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JAMES WATSON ON: The Discovery / The Controversy / The Legacy

The paper begins with a deceptively simple request: "We

wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.).

This structure has novel features which are of considerable biological

interest."

And so begins one of the most famous scientific publications of the last

century. Its co-author is sitting behind his recently tidied desk at Cold

Spring Harbor Laboratory, and to his right is the foot-high double helix model

of DNA he brought to the lab for his first public lecture after solving the

long-sought after structure with Francis Crick in 1953. Behind him is a collage

of art and accolades, and to his left, a pinup calendar picturing a young

woman in a red dress.

At 74, James Watson is as brash and blunt, as charming and anachronistic as

he was 50 years ago, when the young ornithologist- turned-virologist from

Chicago with a self-admitted phobia of chemistry and an obsession with DNA went

to Cambridge University in England and turned the scientific world on its ear.

He steps around his desk, retrieves a copy of the original paper and reads

the last sentence aloud: "It has not escaped our notice that the specific

pairing we have postulated immediately suggests a possible copying mechanism

for the genetic material."

And then he giggles.

"I wanted to say nothing, and Francis wanted to say more, so it was a

compromise," he says. Of course, he realizes that the structure, with its

paired genetic letters like steps on a spiral staircase, paved the way not only

for learning how the molecule copied itself but also for how it stored

information and transferred it to usable form. And of course he realizes that

the sentence has become a running joke among scientists as the epitome of

understatement, that they have only to recite the first few words to elicit a

chuckle.

Especially when the scientific community is planning a large commemoration

of the discovery's 50th anniversary, and when other researchers such as Richard

Gibbs, head of Baylor College of Medicine's Human Genome Sequencing Center in

Houston, compare the achievement to Einstein's E=mc2 equation. Or to the

printing press.

Others may beg to differ, but Watson and Crick's achievement, with some

timely assistance from their competitors, is credited with ushering in a new

era of discovery in biology. As the director of Cold Spring Harbor Laboratory

for 26 years and its president for the past nine, Watson also is credited with

transforming the institution into a molecular biology powerhouse and for

guiding the mammoth Human Genome Project through its formative years in the

late 1980s and early 1990s.

Along the way, Watson has encountered more than a little controversy. For

instance, he pays little heed to critics questioning his acceptance of genetic

enhancement ("If you knew how to do it, what woman would let her daughter be

born ugly?") or naysayers doubting the affordability of the accumulating

genetic know-how.

"The well-to-do, you know, probably had the first television sets," he

says. "But that's not a reason for not building a television set."

And he's frankly mystified why everyone is making such a big deal over

human reproductive cloning. "It's not like a nuclear bomb going off," he says.

In the early 1950s, biologists were concerned with an entirely different

set of questions, mainly whether protein or DNA held the secret to genetic

inheritance. Most researchers had placed their bets on proteins, and the race

to solve DNA's structure had few entrants.

Chemist Linus Pauling, perhaps best known for his discovery that many

proteins are shaped like a corkscrew, had jumped into the DNA contest. But his

model yielded a fundamentally flawed three-chain helix with its backbone in the

center.

"His model was awkward and didn't explain the data," Watson says. At King's

College in London, two other researchers named Maurice Wilkins and Rosalind

Franklin were producing fuzzy pictures of DNA crystals from X-rays - but

otherwise barely tolerating each other, much less collaborating.

And about an hour and a half's train ride north, at the Cavendish

Laboratory of Cambridge University, Watson and Crick were busy trying out

different models of DNA with pieces of steel and brass. Watson says plenty of

evidence already existed that DNA formed a double helix, but researchers,

including him, simply failed to connect the dots.

"So I said to Francis, 'You know, if either of us had been chemists, we

should have built a model of DNA in the fall of 1951 when I arrived in

Cambridge,'" Watson recalls. "There was enough data in the literature actually

to get the answer. But the truth, you know, we weren't chemists, so we made

terrible chemical botches."

Then, in the beginning of February in 1953, Watson saw a piece of Rosalind

Franklin's data that jumped out at him: the best-yet photograph of DNA's

crystalline structure. "The main thing, it was just a perfect photograph from a

helix," he recalls.

Only Franklin never showed it to him. Wilkins did. Without her permission,

or knowledge.

The physical constraints revealed by the photograph provided Watson and

Crick with a vital clue to the structure, and Watson hit upon the final

solution on a Saturday morning one month later, one that also suggested a way

for the molecule to copy itself. Watson didn't really relax until a week later,

after he and Crick constructed a 6-foot model with freshly cut metal pieces

and meticulously measured the bond angles to make sure they agreed with the

physical constraints and other experimental observations.

"So, you know, the structure took a, you could say, a physicist and a

bird-watcher 18 months to solve, but if we had been sort of two highly

motivated chemists - you know, six weeks, without the data from King's," he

says.

After Watson and Crick received the blessing from their academic

supervisors, Watson persuaded his sister Elizabeth to type up the 900-word

manuscript, and the researchers hurried it off to the journal Nature. The

article appeared on April 25, 1953, with separate accompanying papers each from

Wilkins and Franklin.

