Their names are permanently linked--to each other and to the molecule whose structure they proposed. They have become so tightly woven into the fabric of biology that it hardly seems possible that they proposed their model only 50 years ago: James D. Watson and Francis H. C. Crick published their structure of B-form DNA in a letter in the April 25, 1953, issue of Nature.

	LUCKY PAIR Crick (left) and Watson relax after the publication of their letter to Nature. A. BARRINGTON BROWN/PHOTO RESEARCHERS INC.

Biologists Watson and Crick described a molecule in which two strands of nucleotides running in opposite directions coil around a central axis in a right-handed helix. The bases on one chain form hydrogen-bonded pairs with the bases on the other, but only in specific combinations. The purine adenine always pairs with the pyrimidine thymine; similarly, guanine pairs with cytosine.

Watson and Crick deserve credit for figuring out--some might say guessing--the structure of DNA, but not for any of the experimental work. Instead, they gathered information from a variety of sources and made the leap to a model of DNA, following the path that Caltech chemist Linus Pauling had taken in solving the structure of the protein a-helix.

Watson and Crick weren't supposed to be working on the structure of DNA. That distinction belonged to researchers at King's College London, most notably crystallographer Rosalind E. Franklin and biophysicist Maurice Wilkins. After a first failed attempt at a model of DNA, Sir Lawrence Bragg, the director of the Cavendish Laboratory at the University of Cambridge, forbade Watson and Crick to work on DNA, but they continued to contemplate the problem anyway.

They were able to figure out the structure by combining knowledge of the chemical composition of the nucleosides with X-ray diffraction patterns obtained by Franklin. From Franklin's work, Watson and Crick knew that the vertical spacing between the stacked base pairs was 3.4 Å and that each turn of the helix was 34 Å or 10 base pairs, with a helical slope of about 40°.

They needed to figure out how many strands were involved and where the bases fit. A key step in figuring out the structure was the recognition of the correct tautomeric form of the bases. Watson and Crick had been working with models of the enol forms of the bases. Jerry Donohue, an American crystallographer who shared an office with them, was able to tell them that the bases would most likely be in the keto form in water.

Once Watson started working with models of the correct tautomers, he realized that the base pairs of adenine-thymine and guanine-cytosine could be held together by at least two hydrogen bonds (C-G was later found to be held together by three) and that the pairs were identical in shape. This base pairing explained regularities of composition discovered by Columbia University biochemist Erwin Chargaff, in which the ratios of adenine to thymine and guanine to cytosine are always approximately 1.

"To organic chemists at the time, it was highly surprising that it was possible at all to get such a detailed picture of a biopolymer as presented in the double helix," says Albert Eschenmoser, chemistry professor at Scripps Research Institute and emeritus professor at the Swiss Federal Institute of Technology, Zurich. "The view of Watson and Crick of the structure of DNA was as close and as detailed as the organic chemists at that time had become able to look at the conformations of their small natural-product molecules."

Watson, Crick, and Wilkins shared the 1962 Nobel Prize in Medicine or Physiology for the discovery of the double helix. Watson is now president of Cold Spring Harbor Laboratory in Long Island, N.Y.; Crick is a distinguished research professor at the Salk Institute for Biological Studies, La Jolla, Calif.; and Wilkins is an emeritus professor at King's College.

"In retrospect, the impact of the advent of the DNA double helix on science is so enormous that contributions of others who made Watson and Crick's model possible are often overlooked," Eschenmoser says. Some of those who are often left standing in the shadows include Oswald T. Avery, the Rockefeller Institute researcher who determined in 1944 that DNA is the genetic material; Chargaff, who determined that the adenine:thymine and guanine: cytosine ratios are 1; and Franklin, whose X-ray diffraction data Watson and Crick used without her knowledge or permission. A name often forgotten is that of Rudolf Signer, who provided the high-quality DNA fibers for Franklin's diffraction experiments.

"What, then, do Jim Watson and I deserve credit for?" Crick asks in "What Mad Pursuit," his 1988 memoir. "The major credit I think Jim and I deserve, considering how early we were in our research careers, is for selecting the right problem and sticking to it. It's true that by blundering about we stumbled on gold, but the fact remains that we were looking for gold."

MATCHED SETS The bases in DNA form specific hydrogen-bonding pairs, adenine with thymine and guanine with cytosine.

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