One could say James D. Watson ignored his way to the Nobel Prize. He ignored scientific data he didn't consider right or relevant. He ignored research problems he considered peripheral to biology's central question: What do genes look like and how do they work? He even ignored the demands of his sponsors about where and what to study -- and once they cut him off. Watson's ignoring ways led him to Britain and Francis H.C. Crick, a brash and charismatic physicist nearly a decade his senior, and together they ignored the director of their laboratory to work out the shape of life's master molecule, deoxyribonucleic acid (DNA), and win a 1962 Nobel Prize. It was a major advance, as big as Gregor Mendel's insights into inherited traits. The discovery showed how genes are passed to succeeding generations and launched the modern science of genetics. Now, more than 35 years later, James Dewey Watson Jr., 61, director of the Cold Spring Harbor Laboratory on Long Island since 1968, has moved on to a new genetics project. For the better part of a year, Watson has been in charge of the National Institutes of Health's human genome project, an effort to identify and analyze in detail every one of the estimated 100,000 genes in the human body. But the challenge is different. Can this quixotic scientist who has lived his life on the frontiers of research pull off the highly complicated and political engineering project that is the biological equivalent of the Apollo moon landing?A Calculated Man One could parody the opening line of Watson's best-selling autobiography "The Double Helix," and say "I have seldom seen Jim Watson in a calm mood." (Watson had begun his chronicle of the discovery of DNA with: "I have seldom seen Francis Crick in a modest mood.") Even as Watson sits at a seminar table listening to a discussion, his face is animated, forehead wrinkling, pale blue eyes constantly shifting beneath his bifocals from a straight-ahead stare to a close examination of the ceiling's corners. In Grace Auditorium at Cold Spring Harbor, where a light-blue double helix on the wall encircles the audience, Watson eschews seats altogether, standing against the wall, arms folded, or perched on a half-wall between the seats and the aisle, watching the speaker's light pointer stab the data graphs projected on the mammoth screen. Gravity seems not to affect the wiry white hair. He has perfected a mannerism in which his left hand absently wanders to the thinning strands and rubs the long hairs backward, ensuring that they will stand out in all directions. Pale and blotchy, Watson avoids the sun; he wears a hat as he strolls the lab grounds to guard his balding pate and freckled face from ultraviolet light. Those close to him say he fears cancer, which afflicts his younger sister Elizabeth. Once, he even threatened to ban all cats from the laboratory's 100-acre campus when the feline leukemia virus, which causes leukemia in cats, was first discovered. Watson's sentences come in fractured staccato bursts, starting with a sharp inhale and ending in a mumble as though the thought, and the voice, had run out of momentum. A conversation can end suddenly when, without a word, Watson's 6-foot, 2-inch, potbellied frame lurches off to collar a passing scientist. Yet Watson is liked by many of his peers. His occasionally brutal toughness is tempered by a charming, affected English eccentricity. He tells revealing stories about himself, such as the practical jokes he has played on colleagues and unusual lunches he has enjoyed with the likes of painter Salvador Dali and actress Mia Farrow. Watson uses Cold Spring Harbor like an English estate. He gathers scientists at lab seminars for wine, cheese and conversation on the lawn below Airslie House, a restored whaling captain's home where Watson and his family live. Other times, he mixes the science cognoscente with the moneyed patrons who support his mission. The goal of the genome project is to know everything about the six-foot-long fibers of DNA inside every human cell. Watson believes the genetic information will prove indispensable in advancing medical treatments for a wide range of diseases, and he is using his Cold Spring Harbor network to garner support. Watson was picked to run the project, in part, for political reasons: Two years ago, NIH had lost the initiative on genome research to the Department of Energy. To regain momentum, then-NIH director James B. Wyngaarden sought out Watson to help get support from Congress, where the father of DNA is known and respected. Watson also has a reputation for combining three not often compatible talents: a knack for picking the right scientific problem, a gift for finding the right people to get it done, and a habit of saying exactly what he thinks. That last trait gets him into trouble. In 1985, for example, he caused a furor with his remarks about women. During a speech at Stanford University, he said, "The person in charge of biology {policy at the White House} is either a woman or unimportant." He had to apologize. His attitudes toward science were molded at the University of Chicago, where he received an undergraduate degree in 1947. As a graduate student at the University of Indiana, he became a member of the "phage group," a cluster of scientists