Fifty years later, Watson anticipates the one question that critics always

ask: Why didn't he give Rosalind Franklin more credit for her role in the

discovery?

"And the answer, though we saw a lot of her - you know, when she was dying

she went and stayed with the Cricks - the only answer I can give - and it

sounds sort of gratuitous, but - was, she sort of flubbed it, and we didn't

want to say, 'Rosalind, why didn't you find the answer?'"

"If you run a race with somebody, and you won, you don't ask them, why did

you lose? You know, it wasn't the same as sort of rubbing salt in the wound?"

At least that's part of the answer. Watson also says Franklin, although

"overequipped intellectually," had the picture for at least nine months and

never did much with it.

"So it wasn't as if, you know, she got a piece of data and we stole it,"

Watson says. "In fact, it was shown to us. And it was shown to us because she

had passed some of her data to Wilkins in preparation of leaving King's."

And besides, he says, the discovery wasn't really accepted by biochemists

until 1958, the year that Franklin died of ovarian cancer.

"You know, now, 50 years later, it's regarded, you know, as being the big

discovery of biology of the century," he says. "But most people didn't think so

when Rosalind was still alive."

Furthermore, he says, neither Wilkins nor Franklin accepted his and Crick's

repeated suggestions that they try model building, nor does he remember

Franklin talking about any of her evidence suggesting a helical structure for

DNA, and nor was he privy to what was discussed at King's College, especially

since Wilkins and Franklin were barely on speaking terms.

"And Rosalind was totally unfriendly to me," he says.

The awkwardness that he and Crick felt, he says, resulted only because they

didn't like beating Wilkins, who was friends with Crick.

"We would have been very happy, you know, for the three of us to have found

it," he says. In the end, the three did receive official credit, sharing the

Nobel Prize in Physiology or Medicine in 1962.

Three decades later, controversy encircled Watson once again when he

resigned as head of the Human Genome Project over the National Institutes of

Health's decision to patent human gene fragments sequenced in the lab of an

ambitious researcher named J. Craig Venter. Watson reportedly said the

automated sequencing machines yielding these "expressed sequence tag" fragments

"could be run by monkeys."

Venter left the NIH one year later, embarking on his own privately funded

effort to beat the Human Genome Project at its own game. In 2000, both sides

declared an uneasy truce, momentarily putting aside their bitterness and

jointly announcing their results.

Despite the turbulence, Watson is still gratified to have played a key role

in the genome project, and touts his decision to fund an arm solely devoted to

exploring ethical, legal, and social implications of the effort. And whereas

the entire project was controversial even at its inception, "almost everyone

now wants to know the genome of the organism they're studying," he says.

But the information is far from complete. Watson likes to tell the story of

the time he went to the White House in 2000 for the joint announcement of the

genome's preliminary draft. A reporter told him he wasn't smiling that much.

"And I said, 'I'll only smile when, you know, we cure cancer.'"

Watson is smiling now, not because he believes a cure is imminent, but

because he acknowledges that a separate prediction on the matter proved, well,

controversial. In 1998, The New York Times quoted him on Page 1 as saying a

prominent cancer researcher would cure cancer in the next two years. Watson

says the quote was taken out of context.

Nevertheless, he cites the quickening flow of cancer information as well as

the development of human insulin and interferon therapy as but a few of the

direct benefits to come from the growing body of genetics data. Not to mention

longevity.

"We're going to live longer and we're going to have better lives because of

all this knowledge. And so, I jokingly say, 'Well, there will be a need for a

lot more plastic surgeons.'"

"I grew up thinking men died in their 60s," he says. "They did, you know,

before antibiotics. And, I suspect, if there wasn't antibiotics I wouldn't be

living now, because I get terrible infections. They would have knocked me off."

If death doesn't scare him, the thought of future children having their DNA

"fingerprints" taken at birth does, and he cites privacy and freedom as two

major concerns. But then again, "there are so many people and it's frankly so

easy to be a terrorist, that people are going to ask more, 'Who can lie?' for

better or worse. And the best way of saying who someone is, is a DNA

fingerprint."

In fact, he says the biggest surprise of the past 50 years is the

technology that makes such DNA fingerprinting - at least in criminal cases -

possible.

He also professes surprise at the anger of women over the title of his most

recent book, "Genes, Girls, and Gamow," the sequel to his bestselling

autobiographical account of the original discovery, "The Double Helix." He says

Crick didn't care much for the sequel either, but Watson merely shrugs.

"I just felt that since everyone said it was a great discovery ... you

might as well say, 'Well, what was it like afterwards?'"

His answer is that the initial happiness lasted for about four months,

until his scientific curiosity led him to a new obsession, with DNA's chemical

cousin, RNA.

But the original double helix discovery still merits some personal pride.

"People say, 'Well, what was the best period of your life?' and when you're

next to your wife, you have to say, 'Well, when I got married or we had

children,' but it's hard to say, 'Well, that wasn't pretty good,'" he says.

And then he laughs.

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