DNA, the Keeper of Life's Secrets, Starts to Talk

By NICHOLAS WADE

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  evolution 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.