from across the country, who in the 1940s and '50s used viruses that infect bacteria to launch the field of molecular biology. Several of them went on to win Nobel prizes. They came together for the long summer seminars at Cold Spring Harbor Laboratory, which Watson first attended in 1948. It was there that he honed his craft of asking the right questions and arguing a point. An enduring image is of Watson in intellectual combat, pushing one position, casually rejecting another as ridiculous. "If there is a disagreement, it should be known. {Otherwise} people don't know what you think," Watson said. Shade the truth, fudge the data, and someone will jump all over the misstatement. Watson does that better than most. "A good scientist values criticism almost higher than friendship," Francis Crick once said. "No, in science, criticism is the height and measure of friendship." That Watson is blunt, colorful, occasionally outrageous, is not accidental. He has toyed with a title for the autobiography he intends one day to write. "Calculated Bizarreness" was an early version; now he thinks it might be "Calculated Madness." Watson admits, however, that he tries to keep himself under control. "I have to be a lot more cautious," he says. "I am more sensible than I seem. Even when I say outrageous things, I know exactly what I am saying and why. It is not as uncontrolled. It is pretty calculated." Chicago Quiz Kid Jim Watson was a Quiz Kid. The old radio show was broadcast from his home town of Chicago beginning in 1940 and moved to television in 1949. Each day, five children would struggle with the questions and at the end of the week, the three best moved on to the next round. Watson appeared on the radio version when he was 12. "The only reason I was on was that the producer of the program {Louis Cowan} was literally our next-door neighbor," Watson said. "I was bright enough so that I knew a lot of facts." As a youngster, Watson had two skills: he could read fast, reportedly between 400 and 500 words a minute, and he could remember seemingly endless amounts of information. But he had some holes in his education. "I lost {on the Quiz Kids} when they had a Jewish girl and asked a lot of questions on the Old Testament," Watson said. Watson, born an Irish Catholic in Chicago on April 6, 1928, said he had never studied the Old Testament. His family lived on the South Side, between the Carnegie steel mills and the University of Chicago. James Dewey Watson Sr. collected money for a correspondence school, "so he had a miserable job," said his son. His mother, Margaret Jean Mitchell Watson, worked for the University of Chicago in the admissions office. "When I got a scholarship {to the university}, I was not hurt by the fact that my mother knew the head of the committee." The family was active in Democratic politics; his mother ran a voting booth in the family's basement for $12 a night during elections and was a precinct captain. Watson family attitudes: "Unions were good; The Chicago Tribune was bad; Roosevelt was good; Churchill was good," Watson said. His mother had politics; his father watched birds. Jim Jr. went along, and that helped spawn his interest in science. His appearance on the Quiz Kids earned him a $100 war bond, worth about $75, which he cashed to buy a pair of Bausch & Lomb binoculars that he still uses. Watson was a product of the Robert Hutchins philosophy of education. Hutchins, then the president of the University of Chicago, thought high school instruction was inferior, so he brought bright high school students into the university at an early age. Watson entered at 15. He had his Ph.D. the month before his 22nd birthday. "I never felt myself smart as a young kid," Watson said. In a 1981 speech, he told the story of how his natural curiosity caused him to sneak into the desk of his grammar-school teacher to look at his IQ score. "And it was pretty low, that is around 120." But his ego had been inflated by being a Quiz Kid, so "I knew I wasn't hopeless." Watson always had a contrary streak. If he wasn't interested in a subject, he didn't work hard; he got Cs in English, Bs in math, As in biology and social sciences. "I think they never accepted me to CalTech because I got a C in physics," he said. Watson claims the accelerated education didn't hurt him emotionally, even though many of his friends would describe him as sometimes painfully shy, especially around women. "I never even tried to be an adolescent," Watson said. "I never went to teenage parties. I never tried to talk like a teenager. That probably made people dislike me . . . . I didn't fit in. I didn't want to fit in. I basically passed from being a child to an adult." Watson has no regrets. "I think I was very lucky. You generally don't learn anything from your own peers." After Chicago, Watson worked on his Ph.D. at the University of Indiana, where he came under the tutelage of Salvadore E. Luria, a future Nobel winner and one of the founders of molecular biology. Through Luria, Watson entered the phage group and met Max Delbruck, a physicist who taught biologists how to think in terms of math and physics. "I easily identified with Max because he was tall and thin," Watson said. "He played tennis; I wanted to play tennis. His wife was very pretty, and