and they put it in front of you and go, oh no,

Paul Nurse (31:53):
You know, I’m not a great fan of sushi. I, I feel I should get grown up and like it, and I’m doing my best and it’s, it’s beginning to grow on me, but whereas everybody else says, this is amazing. I’m sort of saying, well, I wish it was cooked <laugh>

Peter O’Toole (32:08):
So it’s raw fish more than anything else. It’s just not

Paul Nurse (32:12):
Somehow I’m not sophisticated enough

Peter O’Toole (32:16):
TV or book,

Paul Nurse (32:18):
Book,

Peter O’Toole (32:19):
Fact or fiction.

Paul Nurse (32:21):
Actually, I tell you, I have both always running at the same time.

Peter O’Toole (32:27):
What do you have at the moment?

Paul Nurse (32:28):
I have Hillary Mantel’s third one one the of, you know, the Cromwell series and I I’m reading Ravelies latest book which is all about Heisenberg.

Peter O’Toole (32:48):
Okay. Favorite movie.

Paul Nurse (32:52):
I’m going to say the seventh seal. It’s a Bergman film from the fifties.

Peter O’Toole (32:57):
Okay. I didn’t know that one. I, and what about I, I should have asked this all my guests and I haven’t a favorite Christmas movie. These can sometimes be quite revealing.

Paul Nurse (33:05):
Oh my goodness. I I’m not, this is awful. I’m not sure I have a favorite Christmas movie. I’m so sorry. I don’t think,

Peter O’Toole (33:17):
Did you ever have a, you’ve got two daughters. Did you ever sit down and watch a similar movie each year with them at Christmas?

Paul Nurse (33:25):
I used to watch that is true. We did, of course watch The Snowman with Raymond Briggs now. I’m not sure it was my favorite film, but it certainly was theirs. And I did meet Raymond Briggs. In fact, I, we hired a cottage off him for a week, about 40 years ago, 30 years ago. But The Snowman has, is now transferred to my grandchildren.

Peter O’Toole (33:48):
Okay. How many grandchildren?

Paul Nurse (33:51):
Four grandchildren, three boys, essentially five years age of age, two are twins and one granddaughter of eight, ah,

Peter O’Toole (34:01):
Fun Ages.

Paul Nurse (34:02):
Sorry,

Peter O’Toole (34:03):
Fun ages. And I hope you,

Paul Nurse (34:04):
Yes, they’re very, very nice ages. Yes. Very nice ages. I wouldn’t say restful though.

Peter O’Toole (34:10):
Good. Good to be your grandparents who can be round them when they’re lively and then, and then

Paul Nurse (34:15):
I know that’s what everybody always says, but their parents always want to delay that particular part.

Peter O’Toole (34:21):
And another favorite question I like to ask is why is your favorite item of clothing?

Paul Nurse (34:28):
Well, you know, I, I ha they are accessories. Now. This is going to I, I was once phoned by a fashion editor from one of the heavy newspapers and the fashion editor wanted to do fashion piece. And for some reason, phoned me phoned me up and I found this so ridiculous, cause I’m a very scry person that I began to make fun of myself talking about it. So I said, I made because my body isn’t suitable for clothing really, I, I major on accessories. And I went into bags and hats and scars and the fashion editor was so convinced by my discussing this, that she took it all seriously. And I ended up on the fashion pages of the, I think it was the times with Benedict Cumberbatch. In fact, the actor who was, have I got that right? No, I didn’t quite get right. But and of course he is a fashion icon, but I certainly am not

Peter O’Toole (35:31):
How many years ago do I have to go and find that from,

Paul Nurse (35:34):
You know, it’s, it’s, it’s not so long ago, 10 years ago.

Peter O’Toole (35:39):
I, I, I lost Bitesize type Bitesize team to try and find that one out. Cause that sounds brilliant. <Laugh>

Paul Nurse (35:45):
It, it very, very funny. It is very, very funny. Everybody who knows me and knows me what a scruff bag I am is always makes fun of me when they or did when they saw it.

Peter O’Toole (35:55):
So think thinking of the Times the newspaper I, I wouldn’t associate you with someone who would be naturally a, a times reader.

