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Care
Research
Academy
Prinses Máxima Centrum

"Nature really isn't that complicated"

The new auditorium was officially opened last Thursday with a combined lecture  by Hans Clevers, the current scientific director of the center and the new man in that position, Alexander Eggermont. Hans Clevers talks about his 'signature' as a departing member of the Máxima's board of directors; about the necessity of competition, about the effect of a 'flat' organization and of course about the launch of Princess Máxima Center. An interview with a man to whom a statement by a famous footballer applies: "you only start seeing it once you get it".

As Hans Clevers speaks, his eyes smile almost laconically. He is dressed in jeans and a casual shirt in his office at the Hubrecht Institute. The room has a somewhat classic look: alongside DNA art on the wall there are certificates right and left, a full desk in the corner and a wooden meeting table.

The beginning
"The very first time we talked about my role at the Máxima? Of course I knew about the initiative, but the very first time I really talked about it was with Rob Pieters as the sun set on a terrace by the sea in the south of France. I believe in Nice. And the first concrete request to join the Máxima's Board of Directors came from Jaap Maljers, then a member of the Supervisory Board at KiKa (childhood cancer research foundation), and that was over dinner at my home in Amsterdam. I remember I had just bought my first painting by Karel Appel.

I knew about the initiative by Rob Pieters and Huib Caron, who have been working together for some ten years. They were seeking support from various cancer researchers in the Netherlands and looking for a home for the initiative. I then campaigned with Edward Nieuwenhuis, then the head of the Wilhelmina Children’s Hospital (WKZ), to get it launched in Utrecht – in the center of the country, right beside the Netherlands' biggest dedicated children's hospital. That proved far from straightforward, because initially the teaching hospitals were against it. But Jan Kimpen, then head of University Medical Center Utrecht, took the decision to say: you guys are welcome in Utrecht.

However, within the structure which then emerged, science was not represented at the very highest level. At that time, there were no scientists on the board and that is essential at the heart of what we call a 'comprehensive cancer center'. Quality care, quality research and quality operational management together in one place, based on the example of the Netherlands Cancer Institute (NKI) and the Antoni van Leeuwenhoek Hospital (AvL). I then took the initiative to write a confidential letter to the board and the supervisory board together with a number of researchers and other colleagues of high standing. The thrust of our letter was that we felt that this was a unique initiative for the Netherlands, but that it would be a missed opportunity if science was not represented on the board. In order to prevent science from becoming a football in between all kinds of other interests.

After all, like healthcare, science is a profession and you need the best professionals to practice it. But that letter came back to me like a boomerang. Because I never intended to become a board member myself. When I was young, I was head of a department in a teaching hospital for 10 years and by the end I had had enough of the endless meetings and administrative hassles. So my wife said, "Remember why you left it all behind back then; that's not what you want."

But out of a sense of responsibility, I did accept the role, but only on a 50/50 basis. I started work at the same time as Diana Monissen (chair of the board of directors). We soon moved in here at the Hubrecht Institute and into two 'corridors' at WKZ – that was strategically a very good move by Rob. It’s worth adding that Edward Nieuwenhuis had to fight hard for that. He really deserves credit for it. Because working with WKZ helped us to get our care up to speed.

My right-hand man Laurens van der Flier and I started work on 1 January 2016 with researchers Frank Holstege and Patrick Kemmeren; they don’t have a background in pediatric oncology but they are unrivaled DNA experts. Our task was to set up a top European institute, so I felt we needed to start hiring. Fortunately, Rob Pieters had already formed a strong SAB (scientific advisory board) including Bill Evans, the head of St. Jude Children’s Research Hospital in Memphis (USA). Thanks to that SAB, we were able to recruit good people who we all supported. The bar was high: eventually, we whittled the field down to around six or seven researchers drawn from the various pediatric oncology centers. I had to disappoint a lot of people at that time, because in addition to those researchers we were also hiring people to conduct truly high-quality fundamental and translational research.

We then put them together in open-plan areas and with all the facilities they needed. No separate islands but a flat organizational structure. In other words, based not on titles, ranks or personal preferences but on the content of their research. In this way, we established research groups led by so-called Principal Investigators. Together with the doctors, they decide what research needs to be carried out.

The necessity of competition
What we tell the PIs is: don't spend too much time in meetings, spend it doing science. And that works, because as a result we now have ERC grants, the most prestigious grants worth between one and two million euros, against the backdrop of unbelievably intense competition in Europe, including young people like Jarno Drost, Anne Rios and Jan Molenaar. These successes in turn help us to attract new people who really want to make discoveries.

