René Medema

Abstract

René Medema is Director of Research at the Netherlands Cancer Institute. After graduating in Chemistry and completing his PhD research on signal transduction by p21ras in Leiden, he went to the Whitehead Institute (Cambridge, Massachusetts) for his postdoctoral training. There he studied cell cycle control, a topic that he continued working on as group leader and professor at the University Medical Center Utrecht, and currently at the Netherlands Cancer Institute in Amsterdam. Over the years, his group has made several key contributions to our general understanding of cell division, particularly under conditions of cellular stress. How did you, a chemist by training, end up in biology? As a teenager, I was fascinated with the notion that simple molecules can get together to make a living cell. I wanted to understand the chemistry of biology, but saw how my older brother — who studied Biology — had to study the animal and plant kingdom, and I thought: that is utterly boring! So I decided to go into Chemistry, instead. My dad is a hardcore chemist, so I didn’t fall far from the tree. However, about 2.5 years into my studies I felt stuck because all I was learning about were molecules. The living cell seemed to be so remote. How did you handle this problem? My fascination took over from the curriculum. At a random party, I met someone who told me he was doing an internship in the medical faculty, where he studied how oncoviruses infect and transform the cell. That was an eye-opener for me. I thought: wow, this is something I want to study. So I just went to that medical faculty and knocked on their door, without ever checking if this would fit in my curriculum. After a 1.5 year internship, and another one in life sciences abroad, the dean didn’t want to give me my Chemistry diploma because I hadn’t stuck to the rules. Luckily, I managed to convince the dean that I really had done serious internships. How should researchers determine their direction in science? I always made my choices based on what inspired me, and that’s what I keep telling people now. Today’s trainees often ask me: “where are the future developments?” or “which techniques should I learn?” I think it’s all quite irrelevant. First and foremost, you should base your decision on what interests you and which people inspire you because they’re going to encourage you to grow and develop in meaningful ways. I think those were the primary criteria I used — unconsciously — to decide who were going to be my PhD and postdoc supervisors. So much of how your career develops is determined on where you start out. Were you lucky in this respect? Well, I did know what fascinated me. But this guy at the party could’ve been in a horrible lab with a bad reputation nationally, and everybody would’ve perceived my internship as a bad choice. Then it would’ve been an uphill battle to get a job. Now you’ve got yourself the job of Scientific Director of the Netherlands Cancer Institute. You love being a scientist, so why did you become a director? On days that I do my administrative tasks, I do miss being close to where the discoveries are being made. At the end of a day full of meetings in my office, which I do two days a week, I often walk upstairs to the lab to ask people: “what did I miss?” And I still mainly consider myself a scientist. But as a researcher, you realize that much of what we can accomplish is about how we organize research. Maybe it’s a bit of a masochistic approach, but I think somebody has to take the responsibility to try and arrange that in the best possible way. Working at a clinical department in Utrecht, I realized that ensuring basic research makes it to the clinic is much more difficult than I thought. I had ideas about how that should be done. The quality of the basic biology program here at the Netherlands Cancer Institute is fantastic. I see it as my duty to maintain this high standard but also to improve the way basic science is translated to the clinic. How do you wish to improve this translation? Basic science depends on selecting the best, most creative single individual, giving him or her the task to do fundamental science, and embedding them in a situation where research support is optimal, both in terms of core facilities as well as in terms of close contacts with scientists that are interested in making the translation. That last part requires a team effort and a very different approach than we are used to in basic research. The organization and infrastructure for this type of research needed strengthening in our institute. We have to make sure that the right people work together to make this happen. This also requires that we identify more excellent clinicians with a vested interest in research. What are the biggest challenges science faces today? The scientific community has to do a better job explaining to society why fundamental science is important. If we don’t do that well, we run the risk of being perceived as interested only in our own hobbies. At the same time, I think it’s a problem that society and funding bodies keep pushing for research with visible impact. If every individual scientist has to worry about impact, we would all end up doing the same things and we would run out of new ideas very soon. Blue-sky researchers applying for grants shouldn’t be bothered with the question of impact — we should only ask if they are really pushing forward to uncover new ground. The issue of impact has to be addressed at the level of the entire organization, not at the level of the individual researcher. So, why is fundamental