Evidentia

Sir John Sulston

One of the most interesting interviews I ever conducted, and one of the most astonishing, was with Sir John Sulston, head of the British part of the Human Genome Project. Astonishing, because early on the morning of the interview I called him by telephone, asking what would happen to our appointment  if he learned later that day that he had been awarded the Nobel Prize for Medicine. This was all for a three-hour radio documentary series I was doing for CBC Radio, entitled When the Machine Awakes. (The French-language version of the same documentary series, three hours’ worth on Radio-Canada, was called Quand la machine s’éveillera.) Here are five questions and responses from the interview.

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George: So, congratulations! I feel like something of a prophet here, because I called you just this morning, and said  – “if you win the Nobel Prize, won’t that bounce our meeting or something!”

John: That’s right! And I said, “what Nobel Prize?!” Because I didn’t know anything about it – I really didn’t! In fact, you’re not the first person. There was somebody else that I was talking to just the end of last week, who emailed me, and said, you’re very good at keeping a secret! I have to email him back and say, I had no idea!

George: What do you feel is the significance of this Nobel Prize?

Sir John Sulston receiving the Nobel prize from the King of Sweden

John: I think it’s as so often with the Nobel committee, it’s very firmly about fundamental work. It’s saying that something was built up by Sidney Brenner and the group he drew around him, that has really contributed very heavily to our understanding of the mechanism of our own bodies. And it’s interesting to look at the water that flowed under the bridge since then. I think what we’ve learned was only guessed at then. But what we’ve very clearly is what a unity of life there is, how the mechanisms that we had begun to uncover in those days in the worm are found in our bodies. And the reason for the citation, is that genes that control cell death pathways in the nematode are also found in humans, and are therefore very important medically of course, because if they go wrong, then they cause trouble, either by cancer or degeneration or whatever. And so I think they are showing they have taken a very long view of the work.

A nematode up close

George: What do you think your work will lead to?

John: It will lead, in a sense, to everything, but only through a lot of work by other people. I mean, take one good mid-term example, because there are things that are happening immediately now, like diagnosis, there are things that won’t happen for a long time like most forms of gene therapy. A good mid-term one is the work on cancer. The work that is being done on cancer by the cancer screening group here under Mike Stratton* is using the information from the human genome to look systematically through tumours and find out what’s wrong with them, in the genetic sense. The important thing about a tumour is that its DNA is altered. It’s not that there is something else wrong with it. We know that the DNA is altered. The cells carry on behaving in a different way. They are not responding to the signals that say “stop growing” from the body. Now if we can find out for any particular tumour which particular genes have gone awry, which particular genes it needs to keep growing and destroying the patient, then we can hopefully, very likely, in due course, make drugs to stop it or maybe anti-bodies or maybe some other means for getting at those positions. The point is what you are doing this way is finding targets. You are searching now in a systematic way, with a full knowledge of the human genome. But now, it’s not that it comes out automatically from the human genome. The data is there for people to use. Mike Stratton’s group finds the targets. It then requires years, maybe decades, of dedicated work by large groups of people in pharmaceuticals, to find the actual cures. So you see, what you have to say over and over again: this is a beginning. It is the beginning of everything, and yet itself is nothing until it is transferred into real useful practice by these other people.

George: If the cells consist of machinery, if the genome works as a kind of mechanism, a very complex mechanism or programming, is the human being, at least from the physiological point of view, a machine of sorts?

John: Oh yes, it’s a very beautiful machine, a very complex machine, but it is a machine. That’s what we mean by understanding. And it’s very proper to call it that. It just is sometimes misunderstood as being too simple, like a couple of gear wheels or something, and of course it’s much more than that. I think it’s useful to think about the word “programme” as well. The point about complex programmes, is that they have iterative loops, and that those will trigger new bits of the programme. It’s not a simple A to B process. It’s a pathway, going through a whole series of processes. Complex computer programmes are like that anyway. That’s why computers crash, because it’s not the computer that’s crashed, it’s because the programme that it is running has got itself into a position that was not anticipated by the designer. Because the designer couldn’t anticipate all the possibilities. So, what we’re looking at is a complex unfolding of the information of the genome, through a computational process that is expressed in the physical properties of the molecules which it generates. That’s the problem we have to solve.

Human epithelial cells, used to study cancer

George:  But in your book, The Common Thread, you also defended towards the end the uniqueness of each human being, that the programme per se cannot be applied universally in all its aspects.

John: Yes, you’re quite right, and thank you, that’s a very important point. Because of course in the course of this unfolding, the programme is also interacting with the environment, and – the case very importantly with human beings – is thinking. It’s actually producing a thinking machine. And that thinking machine is thinking about itself. And it’s learning, and combining what it learns into new patterns, the thoughts, the ideas, the observations that combine into new patterns. So what happens is that we end up with a probably fully unpredictable situation, because exactly what we think or do, at any particular moment, is at the very least down to chance, and nevertheless I think the question is whether it is down to free will, and there you have to say “do I believe that there is something else, apart from the machine, or is this sense of being a self-conscious person, with free will, that says “I am”, is it just what it feels like to be a very complex machine? I find the second quite a satisfying explanation, but clearly if one really really understand how one works, it might be hard for us, but it won’t be so hard for our children’s children, because in their generation, I think, people will have got to that position of understanding, and they’re going to say, “fine, that’s what it feels like,” so I’m going to go on and be a really fine human being anyway.”

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*For more information on Mike Stratton’s research work, please consult the following site:

http://www.sanger.ac.uk/research/projects/cancergenome/