This year's Nobel Prizes are starting to be announced, and already there's a local winner. Dr. William Kaelin of Harvard Medical School and Dana-Farber Cancer Institute has won the Nobel Prize in Medicine for his work on how cells adapt to the availability of oxygen. Dr. Kaelin spoke with WGBH Radio’s Arun Rath about his research. This transcript has been edited for clarity.
Arun Rath: First things first, how did you get the news?
Dr. William Kaelin: I received the news in the classical way, meaning with an unusually early phone call. I got a phone call about 10 minutes to 5 a.m. I thought it was either a very poorly timed robo call or, knowing this was Nobel Prize week, that maybe my life was about to change.
I had actually had a dream where I had looked at the alarm clock and saw that the time had already passed, and so in my dream I had already moved onward and had already decided I hadn't won the prize. And then I woke up, and saw that in fact it was only 2 a.m., and realized I had to go back to bed to sort of start the process all over again. And so then when the phone rang, I thought maybe this was another dream, but it wasn't a dream. It felt like a dream as I was speaking to the Nobel Prize committee and getting the good news.
Rath: And so was it total, unequivocal joy?
Kaelin: It is total joy, as well as appreciation and just a time to reflect on how privileged one has been to have been part of this type of work. At the same time, sadly, I lost my wife to cancer in 2015, and she was my partner and my soul mate in everything I did, so it was a little bittersweet as well. My wife Carolyn was a breast cancer surgeon, so whereas I was focused on laboratory work, she was focused on caring for patients, where she was magnificent.
But when we would be silly enough to allow ourselves to dream that this day might happen, we used to like to have fun and imagine what dress she might go out and buy or who we would tell first. I think she would, if she can, be beaming from heaven and enjoying the moment as well, and she certainly would be thrilled that I'm sharing this with my two wonderful children.
Rath: That's lovely, and obviously work like this would seem to honor her memory.
Let's talk about this work, because it's very interesting. You and your co-winners, Sir Peter Ratcliffe and Gregg Semenza, you're being honored for work that sort of explains how individual cells adapt to the availability of oxygen. Could you explain in layman's language, how is that kind of microscopic process important?
Kaelin: So how cells and tissues in the body sense and respond to oxygen is exceedingly important, because life as we know it on the planet wouldn't be possible without oxygen. But oxygen is a very reactive molecule and actually itself can be toxic.
So too little oxygen and you're going to die, but less appreciated is the fact that too much oxygen and you would die. And so cells have to have sort of a rheostat, if you will, that allows them to understand whether they're getting enough oxygen, and if they're not getting the right amount of oxygen, to adapt accordingly.
So for example, if you and I climb to the top of Mount Everest, our bodies would immediately sense that they're not getting enough oxygen, and this would be detected at the cellular level using the mechanism that my cohorts and I helped to discover.
And so for example, if you were at the top of Mount Everest, your body would know it wasn't getting enough oxygen and it would try to adapt in part by making more red blood cells so you could carry more oxygen in your blood. But how cells and tissues sensed and responded to oxygen was a black box until the 90s, and it was around that time that Drs. Semenza and Ratcliffe, as well as myself, began to try to understand the molecular circuitry that controls oxygen sensing. And once we understood the pathway or circuit, it was immediately apparent that there were a couple places you could intervene with drug-like chemicals to either turn the pathway on or further activate the pathway such as you might want to do in diseases like anemia, heart attack, and stroke where there's a problem with the adequate delivery of oxygen.
Conversely, we now well appreciate that certain cancers have co-opted this pathway and wouldn't survive without this pathway. And so here we've helped develop drugs that actually inhibit the pathway so we can play both sides of the street. There are some diseases where you want to activate this molecular pathway and there are other diseases, especially cancer, where you want to dampen down the activity of this pathway.
