The Double Helix Revisited

By James Watson

None of us so privileged few who first saw the double helix in the spring of 1953 ever contemplated that we might in our lifetime see it completely decoded. All our dreams at the time centered on the next big objective--finding how the four letters of the DNA alphabet (A, T, G and C) spell out the linear sequences of amino acids in the synthesis of proteins, the main actors in the drama of cellular life. As it turns out, the essence of the genetic code and of the molecular machinery that reads it was solidly established by 1966, only 13 years after Francis Crick and I discovered the double helix.

Then the creative juices of science turned to how to read the messages of DNA. To our surprise, Frederick Sanger at Cambridge University and Walter Gilbert at Harvard, working independently, needed less than a decade to develop powerful methods for determining the order of DNA letters. At roughly the same time, Herbert Boyer and Stanley Cohen devised elegantly simple procedures for cutting and rejoining DNA molecules to produce "recombinant DNA."

Then voices of doom proclaimed that these procedures would create life forms as threatening to our existence as nuclear weapons. Such false alarms held us back only a few years, however. By 1980 the immense powers of recombinant DNA were let loose for the public good. Soon they were to change irreversibly the faces of biology and medicine and bring modern biotechnology into existence.

It was my desire to help speed up human genetics that drove me in 1986 to become an early partisan of the Human Genome Project, whose ultimate objective was to sequence the roughly 3 billion DNA letters that comprise our genetic code. Though many young hot-shots argued that the time for the project had not yet arrived, those of us a generation older were seeing at too close hand our parents and spouses falling victim to diseases of genetic predisposition. And virtually all of us knew couples rearing children whose future was clouded by a bad throw of the genetic dice. So the National Academy of Sciences assembled an expert committee that reported one year later that the human instruction book could be established within 15 years--if we assembled the appropriate scientific leadership and gave it $3 billion to spend wisely over those 15 years.

Our first report emphasized that we should begin by sequencing the relatively tiny genomes (1 million to 13 million letters) of bacteria and yeast and then move on to the 100 million-letter-size genomes of worms and flies. We were confident that by the time we were done, sequencing technology would cost less than 50[cents] a letter, and that by then, we would be ready to tackle the human genome. We were also confident that genomics would pay scientific and medical dividends long before the final letters of the human genome were in place.

So when I went up to Capitol Hill in May 1987 with the N.A.S. report in hand, I promised that long before the genome project was completed we would have cloned many of the key genes predisposing humans to Alzheimer's or to cancers of the breast and colon, all diseases known to run in families. Happily, time has seen our science so move.

Congress accepted this message much faster than many of my fellow molecular biologists, soon appropriating moneys that let the genome project start with a bang. In October 1988, I went to Washington to direct the National Institutes of Health's major role in the effort. From the start, I worked to ensure that the project was an international one, supported by all the major countries of the developed world. That way no one nation or private body would be perceived as controlling the human genome. We also wanted all the data placed on the Internet so that they would be available, free of cost, all over the world.

Today those involved in the international consortium take pride in posting their new DNA sequences on the Web within 24 hours of assembly. Twelve years ago, no one could have imagined that nearly 500 million base pairs of assembled DNA would be posted in just one month.

With the project essentially complete three years ahead of schedule, we must note the change of heart of its early enemies. Instead of wanting us shut down, as they did as late as 1991, they now beg us to move quickly on to the genomes of the mouse, the rat and the dog. Equally important, we note that no other big science project, save possibly the Manhattan Project, has been carried out with such zeal for the common good. In sharing their sequences so freely and so quickly, members of our genome community have little time left to promote their scientific reputations.

By contrast, the large infusions of private capital over the past two years support companies that aim to find and patent key DNA sequences before they become publicly available. Not surprisingly, the leaders of these companies have implied that those of us who started the project were no longer needed. To our vast relief, the publicly supported effort received not less but more money. Our backers want to ensure that all the essential features of the human genome are available without cost to all the people of the world. The events of the past few weeks have shown that those who work for the public good do not necessarily fall behind those driven by personal gain.