“Cancer, in reality, is more than 300 different diseases with a common feature. There will never be a single cure”
Back “Cancer, in reality, is more than 300 different diseases with a common feature. There will never be a single cure”
“Cancer, in reality, is more than 300 different diseases with a common feature. There will never be a single cure”
Paul M. Nurse, Nobel Prize in Physiology or Medicine in 2001, gave the inaugural conference of the MELIS Biomedical Research Symposium, entitled “Cell Cycle Control”. It took place in the auditorium of the Barcelona Biomedical Research Park (PRBB) on 20 October. We took advantage of his visit to UPF to chat with him a while.
Paul M. Nurse was born on 25 January 1949 in London. He studied biochemistry at the University of Birmingham, where he graduated in 1970. In 1973 he completed his doctorate at the University of East Anglia in Norwich. In 1984 he joined the Imperial Cancer Research Fund (ICRF), where he remained until 1988, when he became head of the Department of Microbiology at the University of Oxford. After his stay in Oxford, in 1993 he returned to the ICRF as director of Research until 1996, when he was appointed director general. In 2003 he became president of Rockefeller University in New York and in 2010 he became the director of The Francis Crick Institute, in London, one of the most important biomedical research centres in the world.
In 2001, this English biochemist shared the Nobel Prize in Physiology or Medicine with Leland H. Hartwell and R. Timothy Hunt for having identified, cloned and differentiated using molecular and genetic techniques the protein cyclin dependent kinase CDK, one of the key regulators involved in the cell cycle.
On 20 October, he gave the inaugural conference of the MELIS Biomedical Research Symposium, entitled “Cell Cycle Control”, which was held in the auditorium of the Barcelona Biomedical Research Park (PRBB). The event was presented by José Ayte de l’Olmo, a researcher with the UPF Department of Medicine and Life Sciences (MELIS), who did his postdoctoral studies at Nurse’s laboratory in 1998 and 1999.
When did you decide to become a scientist?
I think my first interest in becoming a scientist was when I was quite young, I was 8 or 9 years old, and I saw Sputnik II, the second artificial satellite crossing the London sky, it was carrying a dog called Laika, and I also had a dog, and I felt empathy with that dog up there in the sky. This got me interested in astronomy, and then I took an interest in natural history. My interest was aroused at rather an early age and when I was about 15 or 16 I thought I would probably like to be a scientist.
What are the most important skills for being a good scientist?
There are many ways you can be a scientist and therefore there is no single attribute or specific characteristic. For me, you need to be pretty curious about the world and how it works, combined with perseverance to keep going, even when things aren’t going so well. Curiosity and perseverance, and I suppose respect for observation and data, you can’t stray far from that, combined with rigorous thinking. But curiosity is the main driving force.
Your beginnings are quite different from other scientists: you were rejected by several universities. What happened at the start of your career?
I came from a working-class family, it wasn’t an academic family, I wasn’t very good at exams. I was particularly bad at languages and I never managed to get even the most basic grades, and that prevented me from going to university. I was working as a technician when the University of Birmingham broke its rules to admit me. And I’ve always been grateful for that. When I went to uni it was as if I had gone to heaven, it was a huge transformation for me because I had been working as a technician and suddenly I was in a place where I was just thinking about ideas and thinking about what the world meant. And I was getting paid! It is a privilege and I can say that I have been paid my whole life to pursue my curiosity, I can’t imagine a greater privilege, I am such a privileged person.
What does it mean to be a biologist?
Biology is a broad subject, from the study of the molecules of life and the details of their structures to the study of entire ecosystems or even planetary light systems. You can’t really understand any part of something without some sense of the whole.
A biologist, a good biologist, needs to have this breadth of thought. I’m not saying that all biologists do, but to my understanding, a good biologist has to take that breadth. This is one of the reasons why I’m not so keen on specialized biological causes, at least you need to have that breadth of gaze at some point in your university career. After that, maybe you can specialize.
Put simply, why is it important to understand the cell cycle?