People have suggested, sometimes as an accusation, that I have introduced a 'system of champions'. But the fact is, although some may seek to deny it, that the development of science no longer takes place the way it used to: quietly conducting research and publishing a book after ten years. That's history. Discoveries are now often made simultaneously in different places around the world. On top of that, consider that there are no fewer than 2.5 million biomedical researchers worldwide, working on around 5,000 diseases. So if a new technique becomes available, or if a new hypothesis emerges, then the 'winner' is the one with the best people and the best equipment who can mobilize the most resources. Currently, that is almost always somewhere in the United States. And it will surprise no one that in the future it will mainly be in China. So if we want to compete to bring the best researchers to the Máxima to study the origins of pediatric cancer, it's very simple: it's up or out. That's how it is.

That means that as a scientist you have to enjoy competition, while always striking a good balance in terms of cooperation and collegiality. And you have to have a huge tolerance for frustration, because of course a lot of things don’t work. In that regard I believe it does help that we work with pediatricians. I think of all doctors, pediatricians are perhaps the nicest group of doctors to work with: less ego and more idealism than what I have experienced at various teaching hospitals.

The opening
What came as a pleasant surprise to me in the run-up to the opening is how much you can achieve with a group of people who really believe in something and are passionate about getting it done. At the launch of our center, naturally a lot was demanded of everyone, but it does show that when a group of people really put their shoulders to the wheel, anything is possible. As a result, we managed to set up a completely new organization from scratch in quite a short time, not organically and not with little steps but with huge steps. We laid down a blueprint for the launch of a medium-sized hospital, something that did not exist before.

What I underestimated is how complex the hospital sector has become; the incredibly large number of people you need who are not doctors or nurses but who are essential to keeping the place running. I had to get used to that.

By the way, it was a brilliant move by Diana Monissen (chair of the board of directors) to hire Ben van Miltenburg (responsible for the transition). That was at a time when it was becoming difficult to keep an overall perspective and define priorities: what do we do first, what next, who is responsible, how is our progress, can we still launch safely? And so on. And what Diana in particular did very well was to get the outside world on board: the health insurers, the media, the royal family and ultimately also the other hospitals.

The successor
I hope that Alexander Eggermont, (successor to Hans Clevers on the board of directors, ed.) will stick very firmly to the structure that is now in place and that is proving its worth. But there are still gaps. What I didn't bring to the table was experience with trial activities. Trials take place in three phases: the first is safety. After that comes the dose-finding phase, identifying the correct dosage and measuring the effects in a relatively small group of patients, while the third and final phase is the registration phase, in which you involve as large a group of people as possible. These trials, which Michel Zwaan is already hard at work on, are crucial for the Máxima if it is to play a significant international role in introducing new therapies. And Alexander has a wealth of experience in doing that.

The threats
We are by definition a monopolist in the Netherlands, which means there is a very real danger of navel-gazing because you think you are the best. And that's true, because there is only one. But at the same time you need to realize that also means you are the worst. So you have to have your focus firmly fixed outwards: to think and act internationally. We still don’t do that enough. What do St. Jude’s in Memphis, the Stefan Pfister institute in Heidelberg and SickKids in Toronto do? They don’t rest on their laurels, they press ahead. By creating that monopoly, we have taken a huge responsibility on our shoulders: the buck stops with us. That's not an issue right now: we are still starting out and we are still on an upward trend. But we draw up our own guidelines and standards; we need to be very conscious of that.

The opportunities
The fact that in the future we will be employing 500 researchers, that we do everything we do well and that we are able to collaborate with anyone in the world. I am convinced that in the biomedical sciences we can understand and solve everything because, you know, biology really isn't that complicated. It is an accumulation of small things which in themselves are understandable: you are faced with a large number of facts, most of which you don't yet know but whose solutions are within reach. And when you do have the solution, it is always simple. Indeed, as long as you are still giving complicated answers, it means you don't understand it yet. But I am truly convinced that we can solve all the problems in biology. 30 years ago I thought: it's getting harder and harder to discover something new. But that's not true at all: the technological possibilities are growing even faster than the available knowledge: we're simply moving up to the next level armed with more weapons.

And again Hans Clevers flashes that mildly ironic "you only start seeing it once you get it" smile. That's exactly his field of work as head of a research group at the Máxima. In the manner he himself introduced: based not on rank but on content and pure science.