Molecular Structure of Nucleic Acids: The DNA Double Helix

By early 1953, several laboratories were competing to determine the structure of deoxyribonucleic acid. Linus Pauling at Caltech had proposed a triple-helix model, later shown to be incorrect. At Cambridge, James Watson, a 24-year-old American biologist, and Francis Crick, a physicist-turned-structural biologist, were building physical models using known bond angles and Erwin Chargaff's 1950 finding that DNA contains equal amounts of adenine and thymine, and of guanine and cytosine.

Two pieces of evidence came from X-ray diffraction work at King's College London. In May 1952 Rosalind Franklin and her graduate student Raymond Gosling had taken a very clear photograph of the B form of DNA, labeled 51, and Franklin had concluded that the phosphate backbone lay on the outside of the molecule. Gosling gave the photograph to Maurice Wilkins, who showed it to Watson without Franklin's knowledge, and Max Perutz passed Watson and Crick a Medical Research Council report with her unpublished measurements. They built these data into their model and published a one-page letter in Nature on April 25, 1953. The same issue carried papers from Wilkins's group and from Franklin and Gosling.

Because each strand was the complement of the other, the sequence of one strand specified the other entirely. Watson and Crick ended their letter by noting that "it has not escaped our notice" that the pairing suggested a possible copying mechanism for the genetic material. Each strand could act as a template for a new complementary strand, producing two identical double helices from one.

Watson, Crick, and Wilkins shared the Nobel Prize in Physiology or Medicine in 1962. Franklin had died of ovarian cancer in London on April 16, 1958, at age 37; only two Nobel Prizes had ever been awarded posthumously, and a formal ban followed in 1974. None of the three laureates credited her contribution at the time. Her role became widely known after Watson caricatured her in his 1968 memoir, The Double Helix.

The model set off a decade of rapid discovery. In 1961 Crick, Sydney Brenner, and colleagues reported that the genetic code is read in groups of three bases, and that August Marshall Nirenberg announced in Moscow that he and Heinrich Matthaei had cracked the first word of the code. By the late 1960s, the mechanisms of transcription and translation were broadly understood, and recombinant DNA methods followed in the 1970s.