ifty years ago, on Saturday, Feb. 28, 1953, two young scientists walked into the Eagle, a dingy pub in Cambridge, England, and announced to the lunchtime crowd that they had discovered the secret of life.

By divining the chemical structure of DNA, the archive of life, James D. Watson and Francis Crick had seen how the molecule could encode information in the copious quantities necessary to program a living cell.

Years later Dr. Crick's wife, Odile, told him she had not believed him, he has written. "You were always coming home and saying things like that, so naturally I thought nothing of it," she said.

But on that occasion the claim was true, and it set in motion a revolution that has continued to unfold to this day, much of it guided by the two original discoverers.

Research is a slow process, often with years between each eureka, and even today the DNA revolution remains largely behind laboratory doors, in the form of biologists' ever intensifying understanding of the mechanisms of life. But a few powerful inventions — forensic DNA, a new wave of DNA-based drugs — have already had considerable effect, and many researchers believe they are just a foretaste.

They expect new medical treatments and diagnostic tests, based on a thorough understanding of DNA, for cancer, heart disease and other long intractable maladies. Yet like any powerful technology, DNA will doubtless bring vexing choices: whether to modify the human genome with inheritable genes that will eliminate disease and enhance desired qualities, for one.

And there are outright dangers, like the possibility that DNA techniques will be used to make novel biological weapons.

The 50th anniversary of the discovery of DNA's double helix may be more than just a round number. It comes while both its founders are still alive and active: Dr. Crick published an article on the nature of consciousness just this month.

The human genome, obtained in a very rough draft in 2001, is becoming more polished. New technologies have been invented for interpreting the genome's enigmatic archive. Biological laboratories are engaged in a thousandfold scale-up, from studying one gene at a time to examining whole genomes. And DNA, after a long gestation, is in the throes of passing from a pure science to an applied one.

After figuring out the structure of DNA, Dr. Crick and Dr. Watson realized that the sequence of units in the DNA must carry the code in some way for the structure of the proteins that are the working parts of a cell. But they did not foresee that the entire genomes would one day be decoded.

"Did we appreciate how important DNA was? Yes we did," Dr. Crick said in an interview this month from his home in Southern California. "We did see the shape of the genetic code. But we didn't foresee rapid sequencing."

Although the text of the genomic message is an eye-glazing march of A's, G's, C's and T's that then require years of interpretation, the genome era has already raised biology to a new scale of operations and amplified the tools at biologists' disposal.

"The pace of discovery is going unbelievably fast," Dr. Watson said in an interview last month at his Cold Spring Harbor Laboratory on Long Island.

The Genome Era

Learning to Read
DNA's Full Story

The Watson-Crick discovery showed that DNA records genetic information in the form of a four-letter alphabet. But obtaining the text of the message that evolution has taken some four billion years to compile was no easy task. It was another 20 years, in the mid-1970's, before one of their Cambridge colleagues, Dr. Fred Sanger, worked out an ingenious method for determining the order of the letters in a stretch of DNA.

But Dr. Sanger's method was manual and could decode long DNA messages only with great difficulty. Others, chiefly scientists at Applied Biosystems, had to automate the method and design DNA sequencing machines that could handle genome-size lengths of DNA. Another essential advance was the PCR technique, invented by Dr. Kary Mullis, for amplifying defined stretches of DNA into workable quantities.

The genome era began on May 25, 1995, when Dr. J. Craig Venter announced that he had decoded the first genome of a single-celled organism, a bacterium known as Haemophilus influenzae. Since then about a hundred bacterial, plant and animal genomes have been decoded, including the C. elegans roundworm, the Drosophila fruit fly and the mouse — laboratory organisms of vital interest to biologists.

With whole genomes available for study, biologists can at last begin to see the precise mechanics of natural selection, the process that Darwin intuited without any knowledge of its physical basis.

As each new genome is deciphered, the tree of life comes into clearer focus. Even creatures as far apart as man and mouse have turned out to possess amazingly similar sets of genes, each with a similar sequence of DNA units. So far each new genome has turned out to have some novel genes special to its own species, as well as a core set having to do with the cell's basic operations, which seem very ancient and probably trace back close to the origin of life.