Paul Nurse (36:05):
I do read the Times to see what the other side thinks. I’m on the left some people might call me on the champagne left, I suppose. But I’ve all, I’ve been a labor party member for 40 years or longer now only nearly 50 years. But I work with a range of of political opinions and in recent years nearly always with the Tory party. So I do get on well with a number of those not all members of the Tory party and the certain sec flanks and sectors. I, yeah, don’t worry, but many are doing their best. And I may not agree with them all politically, but I, we work together. We work together well, so I’ve done a lot of that. So although I’m personally labor left I’m can work perfectly well with the more moderate part of the Tory party.

Peter O’Toole (37:01):
Would you ever be tempted to become a politician

Paul Nurse (37:06):
In a job like this? You’re always partly a politician to be fair. I don’t think I find politics sufficiently. Interesting. If I can be honest with you even running an Institute and so, although I I’m really fired up by it, it doesn’t compare with still doing research. So I still have a lab just through that wall. I have six graduate students, a couple of postdocs, and that’s what fires me up still. I, I’m not saying I’m as as able as I perhaps was 30 years ago, but it’s still reasonably good. And that’s what fires me up.

Peter O’Toole (37:45):
And how much Microscopy is your team doing?

Paul Nurse (37:47):
A quite a lot? Not, not much high resolution to be fair, but a lot of time lapse on the geneticist cell biologists. And there’s all sorts of clever and I work with yeast and, and you can do amazing experiments with yeast and you can ask fundamental questions often rather simple questions, really clear answers, often quite difficult with more complex systems. So we do a lot of time lapse a lot of analysis with colored proteins to measure levels and, and things of that sort and combine that with the genetics. So we, we have a, a couple of pretty high end microscopes in our microscope room.

Peter O’Toole (38:34):
Not you’re not using the core for this.

Paul Nurse (38:36):
We, they are core facilities. Actually. I bought them on a grant. I I’m actually fully grant funded because I thought I should lead from the front. So, but we bought two Microsofts in different grants over the years, but they are part of the core facility, but they’re next to us. So if we are not using them, other people use them.

Peter O’Toole (38:54):
That’s, it’s a perfect solution, I think. And, and actually keeping on the science, you, you mentioned you’re still in yeast and yeast is a really useful model. There will be some in the community saying, oh, really? Are we still using Jasophna? Are we still using yeast? You know, why aren’t we using mamalian systems? God, just, just one minute justify why yeast? I, I, I, I think I know the answer to this will. Why is he still so fundamentally important as a tool?

Paul Nurse (39:18):
Well, the first thing I’ll say people have been saying that to me since 1970, why am I bothering to work with yeast? And I should say that four of the last 20 years, Nobel prizes have been awarded to yeast work. So that’s something to think about why are we still using it? Because you can do the most beautiful experiments with great precision and come to very, very reliable answers. Working with mammalian cells is much, much more difficult and you’ll find the ideas and hypotheses change because of problems with the experiments. And we suffer much less from that with yeas because the experiments can be so rigorously carried out.

Peter O’Toole (39:54):
So not just because you’ve worked at the Guinness brewery at some point and all the yeast involved in that, there there’s a nice synergy. There’s, there’s a thread going through here. There is,

Paul Nurse (40:03):
There is

Peter O’Toole (40:04):
Actually, I, I had an email just before we call from a, one of our leading yeast scientist. Who’s just been funded by Wellcome Trust for, for another three years, which is fantastic news. Actually,

Paul Nurse (40:15):
I’m funded by, I have a, an investigator award from The Wellcome Trust. I mean so they fund not quite all my work. I had a couple other grants, but they, they funded me since I came back from the US.

Peter O’Toole (40:28):
So do you remember what your first microscope was?

Paul Nurse (40:31):
The first microscope that I remember and I have, I have two microscopes. I have a a west German Zeiss photo microscope, two, which you may remember, and when they wanted to throw it out, I took it home and it’s in my house in my loft, cause I spent so many hours looking down it and then I had something, I called a, a plate microscope for looking at colonies of yeast on agar plates. So not even with cover slips and so on, which I bought from east Germans Zeiss. I, I was working the University of Sussex setting up my lab, didn’t have much money. And I, I bought that from east Germans Zeiss and I still have that one too. It’s just corridor here. And I’m, I’m keeping it it’ll go somewhere eventually. And so it’s two Ze microscopes, east German, Western.

Peter O’Toole (41:28):
So I asked you if you’d ever be a politician now and you you’re very much happy in your research scientist at the age of when you were a school. Boy, what did you want to be at that age? So age 10 to 12, what was your ambition?