The cell is the basic unit of life. The simplest living organisms are, in fact, just individual cells. And a basic characteristic of all life is that it reproduces, and a simple manifestation of this is the growth and reproduction of a cell dividing from one to two. This process is the basis of all growth and development in every living being on the planet, from a single cell, bacterium or yeast to the human being. Understanding what controls this process of reproduction, the series of events that we call the cell cycle, from the birth of the cell to the eventual division of this cell in two, is one of the most fundamental characteristics and phenomena of all life. And what has perhaps been very surprising to all of us, and my research centred around this, is the way it is controlled in all plants, animals and fungi. In fact, it’s exactly the same and it’s been that way for a one thousand, five hundred million years, and that’s what my research contributed to.
It is simply extraordinary that once the birth of what we call eukaryotic life, that is, fungi, plants and animals was invented, all cells got set in the same way of controlling their division. Therefore, the cells in me are controlled by the same types of molecules that control the division in yeast, for example, so it is not only a fundamental but a universal process.
It is also, of course, important to understand diseases. Cancer, one of the most significant diseases of humankind, involves uncontrolled cell reproduction, where cells divide out of control in the wrong place and at the wrong time. Understanding how cells control their reproduction is also very central to understanding cancer. So this is what I dedicated my life to.
Understanding how cells control their reproduction is also very central to understanding cancer. So this is what I dedicated my life to.
Your work is mainly related to basic research. Why is it so important?
When you think about research, it’s very important to recognize that there’s a real spectrum of research. It ranges, on the one hand, from what I call discovery research (some people call it basic or pure research, but I don’t like the word ‘pure’ because it implies that everything else is inferior, which I don’t think is right), but discovery research is about understanding how everything works. At the other end are applications for the public good, and this tends to be different because you have a particular need. The way science is done across this spectrum is really very different. The discoveries part is not controlled by any top-down boss or leader, it encourages individual creativity to discover things. When it comes to looking for applications it’s different because then you have to follow programmes. Now, the reason you need all this is that I’m translating research for the public good, in some way it depends on the knowledge produced by the discovery.
If you only invest in one part of the spectrum and not the other, you don’t actually get an understanding of the world or its use for useful purposes. There’s a good metaphor here, you could decide that you only invest in application. This is like building a very tall building without investing in the foundations, you go high, but then everything will collapse. What you need is an excellent foundation and the investment for a bigger construction. The foundation is the discovery, or the basic research, growing higher leads you to applications and usefulness.
How far are we from finding a cure for cancer?
There is often talk of finding a cure for cancer, but it must be recognized that cancer is actually more than 300 different diseases. They have a common feature, uncontrolled cell reproduction, which is why we group them all together as cancer. But in reality, the causes of cancer in all those diseases are very different, and that means that their treatment is also very different, so there will never be a single cure for cancer.
In my view, there are some common treatments, such as chemotherapy, that traditionally use poisons, and it’s just a matter of whether you poison the human being or the cancer first. But what is happening now is that knowledge about how individual cancers arise means that we can be more specific about what has gone wrong in a particular cancer. And this is where I think the cancer will go, I prefer to think not about just one cure because it will require a long period of research over many decades until we get more general coverage of all cancers.
What is happening now is that knowledge about how individual cancers arise means that we can be more specific about what has gone wrong in a particular cancer.
What do you think are the main challenges for biology and biochemistry in the near future?
I think the main challenges that we will see in the coming decades is a more complete and greater understanding of how a cell works, because the cell is the simplest entity that exhibits all the characteristics of life. I believe that the coming decades will take us through the combination of increasingly sophisticated chemistry and biochemistry together with the application of computer analyses. We will gain a much better understanding this century than we have so far about what life is and how it works. But also, when you understand things, you also generate possibilities of using an understanding for a useful application. In general, we think about human health, cancer, infectious diseases, muscle decay, neurodegeneration, but we have the possibilities of a second industrial revolution that is more based on life.
You direct the Crick Institute. What are its goals?