I liked her." The culture of Cold Spring Harbor, where the phage group met every summer, set a premium on cooperation among scientists and the sharing of research. "It was very uncompetitive. Data was passed around. You were trying to get to the truth," Watson said. But there also was an undercurrent of intellectual arrogance. Watson once described it this way: "There was not competition between good people. There were fools and those who knew what to do." For the "fools," the criticism was harsh and the result predictable: "The bad guys just stopped coming around," said Watson. But for the guys -- and there were mostly guys, back then -- who kept coming, the phage group was home. "As long as you felt part of the group, you were totally secure," he said. The Cavendish Labs Actor Jeff Goldblum ("The Fly," "Big Chill") played Jim Watson in the 1987 BBC movie called "DNA -- The Secret of Life." It was a story of the heady days in 1951 in Cambridge, when Watson, then 23, met and intellectually merged with Francis H.C. Crick, then 35. The young American, tall, skinny, frenetic and crowned with a short American haircut, stood out in sharp contrast to the older more refined Crick, who though equally intense, was more debonair. Most thought both were brash and arrogant. Watson and Crick didn't care. Even though Watson had come to work with others in the laboratory, he quickly found a soul mate in Crick. The two shared an office in The Hut, a shabby shack among the stately academic buildings of Cambridge. According to one account, "a casual visitor, glancing inside The Hut, would hardly have recognized it as a scientific laboratory." In "The Double Helix," Watson describes how he let his hair grow long, English length, to hide his Americanism. He lived a frequently tieless, rumpled existence. And he loved it. Initally, Watson hated the Goldblum movie. "There was this crude anti-American thing of making me chew gum," he once complained. But Goldblum caught Watson's intensity. He lived for the gene. "I know my sister {Elizabeth, who would come to visit in England} used to be somewhat embarrassed by me," Watson said. "I wasn't the sort of person you asked to go to a dinner party when I was 22. I would neither amuse them nor put them at ease. The only thing I cared about was the gene -- and girls." The story of the discovery of DNA has been told before. Watson and Crick had to sneak in their model building almost behind the back of Cavendish director Sir Lawrence Bragg. Crick was supposed to be finishing his war-delayed Ph.D. Watson was supposed to be learning biochemistry and working with viruses. Instead, both gathered gene facts, mostly from the work of other scientists. The key data came from the Kings College X-ray crystallography labs of Maurice H.F. Wilkins, who shared the Nobel Prize in 1962, and Rosalind Franklin, who died of cancer in 1958 at the age of 37. It was their splotchy photographs of X-ray beams bouncing off DNA crystals that allowed Watson and Crick to build the model. Watson solved the structural mystery by sitting in their Cavendish office one morning, impatiently cutting out cardboard molecules and arranging them to fit all the known chemical and X-ray facts. He found a fit, a model was born, the competition at CalTech (two-time Nobel winner Linus Pauling) was beaten, and Watson and Crick became famous. The subsequent relationship between Watson and Crick has been occasionally rocky. Crick reportedly was furious at Watson because of his portrayal in "Double Helix." Crick declines to discuss that these days. Today, Watson, who only sees Crick about once or twice a year, speaks of his former partner in glowing, warm terms. "I am enormously in debt to Francis for his ability to be so sensible and intelligent." They now work in different fields, Watson on genes and in administration, and Crick on the brain at his Salk Institute lab in La Jolla, Calif. But the names Watson and Crick are forever linked in the minds of generations of biologists. Harvard Daze The time after the double helix discovery was "one of doubt and anticlimax," Watson once said. Watson was haunted by a fear that his DNA discovery with Crick had been a lucky shot, a flash in the pan. "We had done something very good. Now what do you do?" he asked. "I worried about whether I would be part of the next step {in the advances of genetics}." From England, Watson moved in 1953 to southern California, to the technical training ground of the Golden State: the California Institute of Technology, CalTech. It also was the home of his archrival in the race to discover the double helix, Linus Pauling. Still, Watson described it as "exile." He stayed only two years. There were other difficulties in his personal life as well. He was a bachelor, and still shy. And the DNA discovery changed many of his professional relationships as well, sometimes causing distances to develop between Watson and old friends, such as Max Delbruck. "Max disapproved of me so much," Watson would remember much later. "I had lost the innocence of the phage group." The breakdown in their friendship caused Watson to cling to Crick ever more tightly. "That was a mixed bag. Francis was charismatic in a different way, but not necessarily fatherlike, whereas Max was fatherlike." From