Paul Nurse (41:41):
Yes. So age 10, 12, I was thinking about what to do and I, I did like literature. I, I know that I can’t speak foreign languages or anything, but I liked literature and I liked theater in particular. In in fact we didn’t go onto all my hobbies, but I’m in, I’m going to the theater tonight, for example. And so I did wonder about doing English and I did wonder about doing the sciences and biology at the time I was interested in natural history and ecology and I was thinking of going to university to do ecology. I have to say. And then when I did get to Birmingham, I only needed one major field trip to the Isle of Man in March in howling Gale and rain when going out at 5:00 AM to when the tide was low to realize this wasn’t what I wanted to do. So I abandoned the ecology. Partly because it was so cold, wet and miserable, partly because you couldn’t do so easily controlled experiments. And so I gradually receded into thinking about cells as the simplest entity that you can truly say is alive and thinking about what is living and what it means to be alive.

Peter O’Toole (43:05):
You just chose the easy life. Then

Paul Nurse (43:06):
I chose the easy life I wanted to have warm feet And dry feet.

Peter O’Toole (43:14):
What about your inspirations throughout your career? Have you got one or two inspirations or people who, you know, you look up to?

Paul Nurse (43:22):
When I was a little older, still a school boy, 16, 17 I was a great admirer of the evolutionary biologist, John Maynard Smith, who became the Dean of the, the University of Sussex where I also, I, I got to know quite well when I was there and he was, he was important at that time for me. And he wrote popular books on mainly on evolution. And I devoured those when I was 15, 16, 17, I think a little later in my life. And my heroes were the great really molecular geneticists early on in the molecular biology revolution. I’m thinking of Jacques Monod, I’m thinking of of Sydney Brenner and Francis Crick, for example, these sorts of characters who indeed carried out the most beautiful experiments. I mean, to go back to that often were with very simple organisms, bacteria, phage viruses, and worked out the genetic code.

Peter O’Toole (44:27):
Excuse me. The, the next question I realized we, we, we are on a time limit today. So when have you, what, what is the most fun time of your career?

Paul Nurse (44:40):
Well, my working career would be in, in, in the seventies, late seventies, early eighties, when I devised working with yeast with vision yeast and searched for cell cycle mutants. So it was very directly connected to the problem I was interested in. I did a lot of screening using our east German’s Zeiss microscope to look for cell cycle mutants. I defined with colleagues of course, maybe 30 or more cell cycle genes. And that was, that was very exciting. And then there was one particular experiment, which was when I, I was working in Edinburgh and I discovered by accident. I wasn’t looking for it. Under the microscope what I called a, we mutant it was a fission cells that were dividing at a small size. And I haven’t imagined that before. I mean, the mutant I’d got the ones that couldn’t divide, so they got very long and elongated and enlarged, and then it suddenly just, you know, within seconds of seeing this, I thought this is a cell that is dividing early before it’s grown enough. And that must mean it’s altered in a control, which is rate limiting for the whole cell reproductive process. So it probably means that this gene is defining the major rate limiting step of, of the cell cycle. Now I’d, I’d never thought of that and to look for it, which is the way this is supposed to go. I discovered it by accident and then went back and recreated that thinking that’s a gene, I called we one and that did indeed do exactly what I just said. And the rest of that part of my career was working out how that worked. And to do that, I had to do the second exciting thing, which to develop again with colleagues, molecular genetics, I mean how to clone genes, how to make libraries, how to gene edit, which was done in yeast in 19 78, 1980, or I did it for vision use, for example Devi the techniques for doing that in, in ed the late at seventies and that allowed these genes to be cloned. And then you could sequence them and find out what they did. It took, I remember over a year to sequence one gene, if you can imagine that over a year to sequence one gene, people just can’t imagine it now. And that eventually identified the control network, that controlled cell cycle progressioning involves these cycling dependent kinases CDKs, which were isolated in fission yeast and also in budding yeast initially. And so that was the second sort of period. Then the third one, which is in the eighties was when people said, well, why are you bothering to work in yeast yet? Again, I get asked that question every five years. And I thought, well, I better see whether it’s the same in humans. So I took the very first human cDNA library that ever been made from Berg. He gave it to me within weeks of making it I’d have to say generously, it’s very generous, often science like Brian and I doctored it a bit to get it to work in fission yeast and sprinkled it basically on a mutant that was defective in this CDK gene and to see whether there was a gene in humans that could substitute for the gene in yeast. So to look for functional equivalence. Now this was an experiment. Nobody expected to work. I, I was working in ICRF at Lincoln’s inn, at the time because yeast and humans, divers certainly a billion a years ago, probably one and a half, 1,500 million years ago. And I was demanding that the genes remain conserved for 1,500 million years. I mean, you unbelievable time, but it did work. And Melanie Lee, who was working in my lab isolated the human gene, we sequenced, it had remarkable sequence identity despite that divergence. And so those were my most enjoyable three occasion, all of which were sort of advances of a certain sort, which compensated for the many failures that go on in between.

