Helical structure of crystalline deoxypentose nucleic acid. Offprint from: Nature, Vol. 172, No. 4382, October 24, 1953.

[London: Macmillan, 1953].

First edition, extremely rare separately-paginated offprint (journal pagination 759-762), in which Wilkins and his colleagues gave the first analytical demonstration of the general correctness of the double-helix structure of DNA put forward by Crick and Watson six months earlier. “After the publication in Nature by the two groups [Watson-Crick at Cambridge and Wilkins’ group at King’s College, London] in [April] 1953, Wilkins proved that the Watson-Crick model was unique – that is, no other model would give the same diffraction patterns. His data also allowed Wilkins to readjust and refine the Watson-Crick model” (Magill, p. 3997). “Exact information about the molecular configuration of deoxypentose nucleic acid may well serve as the basis for understanding its biological function. It has been shown by X-ray diffraction that molecules of deoxyribonucleic acid (in the form of sodium salt) exist probably in a helical configuration when in the paracrystalline state. Proof of the helical structure would be difficult to obtain from the two-dimensional view of the molecule provided by study of the paracrystalline material. The regularity of the molecule is so great, however, that it may be crystallized in fibres with a remarkably high degree of molecular order, and X-ray study of oriented crystalline deoxyribonucleic acid has enabled a three-dimensional view of the geometry of the molecule to be obtained. The purpose of this article is to describe in a preliminary way further three-dimensional data of this kind and to suggest that proof is now available that deoxyribonucleic acid consists of two helical intertwined polynucleotide chains and to show, as a result of molecular model building, that this structure may be of the type suggested by Watson and Crick. Franklin and Gosling have recently published two- and three-dimensional Patterson diagrams of crystalline calf deoxyribonucleic acid [‘Evidence for 2-Chain Helix in Crystalline Structure of Sodium Deoxyribonucleate,’ published in the same volume of Nature], and by means of these arrived at conclusions in many ways similar to ours … clearly all doubts about the basic geometry of deoxyribonucleic acid must be eliminated, for only then can the structural chemistry of its specific biological properties and the structure of nucleoprotein be approached on a sound basis” (p. 1). In this paper, Wilkins and his collaborators also showed that the DNAs from different biological sources were basically the same: “We have found no difference in the diffraction patterns of crystalline deoxyribonucleic acid from calf thymus, mouse sarcoma, human white blood cells, E. coli, pneumococcus and Paracentrotus sperm, although the ratio of the bases in the deoxyribonucleic acids varies considerably with species” (p. 2) – “this was important evidence for the generality of the DNA structure” (Magill, p. 3996). Wilkins was awarded the Nobel Prize in Physiology or Medicine 1962 (shared equally with Crick and Watson) “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.” Not on OCLC, but COPAC lists one copy, at the Royal Society, and there are two in the archives of King’s College, London. No copies in auction records.

“X-ray crystallography provides a way of deducing the structure of a molecule by analysing the diffraction pattern produced when a beam of X-rays falls on a crystal in which the molecules are regularly arranged in three dimensions. The pattern is nothing like a conventional photograph: it shows a set of spots of varying intensity and inferring the structure from the pattern is not a direct process. This is because each spot corresponds to a diffracted wave from the molecules lying in a particular set of planes in the crystal. The molecular structure of the crystal could be reconstructed mathematically from a knowledge of the amplitudes and phases of the diffracted waves—amplitude means strength of the wave (which is measurable from the spot intensity); and phase means the positions of the peaks and troughs of the wave relative to some reference point, but the phase is lost in the recording” (Klug, pp. 4-5).

“Wilkins was a senior member of the MRC Biophysics Unit at King’s College, London, set up by (Sir) John Randall in 1946 after the War to carry out ‘an interdisciplinary attack on the secrets of chromosomes and their environment’. Wilkins worked to develop special microscopes, but having heard of the greatly improved methods devised by Rudolf Signer at Berne for extracting long unbroken molecules of DNA, he obtained some of the material and found a way of drawing uniform fibres from a viscous solution of DNA. Examination under polarized light showed them to be well ordered, characteristic of long molecules oriented parallel to one another. He enlisted the help of a graduate student in the Unit, Raymond Gosling, who was studying ram sperm by X-ray diffraction. By keeping the fibres in a wet atmosphere, Gosling and Wilkins obtained the X- ray diffraction photograph that Wilkins later showed at Naples and which so excited Jim Watson” (ibid., pp. 7-8).

