“This structure has novel features which are of considerable biological interest” is one of science’s most famous understatements. James D. Watson and Francis H. C. Crick penned it for their report in the April 25, 1953, issue of Nature, in which they proposed the double helix model for the structure of DNA, the breakthrough that opened up our understanding of molecular biology and genetics.
To mark the 50th anniversary, Scientific American Editor in Chief John Rennie recently spoke with Watson in his office at Cold Spring Harbor Laboratory on Long Island, where he was director for 25 years. Watson reflected on the origins of the double helix discovery, the current state of molecular biology, and controversies surrounding genetic science. (Because of poor health, Crick was not available for comment.)
Here is an abridged, edited version of that conversation.
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SCIENTIFIC AMERICAN: DNA is no longer just a scientific entity. It’s erupted as this huge cultural phenomenon, as a metaphor for our natures. It’s in our daily conversation, in art. When you were working on the double helix, did you foresee DNA ever becoming this well known?
JAMES WATSON: No, no, we couldn’t. Because no one had ever sequenced DNA or amplified DNA.
The famous Australian immunologist [Frank Macfarlane] Burnet published this article in a medical journal that came out in 1961 or 1962, in which he said DNA and molecular biology will not have an influence on medicine. Because that’s only possible when you can read the DNA. That’s why the Human Genome Project is so important.
Back in 1953, all we wanted to do was find out how DNA provided the information and what the cellular machinery was for making proteins. That’s really all; we didn’t think about gene therapy. It took about 15 years before people began to think about that, around 1968—once restriction enzymes came along and, soon after, DNA sequencing.
SA: You’ve said that you first became involved with research on DNA because of your interests in evolution and information.
JW: [Physicist Erwin] Schrödinger probably wasn’t the first, but he was the first one I’d read to say that there must be a code of some kind that allowed molecules in cells to carry information. By the time Schrödinger’s book [What Is Life? (1944)] came out, a few people, such as [biologist J.B.S.] Haldane, were making that connection between genes and proteins. Back in those days the amino acid sequence for a protein hadn’t been worked out. You knew there was some sequence, but that’s all. It was only our getting the DNA structure and [chemist Frederick] Sanger sequencing the first polypeptide [protein] chain that let some air in.
SA: So would you say that your work was driven more by fascination with that idea than by ambition?
JW: I was born curious. I would rather read economic history than history, for example, because I liked explanations. And so if you wanted an explanation for life, it had to be about the molecular basis for life. I never thought there was a spiritual basis for life; I was very lucky to be brought up by a father who had no religious beliefs. I didn’t have that hang-up. My mother was nominally a Catholic, but that’s as far as it went.
SA: As we look back on the race for the double helix, it’s obvious that individual personalities strongly influenced the specifics of who found it first and how. And yet the discovery at roughly that time also seems to have been inevitable. There were so many of you who were so close—you and Crick, Linus Pauling of the California Institute of Technology, Maurice Wilkins and Rosalind Franklin of King’s College. If you and Crick had not made the discovery when you did—
JW: I can’t believe a year would have passed.
SA: There has always been controversy about Wilkins showing you Franklin’s crystallography images without her permission, giving you and Crick an important clue to DNA’s structure. In retrospect, would it have been more appropriate for the Nobel committee to have given the prize to her, along with you and Crick, rather than to Wilkins?
JW: I think not. Wilkins gave us the crystalline photograph of the A form, and she gave us the B form. So you could have said that in an ideal, perfect society, they would have gotten the chemistry prize, and Crick and I would have gotten the biology prize. That would have been a nice way to honor the four of us. But no one thought that way.
We’re very famous because DNA is very famous. If Rosalind had talked to Francis starting in 1951, shared her data with him, she would have solved that structure. And then she would have been the famous one.
SA: In a century, we went from rediscovering Mendel’s laws and identifying chromosomes as agents of heredity to having the human genome largely worked out. Finding the double helix drops neatly in the middle of that span. How much, with respect to DNA, is left for us to do? Are there still great discoveries to be made, or is it all just filling in details?
JW: The major problem, I think, is chromatin [the dynamic complex of DNA and histone proteins that makes up chromosomes]. What determines whether a given piece of DNA along the chromosome is functioning, since it’s covered with the histones? You can inherit something beyond the DNA sequence. That’s where the real excitement of genetics is now.
And it seems to be moving pretty fast. You don’t really want to make a guess, but I’d guess that over these next 10 years, the field will be pretty played out. A lot of very good people are working on it. We have the tools. At some stage, the basic principles of genetics will be known in terms of gene functioning, and then we’ll be able to apply that more to problems such as how the brain works.
SA: If you were starting out as a researcher now—
JW: I’d be working on something about connections between genes and behavior. You can find genes for behaviors, but that doesn’t tell you how the brain works. My first scientific interest was in how birds migrated. Until you know how the bird brain works, you’re not going to know how genes can tell that bird where to migrate. Because, you know, that mother bird isn’t telling the young one where to go! So it’s got to be inherited.
There are lots of other big behavioral things [to solve]. Some people say they’re mystified that men can like men, but I say, “It’s just as mysterious as why men like women!”
These things are so difficult. Francis insists that brain research doesn’t have [the equivalent of] a DNA molecule. It doesn’t have a central thing from which everything else flows.
SA: You have a reputation for being outspoken, and you get criticized for it. Do you have any regrets about things you’ve said?
JW: Occasionally. I think there’s something in me of that same weakness that is so apparent in [tennis champion] John McEnroe. I just can’t sit while people are saying nonsense in a meeting without saying it’s nonsense!
SA: On the subject of politics, many gene-related issues are in the public arena these days: genetically engineered foods, cloning, DNA fingerprinting and so on. How much confidence do you have in the political supervision of these?
JW: I think they’re so contentious that the state shouldn’t enter in. Yes, I would just stay out of it, the way [government] should stay out of abortion. Reproductive decisions should be made by women, not the state.
I mean, cloning now is the issue. But the first clone is not like the first nuclear bomb going off. It’s not going to hurt anyone!
I know a famous French scientist who never had children because there was madness in his family. He didn’t want to take a chance on more madness. That’s what I mean. Cloning might mean you would know there wasn’t going to be any more madness. I think the paramount concern should be the rights of the family, as opposed to the rights of the state.
People say, “Well, these would be designer babies,” and I say, “Well, what’s wrong with designer clothes?” If you could just say, “My baby’s not going to have asthma,” wouldn’t that be nice? What’s wrong with therapeutic cloning? Who’s being hurt?
If you thought every plant was the product of a god who put it there for a purpose, you could say that you shouldn’t change it. But America isn’t what it was like when the Pilgrims came here. We’ve changed everything. We’ve never tried to respect the past, we’ve tried to improve on it. And I think any desire to stop people from improving things would be against the human spirit.
An extended version of this conversation and a list of suggested readings is available at www.sciam.com. Watson’s latest book is DNA: The Secret of Life (Knopf, 2003).