I run a biomedical research institute in London called Francis Crick Institute. It’s pretty big, about 1,500 researchers work there, I think it’s the biggest under one roof. We are a discovery institute, we’re not a translational institute, which is often talked about, because our approach is slightly different. We believe that one way to make useful discoveries is to get highly accomplished individuals exploring across wide areas and recruiting the very best and not telling them what to do, but letting them work out what to do.
We’ve got bright young people starting new projects, discovering new things in a highly interactive and multidisciplinary environment. But it’s a different way of approaching it, it’s like a kind of controlled anarchy, we let the thing grow, and then we harness what we think might be interesting and try to see if we can push it further.
Often people who are good at discovery are not good at transferring knowledge. People who are good at discovery are generally very difficult to control, but people who need to perform the translation and the application need to work to a more standard programme. Very often you need different types of people.
How do you combine directing the largest research centre in the UK and continuing your research?
When I think about my career, I’ve always done research and run organizations, and I’ve never stopped having a laboratory. I spend a lot of time in my lab, probably almost half my week. I mean, it’s not a few hours, it’s a lot of time, either in my lab, or thinking about things that are relevant to my lab.
Actually, even though I direct large institutions, I don’t get the same pleasure or satisfaction out of that as I do from running my own small lab. I feel privileged to be able to work in my lab and I feel that I have to pay something back by doing a task I am quite good at, although it is not what gives me deep satisfaction. Of course, I’m satisfied with what we do, but it’s not deeply satisfying. And running an institution has a lot to do with identifying people who are of high quality, who will do the work for you. I spend a lot of time thinking about the people who will run things, making sure they are good quality, but also with the right character to help them. That’s how I manage the work crews, because most of the day-to-day operation I like to set up so that if I’m not there, it works on its own. My job is to handle crises and deal with long-term planning and choosing the people to lead the different issues more in the day to day.
You work mainly with PhD students.
It’s pretty weird, I work with people who are 50 years younger than me, and we actually have a pretty good relationship. They put up with me, they even go to the pub with me. What I like is that we contribute different things, they have an intelligence, a speed of thought and technical skills that I no longer have. I have a depth of thought and extensive experience of how to get things done that complements their skill set. So we all work and learn from each other.
I particularly enjoy graduate students because I like training people, I like to have people who are a blank canvas and are not yet worried about a job, or seek high-profile publications necessarily, they want to be trained and they are fearless. I visit the lab every time I’m there, every day. I walk around the lab talking to people, sometimes just for two minutes, sometimes for two hours, but just walking, and if they don’t want to talk to me, that’s fine. But that’s what gives me pleasure, because I’m deeply involved in what they’re doing. I don’t want to run a lab like a manager, when I run an institution I can delegate work to other people; in the lab, I’m part of the job.
What is the best thing about receiving a Nobel Prize?
The Nobel Prize is important, and I can’t pretend it isn’t. I never dreamed, when I was 17 and trying to get into university, that I would win a Nobel Prize; it was way beyond my wildest dreams. But it’s like having another job, because you get asked to do so many kinds of ceremonial events, and I probably say ‘no’ to things two or three times a day, some people get overwhelmed by that.
Another hazard of winning a Nobel Prize is a disease I call “Nobelitis”, because people start talking to you as if you understood everything, and the disease is when you start to believe that you understand everything. There’s a danger because somehow you’re up on a pedestal and, of course, you’re no different than you were before. But in my case, at 50, I still had 20 or 25 years of my career ahead of me, so I had to be disciplined and say: I’m not going to become a professional Nobel Prize winner, I’m not going to go to all the meetings and banquets and whatever, I have to keep my lab running and direct the institutions I belonged to and choose very few of those other things.
I never dreamed, when I was 17 and trying to get into university, that I would win a Nobel Prize; it was way beyond my wildest dreams.
What did it mean to win the Nobel Prize?