This genomic data — three billion units apiece for animals like mice and humans — has presented biologists with a whole new set of challenges. New devices, called microarrays or expression chips, have been invented for examining the activity of thousands of genes at a time. A set of special chemicals, known as an RNAi library, was announced last month for inactivating each of the genes in the laboratory roundworm.

A thriving new branch of science, often called computational or "in silico" biology, has emerged to analyze the genes and other component parts of a genome and to compare one genome to another. These techniques, developed for handling many genes at a time, give biologists hope that they can understand the whole human genome, now thought to contain some 30,000 or so genes.

"A constellation of things is going on that make this a special time in biology," said Dr. Thomas Cech, president of the Howard Hughes Medical Institute, which finances major biomedical research. "Many of us underestimated how powerful a tool the genome would be. To be able to ask a question of 30,000 genes at the same time and let the system tell you the answer is incredibly exciting. You can unveil a process in a single-celled organism and then use computers to discover by in silico experiments the human counterpart. That in itself has largely transformed the way a lot of biology is done."

The ability, gift of the genome sequence, to track thousands of genes at the same time puts biologists in the position of being able to analyze the living cell in action as it does its housekeeping or responds to the ceaseless chatter of signals from its neighbors.

The genomic era is also bringing about a quantum leap in biologists' capabilities, drawing almost within contemplation one of biology's ultimate goals, that of understanding a whole organism in terms of its DNA.

The Impact on Society

Technology's Potential

Is Already Evident

For now, the DNA revolution is largely confined to understanding nature, not changing it. Yet the few applications that have already appeared leave little doubt of the technology's potential.

DNA as a means of individual identification, first invented by Sir Alec Jeffreys of the University of Leicester in England in 1984, has developed into a hallmark forensic technique, strong enough to overturn verdicts based on shakier forms of evidence like eyewitness testimony.

Applied to stored biological evidence, DNA fingerprinting has proven the innocence of many convicted inmates. To date the Innocence Project at the Benjamin N. Cardozo School of Law, run by Barry C. Scheck and Peter J. Neufeld, has exonerated 124 people. In Illinois, DNA evidence cleared so many death row inmates that Gov. George Ryan lost confidence in his state's justice system. Just before leaving office last month, he commuted all death sentences to prison terms of life or less.

DNA testing has jolted the justice system because, properly used, it is an almost infallible identifier of biological tissue. In Britain, which collects DNA from everyone convicted of a crime, a growing database has allowed the police to score many "cold hits," the match of DNA from tissue at a crime scene to someone not on any list of suspects. The impressive reach of DNA fingerprinting, both to snare the guilty and clear the innocent, has prompted suggestions for larger DNA databases, as well as counterarguments from civil libertarians.

DNA is also an unrivaled genealogical archive. By examining the DNA of the living, biologists can reach back and resolve many otherwise inaccessible questions. DNA evidence has added weight to the oral tradition, dismissed by almost all historians, that Thomas Jefferson had a second, unacknowledged family with his slave Sally Hemings. From the DNA of people living today, geneticists can infer the size of the ancestral human population and track its movements across the globe as the first modern humans dispersed from Africa.

DNA has already been used to modify crops, building bacterial genes for countering insects into corn and cotton, and adding genes from daffodils and bacteria to help rice make vitamin A. But the artificial mingling of genes from different species makes some people uncomfortable, and genetically modified crops have encountered resistance, especially in Europe.

A new wave of DNA-based drugs is slowly reaching the market, beginning with genetically engineered forms of insulin and growth hormone and now including highly ingenious substances, based on a deep genetic knowledge, like Enbrel, for rheumatoid arthritis, and Gleevec, a startlingly effective treatment for chronic myelogenous leukemia.

The Next Phase

Disease Genes

Proving Elusive

Waiting in the wings is a new wave of DNA-based diagnostic tests. One is a test for an errant gene that is mutated early in many cases of colon cancer. Developed by Dr. Bert Vogelstein of Johns Hopkins University, the test is applied to a stool sample and, together with other genetic tests, could provide a cheaper and more acceptable screen for colon cancer than colonoscopy.

The 30,000 or so genes in the human genome can now be programmed into microarrays and used to profile the characteristic pattern of gene activity in a cancerous cell.

