The Winning Discovery

New Zealand-born biophysicist Maurice Wilkins led the laboratory at King's College, London, that competed with Watson and Crick in the race to discover the structure of DNA. (National Library of Medicine, photo B09719)

"In the process of [scientific] discovery," N. A. Tiley's book on key DNA research, Discovering DNA, quotes eminent modern science historian Horace Freeland Judson as saying, "there comes a unique moment: where great confusion reigned, the shape of an answer springs out—or at least the form of a question." Great confusion certainly reigned in the DNA race at the start of 1953. Watson and Crick had made a preliminary guess about DNA's structure in late 1952, but Rosalind Franklin had shown that they were wrong. Franklin, in turn, insisted that the molecule could not have the overall shape of a helix, which also proved to be a mistake. Finally, Linus Pauling announced in January 1953 that the DNA molecule contained three helix-shaped backbones. That conclusion was quickly shown to be incorrect as well.

For James Watson, the shape of the answer to the DNA puzzle began to appear on January 30, 1953, when he visited Maurice Wilkins at King's College. Even though the two men were rivals in the DNA race, they had become friends. During this visit, Wilkins showed Watson an X-ray photograph that Rosalind Franklin had made of DNA. As Watson looked at this picture, which was clearer than any others he had seen, "my mouth fell open and my pulse began to race," he wrote later in his memoir of the DNA discovery, The Double Helix. He realized that the DNA molecule most likely had two parallel, helix-shaped backbones.

Watson hurried back to Cambridge and described the photo to Crick. With the question of the backbones answered to their satisfaction, the pair turned their attention to the second major question: how the bases were arranged within the molecule. Crick concluded

Solving Problems: X-Ray Crystallography

British physicist Lawrence Bragg invented X-ray crystallography in 1912. In this technique, a beam of X-rays is passed through a solid. Some of the rays bounce off atoms in the molecules within the solid, thereby changing the angles at which the rays strike a photographic plate on the other side of the solid. A photograph made from the plate shows a pattern of dark dots or smears on a light background. Interpreted by experts, photos of this kind reveal information about the three-dimensional placement of atoms within molecules—in other words, the molecules' structure.

At first, Bragg and his followers applied X-ray crystallography only to solids that had an orderly structure, which let the solids form crystals. In 1934, however, Desmond Bernal and W. T. Astbury, two other British scientists, showed how to use the technique to analyze substances with large, complex molecules that cannot form crystals, such as proteins and nucleic acids. Rosalind Franklin was a specialist in this new type of X-ray crystallography.

Franklin and other experts such as Dorothy Crowfoot Hodgkin used X-ray crystallography to work out the structure of many important biological molecules, including cholesterol and penicillin, during the late 1930s and 1940s. They became able to unravel even more complex substances in the 1950s, when computers took over the difficult mathematical calculations involved in interpreting the X-ray photographs.

that the bases must be inside the backbones, stretching between them like steps on a twisted ladder. At first, Watson thought the bases might appear as pairs of the same kind of molecule—adenine and adenine, for example. That did not fit what was known about the size of the space between the backbones, however.

Too impatient to wait for new metal models to be built, Watson cut model pieces from cardboard and began trying different arrangements. Two of the bases, adenine and guanine, were larger than the other two. Pairs of large bases were too big to fit between the intertwined backbones, and pairs of the smaller bases were too small. As Watson played with his cardboard cutouts, however, he noticed that a pair consisting of adenine, a large base, and thymine, a small one, had exactly the same size and shape as a pair made up of gua-nine and cytosine. Both types of pair fit nicely if placed horizontally between the two vertical backbones, just as Crick had suggested. A pairing of adenine with thymine and guanine with cytosine would also fit with Erwin Chargaff's finding about the proportions of bases in the DNA molecule. Bonds between the bases' hydrogen atoms could hold the pairs together, Watson believed.

As soon as Crick came into their shared office on the morning of February 28, Watson showed him the matching cardboard base pairs. Crick saw immediately that Watson's discovery meant that the sequence, or order, of the bases along the two backbones was complementary. If a person knew the sequence of bases attached to one backbone, the order of bases along the other could be predicted.

Watson and Crick wrote a short scientific paper that described their proposed structure. The paper appeared in the prestigious British science journal Nature on April 25, 1953. Only one understated sentence near the end of the report hinted at the discovery's importance: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

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