Dig Deeper into the Discovery of DNA

Happy National DNA Day[1], which commemorates the successful completion of the Human Genome Project in 2003 and the discovery of DNA’s double helix in 1953.

Published sixty-four years ago in the journal Nature, James Watson and Francis Crick’s description of the double helix transformed our understanding of life. The paper is concise—only 128 lines—but behind each line is a story. We’ve annotated the paper, filling in the space between the lines to shed light on the personalities, politics, competition, and collaboration that fueled this discovery.

This article is from our classic online collection. It was created as part of our Origins[2] project, which explored the extraordinary places, people, tools, and ideas behind the search for the origins of matter, the universe, and life itself.

Follow the links to our annotations.

To demonstrate the DNA structure in detail, Watson and Crick built a large model of the molecule.

Credit: A. C. Barrington Brown. Photo Researchers, Inc./Science Photo Library

reprinted with permission from Nature magazine

J. D. Watson and F. H. C. Crick (1)[3]

April 25, 1953 (2)[4], Nature (3)[5], 171, 737-738

We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.

A structure for nucleic acid has already been proposed by Pauling (4) [6] and Corey1. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfactory for two reasons:

(1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other.

(2) Some of the van der Waals distances appear to be too small.

Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defined, and for this reason we shall not comment on it.

We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid (5)[7]. This structure has two helical chains each coiled round the same axis (see diagram). We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining beta-D-deoxyribofuranose residues with 3′,5′ linkages. The two chains (but not their bases) are related by a dyad perpendicular to the fibre axis. Both chains follow right-handed helices, but owing to the dyad the sequences of the atoms in the two chains run in opposite directions (6) [8]. Each chain loosely resembles Furberg’s2 model No. 1 (7)[9]; that is, the bases are on the inside of the helix and the phosphates on the outside. The configuration of the sugar and the atoms near it is close to Furberg’s “standard configuration,” the sugar being roughly perpendicular to the attached base. There is a residue on each every 3.4 A. in the z-direction. We have assumed an angle of 36° between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is, after 34 A. The distance of a phosphorus atom from the fibre axis is 10 A. As the phosphates are on the outside, cations have easy access to them.

The structure is an open one, and its water content is rather high. At lower water contents we would expect the bases to tilt so that the structure could become more compact.

The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases. The planes of the bases are perpendicular to the fibre axis. They are joined together in pairs, a single base from one chain being hydroden-bonded to a single base from the other chain, so that the two lie side by side with identical z-coordinates. One of the pair must be a purine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine position 6.

If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms (that is, with the keto rather than the enol configurations) it is found that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine) (9)[10].

In other words, if an adenine forms one member of a pair, on either chain, then on these assumptions the other member must be thymine; similarly for guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if only specific pairs of bases can be formed, it follows that if the sequence of bases on one chain is given, then the sequence on the other chain is automatically determined.

It has been found experimentally (10)3,4[11] that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribose nucleic acid.

It is probably impossible to build this structure with a ribose sugar in place of the deoxyribose, as the extra oxygen atom would make too close a van der Waals contact.

The previously published X-ray data5,6 on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications (11)[12]. We were not aware of the details of the results presented there when we devised our structure (12)[13], which rests mainly though not entirely on published experimental data and stereochemical arguments.

It has not escaped our notice (13)[14] that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.

Full details of the structure, including the conditions assumed in building it, together with a set of coordinates for the atoms, will be published elsewhere (14)[15].

We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances. We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King’s College, London (15)[16]. One of us (J. D. W.) has been aided by a fellowship from the National Foundation for Infantile Paralysis.

1 Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc. U.S. Nat. Acad. Sci., 39, 84 (1953).
2 Furberg, S., Acta Chem. Scand., 6, 634 (1952).
3 Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff, E., Biochim. et Biophys. Acta, 9, 402 (1952).
4 Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952).
5 Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ. Press, 1947).
6 Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta, 10, 192 (1953).


(1) It’s no surprise that James D. Watson and Francis H. C. Crick spoke of finding the structure of DNA within minutes of their first meeting at the Cavendish Laboratory in Cambridge, England, in 1951. Watson, a 23-year-old geneticist, and Crick, a 35-year-old former physicist studying protein structure for his doctorate in biophysics, both saw DNA’s architecture as the biggest question in biology. Knowing the structure of this molecule would be the key to understanding how genetic information is copied. In turn, this would lead to finding cures for human diseases.

Aware of these profound implications, Watson and Crick were obsessed with the problem—and, perhaps more than any other scientists, they were determined to find the answer first. Their competitive spirit drove them to work quickly, and it undoubtedly helped them succeed in their quest.

