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Genes, Girls, and Honest Jim

April 15, 2003 | Honest Jim Watson remains as charming, humorous, obstinate, and outrageous as ever.

Shortly after receiving the Distinguished Service Award at the Miami Nature Biotechnology Winter Symposium last February, James D. Watson slipped away from the hordes of autograph seekers to sit down with Bio·IT World Editor-in-Chief Kevin Davies, along with Phil Campbell (editor, Nature), Meirion Jones (BBC), and conference organizer Bill Whelan. As the resulting conversation, extracted below, illustrates, the president of Cold Spring Harbor Laboratory remains as charming, humorous, obstinate, and outrageous as he evidently was half a century ago. Expounding on the double helix (the molecule and the book), cloning, and his favorite genomes, with references to Genghis Khan and Gwyneth Paltrow, Ben Stiller and Shakespeare, the man E. O. Wilson once called "the Caligula of biology" shows that, even at 75, he still relishes living up to his nickname, "Honest Jim."

BW: In the original 1953 paper in Nature, I don't think the term "double helix" was used. When was it first used?
(pause)... I don't know (genuinely puzzled)...

KD: How would you characterize your relationship with Rosalind Franklin after the discovery of the double helix?
Brenda Maddox writes a lot about this [in her biography, Rosalind Franklin] ... I couldn't remember what I said to Rosalind. I remember going to see her in May [1953] in London, but I don't know what she and Maurice [Wilkins] might have said to each other. Francis [Crick] never talked to her about it — we were embarrassed to talk about her spilt beans, you know, that she didn't build models.

KD: Was there a perception there was something amateurish about building models in those days?
She wanted to get answers through crystallography. [Linus] Pauling wanted to get answers as a structural chemist. It was trying to use your own training. She wanted to use her own way to get the answer. J.D. Bernal [the crystallographer who recruited Franklin in 1953] pointed out that intelligent people can, in retrospect, act very stupid ...

There were five of us [Gunther Stent, Seymour Benzer, Wilkins, Watson, and Crick] for whom Schrödinger's What is Life? was really pivotal ... Until [the 1950s] you would just say that DNA was someone else's problem. There was no discussion as to whether the information was more important, the script versus the actress. You could always argue either way ... Is [Sir John] Gielgud more important than Shakespeare?

PC: Francis Crick said it was unappreciated how long it took for the model to take hold. Can you comment on why that was?
Biochemists were working on proteins — they didn't like that suddenly the molecule they were working on wasn't the important molecule! Fred Sanger didn't like it ... the Cambridge biochemists called it the 'W-C structure' ... they didn't like it ... So we deserved it, at least believing our objective was the big objective.

BW: What determined the order of authors on the Nature paper?
I thought my name should be first, because it was my problem. Within a week of seeing the base pairs, Francis thought it was his problem ... He gets credit for the central dogma [DNA›RNA›protein], when Francis will tell you it was my idea.

KD: Maclyn McCarty wrote recently that he was upset you didn't cite his classic 1944 paper [with Oswald Avery, proving DNA was the hereditary material]. Have you apologized to him yet?
I don't know why we showed such bad taste! Of course, I didn't know him, and Avery was dead [by 1953]. Yes, it was a mistake ...

And then people said, why did we have this [Medical Research Council report] from King's [College London]? We couldn't have said what it was [in Nature] without telling the story of the double helix ... When I wrote The Double Helix, I didn't feel embarrassed about it. Max [Perutz] got upset for someone criticizing him for showing us the MRC report [including Franklin's data], but it was never written as confidential. My feeling is, once you put something into print, basically it's published.

MJ: You said this was an obsession. Did you have any idea it was going to be this monumental?
Yes! My dream was to find the gene ... There was the general belief, more among biologists I'd say than among biochemists, that this was a big thing.

KD: What applications did you foresee at that time?
None! We were interested in the next question of how the sequence of bases of DNA determined the sequence of amino acids. So George Gamow gets credit for putting that idea in print first, but from the day of my arrival [in Cambridge] ... we knew there was a code.

KD: You've fought for freedom of information to the human genome. Do you think that gene patents should be allowed?
In retrospect, compulsory licensing would have been the best thing ... Myriad [Genetics] might have profited more [on the BRCA breast cancer genes] by licensing and letting many more tests be given ... You can't have a monopoly on genetic information, which is distinct from saying you can't give a patent.