California, Watson spent a year back at the Cavendish and then moved to Harvard in 1956. But his personality quirks and his penchant for extreme practical jokes caused many in that eastern intellectual bastion to view him with suspicion. One practical joke nearly cost him his Harvard job: He invited 200 people to a nonexistent party at the Woods Hole, Mass., home of the late Albert Szent-Gyo rgyi, a Hungarian-born biologist who won the Nobel in 1937 and later headed a lab at Woods Hole. Such jokes were not unusual for Watson. Once, while at CalTech, he wrote a letter inviting Crick, who then was in Brooklyn, to California as an honorary visiting professor. That position, however, had already been given to Sir Lawrence Bragg, the former head of the Cavendish Laboratory at Cambridge who had been Watson's and Crick's boss, but who could not stand the sound of Crick's voice. The letter suggested that Bragg and Crick share the post. Watson, of course, signed the name of his former rival and department head Linus Pauling to the Crick invitation. Fortunately, Crick figured out it was a joke; when Pauling heard about it, he reportedly was not so sure he hadn't sent the letter. At Harvard, his principal collaborator was Walter Gilbert, who later was to win a Nobel for figuring out how to determine the sequence of DNA's subunits. Watson trained young molecular biologists, not only giving them independence to pursue good ideas, but the credit. He never put his name on the scientific publications of those working in his laboratory. "Luria never put his name on my Ph.D. thesis. It came out under my own name," Watson said. "That seemed the normal way to behave." Instead, he put his name on books: "The Double Helix," which came out in 1968, and a new textbook, "Molecular Biology of the Gene," which has gone through four editions, and others. Harvard was important for another reason: "I found I could get on without Francis {Crick}, and that was a happy time," Watson recalled. "It's better not to be dependent on someone." But being at Harvard also had its problems. For example, Watson never liked teaching. "It was the only occasion I had to think. I had to teach something I didn't know," he said. A lecture left him exhausted. The result was nightmares: "I'd be in the middle of the lecture and forget everything I was going to say . . . . The worst part of the nightmares about the lectures was that I had a second lecture to give after I couldn't give the first." There was a second nightmare, too. "I would resign from Harvard and be back at the University of Chicago," Watson said. "I don't know why I had that nightmare." Sometimes, Harvard was difficult. For example, the biology department decided to promote Edward O. Wilson, the founder of the sometimes controversial field of sociobiology, but not Watson. He kicked up a fuss and eventually got tenure. When he came back from Stockholm with his shiny new prize, Harvard declined to give him a raise. Watson was furious. Those experiences crystallized his determination to fight back. "If something really matters, you might as well say what you think," he said. There were half a dozen times in his life, Watson said, where "I had created situations where if I lost, I was out of a job." Refuge at Cold Spring Harbor But Harvard had its attractions -- like Radcliffe College for women. To facilitate work in the lab, Watson said, he developed the habit of hiring Radcliffe women. "My thought was, you will stay in the lab if there are pretty girls working for you," Watson said, who was single at the time. "But that can't be said in today's society. It sounds like sexual harassment." In those days, he got away with saying things like that. It also gave him an opportunity to meet Elizabeth Lewis, a Radcliffe undergraduate. In 1968, he married her. Watson was 39. He sent a postcard from his honeymoon that said simply, "She's 19; she's beautiful; and she's all mine." Twenty years later, the couple lives on the Cold Spring Harbor lab grounds, though no signs mark their residence: Watson feared fame might put his two sons, Rufus and Duncan, at risk of being kidnapped. Watson was devastated when his oldest son, Rufus Robert Watson, 19, developed psychiatric problems. In 1985, the former straight-A student was forced to leave Phillips Exeter Academy, and, after time in private psychiatric facilities, now lives at home. During a speech once, Watson described how he and his mother used to argue about what made a person the way he is: "She said it was heredity; I said it was the environment . . . . I don't really know now." Watson became director of the Cold Spring Harbor Laboratory in 1968. By that time, the well-known facility near Oyster Bay on Long Island Sound was foundering. The century-old whaling port and granary, with buildings dating to the 1700s, was dilapidated, destitute and close to shutting down. His reason for taking the job was personal: The lab had been his proving ground, where his mentors taught him the ways of science. "No other institution plays that social role in science," Watson said of the summer program at Cold Spring. Over the past two decades, Watson has overhauled both the buildings and the scientific mission of the laboratory. He turned out to be an able fund-raiser. Millions