|
Dr. James D. Watson
Nobel Laureate/Co-discoverer, DNA structure; President, Cold Spring Harbor Laboratory
In conversation with Roy Eisenhardt, Common Wealth Club Board of Governors member
Answers to Written Questions from the Floor:
Q: What is the range of DNA expression that you believe is guided by an external stimulus such as trauma or a positive or negative emotional interaction?
A: We know that the way our brain operates can be affected by emotions, and this can affect gene expression. But really, more than saying that, we don't know enough about the brain to answer that question in a useful way.
Q: What do you think is the value of the Minnesota Twin Family Study in understanding the relationship between genetically determined behavior and environmental behavior?
A: The Minnesota twin studies were the study of the personality differences between identical twins and non-identical twins. And they came out, I think, as we all know, that identical twins are more similar in their personality, as well as what they look like, than non-identical twins. And it seems likely that much of this difference will be due to genes, though you can always say intrauterine life can affect such things. I think the more interesting questions come when the identical twins really are different in personality, and you have to ask why, and you go back to location within the womb and so on.
Of course, what happens to you later in life obviously will affect your personality, but I think certainly as you get older, and particularly, if you're parents, you realize that you've had no control over what your children are like. And, you know, it's best to let them have their personality and not try and change them. You can educate someone with facts, but I don't think you can really change what they're like very much. My parents never tried to change me, including not trying to make me write with my right hand when I was left-handed. So I appreciated the fact that people just accepted me as I was. I think it's a really futile thing to make someone interested in something when they're not. Hopeless. It's not to say I'm not a believer that a good environment doesn't count, that bringing young kids to meetings like this is good; it stimulates them, it lets them see adults as opposed to kids, which is always good, it seems to me, for kids. So my parents were very important; without them I wouldn't be here. But on the other hand, I don't think they made me what Ð and certainly when I met Francis Crick's mother, it was clear she had absolutely no influence on him. I always thought Francis was like Henry Higgins in "Pygmalion," and you know, Henry Higgins' mother couldn't control him. You just seemingly come from nowhere, but what you do is just the expression of, I think, your genes; unless you're identical twins, all of us are very different.
Q: Initial estimates before the sequencing of the human genome were 100,000, and the final determination is in the high 20,000s. Why were the estimates so far off?
A: Well, the first guess was maybe we only had 30,000; I said 60,000 because we found others, but now when you can do the genome sequence, you're going to pretty well see the number. It's really not the gene number that matters. All mammals have roughly the same genes. We'll find very little differences. Not only are we almost identical Ð same genes as chimps Ð but the genes that dogs have will prove to be virtually the same as ours. It's really when these genes are expressed for how long during development and what cells that has permeated evolutions. You can change gene expression through mutations faster than you create a new gene. And when you get to things like vertebrates with their long life spans Ð since humans came into existence, maybe 15,000 generations in Homo sapiens, not very many Ð you're unlikely to develop a new gene, but you could change how long a neurotransmitter was present at a given time or something like that, or to the extent; that's easier for chimps.
Q: What do you feel are the most important organisms that we should sequence next?
A: Now I'd say humans, just lots of humans. Clearly, we'll do some dogs, because they look different and the cost of a genome will move down with time. It's about $50 million, it'll move down to $10 million. You know, there are only about 400 breeds of dog. Why not? They're man's best friend. But I think the real payoff, you know, is we want to sequence a lot of different ones now to try and find those parts of the human genome which seem to do something with signals for gene expression. That's why we're sort of running over a variety of different ones, the marsupial and so on. With time I think common sense will just say, Sequence humans because that's what we care about.
Q: What is your view on stem cell research, and how can the scientific community educate the public and lawmakers about the value of this research?
A: The best thing we can do is prove it works. Because if it works, people will use it. It's easy to ban something when it's a future dream because you aren't immediately hurting anyone. But Bush would have a completely different line if it worked. He'd have to say, "Yes." When does health come after religion? I think health is always more important than religious beliefs. I mean, there would be a few people who disagree, but not if they're the sick ones.
Q: Could you characterize Rosalind Franklin's role and importance to your discovery of the double helical structure and comment on the controversy, which has survived for so long?
A: I helped generate the controversy through my book, which tried to tell the story as I saw it on a day-by-day basis. Later, particularly now that I've read a very fine biography of her by Brenda Maddox, I think if we'd known what she was like when we met we wouldn't have been so hostile toward each other. So she took the famous photograph, and when I saw it that day, I said, Boy Ð it was a helix. There were other photographs already existing that should have told me it was a helix, but this was…even a dumb guy would say, It's a helix. It would have taken a little more guts to take the 1938 photograph by Astbury and say that showed that DNA was a helix. Even though now in retrospect, you can see that Linus Pauling should have looked at that 1938 photograph and not come up with such a bad picture.
