Sir John Gurdon Interview: Conversations with History; Institute of International Studies, UC Berkeley
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So, you have become a developmental biologist. How would you characterize the temperament and character required to do this kind of science? You've given us some hints already. Perseverance is clearly one.
Yes. I think that's probably right, because as all of us find that most of the things we try in the lab don't work, at least if they're at all innovative or novel, they usually fail. The question is, do you keep at it or do you just say, "I'll try something else"? My feeling is if you're convinced it's an important problem, maybe the single most important thing to decide, that if you could do it, it really would be worth doing. Then one keeps at it and goes at it different angles, and finally, some little unexpected result comes up which gives you a feeling of how you can make progress in that area. But I must say, I was fortunate in having a complete fascination for both biological things, and also doing things by hand. When I was smaller, out of amusement, I used to make model sailing ships in the shell of a walnut. Doing micro things with hands has always appealed to me.
So, dealing with frustration, experimenting, but of course in your [field], working with a microscopic entity.
In my case, that does appeal to me a great deal, and perhaps I'm rather bad at looking after the people in my lab in the sense that I do an awful lot of my own experiments myself by hand, and they rather have to manage. But I like to hope that that gives them some sort of help, the fact that one can usually do these things one's self.
You told us that you were a humanist become a scientist, and most people probably couldn't [follow] that [path] today. So, what sort of skills do you need? Chemistry, physics?
You mean to be a scientist or a failed classicist?
Well, both! But let's do the scientist, yes.
The positive side first.
Yes, but maybe the other is as interesting.
It's interesting too.
Well, what do you need? I suppose you must have an inherent interest in something that you're trying to study. One thing that was very prominent in my mind and in a way answers both those two questions -- I thought if I'd spent my life as a classics person, I would end up at the end of my career saying I've now achieved the level that everybody else has achieved for the last few hundred years. I wouldn't know more about Homer and Thucydides than anybody else. I might reach the same level -- it wouldn't advance anything in human society, in my view. Whereas in science you felt that at the end of a career you could actually see some genuine progress both in understanding and in practical use of science. So, that was very much in my mind, that I'd like to give my career to something where I can see at the end of it there's been a real advance.
Is there a root of that perception on your part? Is that something you got in your early schooling from the humanities, or from your parents, or ... ?
From parents, if anybody. Maybe it was just sort of innate. Thinking about one's future -- one lives much of one's life by saying, "What am I going to do the next year?" Sometimes you have very bright students, and I sometimes say to the Ph.D. students, "Where will you be in forty years' time?" Most of them say, "I can't tell you. I'll tell you where I'll be next year, but I haven't any idea." And in some ways it's a good thing to think how your career might evolve, if things go well.
Talk a little about the synergy between the individual scientist, his team of collaborators, and the broader scientific community, because when we start talking about your work it needs to be placed in a tradition and with the work of others.
Maybe the comment to make is that in my time there's been a real change from the possibility of someone working almost as an individual as opposed to part of a team. In physics, my understanding is you work in enormous teams with big instrumentation. Things are moving that way, I think, in biological sciences. But I don't think they're going to exclude someone who explores novel ideas. It's rather easy now to get a grant for a huge piece of equipment and to have ten people getting out large amounts of data with sequences, or something which you analyze, but I like to think there's still, and will be for a while, an opportunity to do things on a more individual scale. But not as much as there was. When I started you could work as one person in a field and you wouldn't be worrying every day that you're going to read the results of your work in the paper next day.
What was the evolution of your research up until the sixties, when you made a major discovery, which we will talk about in a second? What problems interested you after your dissertation, and where did they lead you?
After my Ph.D. dissertation my supervisor, my mentor, said, "You should do something completely different." That was right, and that's why I went to Cal Tech where I in fact worked on bacteriaphage genetics. Interestingly to me, I could never make it work at all. Every experiment I did failed completely. But I learned an enormous amount by meeting a number of very interesting people, and the whole idea of how you do science became much more clear to me. So, I went back again to what I'd been doing before but in a more informed way.
What became clearer to you?
How you try to analyze things at a more molecular level, more detailed level. I'm the extreme opposite of the systems biology person who says we must look at everything. I actually can't. I focus more and more down on a tiny thing to understand just one thing, and then try and enlarge afterwards. It became clear after my year in Cal Tech how people can make a molecular analysis. See, something happens in biology; the end result has to be that you understand it in terms of molecules, individual molecules doing something. And my education didn't reveal that! For example, when I was a student we spent three days a week learning about paleontology. We had to learn every dinosaur bone that, as far as I could see, everyone or anyone had dug up. But it wasn't really scientific, it was just a memory test.
So, how did your work of transplanting a specialized cell into a enucleated egg, and then a tadpole emerged -- how did that come about and what were its implications? It was truly a revolutionary moment in developmental biology.
The background there is that the concept of using microglass needles to move things around had been in operation since around 1900 when people, someone called Bataillon, did some work of that kind, but the real advance took place [by] two people in this country called Briggs and King, who were the first to be able to, within the vertebrates, take the nucleus out of a cell and put it into an egg. And it worked extraordinarily well. The odd thing is that a few years later they found that when they started doing this experiment with somewhat later stages of development, taking the nuclei from later cells, it didn't work at all.
So, my supervisor put me onto this, copied their work at a very early stage, and we were lucky in that it actually worked differently, and since the more advanced the cell was from which you took the nucleus, you nevertheless ended up getting normal individuals. That was the breakthrough that made all the difference in my career. You ended up with admittedly a small number of completely normal individuals -- when you take the nucleus out of an intestine cell, put it into an egg, you can actually end up with normal adult fertile animals -- and that made me take a different view of this work from Briggs and King, whom I greatly respected. Indeed, if I'd had their results I'd have reached the same conclusion as they did. But at first it led to quite a lot of controversy. I mean, here was I, just a graduate student, contesting the conclusions of two very highly respected workers. Naturally enough, people didn't believe what I said, and I can see why.
What had they argued, Briggs and his colleague?
They quite reasonably from their experiments had argued that as an embryo develops into a little later embryo and an organism, at a very early stage the nucleus of those cells is no longer able to replace the egg and sperm that normally occupy the egg. So the conclusion was that as development proceeds, the genetic material undergoes some kind of stable change which precludes it then substituting for the egg and sperm. That's a very fundamental question, and it has to do with whether, as we form from an egg, the genome, so-called -- the set of genes -- remains constant or it doesn't. It was a question which had interested scientists for at least fifty years before that, and this was the first really good attempt to answer that question.
May I ask what the animals were that you were dealing with? South African frogs?
It turns out that I was, for an odd reason, but quite a lot of history to how it came, that a South African frog turned out to be a favorite -- one of the most favorite organisms, which ultimately came down to the fact that someone had more children than they could afford to educate in England, so they went all around the world, ending up in South Africa and finally ended up in England, when the animal was used for human pregnancy tests. The spare eggs were then of use to people doing developmental biology. So, I used that. Briggs and King used the American frog, which turned out to be less good for these experiments.
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