research so important? So many things that surround us today wouldn’t exist if it weren’t for curiosity-driven research, such as your mobile phone or new anti-cancer drugs. These things are the results of people’s curiosity that drove them to ask questions like: “why does the earth revolve around the sun?” and “why are we protected from infections?” Everything we can translate to the clinic in the next two years is possible because of decades of basic research. Immunotherapy is a fantastic example. The fruit that this field is bearing today exists because — over the last century — people have investigated details of the immune response that they could not have predicted would help us to develop immunotherapy-based approaches. Scientists should better explain to people what their role is in the whole chain, from discovery to implementation. To make a case for the importance of fundamental science, we can all use examples of blue-sky research from the past that led to the innovations in today’s world. We should talk about this as much as we can, use social media, and tell the story to people who want to hear it. How about the reproducibility crisis? Scientists are more and more perceived as frauds and it would be foolish to say that this problem lies only in the perception. There is a clear flaw in the system and it’s hurting the position of science in society. Institutes should spend a lot of time on trying to crack this problem rather than trying to avoid it. People should be appreciated for uncovering something truthful, even when this means disproving their boss’s ideas. The same goes for negative results. Organizations should change their culture into one where you don’t walk away from negative results — you embrace them. It would be foolish to think that we could develop a system where negative findings are as newsworthy as new discoveries, but we have to realize that they are equally important! So we need better rewards for any solid, truthful findings, even if they are negative. What’s cancer research’s biggest enemy? The fact that cancers continue to evolve in ways we don’t really understand. If you’re treating a cancer, you may actually be treating a thousand different diseases in one single patient at the same time. That’s a huge problem that will take us years of work. What do you do when you’re not working? I’m the classic, middle-aged guy that dresses himself up in Lycra and sits on a race bike to feel good about himself. Luckily, my wife also developed a passion for this sport and we both like uphill climbing. We have participated in several biking fundraisers in the mountains — including the Alpe d’HuZes and Stelvio for Life — and hopefully more to come. Also, I like to cook. This has replaced certain aspects of life in the lab, since I don’t get to do experiments myself anymore. I also have a wife, two daughters and a son, who fill my life in very meaningful ways when I’m not working. Having kids is great and has some parallels with having graduate students in the lab: they need to learn a lot, you get to see how they grow up, and you get to contribute to their development. Was your first experience on children or grad students? Haha, first on children. And that was actually very helpful. The toughest thing about raising kids is to stick to your principles. You love your kids, so you always want to be their best friend. But you can’t. The same goes for working with people: you want to be their inspiration and give them positive vibes, but sometimes you just have to be tough on them. Who inspires you? I get inspiration from anybody who is passionate about his or her research — people that think out of the box and dare to break through boundaries. Creativity per se inspires me, for example in the advertisement industry, where you can sometimes see interesting, disruptive changes that draw a lot of attention. So I guess you could say that people that try to solve problems in a disruptive way inspire me. My supervisor in Cambridge, Bob Weinberg, was a true inspiration to me. He taught me that all you’ve got to do is ask a simple question and do everything you can to answer it. That seems utterly simple, but it could mean that you need to develop tools that do not yet exist. Most discoveries are made when new tools or technologies are introduced, but many discoveries are also made as a result of serendipity, when the outcome of an experiment does not make any sense and the researcher wonders what the explanation could be. So you certainly should keep an open view. Too often we get tangled up in distractions, though. How can scientists do better? I think humans are lazy by nature and we often make the mistake of falling back on tools and skills we’re already familiar with. That’s the wrong approach. You’ve got to ask yourself: “what is it that I really want to know?” I learned that the hard way early in my career. I wanted to get a paper out as quickly as possible and kept using the same single-minded approach over and over without considering alternatives. As a result, I could never really answer my research question and kept going in circles around the problem. If you try to resolve a question in a way that won’t allow you to fully resolve it, then you’re being counterproductive. So challenge yourself continuously. Share your early-stage ideas with the most critical people around, rather than seeking criticism only when you’re done. That’s a frequent mistake. People want to present something that’s perfect; I think that’s a waste. Make sure you know your competitors and talk to them rather than hiding from them.