By Jessica W.

In 2019, Dana-Farber Cancer Institute’s William G. Kaelin Jr., MD won the Nobel Prize in Physiology or Medicine for his groundbreaking research on how cells sense and adapt to oxygen, which can help fuel further breakthroughs in medicine. As Dr. Kaelin is a former Winsor parent and his office is right across the street from Winsor School, I thought it would be meaningful to ask him a few questions regarding his own experiences and advice for students who are interested in joining the STEM field. 

1. What led you to focus on how cells sense oxygen?
   
   

When I was learning how to be a scientist, I became a postdoctoral fellow and I worked on a gene called the Retinoblastoma gene (RB). This is a tumor suppressor gene that contributes to cancer when it’s inactivated. When I started my own laboratory, I was looking for something new to work on, and a paper appeared on the isolation of the von Hippel Lindau (VHL) gene, which is another so-called tumor suppressor gene. I knew from my clinical training that people who had inherited a defective version of the VHL gene developed a variety of tumors including kidney cancers and blood vessel tumors. 

Like the RB gene, the actual sequence information in the VHL gene didn’t provide a clue as to why loss of the VHL gene would cause cancers, so that seemed like an interesting puzzle to work on. More importantly, I knew from my clinical training that the tumors linked to loss of the VHL gene were notorious for inducing new blood vessels as a way of supplying them with blood and also could stimulate the production of red blood cells. That was the clue that the VHL gene must somehow be involved in oxygen sensing because low oxygen can stimulate new blood vessels and red blood cells; the oxygen sensing system was altered in these tumors. Since there are many diseases where oxygen delivery is part of the problem, such as heart attack and stroke, this seemed important to work on. 

2.    Now, as a well-known and celebrated scientist, what factors influenced your success?

I was a late bloomer in school; I didn’t really excel until I was a senior in high school. Stepping back, one thing that saved me was that I was always pretty good at mathematics. I was interested in science, but I didn’t like biology because it was fairly descriptive and phenomenological and required a lot of memorization. I liked chemistry and physics better because they were more quantitative and mechanistic. When I was a junior, my high school got a computer terminal, and I became interested in computer programming because it was a nice way to see mathematical thinking in good use. 

One day I saw a pamphlet in the wastepaper bin next to the computer terminal about a student science training program that was going to be held at Florida Atlantic University the summer between my junior and senior year. This program was going to be for 32 “gifted students in mathematics and computer science.” It really changed my life because when I got down there, I realized I liked school much better when it was challenging and when I was surrounded by very intelligent people. I quickly discovered that even though I could hold my own with these people in terms of doing the work, I absolutely had the worst high school grades among the 32. They were the type of students who would sit in the front of the classroom, be engaged, take books home, and do all the work…that really didn’t describe me at the time. 

So I decided my senior year that I would sit in the front of the classroom, rather than the back, and I’d actually take my books home and do the homework and extra credit problems. I challenged myself to see if I could actually be a good student and fortunately the answer was yes, if I actually applied myself.  I certainly had some exceptional high school teachers who, despite my suboptimal study habits up until senior year, taught me quite a bit. In particular, I had a wonderful chemistry teacher and outstanding physics and mathematics teachers.

Being a late bloomer worked out well because by the time I got to college, I wasn’t completely and utterly exhausted from years of coursework- if anything, I was just getting started! I did very well in college, majoring in mathematics and chemistry. The one exception was my independent study project working in a laboratory. I was completely lost (in hindsight, due to a lack of supervision and being given an impossible project) and got a “C-.”  My advisor told me my future “lies outside the laboratory.” I thought medicine offered a career that combined science and mathematical thinking. So I went to medical school with the anticipation that I was going to be a clinical doctor, not necessarily a researcher. 

3.    What do you find most rewarding and meaningful about being a scientist, especially as a Nobel laureate?

I have been asked many times these past months, what’s the secret to winning a Noble prize? How does life change when you win the Nobel prize? I have tried to be consistent over time, starting long before I won the Nobel prize, in keeping prizes in perspective. Being a scientist is a great privilege if you enjoy it. Most people go to work because they have to put food on their table and a roof over their head. To them, work is work, whereas if you enjoy science, like I do, I feel like I’m getting paid to play instead of work. In fact, sometimes I feel guilty that people actually pay me to do this. It’s a wonderful thing to do a job because you enjoy it so much, that’s already a prize in itself. 

Another prize is being surrounded by smart people and being stimulated by their ideas and insights. I enjoy being part of the discovery process and solving interesting puzzles. It’s rewarding when you are the first person to solve a scientific puzzle and realize that you now understand something that has never been understood before. It’s especially rewarding when the answer to the puzzle seems elegant. For example, when we were studying oxygen sensing, it was an interesting puzzle to work. But when we saw the answer, we realized the answer was beautiful. The fact that the answer was beautiful wasn’t a tribute to me, it was a tribute to nature. It was so satisfying to now understand the answer, see it, marvel at it, and, in this case, we understood almost immediately that this was going to have some practical applications. That is also a prize; having something actually benefit other people and publishing things that are sufficiently true that other people can not only replicate your findings, but also build off of them. To me, the real prize is leading a life of a scientist and occasionally, if you’re very lucky, doing things that help other people. 

4.       What is your advice for the younger generation that is interested in STEM?

The most important courses I took were the courses that taught me how to think clearly and rigorously. Majoring in mathematics, as I did in college, was extremely useful because mathematics is a discipline that teaches you to think diligently about problems. I would say, strive to push yourself to take courses that make you think rigorously. Sometimes it’s the course itself, sometimes it’s the teacher, sometimes it’s both.

 I would certainly not take courses just because they’re easy classes, or because it seems like the simple path to, for example, medical school or a Ph.D. in physics. I found that in college, often times when I took the so-called difficult classes and really challenged myself, I tended to do quite well. However, in rare occasions, I would take a course that was supposed to be easy, but I realized if they were easy for me, they were easy for everyone, so there was less of an opportunity to shine. 

If you take a challenging course and you find out, despite your best efforts, you’re just can’t excel at it, it’s also a good thing to learn as a young person. I realized that I tended to like the things I excelled at, and tended to excel at the things I liked. It was a positive feedback loop. I’d say, find things that you both enjoy and excel at, but don’t take courses simply because you think you’ll get a good grade or because somebody told you to take it.