Once I got the Nobel Prize, I didn’t notice much difference in how people interacted with me. I think people quite like shooting you down, actually, especially anonymously. So, I had the same problems to publish as I did before, to win grants and research subsidies… so there were no changes.
I think the public takes you more seriously, and that’s something I should stress. That means you have to speak with care, because if a scientist goes on the radio or on television and says something that is not sensible, people simply forget it; but if it is a Nobel laureate then there is a danger that you have too much influence in an area that you do not know. You have to be very careful on the public stage, especially with technical issues.
Would you give any advice to young researchers?
The first thing I would say to them is that this is the most exciting time of their life, you have no responsibilities to lead other people and you’re generally not receiving grants, it may seem very stressful, but be aware that this is the most liberating and exciting time of your life. Enjoy it! It won’t always be like that.
The second thing I would say is not to be afraid of failing because you will always fail if you are doing something important, and if you are afraid of failing, you will become increasingly timid; be prepared to fail. I’m not saying to be sloppy and make mistakes, that’s quite different.
Be prepared to be bold, because boldness is where you achieve progress. But also be prepared to be bold and that the results may turn out wrong and, if they are wrong, embrace it. I always say that if you have a great idea and it’s wrong, you yourself have to show it’s wrong. In other words, attack your own idea, it is better for you to destroy your own ideas than someone else doing it for you. So, don’t be afraid to fail.
Thirdly, that it’s hard and difficult, and you need to be passionate. Things that fail don’t work, I can’t tell you how many experiments have failed, but it’s hard, so you have to persevere, you really have to persevere, and you have to be a bit tough to do that. I must add that you must never be tempted to take shortcuts. If you’ve done your best and failed, it’s not a problem, but if you’re being sloppy, then that is a real problem.
And finally, going back to passion, passion means you need something to drive you. Most scientists’ discoveries are driven by curiosity. Some have different passions, they want to be famous, others want to be rich, that’s pretty stupid, because most of us don’t get rich, but some people think they could make it and of course some do. But whatever it is, you have to be passionate to keep going.
Do not to be afraid of failing because you will always fail if you are doing something important.
You mention that failure generates great fear among young researchers, but isn’t failure a way to progress in science?
You learn by failure. In fact, you have a hypothesis, you devise experiments to test the hypothesis, and if the hypothesis fails the test you could say that’s a failure, but it actually means that the hypothesis is wrong. We know how to construct a new hypothesis or amend the old one to make progress. So, failure is actually part of discovery, if you just discover what you expected, you’re not really pushing the frontiers of knowledge. You’re bound to be wrong, sometimes, almost certainly most of the time. Failure is part of the creative process.
And how is Brexit affecting your research plans?
Brexit has been a disaster for UK science, it is really disturbing for me, personally and emotionally committed to Europe, the whole of Europe, both politically and scientifically. I see the European Union, and it is by no means perfect, but it is doing everything in its power to do so. And the United Kingdom, which was an important and good influence in the European Union, just walked away, and I don’t think it knows what on earth it was doing. Let me remind you all that the vote was almost 50-50, yet we have suffered the most difficult part of Brexit in the UK. Look at the chaos my country is in today, the root cause of which is Brexit and the arrogance of Brexit. I think what we are seeing is the unravelling of the Brexit agenda, it may take years to reverse, but it will be reversed, because in economic terms we are much better in a larger market; a smaller market immediately restricts what we can do, we are much better having regulations that can protect the environment and people.
In my field, in science, we are better together, we collaborate, we interact, we talk together. We must overcome this and acknowledge the value of working together in liberal democratic societies that respect the power of reason and respect science in particular. We have already seen what happens when this respect disappears.
What would you like to say to a young scientist who may be thinking about starting a research career?
I would say to someone who’s thinking about becoming a scientist that it’s a fantastic opportunity for some people, not all people. And I think there has to be a self-awareness that we shouldn’t glorify and say this is wonderful for everyone because it’s not. Remember that it is a tough route, you’ve got to work hard and you fail a lot, but you always get the support of your colleagues, so that’s also an important part of science.