Every year at our Symposium and Awards Luncheon, the Breast Cancer Research Foundation honors one researcher’s groundbreaking contributions in their field with the Jill Rose Award for Scientific Excellence.
At this year’s event on October 16, we are proud to recognize Dr. William G. Kaelin, Jr. Last year, Dr. Kaelin, a BCRF grantee since 2006, won the Nobel Prize in Physiology or Medicine for his contributions related to how cells sense and adapt to oxygen availability.
Dr. Kaelin recently spoke with us about his BCRF-supported research, what it’s like to get the 4:40 a.m. Nobel Prize announcement call, and how he has fared working from home during COVID-19.
As far back as when I was a medical student, I remember thinking cancer was very interesting from both the scientific and clinical points of view. Like most people, members of my family had been diagnosed, so I was always curious about what causes it.
I did a limited amount of cancer research as a third-year medical student at Duke. But frankly, I had a really terrible laboratory experience earlier, as an undergraduate. For that, and other reasons, I didn’t think I was going to be a cancer researcher. By the time I was a resident at Johns Hopkins, a revolution in molecular biology was just getting started. I was hearing from others how this would change our ability to study diseases. I came to Boston in 1987 to do my clinical training in oncology still convinced I was going to be a clinician, but it became very clear that our understanding of various cancers at that time was too rudimentary—and, as a result, many available treatments were very crude.
With some trepidation, I decided to give laboratory research one more try. Fortunately, I had a terrific mentor, Dr. David Livingston, who is also a BCRF grantee. David taught me how to be a scientist. It was a very exciting time in cancer research, because some of the first cancer genes were being isolated and studied. I decided I really wanted to try to contribute to a better understanding of cancer causation and try to translate that into better treatments. I thought: As long I feel like I’m contributing, I find the work exciting, and someone’s paying me to do it, I’ll keep doing it. Otherwise, I’ll put my white coat back on as a clinical doctor. But that was 30 years ago—and I’m still doing research.
From 40,000 feet, our work relates to how normal cells and cancer cells use and sense oxygen. With BCRF help, we’re trying to see if we can translate that knowledge into better therapeutics for breast cancers.
To give more background, we started with some unusual tumors that are linked to mutations in a gene called VHL. We could see that in those tumors, their ability to sense—and respond to—changes in oxygen was clearly abnormal. Starting with that clue, we eventually worked out the molecular circuit, if you will, that allows all the cells in our body to sense and respond to changes in oxygen.
All cancers have to solve the problem of getting enough oxygen to grow. Part of our BCRF-funded work is to try to see if we can better understand how the oxygen-sensing pathway gets hijacked by breast cancer cells and then figure out if we can somehow pharmacologically intervene. In addition, our work has led us to appreciate that within the cell a number of processes and proteins are exquisitely dependent on oxygen. We’re trying to find those weak links in breast cancer cells.
BCRF is very wise—and should be applauded—for supporting not only late-stage breast cancer research, but also the more basic, mechanistic research that could actually touch many other cancers. It’s always easier, I think, to find support for very late-stage research. It feels like you’re on the five-yard line, and you don’t have much longer to go for a touchdown. Everyone gets excited when they can see the end zone. But we cannot lose sight of the importance of that earlier work that lays the foundation for big transformative steps forward. BCRF funds both.
Because I won the Lasker and Gairdner awards, I like to say I thought there was a “non-zero” chance I could receive the Nobel. I’m embarrassed to say I did go to bed with my cellphone at my bedside table with the ringer on, which I never do. It went off at 4:40 in the morning. The incoming call was from a number that had too many digits to be local. When I picked up, a very distinguished Swedish gentleman started talking. It almost felt like I had been inserted into a movie about my life, and I was now an actor participating in this one very important scene.
I had several feelings simultaneously. One was that I’ve had a very privileged life scientifically. The second was that my late wife Carolyn [a breast surgeon who passed away from brain cancer and had also been treated for breast cancer] should have been there, because she was my partner in everything I did. When I got that call, I realized life was about to change.
No matter what you do in life, having people you respect and admire say you’ve done a really great job feels good. BCRF is the premier funder of breast cancer research in the world, as far as I’m concerned, so it feels terrific to get this recognition. Secondly, because my wife was not only a breast cancer surgeon, but also a breast cancer survivor, I feel a special connection to BCRF. I like to think I’m sharing the award with her.
The final thing I would say is I actually had the privilege of getting to know Evelyn Lauder. I thought she was an amazing woman, and she shared a lot of qualities with my late wife. The legendary kitchen table meeting where she and Dr. Larry Norton created BCRF has changed breast cancer research around the world.
In research funding, there’s a bit of a catch-22 that if you don’t have a track record in a certain area, it is very difficult to get funding to get started in a new area. But BCRF allowed me to be very nimble and to quickly start using the knowledge we had generated in other contexts and apply it to breast cancer. Frankly, it’s become a very significant part of my laboratory. Because I now have BCRF support, I can try experiments that conventional funders might think would be too risky. It’s really liberating and reaffirming to have that support.
There are certain gifts we can give, not only to ourselves, but also to future generations. Two that immediately come to mind are knowledge and art. Research is a wonderful thing to support. I wish I could say cancer is going to hit the pause button, because of COVID-19, but that’s not happening. It’s so important that we maintain momentum and encourage young scientists to enter this [field]. The tools we have available to study cancer today are a quantum-leap forward, compared to when I was first getting started as a researcher. It’s palpable that this is a special moment in time—and we should be doing everything we can to accelerate progress.
I love to bicycle. I just completed the Pan-Mass Challenge, which is 192-mile bike ride that raises money for Dana-Farber. I like to go on long walks, read, and go to nice restaurants (when we were able to do that) with friends.
I usually read fiction. The last novel I read and enjoyed very much was called The Essex Serpent, which my daughter recommended, as well as Birds Without Wings. Lately though, I’ve been reading more non-fiction. I loved Brave Genius, a book about the unlikely friendship between the molecular biologist Jacques Monod and the author Albert Camus during the German occupation of France. I also recently read a great book called The Idea Factory, a history of the Bell Laboratories and how they changed the world.
Fortunately, my lab is now fully operational, though I’m discouraged from going into the institute, because we’re trying to minimize the number of people going in and out every day. I’m doing lots of Zoom calls, reading and reviewing papers and grants, the usual sorts of things. I’m trying to stay somewhat physically active. I have a trainer I work with twice a week who beats me up. I watch and read the news some, because I feel like I have to know what’s going on, but I’m trying not to do too much of what my daughter calls “doomsurfing.”
That’s simple: We’re not done.
I lost my wife to cancer in 2015. I work at the Dana-Farber Cancer Institute. I see the patients in the waiting areas and getting their treatments. Just this past month, my aunt was diagnosed with melanoma, and fortunately, she’s going to do well. This is my calling.
This interview has been edited and condensed.
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