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John Sulston
John Sulston
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John Sulston Interview

Nobel Prize in Medicine

June 11, 2004
Chicago, Illinois

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  John Sulston

It seems a major turning point in your career was when you came to the United States, as a graduate of Cambridge University, to do postdoctoral work in San Diego. How important was that to you and what was that experience like?

John Sulston: Oh, that was tremendous. I mean, that really was a bursting out. It was leaving my country that I'd grown up in. I was more hidebound by it than one realizes.

When you've lived in one country all your life, then you have a set of rules, a set of social etiquette that you live by. And you have no idea how narrow those are until you move. And moving, at that time, from England to the west coast of California, really was going into something very different in terms of the way society ran. Of course, not that difficult a transition because of the language, but nevertheless, a big change. And the other thing was the sense of being given, now, a very long rein. Up to that point I'd been quite organized. My supervisor had pretty much laid out the style of work. But now, suddenly, I was with somebody who just wanted to open it all up and encouraged me to think more broadly. And that was Leslie Orgel, because that was the style of his operation. And also, the style of the subject. Because the work was about the origin of life, which is a very big, very open topic. Nobody knows what the conditions are -- were, rather -- on the primitive earth. And therefore, you don't even know what all the parameters are. And so the aim is to contribute to finding that out. So it's a very, as one might say, a "polymathematic" sort of subject, where you can think anything and it may be relevant. You ought to have to try to think about all of it. Now, I'm not very good at that, he is. He has a much larger intelligence than I would ever aspire to. But to be part of his group doing this was tremendously mind-expanding. And, I think, also, it confirmed me in the idea that all I really wanted to do was to carry on doing science in some form. Because I was able to do anything, I was obviously choosing to do science. What you choose to do when you have a completely free choice is obviously what you should do, because that's what you're interested in.

Is that where you first encountered the worm?

John Sulston: No.

That came later?

John Sulston: That came next.

How did you get your first job?

John Sulston Interview Photo
John Sulston: I don't think I've ever had a proper job, really. I've never answered a job advertisement. So what do we mean by first job? Post-doc is soft money, it's a temporary job, but it's a job. From there I was invited to join Sydney Brenner's group, and that's where I met the worm. Back in England, in Cambridge.

The way you write about it, this first postgraduate position was utterly by chance. You didn't know what you were going to do and you saw something, you applied for it, and to your great surprise you got it. Is that right?

John Sulston: Well, it was more being passed on, in a way. Of course, I had some volition. I wasn't forced to do it. When I came from England to California, what led to that was the connection between my graduate supervisor, Colin Reese, who was a colleague of Leslie Orgel. I think there was actually a previous graduate student who went the same route as me. So it was a kind of channel that was available. Sir Colin said to me, "Would you be interested in going to work for Leslie, if he wants you?" And I said, "Oh sure, why not. We might as well go to California. Why not?"

Actually, there was a reason, as well. I had been educated as a chemist, yet I knew I wanted to do something in biology. This idea of working in prebiotic chemistry, the origin of life, was attractive. So definitely there was something there. But at that stage, and it's true in general for people doing their first postdoc, you don't have to worry too much because you can develop your science out of that if you want to, or you can just treat it as an episode, and then go on and do something else. In my case, it sort of was the second. I went on and did something else. I did have more than one offer.

One or two people had mentioned to me that they'd be very happy to offer me a position in their labs. These were in America, because there were a lot of jobs around at that time. This was the mid-to-late '60s. And so people saw me working away. I got some publications from both the groups I'd been in. People thought, "Oh well, tie in. Why not?" And so I could have had opportunities, but we both wanted to go back to England, because our parents were there, and sort of a sense of roots. My wife was keen to go back. So we were particularly interested when this offer came in from Cambridge, from Sydney Brenner, who was starting work on the nematode worm Caenorhabditis. And that really was the beginning of a much more important phase, to me, or at least long-lasting phase. This was working on the worm. And that was a chance, and it had to be by chance, because nobody knew about this worm. There was no publication record, really. There was some old publications, but nothing new. Sydney Brenner was really starting at almost from scratch to make this into an important biological system of finding out how animals work. And so I came in -- I only came in for a year to start with -- and then at the end of the year, he said, "Do you want to stay?" And I said, "Oh yeah, sure. Why not?" At least we were doing something. And then eventually, having achieved some things, I was given a tenured position. And that, if you like, was -- finally -- the proper job. Because when you have tenure, then you can stay as long as you like. But by that time I was very far dug into the worm. I had lots of lines of research going on, which I was enjoying, and it was just obvious to carry on working on those.

When you started out, could you have imagined that you would spend 30 years studying the nematode worm?

John Sulston: Oh no. One doesn't think in that way.

There was one moment, in particular, where I remember asking whether I ought to do what I was doing. But it wasn't working on the worm as a whole, it was following a cell lineage. There came a point, because one of the things that I learned to do, and became my sort of identification for a while, with the worm, was looking to see how the first cell divides to two. Each of those divide again to get the pattern of cell divisions. It sounds pretty unimportant, but the key thing is that one wants that pattern to provide the map, as it were, onto which we are going to place the gene activities. Because in the end, something develops, as we do, from a single cell, through lots and lots of cell divisions to multiple cells, through a whole series of signals, of controls. We wanted to find out what those controls were. People were doing it in other organisms, too. People were looking at the fruit fly, for example, very productively. But the worm had its own particular power, which is that you could follow the cell lineage, because it was constant from one out to about a thousand cells, when the thing is finally mature. So I, along with some colleagues, followed that process. And I came to a point where I knew that I had all the techniques I needed to finish the most difficult part of it, which was looking to see what happened in the egg. But I also could calculate that it was going to take me one and a half years of just sitting every day and looking down the microscope. I talked to John White about it -- he was my colleague working on the anatomy of the worm -- and I said to John, "Is it worthwhile? Do I really have to spend a year and a half looking down the microscope?" John said, "Yes, you can do it. You should do it. We need it." And so, with that sort of encouragement from him, Bob Horvitz and others, I just did it. But that was a moment when you said, "Well, is it really worthwhile doing what I'm doing? And I couldn't be certain, and lots of people were a little skeptical. But anyway, I did it, and it turned out to be a useful body of knowledge.

[ Key to Success ] Perseverance

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