When he was seventeen, there were two careers Daniel considered pursuing. “Civil aviation pilot, that seemed attractive. The selections were strict. I managed to make it all the way to the final round: one week of flying at the National aviation school. But there were more pilots than planes back then. The odds were not in my favor.” But he already had an alternative in the back of his mind that was just as exciting: working as a cancer researcher. “That’s why I decided to study medical biology. For my PhD studies, I joined the lab of professor Lex van der Eb in Leiden. That was a tough educational experience; I was thrown into the deep end.”
Halfway through his PhD program, Daniel lost faith. “My research into tumor viruses didn’t work out the way I’d hoped. I worked long days but there was no publication in sight. Then I read an interesting paper by a research group in Boston, which used a similar experimental system. I made the bold decision to contact them. In hindsight, that may have been one of the best decisions of my career.” He was invited to spend two months in Boston. “Sometimes I worked for eighteen hours a day, but it felt like coming home. They formed a close and enthusiastic group, that was an eye-opener for me.”
But his research didn’t start smoothly. “I was halfway through the two-month period and still hadn’t made any progress. That one fateful night, after midnight, I had enough of it. Again, my blot didn’t show the results I had been hoping for, so I decided to take a long stroll through the city.” Daniel recalls it well. “It was freezing, about twenty-five degrees Celsius below zero, and I felt sorry for myself. I seriously considered switching careers that night.” The next morning, he looked at the blot again. “Then I noticed something that had escaped my attention that night: one of the lines had moved just a little bit. That suggested an important protein modification. Yes, that was a little Eureka moment. I was happy I hadn’t trashed that blot the night before.”
Upon his return to Leiden, they immediately started extending his findings. “As it turned out, I had discovered a new gene functionality that played an important role in cell division. That resulted in a nice thesis after all. But equally important was the little network I had created in Boston, albeit rather unintentionally.” With a Fellowship from the Dutch Cancer Society, he started working as a Postdoc at the Dana-Farber Cancer Institute at Harvard. “My girlfriend – now my wife – joined me. That was a dynamic period in my life, with long days at the lab, but it was also an inspiring time during which we made a lot of new friends.”
He did his second Postdoc with René Bernards. “He encouraged me to explore new territories. In 2002, I became a Fellow at the NKI. In my postdoctoral trainings I learned to think in possibilities rather than impossibilities. Try it, instead of: it will never work.” That attitude – and, in his own words, some luck – led to interesting discoveries also in his own lab. “For example, we used an advanced technique to investigate all 25,000 genes for their potential contribution to metastasis. We didn’t seem to find any, and I remember telling my technician to throw out the cell culture dishes. But once I got back to my room, I realized that we had been too impatient, so I ran back to the lab. Just in time. Two weeks later, we indeed observed the result we had hoped for. That yielded a new metastasis-gene and a nice publication.”
Daniel and his group spent the following years studying the development and treatment of melanoma. For a long time, there was no treatment for that tumor type. “That changed about ten years ago, with the introduction of precision medicines. The problem was that patients commonly acquired resistance. Immunotherapy was introduced around that time, another major step forward.” He vividly remembers a conference in Zürich, Switzerland. “The very first results of an immunotherapy trial were presented. There was a spontaneous round of applause halfway the presentation, which is highly unusual. It left quite an impression on me. Once back home, I decided to re-focus the lab again. Despite the great enthusiasm, I was convinced that resistance would soon become a significant problem for immunotherapy as well. We had the right tools in my group to investigate that. From then on, we would be focusing on immunotherapy resistance.”
That was a leap into the unknown for Daniel. “Honestly, I could hardly distinguish a B cell from a T cell at the time! And resistance to immunotherapy wasn’t even demonstrated, so it was quite a risky decision. But it turned out to be the right one. We entered the field of immuno-oncology with a publication in Cell. The NKI is the perfect place to translate fundamental research into clinical benefit. That is an important goal for me personally. In that context, I recently co-founded a spin-off company for development of new immunotherapy.”
Nowadays, he travels the world to deliver lectures. But when he hops on a plane, he never regrets his choice to be a passenger instead of a pilot. “As a researcher, you are in the privileged position of being able to peek into the infinitely fascinating treasure room that the cell is. And thanks to various revolutionary technological developments and because I am surrounded by young researchers who seem to be getting smarter every day and keep me on my toes, my work is as exciting as never before.”