The Nobel Prize in Chemistry 2012
Robert J. Lefkowitz, Brian K. Kobilka
Interview with Brian K. Kobilka
"... If you're really interested in something enough, you just keep working on it ..."
Telephone interview with Brian K. Kobilka following the announcement of the 2012 Nobel Prize in Chemistry, 10 October 2012. The interviewer is Nobelprize.org's Adam Smith.
[Brian Kobilka] Hello.
[Adam Smith] Oh hello, may I speak to Brian Kobilka please?
[AS] Oh hello, this is Adam Smith, calling from Nobelprize.org, the website of the Nobel Prize. We have a tradition of recording extremely short interviews with new Laureates. Could we speak for just a very few minutes?
[AS] [Laughs] Thank you. I know it's the middle of the night there. First of all, sincere congratulations on the award.
[BK] Thank you.
[AS] I imagine the household was asleep when the call came?
[BK] Yes it was.
[AS] Who took the call? Did you get it?
[BK] Well, the first call I think, didn't get answered. [Laughs] And the second one I did.
[AS] So they keep trying.
[AS] And what are one's initial thoughts on getting that call?
[BK] I thought it was some friends, initially. But I don't have friends that have a really good Swedish accent, so then I started believing it.
[AS] [Laughs] Do you feel that this is an utter surprise?
[BK] Ah, yes.
[AS] How nice, how nice.
[BK] It's very nice.
[AS] So you've been awarded the Prize for your studies on G-protein-coupled receptors, and since the eighties when you joined the Lefkowitz lab, you've been trying to disentangle the structure of those receptors. For those who've never seen one, could you describe what they look like? Their beauty?
[BK] Oh, that's really tough. I'm trying to think of something in nature that I could use as an example, but there really isn't anything you encounter in the day that you could say is a good model for it. But to be able to see it for the first time is really amazing, in three-dimensions. So that was probably, there were times when you see some of the structures that we've got, and particularly the one last year where you see everything together and how it works together. It was really, really very satisfying.
[AS] So this is the entire complex together, with the G-protein attached and the ligand in place?
[AS] That's an amazing feat. It took so many years to get to that point. And many, I think, felt that it was an almost impossible task. What kept you going?
[BK] I don't know. It was just something that I really wanted to see and I had a great group of colleagues working on it, and we were all excited about doing it. And, we just kept making incremental improvements in what we were doing and finally we succeeded. As I said, it was really a group effort. A lot of people involved and it was a very exciting project.
[AS] And it's strange as these receptors are normally said to mediate the actions of about half the medicines we take, and yet, nobody really knows about them. It's amazing. We're full of them and they are so important but they're rather unknown.
[BK] Yes, and we don't really know how to control them very well yet. So the medicines still aren't perfect. They have side-effects. Some of these are because targeting for one receptor, they are still kind of promiscuous and they'll bind to another type of GPCR, so we still have quite a way to go before we can really take advantage of what we know about them in terms of therapeutics.
[AS] Now, you are a notoriously self-effacing person and quite a quiet person, I gather. How do you feel about the prospect of the deluge of press attention that's about to arrive?
[BK] I'm not really looking forward to that.
[AS] You tend to avoid the limelight, as far as I know.
[BK] Yes, and as I said, I am not looking forward to that at all.
[AS] Maybe you can minimise the impact. You've been awarded with Bob Lefkowitz, with whom as I say, you worked in the eighties. And in a way, you're very different characters. How did the two of you mesh together?
[BK] Oh we mesh together very well. In fact, we still speak on a regular basis. And, in fact, we are just starting to put together a paper that our groups have been collaborating on a project for a couple of years, and we've gotten, made some progress. So, yeah, he's a fantastic mentor. We are quite different, but I think, sometimes that works out well.
[AS] Yes. It's a marriage of opposites.
[BK] And I couldn't be happier for him.
[AS] It's a lovely pairing. Really, really nice. Just one last thought. The field of structure solving in GPCRs is quite a competitive one, with people racing to get to the first structures. Again, how does one deal with the competition element of it?
[BK] I don't know how much it affects you. When you have a goal, you obviously want to be the first there. Scientists are sometimes as competitive as professional athletes, maybe. But you can't worry about it too much, or it will distract you from your goal. So I'm not sure what else to say about that. But if you really want something bad enough, if you're really interested in something enough, you know, you just keep working on it.
[AS] Thank you. That's a lovely answer. Just personally I just want to say that once when I was the editor of Nature Reviews Drug Discovery, you contributed beautifully to some GPCR features we were doing so it's a particular pleasure for me, individually, to be speaking to you now.
[BK] Oh, well thank you. Was that the collection of comments?
[AS] That's right, that's right. It was the state of GPCR research, back in 2004.
[BK] I think at that time I said someone would get a GPCR structure soon.
[BK] Yes, I remember making some comment to that effect. [Laughs] I think that was quite a bit before we got the structure.
[AS] So when you said someone, did you have yourself in mind? Or were you not that certain.
[BK] Well, I hoped it would be me [Laughs]. I wasn't very confident at the time we would get it.
[AS] There's a difference between, yes, certainty I suppose and confidence. Because you seem to have remained confident in the ability to get somewhere, even though you weren't certain you'd make it.
[BK] That's true, I think I was somewhat confident. I think I had worked on it long enough. I think I knew the protein really well. So somehow, I mean, you've got to believe you can do it, otherwise ... [Laughs]. I mean, it's sort of a struggle because you have to get funding and keep the lab going. You have to believe in yourself to some extent.
[AS] Well it's been a great pleasure to speak to you and I can picture the scene. Presumably all of the family is now up as well?
[BK] My wife and I are up, and kids have heard about it. And I have to tell that I have one of those rare marriages where my wife and I have been working together in the lab, ever since I was in the Lefkowitz lab, and we still work together. So it's particular satisfying because she shares a lot of the credit for my success in the field and so I feel like I'm sharing it with her as well.
[AS] That's lovely, that's really nice. I suppose the Nobel Prize is always a family prize but this makes it even more so.
[AS] Lovely, the kids are aware, but are they going to go back to sleep or what do they do?
[BK] Well my kids are kind of old.
[BK] My daughter is going to turn 29 soon and my son is 31. So they are not here in the house with us. But we texted them, and they woke up and they called us.
[AS] So there are sleepless people all over the States now.
[BK] Yeah, yeah.
[AS] When you come to Stockholm in December, we have a chance to interview you at a greater length and I very much look forward to that.
[BK] OK, thank you.
[AS] Lovely, best of luck with the day. Thank you.
[AS] Bye bye.
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