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s was normal for a Saturday morning, I got to work at Cambridge University's Cavendish Laboratory earlier than Francis Crick on February 28, 1953. I had good reason for being up early. I knew that we were close—though I had no idea just how close—to figuring out the structure of a then little-known molecule called deoxyribonucleic acid: DNA. This was not any old molecule: DNA, as Crick and I appreciated, holds the very key to the nature of living things. It stores the hereditary information that is passed on from one generation to the next, and it orchestrates the incredibly complex world of the cell. Figuring out its 3-D structure—the molecule's architecture— would, we hoped, provide a glimpse of what Crick referred to only half-jokingly as “the secret of life.”
We already knew that DNA molecules consist of multiple copies of a single basic unit, the nucleotide, which comes in four forms: adenine (A), thymine (T), guanine (G), and cytosine (C). I had spent the previous afternoon making cardboard cutouts of these various components, and now, undisturbed on a quiet Saturday morning, I could shuffle around the pieces of the 3-D jigsaw puzzle. How did they all fit together? Soon I realized that a simple pairing scheme worked exquisitely well: A fitted neatly with T, and G with C. Was this it? Did the molecule consist of two chains linked together by A-T and G-C pairs? It was so simple, so elegant, that it almost had to be right. But I had made mistakes in the past, and before I could get too excited, my pairing scheme would have to survive the scrutiny of Crick's critical eye. It was an anxious wait. But I need not have worried: Crick realized straightaway that my pairing idea implied a double-helix structure with the two molecular chains running in opposite directions. Everything known about DNA and its properties—the facts we had been wrestling with as we tried to solve the problem—made sense in light of those gentle complementary twists. Most important, the way the molecule was organized immediately suggested solutions to two of biology's oldest mysteries: how hereditary information is stored, and how it is replicated. Despite this, Crick's brag in the Eagle, the pub where we habitually ate lunch, that we had indeed discovered that “secret of life,” struck me as somewhat immodest, especially in England, where understatement is a way of life.
Crick, however, was right. Our discovery put an end to a debate as old as the human species: Does life have some magical, mystical essence, or is it, like any chemical reaction carried out in a science class, the product of normal physical and chemical processes? Is there something divine at the heart of a cell that brings it to life? The double helix answered that question with a definitive No.
Charles Darwin's theory of evolution, which showed how all of life is interrelated, was a major advance in our understanding of the world in materialistic— physicochemical—terms. The breakthroughs of biologists Theodor Schwann and Louis Pasteur during the second half of the nineteenth century were also an important step forward. Rotting meat did not spontaneously yield maggots; rather, familiar biological agents and processes were responsible—in this case egg-laying flies. The idea of spontaneous generation had been discredited.
Despite these advances, various forms of vitalism—the belief that physico-chemical processes cannot explain life and its processes—lingered on. Many biologists, reluctant to accept natural selection as the sole determinant of the fate of evolutionary lineages, invoked a poorly defined overseeing spiritual force to account for adaptation. Physicists, accustomed to dealing with a simple, pared-down world—a few particles, a few forces—found the messy complexity of biology bewildering. Maybe, they suggested, the processes at the heart of the cell, the ones governing the basics of life, go beyond the familiar laws of physics and chemistry.
That is why the double helix was so important. It brought the Enlighten-ment's revolution in materialistic thinking into the cell. The intellectual journey that had begun with Copernicus displacing humans from the center of the uni verse and continued with Darwin's insistence that humans are merely modified monkeys had finally focused in on the very essence of life. And there was nothing special about it. The double helix is an elegant structure, but its message is downright prosaic: life is simply a matter of chemistry.
Crick and I were quick to grasp the intellectual significance of our discovery, but there was no way we could have foreseen the explosive impact of the double helix on science and society. Contained in the molecule's graceful curves was the key to molecular biology, a new science whose progress over the subsequent fifty years has been astounding. Not only has it yielded a stunning array of insights into fundamental biological processes, but it is now having an ever more profound impact on medicine, on agriculture, and on the law. DNA is no longer a matter of interest only to white-coated scientists in obscure university laboratories; it affects us all.
By the mid-sixties, we had worked out the basic mechanics of the cell, and we knew how, via the “genetic code,” the four-letter alphabet of DNA sequence is translated into the twenty-letter alphabet of the proteins. The next explosive spurt in the new science's growth came in the 1970s with the introduction of techniques for manipulating DNA and reading its sequence of base pairs. We were no longer condemned to watch nature from the sidelines but could actually tinker with the DNA of living organisms, and we could actually read life's basic script. Extraordinary new scientific vistas opened up: we would at last come to grips with genetic diseases from cystic fibrosis to cancer; we would revolutionize criminal justice through genetic fingerprinting methods; we would profoundly revise ideas about human origins—about who we are and where we came from—by using DNA-based approaches to prehistory; and we would improve agriculturally important species with an effectiveness we had previously only dreamed of.
But the climax of the first fifty years of the DNA revolution came on Monday, June 26, 2000, with the announcement by U.S. president Bill Clinton of the completion of the rough draft sequence of the human genome: “Today, we are learning the language in which God created life. With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal.” The genome project was a coming-of-age for molecular biology: it had become “big science,” with big money and big results. Not only was it an extraordinary technological achievement—the amount of information mined from the human complement of twenty-three pairs of chromosomes is staggering—but it was also a landmark in terms of our idea of what it is to be human. It is our DNA that distinguishes us from all other species, and that makes us the creative, conscious, dominant, destructive creatures that we are. And here, in its entirety, was that set of DNA—the human instruction book.
DNA has come a long way from that Saturday morning in Cambridge. However, it is also clear that the science of molecular biology—what DNA can do for us—still has a long way to go. Cancer still has to be cured; effective gene therapies for genetic diseases still have to be developed; genetic engineering still has to realize its phenomenal potential for improving our food. But all these things will come. The first fifty years of the DNA revolution witnessed a great deal of remarkable scientific progress as well as the initial application of that progress to human problems. The future will see many more scientific advances, but increasingly the focus will be on DNA's ever greater impact on the way we live.
The key to Mendel's triumph: genetic variation in pea plants