For most scientists, a Nobel Prize is the capstone of a career.
But in the 50 years since their breakthrough discovery of the structure of DNA, James D. Watson and Francis H.C. Crick have continued to pursue the frontiers of knowledge, albeit along different paths.
Watson, once the brash whiz kid from Chicago, has become the "dean of DNA," as one colleague calls him. Buoyed by his gossipy 1968 bestseller The Double Helix, he abandoned his laboratory bench for an administrator's desk, pushing for a cancer cure and a complete map of the human genome.
He stands today as the most visible figure in the continuing genetics revolution, though his penchant for speaking his razor-sharp mind has left a trail of enemies -- and admirers.
Crick, who was raised in a middle-class English family, remains a researcher at 86 and co-wrote yet another scientific paper that was published just last month.
After the 1953 coup, Crick pushed on to work out the mechanics of DNA before his restless mind led him to explore more cosmic questions, such as the origins of life on Earth. For the past two decades, he has searched for the scientific basis of human consciousness.
As the world marks the 50th anniversary of the discovery of the double helix with celebrations this week in New York and this spring in England, Australia and elsewhere, admirers are honoring Watson's and Crick's lifelong contributions to science, not merely the discovery that earned them the 1962 Nobel Prize.
At 74, Watson crisscrosses the country attending scientific meetings and ceremonies. In rambling lectures and interviews, he extols the promise of genetic research even as he recalls with self-deprecating humor how he and Crick made history.
"I think the biggest opportunity is curing cancer," he said recently while sipping coffee in his office at Cold Spring Harbor Laboratory in New York. "We really know a lot about that disease."
Watson is president of Cold Spring Harbor, the former biological field station on the north shore of Long Island that he took over in 1968 and steered toward a genetic cure for cancer. He relinquished administrative oversight nine years ago, but the institution's 350 researchers remain among the most frequently cited in scientific literature.
His wispy white hair remains as unruly as it was in his youth, as does his willingness to say whatever comes to mind.
"I think it's very important to study intelligence," he said in a recent lecture, acknowledging the notion's political incorrectness. "Some people are stupid because of their genes."
Watson recalls growing up poor on the south side of Chicago, where he absorbed his parents' philosophical skepticism. "Don't believe anything unless there is evidence," he says.
An avid bird-watcher in his youth, he was drawn to molecular biology by a book on genetics that he read at the University of Chicago -- the same book that inspired his future partner, Crick.
As a researcher, Watson never achieved another breakthrough on the level of the double helix, despite nearly 20 years of lab work. Instead, he evolved into a scientific talent scout who attracted bright young minds and motivated them.
But Watson's passion for molecular biology -- and, to some, his arrogance -- got him into scrapes over the years. In the 1950s, while carving out a molecular biology department at Harvard University, he clashed with Edward O. Wilson, a Pulitzer Prize-winning author and noted expert on ants.
"I found him the most unpleasant human being I ever met," Wilson wrote in his memoir, Naturalist, dubbing Watson the "Caligula of biology."
Wilson and others, however, came to respect Watson's administrative abilities.
"The way he built up Cold Spring Harbor Laboratory was just extraordinary," says Dr. Victor A. McKusick, a pioneer of medical genetics at the Johns Hopkins University.
Among those impressed by Watson was Carol Greider, who spent 10 years at Cold Spring Harbor and found a potential clue to the cause of cancer in the ends of chromosomes, called telomeres.
"He would walk into my lab on a Saturday and ask me about a paper he had just read on telomeres," says Greider, now interim director of molecular biology and genetics at Johns Hopkins. "I was really just flabbergasted the first few times it happened, that he would follow so closely a field that was not really his specialty."
Watson's takeover of Cold Spring Harbor coincided with the successful conclusion of another obsessive quest -- finding a mate. At 40, he married a Radcliffe College sophomore named Elizabeth Lewis who was helping in his Harvard lab. They had two young sons, one of whom suffers from serious learning disabilities -- fueling Watson's belief in giving parents a chance to fix genetic flaws in their offspring.
"We have a son who's never had a chance to succeed, and that's awful, you know?" he said. "So I speak from a very personal viewpoint that evolution isn't kind, and we shouldn't let things as they are."
In the late 1980s, Watson lobbied Congress to fund an ambitious project to map all 3.2 billion chemical building blocks in human DNA. But he quit the Human Genome Project in 1992 in a dispute over plans to patent bits of genetic information that had been developed. Still, many credit his early vision and leadership of the genome effort, which is nearing conclusion.
"Watson had more influence than anyone else in strengthening the growth, the focus of biology," says biographer Victor McElheny.
Although Watson plans to attend many of the DNA anniversary celebrations, his one-time partner and old friend Crick is shunning them. Crick videotaped messages for this week's events in New York, but he declined a request to be interviewed.
The quick-witted, booming-voiced Crick, whom Watson describes as a "soul mate" during the race for the double helix, has curtailed his activities recently while undergoing treatment for colon cancer.
