Why is fundamental research so important to cancer treatment?
“Because of the complexity of cancer”, says Thijn Brummelkamp. You have to understand so many things before you can comprehend cancer, let alone treat it. Consider the ways proteins are transported, DNA is repaired, cells turn genes on and off or stick to other cells, and so on. You cannot apply what you do not understand.
“But it is becoming harder to get this type of research funded. That is why it is essential that we prove the importance of this kind of research to society. In April, for example, an article was published in Science Translational Medicine that showed that nearly all of the 28 most transformative drugs are rooted in fundamental discoveries. The incubation period is about 30 years, although that may be shorter for newer medicines. The article concluded that it is essential that we as a society boost our support for fundamental research.”
What is fundamental research exactly?
“That's a good question. When does research stop being fundamental, for example? It's often referred to as curiosity-driven research: you conduct research because you want to find out how it all works. Gaining knowledge is the driving force, and its counterpart is application-oriented research. When conducting fundamental research, you don't know whether anyone will ever be able to apply your results. Maybe, maybe even soon, maybe much later, and maybe never. The things we discover out of sheer curiosity could lead to something important in the future.
“We can also look at the content, at the things we discover. Fundamental research literally lays the foundation on which you can continue to build. You may have discovered something that helps you understand or investigate numerous other things. It can provide a range of new possibilities that you had never thought of before. This means that you are expanding the boundaries of knowledge. It also generates questions you did not even know were there to ask.”
Why does fundamental research belong in the Netherlands Cancer Institute?'
“A cancer institute should dare to take risks, more than anyone. This means that you may even attract scientists who don't conduct cancer research at all. Ronald Plasterk was one of these people. Before his political career, he was one of the best molecular biologists in the Netherlands. He did not work with cancer at all; he worked on the C. elegans worm, which can't even develop cancer. Yet he did his research at the NKI. Together with a group of American researchers (who received the Nobel Prize for their work), he made important discoveries concerning RNA interference, a process that allows us to selectively block the effects of genes. This mechanism was discovered in those little worms. Reuven Agami and I took his results a step further in Rene Bernards' lab, and turned it into an instrument that can be used for genetics in human cells. Rene made a number of discoveries using this tool, which he later elaborated on in the Dutch TV show De Wereld Draait Door. This instrument would be the only way to selectively switch off genes until 2013, with the discovery of CRISPR Cas9. The pharmaceutical industry also often used this technology to find targets for medicines. But I dare say that we would never have figured this out without Plasterk's worm.
“It is also fantastic to facilitate conversation between fundamental researchers and clinicians. As a clinical researcher, you can always appeal to a group of motivated, fundamental researchers. “Do you understand why…?” is a question we hear often. “Do you understand why the cell nucleus always looks so different in that tumor?” “How can those tumor cells become resistant to drugs so quickly?” or “Why don't those moles divide?” “Can you have a look?”
“And then there are the people we train. You can't forget that a lot of people come here to learn something new. And you want to show them the full breadth. You want to show them how ideas are born, what's possible, how research works. You want to show them that something can be very exciting one moment, and the next moment it's something else entirely. A good education program exposes researchers to a variety of research questions and approaches.
What kind of research do you do yourself?
“Everything I do falls under experimental genetics. At present, my group is tracking countless proteins that are made in our cells with the help of DNA sequencing and computers. I received a Vici grant from NWO for my research last year. All those 100,000 proteins that are synthesized by our bodies have a whole life of their own: they are created, they have friends who help them, they have to let the cell know they are there, they are destroyed, and they perform their function. We want to know which genes influence all these different proteins, and how the genes work together to make us function as an organism. Nobody else in the world is doing that.
“I am one of those researchers who sometimes study things other than cancer. Over the past years, our group has made discoveries about the cell skeleton that had been a mystery for forty years. And between 2010 and 2017, I was looking at how viruses enter our cells. That turned out to be much more complicated than people thought. We discovered that you can apply genetics to learn new things about viruses. And the fun part was: you can also apply this to medicines including those against cancer: how do you get them into the cell? So this research ended up contributing to cancer research after all.”
“But please don't think fundamental research is done in a metaphorical ivory tower. We always keep an eye on the potential applications, and I have also set up biotech companies myself. It is amazing how many things you encounter that others can use.”