KD: When you were the original director of the Human Genome Project [1990-1992], did you believe, given the primitive state of the technology at that time, we'd be where we are today?
No. We couldn't see the cost of DNA sequencing going down by a factor of 1,000, which it has.

MJ: Do you think J. Craig Venter should have won a share of the Nobel Prize?
Not the one that was given [in 2002]. Right now, I don't think they should give a Nobel Prize for the human genome; there are just too many people — it would be capricious and arbitrary. Walter Gilbert was a case of a very intelligent person who cocked something up. He got a grant in the summer of 1990 to sequence Mycoplasma. But he had this clever, very sophisticated method of DNA sequencing: He wasn't dominated by wanting the answer, he was dominated by wanting his clever idea to work ... He might have had the [first microbial] DNA sequence done three years before Venter.

MJ: I was thinking more of the shotgun sequencing approach ...
The shotgun approach wasn't Venter's idea ... they were doing shotguns on plasmids. Should you go back and give a Nobel Prize for bioinformatics, or the first person who did sequence comparisons? To me, that may be the way to finally go.

Phil Green [University of Washington bio-informatician] deserves it more than Craig. Phred and Phrap [Green's DNA sequence analysis programs] were absolutely essential ... Craig doesn't have a big brain, I mean, whereas Phil Green has a big brain, Wally [Gilbert] has a big brain, OK?

KD: Do you have an ethical objection to human cloning?
I have an ethical objection to something that would potentially harm the person who was cloned. Knowing what you were going to look like at the age of 70 would be a rather frightening thought! Take a girl knowing that she was going to look like her mother ... Scary!

Often, children are put up for adoption because the parents have mental disease, which is scary ... By the time people are adopting children, it means they are getting older and they want to play safe. Now if you want a child in the United States, it's going to be Spanish, or [from] Peru, or Indian, or Chinese. In my own case, if we had to adopt, I'd rather it look Irish. It looks like you're the parents! You could say it doesn't count, but I think it does count.

It would scare the [crap] out of any child to know you were a clone of Gwyneth Paltrow and there were 50 others walking around London. Anything can be misused, but no one should deliberately produce [a clone] growing up to look like [Manchester United soccer star] David Beckham — you have your whole life to do a good kick in.

KD: Now that the human genome project is substantially complete, what other genomes are you interested in?
The bonobo — because it's a chimp gone soft, no violence. Tame animals have small brains. The bonobo has a small brain, so that they never develop into true adults ... You can just imagine 12-year-olds left by themselves — they would have sex all the time and eat fruit. I find that really very fascinating ... What gene makes tameness? The chimp will be very fascinating ... I'm just curious what makes things.

There was an agreement between the Royal Society and the Chinese government to do Y-chromosome haplotypes ... [Researchers led by Oxford University's Chris Tyler-Smith] find that in northwest China, there's what they call a STAR haplotype that originated about 1,000 years ago, and they look at repetitive DNA sequences so you can see mutations occurring every other generation. And in one place in Pakistan, where they say there are descendants of Genghis Khan ... he killed all the males and impregnated the women.

MJ: How much of your ultimate success did luck play in the discovery of the double helix?
There was luck that Wilkins and Franklin didn't get along with each other, and that Linus Pauling didn't talk to Erwin Chargaff ... You often succeed for reasons out of your control, or maybe you succeed because someone else made a bad decision.

KD: What did you think of Jeff Goldblum's portrayal of you in the 1985 BBC film "Life Story"?
At first I didn't like it, because he was unpleasant. But then people said, 'You were!'

KD: If HBO were to shoot a remake this year, whom should they cast as you?
Well, I used to say John McEnroe, the young McEnroe was the right sort, and the tennis scenes would be better. Goldblum doesn't play tennis ... Or Ben Stiller ... I liked him in 'There's Something About Mary' — that's a great movie!

At least in the United States, I was the only young person who wasn't Jewish; all my friends were Jewish. I thought it was really strange — I'm the only non-Jew, and they cast Jeff Goldblum! But then I realized, I'm culturally Jewish. My mother never believed in the New Testament, you know, 'The meek shall inherit the earth, love thy enemies ...'


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