As president emeritus of the Salk Institute for Biological Studies in La Jolla, Calif., Crick continues to ponder how the brain works to make people aware of themselves and their surroundings -- a field until lately considered more the province of philosophers than scientists.
In his 1994 book The Astonishing Hypothesis, Crick suggested that "your joys and sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules."
Trained as a physicist, Crick ventured into biology after developing mines for the British Navy during World War II. His outspokenness and hostility toward religion helped forge his famous partnership with the skeptical Watson.
Crick remained at the University of Cambridge after the DNA discovery, living in a house he dubbed the Golden Helix as he pursued DNA's underlying machinations. But by the mid-1960s, he concluded that the fundamental questions of genetics had been answered.
After moving to Southern California in the 1970s, he and fellow Briton Leslie Orgel developed the eyebrow-raising theory that life on Earth began with microorganisms from outer space -- probably seeded by an alien spaceship.
Crick later became a leading theorist in the study of how the brain works.
Watson thinks that neuroscience is one of the next big scientific frontiers, one that will keep reseasrchers racing for the rest of this century. Crick finds the field less developed than genetics was when he dove into research in the early 1950s.
"There seems no limit to the problems that now confront us," Crick said in his videotaped remarks. "I shall not live to see their solutions, but many of you should survive long enough to see many radically new techniques and striking discoveries."
The discovery of DNA's structure 50 years ago this week transformed biology and medicine. And we are only beginning to fulfill the promise of the genetics revolution, which will change how we live in countless ways.
State of the Art
People have been genetically modifying plants and livestock for centuries through selective breeding, but the deciphering of DNA's structure opened the door to much more radical manipulation. Among the first modified crops to hit the markets was the Flavr Savr tomato, genetically tweaked to stay ripe longer. Introduced in 1994, it failed to catch on with consumers because of its bland taste.
Farmers embraced genetically modified crops, though, and they now grow more than three dozen types to save on production and labor costs. The most popular -- corn, cotton and soybeans -- have been altered to resist insects or weed-killing chemicals that are sprayed on fields. Two-thirds of the soybeans planted in the United States two years ago were resistant to herbicides, about triple the amount of four years earlier. Scientists also have engineered "yellow rice," a strain rich in vitamin A, to battle malnutrition in developing countries.
In 1996, scientists in Scotland cloned a sheep named Dolly from a cell taken from an adult sheep. The development created a sensation, and opened the possibility of using genetic manipulation to produce entire flocks of prize-winning livestock from a single animal. Many consumers, however, remain leery of "Frankenfoods." Concerns have been raised about the potential for genetically modified crops to harm butterflies, wild plants and even humans. Though research has found no health risks, European countries insist on labeling genetically modified foods, and some developing countries have balked at accepting relief shipments of modified grain from the United States.
Besides producing stronger, more healthful foods, biotechnology has brought breakthroughs in producing drugs, screening for diseases and cleaning up environmental contamination.
Dozens of bioengineered drugs have been approved for various medical conditions; synthetic insulin is used by millions for treating diabetes. DNA manipulation also has yielded new diagnostic tests for AIDS, hepatitis and other infectious diseases.
By mixing and matching the DNA of different bacteria, scientists have created new microorganisms that can clean up oil spills or toxic-waste dumps by "feeding" on the chemicals.
From the crime scene to the courthouse, the use of DNA as proof of identity has changed how crimes are investigated and solved, how victims of mass disasters are recognized, and how paternity disputes are settled.
Developed in 1985 by British geneticist Alec Jeff-reys, the technique is based on the concept that each person's DNA contains unique patterns and that these patterns can be used like a biological Social Security number or bar code.
Although a few scientists still debate the reliability of DNA fingerprinting, most judges and coroners accept its conclusions. From the crash of the space shuttle Columbia to the attack on the World Trade Center, it has proven indispensable in identifying the remains of disaster victims.
As researchers sort through the genetic instructions encoded on DNA, they have linked about 2,800 medical disorders with particular defects in individual genes -- including fatal diseases such as cystic fibrosis. They also have identified genetic glitches that make people prone to more common illnesses such as heart disease, breast and colon cancer, diabetes and arthritis, though the causes cannot be traced to specific genes.
Although scientists have successfully corrected or replaced defective genes in laboratory animals, efforts to try gene therapy in humans have been problematic, marked by the death in 1999 of an 18-year-old participant in a gene therapy trial at the University of Pennsylvania. Human trials of a promising treatment for "bubble boy" disease -- a rare disorder in which children are unable to develop immunity against illness -- were halted this year after two test subjects developed leukemia. Doctors in Philadel-phia recently won government approval, though, to try a new treatment for Parkinson's disease that involves injecting a gene into a person's brain.
On the Horizon
Will DNA someday be used to break encrypted messages for the military or scour genetic databases for signs of disease -- the kind of jobs performed by electronic computers today? That's what the scientists working in the hot field of DNA computing think.