Dr. Todd Golub of the Whitehead Institute Center for Genome Research has pioneered the use of gene expression chips to distinguish, within a given kind of cancer, previously unrecognized subtypes that respond differently to treatment. He hopes the chips will pinpoint both the errant genes special to particular types of cancer as well as gene changes common to all cancer cells.

"We are looking for magic bullets that target particular types of cancer but also for the Achilles' heel that unites many different types of cancer," Dr. Golub said. The tests, though yet to be approved by the Food and Drug Administration, show the likely power and scale of genomic era medicine.

A principal goal of the Human Genome Project was to identify the errant genes that underlie common diseases, like diabetes, cancer, obesity, schizophrenia and Alzheimer's. These disease genes have proved highly elusive, perhaps because it takes several errant genes in combination to cause the disease, and the contribution from each is hard to detect.

A remarkable experiment is now under way in Iceland, where a company called Decode Genetics has constructed a genealogy of much of the population. With it, Decode can build large pedigrees for patients with each disease of interest. The company then scans the genomes of related patients, looking for segments of chromosome they may have inherited from a common ancestor. Within these shared segments it looks for variant genes that may contribute to the disease.

The company has identified several disease-causing genes, including one for schizophrenia, and has inferred the general location of several others.

From disease gene to drug is a long path, but identifying an errant gene gives a deep, often novel, insight into the cause of disease and supplies new targets for drug makers.

The Ethical Frontiers

`Perfecting' Humans,

Endangering Them

Implicit in the understanding of DNA is the possibility of changing it, a prerogative until now reserved for evolution. Gene therapy, the idea of patching up tissues by delivering the corrective form of an errant gene, has so far been a failure. Even when it works, its changes will not outlast the patient.

But another approach, not yet technically possible or acceptable, is to change the human genome in a heritable way. Instead of devising costly drugs or therapies to treat the same diseases in each generation, why not go straight to the source and fix all known errant genes in the egg or sperm? Germ line genetic engineering, as it is called, would make permanent fixes to be passed from one generation to another. Advocates argue that however expensive it might be to produce each perfect baby, the cost would be a fraction of the lifetime health care otherwise needed.

Such proposals arouse serious ethical concerns, from religious objections to interventions that seem to usurp a creator's role, to biologists' fears that genetic manipulation will subvert the essence of human nature.

The DNA revolution is likely to present many such quandaries. It will increasingly provide the means to repair and improve the machinery of life. But human ideas for redesign, which might include items like perfect health and greater longevity, have little in common with evolution's procedure of natural selection, which thrives on mutation and mortality.

Like all technology, DNA may have military uses. Though it is hard to improve on the deadliness of natural scourges, that does not mean it will always be impossible. "If we manage not to exploit biology for hostile purposes it will be the first time our species has ever refrained from such exploitation," says Dr. Matthew Meselson, a founder of molecular biology who has long worried about biological warfare. "And if we don't refrain, I don't know how to predict what course it would take. There is only one human species."

Biologists recognize the depth of public concerns about genetic engineering. Yet most hope that public can be educated to make what they regard as the right choices. Dr. Watson was among the group of scientists who warned in 1974 of the possible dangers of recombinant DNA, the technique that first allowed genes to be moved from one species to another. At the Asilomar conference the next year scientists imposed voluntary restrictions on experiments while the possible hazards were assessed.

Though Dr. Watson soon decided those dangers were overblown, he still believes that scientists should talk frankly about the possibilities, good and bad, of their work.

"It is far better to tell it as it is and take the risk," he said. "We should expect a constant concern from society as to where our knowledge is leading and whether to deploy it. That certainly existed in the past, for instance in the opposition to automobiles. But once you put someone in an auto you won't get them on a horse."

Dr. Watson has recently become an advocate for being open to the idea of germ line genetic engineering. "Some think there is something wrong about enhancing people," he said. Dr. Crick, who has worked for the last 25 years on the problem of consciousness, says he does not expect it will yield to any sudden breakthrough. "At the origin of life things had to be simple," he said. "But when you come to consciousness it's probably a very late development in evolution."

Both at the beginning of life and at its culmination, DNA has more to tell.