poured in, enough to renovate all of the 30-odd buildings on campus. Today, Watson is raising money for a new neurobiology center. Long an anglophile (he still owns a house on Vincent Square in London), Watson revels in the English countryside atmosphere of Cold Spring Harbor. He prowls the grounds, choosing which underbrush to clear, deciding where to build the pond (which leaked) and how the renovations were to proceed. The original exteriors on the buildings were restored with the help and research of his wife. "I like beautiful buildings, just as I am generally dominated by the faces of beautiful girls," Watson said. He even got the lab's trustees to buy the marina across the harbor to preserve the view and the salt marsh. The lab is small compared to other private research centers, such as The Scripps Clinic and Research Foundation and Salk Institute for Biological Studies, both in San Diego, the Wistar Institute in Philadelphia or the Fred Hutchinson Cancer Research Center in Seattle, but Watson has built an intellectual powerhouse. An analysis by the Institute for Scientific Information in Philadelphia determined that "over the past decade and a half, {scientific} papers from Cold Spring Harbor have carried about twice the clout, as measured by citations, as papers from several other premier independent labs." Hunting Down the Genome For Congress, the human genome project is the first billion-dollar biology project, on a scale of landing on the moon or splitting the atom. When the fiscal year opens next month, Watson will have $100 million to get the project started in a big way. Funding eventually is expected to grow to $200 million a year or more, with the final cost expected to be some $3 billion over 10 to 15 years. The major outline of the project is expected to be delivered next month during a scientific meeting in San Diego. "Five years from now, we are going to have a human {genetic} map," said Norton Zinder of Rockefeller University, the scientist picked by Watson to head the genome advisory committee. When the genome project was launched two years ago by a favorable National Research Council report, he said, much of the technology that will now be employed didn't even exist. Since then, Watson and Zinder have brought together some of America's leading molecular biologists to develop the needed technology and design a strategy. Marilyn Zinder has been telling friends that Watson and her husband are the Hardy Boys, exuberant brothers who were the main characters in a series of detective stories for boys. For the two aging scientists, she says, both in their 60s, the genome project is their last great adventure. UNLOCKING THE GENETIC CODE: 36 YEARS OF DISCOVERIES FINDING THE DOUBLE HELIX When James Watson teamed up with Francis Crick at Cambridge University in 1951, scientists were only just deciding that deoxyribonucleic acid, DNA, carried the genetic code, the instructions for making a complete virus, bacteria, plant, animal or human. No one knew what the DNA molecule looked like, how it reproduced so it could be passed to successive generations, or how the information stored in the DNA might direct a cell's activities. By bouncing X-ray beams off crystals of DNA, researchers at Kings College, London, produced smudgy images which, along with other data, gave rise in 1953 to the Watson-Crick model of DNA -- the double helix. It's a kind of spiral staircase, a ladder with sugar and phosphorus molecules forming the outside rails and chemical bases -- adenine, thymine, cytosine and guanine -- forming the steps. MAKING TWO FROM ONE From the double helix model, Watson and Crick immediately saw how exact copies of DNA could be made. The bases, or rungs of the ladder, always paired A (adenine) with T (thymine), and G (guanine) with C (cytosine). Splitting the ladder down the middle produced two separate strings of the letters A, T, C and G. Enzymes, acting upon the DNA, matched each A with a T and each C with a G from a reservoir of bases within the cell, forming new pairs that reconstitute two complete copies of the original double helix. DIRECTING THE BODY'S FORM AND FUNCTION 1 - DNA is like a notebook of blueprints, with each page carrying a code -- the sequence of A, T, G and C -- which directs the production of proteins. This set of blueprints remains in the cell's nucleus as a permanent record of all inherited instructions. 2 - To pass on instructions for the making of a protein, say in a human foot, from the genetic repository to the cell's protein factories, a copy of the DNA blueprint is made. Enzymes encode the DNA information onto ribonucleic acid, RNA, a chemical cousin of DNA. 3 - The RNA, called messenger RNA, travels out of the cell's nucleus to the cell's protein factories. Once at the factory, the single-stranded RNA is read by a protein-making machine that uses the genetic information of As, Ts, Cs, and Gs to determine the order of the 20 amino acids that go into making a protein. 4 - Order of the amino acids, which is determined by the genetic code, determines how the protein folds into a three-dimensional shape. It is this protein's shape that gives the cell its form and function. All the cells together, with all their genetic code displayed, give the body its shape and function.