Think of DNA as nature's version of a supercomputer. The molecule can store huge amounts of information -- indeed, the recipe for an entire person -- and is capable of performing millions of calculations at once.
While electronic computers use a binary system of ones and zeroes, DNA computers hinge on the molecule's four chemical bases and their ability to pair naturally with one another.
Since the mid-1990s, researchers have found problems suited to DNA's quirky calculation method -- trivial puzzles in math, logic, even chess. But as scientists learn to more adeptly manipulate the molecule, they speculate that even more applications will emerge, although it is doubtful that DNA computers will ever be doing your taxes.
DNA is an important, if limited, crime-fighting tool capable of identifying a suspect by matching one genetic sample to another. But what if it could tell police that their suspect was a white male with red hair, blue eyes and a cleft chin?
It is not yet possible to generate a sketch from a scrap of DNA. But by comparing the DNA of hundreds of people, scientists have found patterns that are leading to genetic tests for hair color, eye color and even ethnicity. Other researchers, meanwhile, are working to find markers for bone structure.
The tests are bound to be controversial. Civil libertarians worry that the technique will lead to gross invasions of privacy. Some scientists argue that the strategy is a dead end, that it's impossible to divine a person's appearance from DNA. But British police have solved crimes with the technique and think it may become the ultimate eyewitness.
Scientists announced last year that they had created the polio virus by stitching together snippets of DNA obtained through a mail-order supply company.
Experts wonder whether the capability of creating new life forms is not far behind. Millionaire molecular biologist Craig Venter has embarked on an effort to build a bug from scratch using Mycoplasma genitalium, a bacterium that lives in human genital tracts, as a starting point.
Scientists are debating the usefulness of custom-made microbes. Some worry that terrorists could unleash unstoppable killer bugs. But Venter and others argue that the science will result in microbes that suck greenhouse gasses from the atmosphere, excrete hydrogen fuel or destroy toxic waste.
Doctors helping parents conceive a child through in-vitro fertilization are screening embryos for genetic defects, and some fertility clinics offer prospective parents the opportunity to choose the sex of their baby before the fertilized embryo is implanted in the mother's womb. A Colorado couple recently gave birth to a son chosen through genetic screening so he could provide bone marrow to his older sister, who has a rare genetic disease. Some think, or worry, that engineering the DNA of offspring for desirable traits is only a short step further. Nobel laureate James D. Watson, whose co-discovery of DNA's structure launched the genetics revolution, has asked: "If we could make better human beings by knowing how to add genes, why shouldn't we?"
Text by Michael Stroh and Timothy B. Wheeler Graphics by Denise Murray
The path to the double helix - and beyond
1865 Experimenting with common garden peas, Austrian monk Gregor Mendel shows how traits like color and height are passed from one generation to the next.
1869 Swiss scientist Fredrich Miescher discovers DNA what he calls "nuclein" -- in human pus from hospital bandages.
1904 The term genetics is first used in a letter written by biologist William Bateson, an early proponent of Mendel's ideas.
1909 Danish botanist Wilhelm Johannsen coins the word gene to describe the Mendelian units of heredity. The Word derives thom the Greek genos, meaning "birth".
1910-1913 Studying genetic mutations in fruit flies, embryologist Thomas Hunt Morgan shows that genes are carried on chromosomes, a finding that earns him a Nobel Prize.
1944 Oswald Avery, Colin MacLeod and Maclyn McCarty show that DNA not protein, as many scientist s thought --carries hereditary information.
1953 On Feb. 28, American biologist James Watson and British physicist Francis Crick deduce that the three-dimensional structure of DNA is a pair of intertwined spirals -- a "double helix."
1961-1963 Crick and other scientists begin to map how DNA's sequence dictates the creation of certain proteins.
1968 Hamilton O. Smith and others lay the foundation for modern genetic engineering by discovering that -restriction enzymes" can slice DNA into snippets.
1972 Paul Berg and others splice together DNA fragments from different organisms, sparking heated debate over the safety of "recombinant DNA."
1978 Genentech, the first genetic engineering company, develops the first recombinant DNA drug, human insulin.
1980 U.S. Supreme Court rules that genetically modified organisms can be patented. General Electric Co. gets first such patent, for a bacterium designed to clean up oil spills.
1981 First "transgenic" creatures created when scientists insert foreign genes into the DNA of mice and fruit flies.
1983 First disease gene mapped. Huntington's disease is traced to a mutation on chromosome 4.
1990 The Human Genome Project gets under way. Primary goal: to decode all 3.2 billion chemical building blocks of DNA and map the genes.
1990 First gene therapy, on a 4-year-old girl with inherited Acquired Immune Deficiency Syndrome (AIDS).
1994 The Food and Drug Administration approves the first genetically modified food -- the Flavr Savr tomato, engineered to stay firm longer.
2000 NIH and Celera Geneomics, a Maryland biotechnology firm, announce completed drafts of the entire human genome.
2003 Final human genome to be published in April.