“There are no shortcuts as far as I’m concerned”
Telephone interview with William G. Kaelin following the announcement of the 2019 Nobel Prize in Physiology or Medicine, 7 October 2019. The interviewer is Adam Smith, Chief Scientific Officer of Nobel Media.
William Kaelin likes solving interesting puzzles. A physician scientist, like his fellow Laureates Peter Ratcliffe and Gregg Semenza, he sought to understand the basis of phenomena he observed in patients. “Our story,” he says, “Is really one of trying to generate knowledge and understand how things work.”
William G. Kaelin: Dr Kaelin speaking.
Adam Smith: Good morning, my name is Adam Smith, I’m calling from Nobelprize.org. Well congratulations on the award of the Nobel Prize.
WK: Thank you.
AS: So, it’s early there, 5am.
WK: Yes it is, yes.
AS: Were you sleeping, or …
WK: Oh I was absolutely … I was asleep. And I’m still in a state of shock so I hope I’ll speak coherently.
AS: You sound very coherent at the moment.
WK: [Laughs] You know, I think every scientist in the world dreams of this possibility and knows what today is, but if you’re realistic you don’t think it’s really going to happen, so I try … I try to treat it like any other night so I was asleep.
AS: May I ask you what your first action was on hanging up the phone after hearing?
WK: I was … again I’m in a state of shock, it’s … obviously it’s absolutely wonderful news, but my heart’s still racing and I think it’s all just sinking in, and unfortunately I lost my wife several years ago so I live alone.
AS: I’m sorry.
WK: And so my first thought was that this is something I’d always, if it did happen, wanted to share with her. But I’m just terribly honoured and I’m glad I can share this with so many people, scientifically and otherwise who have supported me throughout the years.
AS: But that must be a great sadness, I’m sorry.
WK: Thank you.
AS: The link that you discovered, the unexpected link between VHL and HIF-1 is an example of just never knowing where knowledge will come from and where questions will take you.
WK: Yes, absolutely. You know, I’m a big believer of curiosity-driven, hypothesis-driven research. I know that’s complimentary to other ways of generating knowledge but I think in the end what drew me to science and what draws a lot of scientists to science is that we like interesting puzzles, like clinical features of patients who had mutations in the VHL gene were a curious constellation of findings but one way to unify them was there was some abnormality in the way the tumours they were developing were sensing and responding to oxygen, and we thought if we could understand that we could understand more globally how cells and tissues sense and respond to changes in oxygen. And since I, like my co-awardees, am trained as a physician, we understood very well the importance of oxygen in so many human diseases. It appeared that in these particular cancers that were linked to VHL mutations that somehow the tumours had co-opted this process for their own benefit, and that, as you know, has turned out to be correct. So now that we understand the pathway there are a lot of opportunities for pharmacological intervention, in diseases such as cancer but also other diseases including heart attacks and stroke. But I come back to what you said earlier – I think in the end it was a very interesting puzzle to try to solve.
AS: You raise a very interesting point that all three of you are physician scientists. That does, I guess, give you a different perspective on your work. Do you think it’s very important that there are more physician scientists coming along?
WK: Well, first of all I’m very proud to share the Prize with two wonderful physician scientists, but I also like to point out to people that I think scientists in general, and in particular physician scientists, are under tremendous pressure these days, to try to justify the importance of their work in terms of potential clinical applicability. And yet I like to point out that our story is one of trying to generate knowledge and to understand how things work. And if you go deep enough and you understand things well enough, occasionally opportunities for translation or therapeutic application will arise. So I’m so happy to be involved with this story because I think that’s how real translation happens. People like to take short cuts, or they are sometimes told to try to take short cuts, but there are no short cuts as far as I’m concerned. I think you have to understand the system that you’re studying, and if you’re lucky once in a while you’ll understand it well enough that, you know, the light bulb goes off and you say ‘Ah-ha, now I can finally do this’. So I hope when people gain a greater appreciation of our stories that, you know, they’ll see that yes we’ve now in some cases enabled new drugs that are starting to be approved or, certainly in some cases, deep into testing, but it really began with some curious clinical phenomena that we were trying to understand mechanistically. And so to answer your question I certainly think we need more physician scientists but I think they also need to be trained to have the tools to do that sort of mechanistic work, rather than taking short cuts and doing things that in many cases turn out to be rather descriptive and don’t really give you the type of knowledge you need to do meaningful translation.
AS: Thank you, that’s a very important point, and beautifully coherently argued at this time in the morning.
WK: [Laughs] Well, I’m trying to listen to myself talk wondering just how I’m doing here, but thank you.
AS: I think you’re doing brilliantly, and no doubt once you’ve had the chance to have a cup of coffee it’ll get even better, because you’re going to have a day of it now aren’t you. Congratulations, and we very, very much look forward to welcoming you to Stockholm in December.
WK: Thank you so much, thank you. Okay, bye bye now.
AS: Thank you, bye bye.
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Their work and discoveries range from how cells adapt to changes in levels of oxygen to our ability to fight global poverty.
See them all presented here.