Peter O’Toole (49:00):
I was gonna say, of course, if that hadn’t succeeded, how things could have been different.

Paul Nurse (49:05):
Completely I had a lot of luck in everything I’ve done a lot of luck.

Peter O’Toole (49:09):
Maybe it sounds also had the failures in-between as, as all labs do have failures in-between and just

Paul Nurse (49:15):
Failures. And, you know, I, I have quite a number of students. I enjoy looking after students. I talk a lot with them every day, really. And the main thing you, you see undergraduates have taught the best experiments that have ever been done, and they think they’re all go in the lab and do the them. And the first thing I have to learn is they won’t. And most of the experiments they do, if you’re at the cutting edge will fail. And so you end up not just being a supervisor, but a almost a psychiatrist to just keep people going in those difficult times.

Peter O’Toole (49:48):
Well, Actually, I, one thing I was gonna comment on, we have, we have really short on time. No, is all the offices at quick are, are glass window doors, top to bottom glass, which actually when those students crash they, they get very upset and actually I’m so actually our, our offices I have a blind so I can pull down. So actually they can just pour out yeah. When, when things are bad.

Paul Nurse (50:14):
Well, yes. So I, I, you’re quite right. It’s full of glass. And you do have to deal with people when they’re sometimes upset. I actually take them out into our public place onto our sofa and people are very discreet and they know something’s not working if that happens. But the plus of it is in the Crick, It’s more difficult to behave badly as a consequence of that. And, you know, with the increased interest in research culture and these sorts of issues in, if you are, as we are, you can’t see quite well. You can see behind me constantly on show, then I hadn’t realized that, but that does, I think, make people think twice before they lose their temper or say things that are not appropriate. So you’re right. People find it difficult to cry in private, but they also find it difficult to shout as well.

Peter O’Toole (51:11):
And one, one final question. Yeah. The future, what’s the next big challenge that we have to embrace in the scientific world?

Paul Nurse (51:21):
Well, for me politically which is not the question you ask, but I’ll come to your question in a moment about scientifically for me it is trying to do my best to for society to recognize that science research and development are key for the future of humankind in all respects. And we have to have a vibrant research culture hopefully connected well with Europe, for example, and I do in wearing my political hat, have quite a lot of of, of work to do in that area. You are actually asking me, however, what is the science question? Well, it’s, it’s very simple for me. We work on a cell, it’s a simplest entity. I’ve said this already, that, that clearly it can be said to be alive. And I think the big problem for at least my area of biology is what does it mean to be alive? How does that cell work? How does it actually produce something that is living? And that makes you focus on the fundamental problems of life, not just the nitty gritty ones, but to focus on what is life and how we can work out how it operates. And that’s the big question. And I think it is addressable with the amazing techniques we have, including microscopy the amazing genetics we have the amazing ability to use information approaches artificial intelligence, machine learning, and so on to address these problems. And I think it’s a very, very exciting time to address what seems a simple problem. What does it mean to be a cell and how does it work

Peter O’Toole (52:57):
Well on that note? I, I, I appreciate your time. Thank you so much for joining me today. Thank you everyone who’s watched or listened to The Microscopists today, Paul please do subscribe to the channels to listen to the future ones and go back into, see those previously. But Paul, your time’s really precious and it’s been tremendous talking to you. Actually, we should do this again. So I’ve still got half a, I’ve still got another half a session to go with you on this. There’s quite a lot of information that I haven’t teased out yet, but Paul, thank you very much for joining me.

Paul Nurse (53:25):
It was a pleasure talking to Peter and I’m very happy to have another conversation whenever you like.

Peter O’Toole (53:29):
Thank you.

Intro/Outro (53:31):
Thank you for listening to The Microscopists, a Bitesizebio podcast sponsored by Zeiss microscopy to view all audio and video recordings from this series, please visit bitesizebio.com/themicroscopists

 

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