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Genes, by mid-twentieth century, were located to the chromosomes, known to be composed of protein and deoxyribonucleic acid, or DNA. The discovery of its molecular structure, by Francis Crick and James Watson, immediately suggested that DNA—not a protein, as was widely imagined—was the master molecule that contains the genes, self-replicates and recombines during reproduction.

James D. Watson Courtesy Bill Geddes

In 1951 Crick, a graduate student at Cavendish Laboratory in Cambridge, began working informally with the American post-doctorate James Watson. Crick had trained in physics and was engaged in X-ray studies to characterize biological molecules. Watson had studied with Salvador Luria, a pioneer in bacterial genetics. Both Crick and Watson were explicitly motivated to investigate DNA by suspicion of its fundamental significance.

For about two years Crick and Watson worked together without success. Emulating the eminent chemist Linus Pauling, who had made an important but failed effort to describe DNA, they began building three-dimensional models, using cardboard cutouts and sheet metal to represent the molecule's chainlike structure. They were aware that DNA might have the general, winding shape of a helix. But how DNA's four bases (adenine, guanine, thymine, and cytosine) were arranged around a sugar and phosphate backbone remained a mystery.

On February 21, 1953, Watson had the key insight. He recognized how two pairs of complementary bases (adenine-thymine and guanine-cytosine) would have identical shapes if held together by hydrogen bonds. Two long chains of such base pairs would likely form a double helix—roughly, the shape of an enormously long, winding, doubled-railed staircase. The DNA molecule, comprised of long strands of such base pairs in specific and varied sequences, could embed genetic information that, if the strands were separated, could be copied.

Francis H. C. Crick Courtesy The Salk Institute

Indeed, with Crick and Watson's discovery, together with evidence acquired over the previous decade, the implication that DNA contained the genes was immediately apparent. On April 25, 1953, Nature published their brief communication, in which they famously noted that "the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Crick and Watson elaborated with a longer paper several weeks later.

Subsequent work made it abundantly clear that DNA, indeed a double helix, was the chemical substance of genes. In 1962 Crick and Watson were awarded the Nobel Prize in Physiology or Medicine, shared with Maurice Wilkins, whose work with Rosalind Franklin on X-ray crystallography had provided crucial evidence.

Discovery of the structure of DNA was the keystone to a half-century of research that initiated a scientific revolution. Biology acquired a molecular and biochemical basis, and research into DNA brought forth new technologies that illuminated the complex chemistry of protein synthesis and reproduction.

Francis Crick became one of the chief investigators of molecular biology through the mid-1970s, before turning to work in neurobiology. James Watson, an eminent figure in genetics research in the United States, became head of Cold Spring Harbor Laboratory and, for a time during the late 1980s, of the Office of Human Genome Research of the National Institutes of Health.

James D. Watson & Francis H. C. Crick winners of the 1960 Albert Lasker Award for Basic Medical Research

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