Disease Models & Mechanisms 2, 113-115 (2009) doi:10.1242/dmm.002592 A MODEL FOR LIFE The cell cycle and beyond: an interview with Paul Nurse Sir Paul Nurse is a recipient of the 2001 Nobel Prize in Medicine for his work on one of the key regulators of the cell cycle, CDK (cyclin-dependent kinase). In this interview with Jim Smith, he discusses his choice of model organism, scientific leadership and the early influences on his career. s his fellow Nobel Laureate Tim ability to interact with people from all Hunt has said, it is difficult to walks of life. think of an abler, or more imag- The interview that follows took place on inative and accomplished, biol- the telephone on 21 October 2008; it has ogist alive today than Paul been edited only very slightly, and we have ANurse. One might add the word versatile to resisted the temptation to change the idio- this description, for on the other occasion syncratic order of my questions! I have written about Paul it was to introduce his published lecture, delivered to Christ’s You managed to define fundamental College Cambridge, on Two Views of parts of the human cell cycle machinery DMM Creation: Milton and Darwin: there aren’t using a simple single-celled organism. many scientists who would attempt such a How did you come to the conclusion that synthesis! That short piece, and Paul’s yeast was the model organism for you Nobel Prize autobiography (http:// and your lab? nobelprize.org / nobel_prizes / medicine/ I originally became interested in the laureates/2001/nurse-autobio.html), provide problem of cell division not so much many of the facts about Paul’s life and sci- because of its relevance to human disease, entific career: about his early life and but because cell division was the basis of all the prescience of Professor Jinks at growth and development. The process of Xenopus with Chris Ford. These experi- Birmingham University, who allowed him reproduction is a crucial characteristic of all ments gave hints, but they were never to start his degree without the required living organisms, which is seen at its sim- strong enough to be published. So the pos- qualification in a foreign language; about plest with cell division. Having got attracted sibility of a human link was always in the how he discovered that cdc2 regulates the to studying the basic process of cell division, back of my mind and later I thought we onset of S-phase and mitosis in fission I wanted a model system that would be ef- could just go for broke and look for human yeast; how he and Melanie Lee cloned the ficient and effective with which I could CDC2 protein kinase. If this worked, it was human CDC2 gene using a ‘rescue’ ap- make rapid progress. I chose a single-celled probably going to work the same way in Disease Models & Mechanisms proach; and about his responsibilities as organism, good for genetics, and which did every eukaryote from human through to Director General of the Imperial Cancer little else except divide. This meant using yeast. I suppose the most astonishing thing Research Fund, which he went on to bacteria or yeast. Bacteria were clearly dif- was the way Melanie Lee in the lab did it by merge with the Cancer Research ferent from eukaryotes, so I went for yeast. complementation. The ways that we had Campaign to create Cancer Research UK. There were just two papers in this area on tried previously relied on structural simi- An addendum to the Nobel Prize autobi- budding yeast from Lee Hartwell and he larity – we’d used Southern blotting, but it ography also describes how Paul felt when showed that it was a good approach, so I was just too crude. We were getting lots of he discovered that the man and woman he wasn’t taking such a big risk in trying to protein kinases but we had no idea if they thought were his parents were actually his develop such an approach with fission were the right ones. We were lucky to get grandparents, and that his biological yeast. the complementation approach to work. mother was the young woman he believed The connection with human biology The principle was a good one but we had was his sister. We did not discuss this part came later, when gradually I realised that we fortune on our side that it actually worked. of his life to any extent, although Paul did had identified important elements in yeast comment that his working class back- that were crucial for control and there was You have stuck with yeast throughout ground might have contributed to his a possibility that these were conserved your career. Have you ever thought of among the eukaryotic world. Some years working with any other organism? before the key experiments, I had tried, un- I’m nervous about working with any other Sir Paul Nurse is the President of The Rockefeller successfully during the time I was in Sussex organism; I understand yeast biology really University, where he is also a Professor and head of the Laboratory of Yeast Genetics and Cell Biology in the early 80s, doing some experiments well and, particularly now that I do other (e-mail: [email protected]) with MPF, maturation promoting factor, in administrative things like running institu- Disease Models & Mechanisms 113 A MODEL FOR LIFE Sir Paul Nurse tions, if I’m going to be helpful to my col- thing I respect, and I apply it to myself as about their job, I have empathy for them. leagues in the lab I need to be really famil- well as to others. So I always wonder, am I When you’re putting yourself into the iar with the system they are working on. I good enough to still be supported on my re- shoes of the person you are talking to, it am familiar with fission yeast and thus I can search alone? The answer to that is proba- does help. Quite often, I have had to tell still be helpful to colleagues in a way in bly yes, but I worry about it, and if I do people that they haven’t got tenure or they which I wouldn’t be able to do if I was to something else that contributes to the com- have to leave and things like that, and this work on flies, worms or frogs, because I munity like running things I feel less guilty is deeply uncomfortable and unpleasant. have never worked with these organisms about it. The point is you have to be sitting in their with my own hands. The other reason is in shoes to do it well and that may be what line with Barbara McClintock’s great quote So you’re covering your arse, as it were? helped me here – that I was not born with that you need to have a feeling for the or- I guess you’re right – I’m covering my arse. a silver spoon in my mouth, if I can put it ganism you work with, and I have a feeling Another reason I work on these adminis- that way. Having had a lot of difficulty for yeast. I can pretend to be a fission yeast trative tasks is that often the people who get getting jobs early on in my life, having and I can do it quite well. I can sort of attracted to running things are not always worked on short-term contracts and so on, imagine how a fission yeast feels, and it the people you want to run things. People and having been rejected by a number of sounds crazy of course, but I can’t so easily who are totally engrossed in the science and institutions that I applied for, I’m used to imagine how a fly feels. If I was starting who are still close to the coalface are the failure and that remains with you. When again today, I would think very carefully right people to be running research science. I’m talking to somebody who has failed at about whether I wanted to go more in the I’m quite good at it and it means that there something, I know I’ve been there too. I’m direction of problems to do with the cell, in is a real scientist doing it rather than a sci- aware of people’s feelings and share their which case I would stick with yeast, or entific administrator. distress. problems to do with the organism in which DMM case I would go for the fly or worm. I still You are good at it – what qualities do you Let me change the subject to the wouldn’t go for work with human, mouse or have that make you so good? UKCMRI. This is a huge new Institute Xenopus. I think Xenopus is very good for Overall, I think I’m a conservative radical. and a fantastic new opportunity. What the in vitro systems but they are just a little What I mean by that is I’m basically problems do you want UKCMRI to too complicated and I’m driven by more radical, but I will only try and bring about address and solve? genetic approaches. radical change from a very strong base. In I would like it to be a powerhouse for the other words, merging the Cancer highest quality biological and biomedical Let me pick up on your remark about Research Campaign and the Imperial research.