Francis Crick

Almost ten years earlier, it had been shown that genes encode proteins, but the chemical nature of the gene remained unknown. Genes were presumed to be composed of DNA (deoxyribonucleic acid), at least in part, but how DNA might encode hereditary information, and whether it acted alone or in partnership with proteins, was a complete mystery. Crick saw that the solution to the mystery lay in discovering the structure of DNA, whose linearity he guessed corresponded to the linear amino acid chains of which proteins are made.

In 1951 a 23-year-old American named James Watson joined the Cavendish Laboratory. Watson and Crick got along well, and they decided to work together on the structure of DNA. DNA was known to be composed of nucleotide subunits, each of which had a sugar (deoxyribose), a phosphate, and a nitrogenous base. The sugars were known to alternate with phosphates to make long strands, off of which the bases projected. The bases came in four types: adenine, thymine, cytosine, and guanine (A, T, C, and G). Shortly before Crick and Watson began to collaborate, American biochemist Erwin Chargaff had discovered that across a wide range of species, the amount of adenine in an organism's DNA always equaled the amount of thymine, and the amount of cytosine always equaled the amount of guanine.

Crick and Watson proceeded to build models of the nucleotides, which they attempted to fit together in accordance with what was known from experimental data. The most important data came from X-ray images of DNA that had been generated by Rosalind Franklin, who also worked at the Cavendish. Using this information, they constructed a model in which the two sugar-phosphate strands wind around each other to form a double helix, their bases projecting inward, like the stair treads of a broad spiral staircase. The two strands are held together and stabilized by the hydrogen bonding between the bases across the interior. These weak chemical attractions, they discovered, are strongest when adenine projects across to meet a thymine, and guanine a cytosine, explaining the ratios discovered by Chargaff. They published their model in 1953. Watson and Crick received the Nobel Prize in physiology or medicine in 1962 for this work, along with Maurice Wilkins of the Cavendish Lab.

After the publication of DNA's structure, Crick turned his attention to understanding the coding function of DNA. He and Watson proposed that the order of bases in a gene encoded the order of amino acids in a protein. Over the next decade, the details of this insight were worked out by a large group of scientists, including Crick, Watson, Sydney Brenner, George Gamow, Seymour Benzer, Marshall Nirnberg, and Har Gobind Khorana. As part of this work, Crick hypothesized the existence of an "adaptor" that intervened between DNA and amino acids. This led to the discovery of messenger RNA and transfer RNA, which serve this function.