Both Pauling and Rosalind should have found the structure. Crick and I shouldn't now be famous for this. Rosalind missed it really because her relations with Maurice Wilkins were very bad. They couldn't stand each other, and Wilkins said it was a helix. And I think that just kept Rosalind from wanting to have it a helix. So late in November of 1951, when we built our terrible model, and we were told not to build any more models, we took down the molds to build the models so they could build models. They never used them. Rosalind, in fact, if she'd just started building models after Wilkins wanted to Ð which was the summer of 1951 Ð she should have had that structure in six months, or sooner. So she really kept herself from being famous. We didn't keep her from being famous. After Pauling came in, we weren't going to, and we still had a chance, we were determined, the people in Cambridge particularly, to get the right answer. So when I wrote The Double Helix, my initial title was Honest Jim. Francis, who's very bright, mistakenly believed that that title meant I believed I was telling the honest truth. In reality, what "Honest Jim" usually means is a used car dealer. Okay? And I had been called Honest Jim by someone who worked in Wilkins'lab.
It was a question: Did we have any right to build models after we saw the photograph? Well, I think we did. Because they weren't building models. It turned out that just that fateful month, Rosalind, because she was leaving King's College, really looked at photograph 51, concluded that the B form of DNA was helical, and she knew the number of base pairs and all that. But at the time we got the answer, she still was not trying to think about how the bases formed hydrogen bonds. There's no reason why she wouldn't have gone on and done that. I'm glad she didn't like Wilkins. You know, I have to say that, because then I would have arrived in Cambridge and the structure of DNA would be solved and I'd still be working on bacterial viruses at somewhere like University of North Carolina. No, no, that's too good a place. No, I meant to say North Dakota, you know, someplace removed from any form of rat race.
Q: What do you believe as of today, 50 years after your discovery, has been the most important application of your insight?
A: Well, I guess it has to be Alex Jeffrey's DNA fingerprinting, the releasing of people from prison who would be there the rest of their lives. That's certainly emotionally the most satisfying. What I'd like to say is, We've cured cancer using this. I think there's still a chance in my life we can say that. That's sort of my current real interest. But I can't say it, so I have to say fingerprinting.
Q: What is your feeling about allowing the patenting of various segments of the human genome?
A: I don't mind the patenting if it was universally licensed so no individuals really controlled sections of DNA so they would be the only ones…. The law is not on our side and getting it changed is impossible because the people who make the laws are lawyers. So they have a real interest in maintaining this diabolical situation where we're constantly suing each other and saying they shouldn't be given. I think people who find a disease gene should get credit. I don't mind their getting a patent. But I don't really like promoting it. I think the sort of sense of outrage many people feel against the company that found the breast cancer genes, patented them and then doesn't let other people into the act Ð it's something that shouldn't have existed. So I should have, early on in the Human Genome Project, tried to get a discussion of where patenting would go. At that time, knowing that Washington is controlled by lawyers, I just thought it was hopeless, that it would finally be decided by courts. Occasionally, the European parliament, which, I think, is not controlled so much by lawyers, really, more by Socialists, I guess, is rather hostile to patents and conceivably that would lead to more common sense. I mean, you really can be tied up by these things. And medicine would move faster if everyone can work on it. That doesn't mean when you found a drug you can't patent that. But it's just sort of the means to find a drug before you've found anything. Sort of monopolies on big fields.
Q: Do you feel that technology Ð for example, nanotechnology Ð would ever evolve to the point where we could artificially create DNA molecules with any desired coding pattern?
A: Oh, we can create them now. Our technology is being more and more miniaturized, so whether you want to call it nanotechnology, we're sort of able to study smaller and smaller amounts of DNA, and that is very useful now that we have 20,000 genes to study at a given time, not three or four.
Q: Could you comment briefly about the pros and cons of therapeutic cloning?
A: I'm in favor. So I can't see any reason not to do it except if you're held back by religious revelation. You know, common sense: Do something if it's going to help humans and you can't see how it would hurt them.
Q: The more sophisticated we get about understanding the degree to which we're genetically determined and we are environmentally determined…is there still an area in the middle left for something that we would call "innately human nature"?
A: Well, I see human nature Ð why we behave different from tigers Ð is due to our genes, not our trainers. So human nature comes from our genes.
Q: Who was the actual supplier of the DNA that they used for the sequencing of the human genome?
A: In the case of the public project, it was a series of anonymous people in Buffalo. For the private project, we know whose DNA it is.
Q: Finally, do you have a comment on the Richard Dawkins theory of the "selfish gene"?
A: Well, I'm a friend of Richard's, and he's very intelligent, and the idea is right. It doesn't mean what it means. To me what's much more interesting is those people who are particularly selfish are so because of their genes, nature versus nurture. Time will tell. When we sequence the genes of, say, 50,000 people, we'll catalog, categorize everyone, and one of the things, besides being thin or fat or unpleasant, will be selfish or generous. And we'll probably come up and find correlations of this with how much dopamine we have or serotonin and things like that. So our personalities come, in a sense, from our neurotransmitters and how they're used. I think they do.
