Interview with the 2007 Nobel Laureates in Physiology or Medicine Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies, 6 December 2007. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.
The 2007 Nobel Laureates met at the Bernadotte Library in Stockholm on 9 December 2007 for the traditional round-table discussion and TV show ‘Nobel Minds’. The show was hosted by BBC presenter Sarah Montague. The Laureates discussed topical issues of global concern, and also answered questions submitted by visitors to BBC.co.uk and Nobelprize.org.
Your questions to Oliver Smithies
Here, Oliver Smithies answers additional questions submitted by visitors to Nobelprize.org.
Telephone interview with Oliver Smithies immediately following the announcement of the 2007 Nobel Prize in Physiology or Medicine, 8 October 2007. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.
[Unknown] – Hello.
[Adam Smith] – Hello, may I speak to Oliver Smithies please?
[Unknown] – Yes, may I ask who is calling?
[AS] – Yes, this is Adam Smith from the Nobel Foundation’s website.
[Unknown] – Yes, just a second please.
[AS] – Thank you.
[Oliver Smithies] – Yes, good morning.
[AS] – Good morning, is that Professor Smithies?
[OS] – Yes, it is.
[AS] – Hello, my name’s Adam Smith. I’m calling from the Nobel Foundation’s official website, Nobelprize.org …
[OS] – Uh-huh.
[AS] – … and we have a tradition of recording very brief interviews with new Laureates and I wondered if you’d mind just answering a very few questions?
[OS] – No, I’d be happy to.
[AS] – Thank you very much indeed. Well, first of all, of course, many, many congratulations on the award.
[OS] – Well, thank you.
[AS] – It’s pretty early where you are, I imagine you were asleep when the call came?
[OS] – Yes, that’s correct. I was just about to shave and have a shower, now, and I would be sleeping still normally.
[AS] – And what was your first thought when the news came?
[OS] – Well, my first thought was to ask with whom it was, because I so much admire the work of Mario Capecchi and Martin Evans. So that’s a big delight to me, to share it with them.
[AS] – And indeed you shared the Lasker Prize with them in 2001.
[OS] – Yes, that’s right. We’ve shared several in the past and they’re both, well I would call them friends really now. I mean we met through science, but we’ve known each other for a long time, and Martin Evans, for example, brought the embryonic stem cells that we used in our work, he brought them himself, in his own pocket.
[AS] – When you collaborated?
[OS] – Well, I suppose you would call it collaboration. It wasn’t an official collaboration, he just brought the cells, at the time. You know, those were … did we actually ever collaborate with him Nobuyo, I don’t know that we ever published together, did we? No, we never actually published together (I’m just asking my wife).
[AS] – But a nice act of generosity.
[OS] – Yes, it was marvelous.
[AS] – And of course the three of you are renowned as the fathers of the knockout mouse, a very widely-used tool now for molecular biology and physiology.
[OS] – Yes.
[AS] – Are you surprised by the overwhelming number of transgenically-modified mice that are now around?
[OS] – Well I suppose I’m not really, it’s just grown, just gradually, and it’s been fairly obvious that they were very useful. I think probably Mario Capecchi’s changing the approach to do knockouts was the catalyst for most of the increase in numbers. My original work was to demonstrate that it was possible to do homologous recombination, and the mice we made, we were thinking about gene correction, we were thinking about correcting genes, and then he realized I think that the most useful thing was to do knockouts, to knockout a gene, if you have to do one specific thing. And that was the catalyst for the big increase, plus a good method of doing it more easily that Mario devised.
[AS] – Yes, because the success rate of transfection was very small.
[OS] – Yes.
[AS] – You’ve described yourself previously as an inventor, and …
[OS] – Yes, I still think of myself as that.
[AS] – What would you describe as the characteristics of a successful inventor such as yourself?
[OS] – Oh, to make things work with minimum stuff, as it were. You use whatever’s lying around, and you see something needs to be done and you try to do it. I think it’s just making things work, you know, somehow. I don’t know that it’s any great imagination, it’s just I need to do this and perhaps I can do it with this little piece of stuff. Or I picked that up the other day and I can use that. My grandfather used to pick up nails and straighten nails, and I still pick up wires and things that I find lying around. “Oh that’ll be useful for something.” And when I was a student they had an expression for me, because of this tendency, they had a rather coarse expression, “NBG BOKFO: No Bloody Good But OK For Oliver”, for things that were lying around, that might be useful.
[AS] – Well obviously you made good use of them in the end.
[OS] – Yes.
[AS] – What gives you the greatest pleasure then? Is it tinkering around, or is it in fact the realized invention once it’s done?
[OS] – No, I think it’s doing it, I don’t think it’s the … I mean I suppose it goes back to the same thing again, when I was a child, they used to say I always said “Ollie do”, before I could speak, I always wanted to do things. And it’s the actual doing of it; the daily experiments. I still work at the lab and still work at the bench, and my enjoyment is just doing the experiments. Of course one enjoys the results, but if you don’t enjoy the doing of it you won’t succeed in science because most of the time you don’t get results that you particularly want!
[AS] – Another word you’ve used to describe yourself is ‘Toolmaker’, and I imagine there’s a special pleasure in seeing the tools you make being so widely used.
[OS] – Oh, yes, that’s absolutely true. I mean I look at a journal and I open the pages and I see people use gel electrophoresis and I see they use gene targeting and you just get a little sort of shared enjoyment.
[AS] – And in your original work do you think there was a Eureka moment, one that you can point to, or was it just a set of …
[OS] – Oh no there’s a very definite Eureka time when I realized how I could make homologous recombination work, and it wasn’t really make it work, it was that I had an experiment that would allow me to find if it was possible, because one didn’t know that it would be possible really, and I have one page in my notebook where the whole scheme is written out in one page.
[AS] – Right.
[OS] – And that was as a result of teaching. I was teaching at the time, a graduate course, and having taught a paper that used a method that I realized would allow me, if I used the same principle as that method I could therefore detect what I thought would be a very rare event. I called it gene correction. So I wrote this page in my notebook and that’s a Eureka page, as it were. Perhaps not a moment, it’s a page. I’ve had a number of Eureka moments, but that was a Eureka page.
[AS] – And how long was it in time from that Eureka page to …
[OS] – Oh, it was more than three years.
[AS] – I don’t want to keep you on the phone long, it’s going to be a busy day for you, but I just wanted to ask; I know you’re a pilot …
[OS] – Yes, I was flying yesterday.
[AS] – So now will you plan a special flight, with loop the loops?
[OS] – Oh no, the aeroplane I fly now won’t … it’s not certified for aerobatics. But no, I flew yesterday, I’ll do my usual flying. I have a motor glider and I had a very good day yesterday. It was one of those days that I always enjoy, the three things: I did some science, I took my wife to lunch and I went flying.
[AS] – Well, it’s hard to better that day but perhaps this one is starting off quite well as well.
[OS] – Well, it’s started well, hasn’t it?
[AS] – Yes, indeed. OK, well I’ll let you get on with your preparations.
[OS] – OK, thank you.
[AS] – Lovely to speak to you.
[OS] – Nice to talk to you, bye, bye.
[AS] – Bye, bye.
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