Watson and Crick’s rapport led them to speedy insights as well. They incessantly discussed the problem, bouncing ideas off one another. This was especially helpful because each one was inspired by different evidence. When the visually sensitive Watson, for example, saw a cross-shaped pattern of spots in an X-ray photograph of DNA, he knew DNA had to be a double helix. From data on the symmetry of DNA crystals, Crick, an expert in crystal structure, saw that DNA’s two chains run in opposite directions.

Since the groundbreaking double helix discovery in 1953, Watson has used the same fast, competitive approach to propel a revolution in molecular biology. As a professor at Harvard in the 1950s and 1960s, and as past director and current president of Cold Spring Harbor Laboratory, he tirelessly built intellectual arenas—groups of scientists and laboratories—to apply the knowledge gained from the double helix discovery to protein synthesis, the genetic code, and other fields of biological research. By relentlessly pushing these fields forward, he also advanced the view among biologists that solving major health problems requires research at the most fundamental level of life.

(2) On this date, Nature published the paper you are reading.

According to science historian Victor McElheny of the Massachusetts Institute of Technology, the publication of this paper helped change how scientists approached biology. Increasingly in the 1950s, biologists were working out the fundamental mechanisms of life—an undertaking that involved figuring out how genetic information is stored and transmitted. The discovery of the double-helix structure of DNA gave momentum to this kind of work.

Historians wonder how the timing of the DNA race affected its outcome. After years of being diverted by the war effort, scientists were able to focus more on problems such as those affecting human health. Yet, in the United States, many research fields were threatened by a curb on the free exchange of ideas. During the McCarthy era in the early 1950s, the U.S. State Department denied American researcher Linus Pauling a passport to travel internationally. Some think Pauling might have beaten Watson and Crick to the punch if Pauling’s ability to travel had not been hampered.

(3) Nature (founded in 1869)——and hundreds of other scientific journals—help push science forward by providing a venue for researchers to publish and debate findings. Today, journals also validate the quality of this research through a rigorous evaluation called peer review. Generally at least two scientists, selected by the journal’s editors, judge the quality and originality of each paper, recommending whether or not it should be published.

Science publishing was a different game when Watson and Crick submitted this paper to Nature. With no formal review process at most journals, editors usually reached their own decisions on submissions, seeking advice informally only when they were unfamiliar with a subject.

(4) The effort to discover the structure of DNA was a race among several players: world-renowned chemist Linus Pauling at the California Institute of Technology, X-ray crystallographers Maurice Wilkins and Rosalind Franklin at King’s College London, and Watson and Crick at the Cavendish Laboratory, Cambridge University.

The competitive juices were flowing well before the DNA sprint was in high gear. In 1951, Pauling narrowly beat scientists at the Cavendish Lab, a top center for probing protein structure, to the discovery that proteins are arranged in structures called alpha-helices. The defeat stung. When Pauling sent a paper to be published in early 1953 that proposed a three-stranded DNA structure, Sir Lawrence Bragg—the head of Cavendish—gave Watson and Crick permission to work full-time on DNA’s structure. Cavendish was not about to lose to Pauling twice.

Pauling’s proposed three-stranded helix had the bases facing out. While the model was wrong, Watson and Crick were sure Pauling would soon learn his error. They estimated that he was six weeks away from the right answer. Electrified by the urgency—and by the prospect of beating a science superstar—Watson and Crick spent four weeks obsessing about DNA in endless conversations and bouts of model-building to arrive at the correct structure.

In 1952, Wilkins and the head of the King’s laboratory denied Pauling’s request to view their X-ray photos of DNA—crucial evidence that inspired Watson’s vision of the double helix. Pauling had to settle for inferior older photographs. In the same year, he was planning to attend a science meeting in London, where he most likely would have renewed his request in person. But it was the McCarthy era, and the U.S. State Department denied Pauling’s request for a passport because of his “un-American” antiwar activism. It was fitting, then, that Pauling, who won the Nobel Prize in Chemistry in 1954, also won the Nobel Peace Prize in 1962, the same year Watson, Crick, and Maurice Wilkins won their Nobel Prize for discovering the double helix.

(5) Here, the young scientists Watson and Crick call their model “radically different” to strongly set it apart from the model proposed by science powerhouse Linus Pauling. This claim was justified. While Pauling’s model was a triple helix with the bases sticking out, the Watson-Crick model was a double helix with the bases pointing in and forming pairs of adenine (A) with thymine (T), and cytosine (C) with guanine (G).

(6) This central description of the double-helix model still stands today—a monumental feat considering that the vast majority of research findings are changed over time.

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