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Genetics & Molecular · 1953

Molecular Structure of Nucleic Acids: The DNA Double Helix

Diagram of the DNA double helix
Public domain (Wikimedia Commons)

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 geneticist, and Francis Crick, a physicist-turned-structural biologist, were building physical models using known bond angles and the base-pairing rules Erwin Chargaff had established: adenine always paired with thymine in equal amounts, and guanine with cytosine.

The critical piece came from X-ray diffraction work at King's College London. Rosalind Franklin had produced an exceptionally clear diffraction photograph, her Pattern B image, that defined the helix repeat distance and the position of the phosphate backbone on the outside of the molecule. Maurice Wilkins showed this image to Watson without Franklin's knowledge. Watson and Crick incorporated its dimensions into their model, publishing a one-page letter in Nature on April 25, 1953. The same issue carried supporting papers from Wilkins and from Franklin.

The structural logic of the model was immediately apparent to biologists. Because each strand was the complement of the other, the sequence of one strand specified the other entirely. The mechanism by which a cell could copy its genetic information was, as Watson and Crick noted with deliberate understatement, "not escaped our notice." Each strand could serve as a template for synthesizing 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 April 1958, at age 37, and Nobel rules barred posthumous awards. Her contribution was not fully acknowledged publicly until decades later; debates about the circumstances under which Watson saw her data continued well into the twenty-first century.

The structural model triggered a decade of rapid discovery. By 1961, Crick, Sydney Brenner, and others had established that the genetic code was read in triplet codons. Marshall Nirenberg cracked the first codon the same year. By the late 1960s, the mechanisms of transcription and translation were broadly understood, and the conceptual and technical groundwork for recombinant DNA manipulation in the 1970s followed directly from the base-pair logic the 1953 paper established.

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Read the original — PubMed

Nature, 1953

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