“Francis and Jim had brought it [i.e., the Double Helix model] into being less than three years after I was given DNA by Signer, Raymond and I had obtained the first clear evidence that DNA was crystalline, and Alec Stokes had pointed out signs that DNA was helical. The structure gave a new sense of direction in our work: many very important possibilities for biological and medical research could grow out of the Double Helix. We were keen to develop our X-ray studies in order to help that growth. Francis and Jim agreed that we should be responsible for extending our work and putting the Double Helix on a more detailed and accurate X-ray diffraction basis. In that way we could get closer to the truth – science cannot give final truth, but it can move in that direction. The Double Helix was brilliant, but already alternative ideas for DNA structure were appearing. Extending our work would help science to make the best choice” (Wilkins, pp. 229-230).

Rosalind Franklin, who joined the King’s group in January 1951, showed that, “depending on the humidity, two forms of the DNA molecule existed, which she later named A and B, and defined the conditions for the transition between them. The A form, which she first called ‘crystalline’, is found at, and just below, 75% relative humidity. Above that point there is an abrupt transition to the B form, which she originally called ‘wet’ … It became clear that all previous workers had been working, unbeknown to themselves, mostly with a mixture of the two forms, or at best with poorly oriented specimens of the A form, and, in retrospect, with occasionally hazy pictures of the B form” (Klug, pp. 9-10).

“In the Nature publications about the Double Helix, attention was concentrated on the B configuration of DNA. In contrast, the A configuration seemed more complicated, and not so easy to define in helical terms. Francis and Jim had made some suggestions about how the B structure might be compressed to form the A structure when the water content of DNA was reduced. Also, the B patterns were much less well defined than the crystalline A. As a result, the X-ray intensities could be more accurately measured for A than for B. In view of these difficulties we decided our first target would be to clarify the nature of the A structure. Herbert Wilson, Alec Stokes and I concentrated on the X-ray aspect, and Bill Seeds mainly built molecular models. We saw [in the offered paper] that there were 11 repeating chemical units per turn of the DNA helix, and that inclining the bases slightly enabled them to keep 3.4Å apart as in the B structure. It was only when we built a model that we were able to see this point. This illustrates how model building is not a mere illustration of thought, but enables the mind to explore and find new structures that may otherwise not appear out of imaginative processes …

“Now that we had the model, we could calculate from it the diffraction pattern we could expect to see; but that was a far from simple process, especially because computers were not yet available except in centres that specialized in mathematical research. Cambridge University had a computer, and Perutz had access to it for his X-ray work. But I was still using simple geometrical methods for the calculations – I had never liked the special X-ray card system that Rosalind and Raymond were used to. But we were able easily enough to adjust the Double Helix model so that it matched the observed diffraction pattern, and we were able to account for all the differences between the A and B patterns” (Wilkins, pp. 230-233).

To determine the quantitative features of the structure of DNA (in the A form), X-ray diffraction photographs (such as the one shown in Fig. 1 of the article) were analyzed. “A qualitative view of the X-ray photograph shows several features which point clearly to the type of structure involved, but the data may be interpreted with more certainty when the reflexions are indexed and intensities plotted … By using a high-resolution pinhole camera, about a hundred and twenty separate reflexions were resolved in the fibre photograph. Intensities were measured using a microdensitometer” (p. 2). The graph shown in Fig. 2 of the article plots some of these intensities and compares them with those predicted on the basis of the Watson-Crick model.

The authors summarize their findings as follows (pp. 3-6):

(a) The structure is helical.

(b) A major part of the helix has one sharply defined diameter of about 18Å.

(c) There are two coaxial 18Å diameter helices spaced half a pitch length apart.

(d) Spaced centrally between the two 18Å diameter helices is one helix of mean diameter about 10Å.

(e) There are eleven nucleotides per turn of one helix.

(f) The nucleotide shape resembles that of a rod inclined to the helix axis.

Born in New Zealand, Wilkins (1916-2004) was brought to England at age 6 and educated at King Edward’s School, Birmingham. He studied physics at St. John’s College, Cambridge, taking his degree in 1938. His doctoral thesis, completed at the University of Birmingham in 1940 under the direction of John Randall, contained his original formulation of the electron-trap theory of phosphorescence and thermo-luminescence. He then applied these ideas to various wartime problems such as improvement of cathode-ray tube screens for radar. Next he worked under Professor Mark Oliphant on mass spectrograph separation of uranium isotopes for use in the atomic bomb and, shortly after, moved with others from Birmingham to Berkeley, California, where these studies continued. In 1945, when the war was over, he was lecturer in physics at St. Andrews’ University, where Randall was organizing biophysical studies. The biophysics project moved in 1946 to King’s College, London, where he became a member of the staff of the newly formed Medical Research Council Biophysics Research Unit. Other staff then or later in the unit included Rosalind Franklin, Raymond Gosling, Alex Stokes and Herbert Wilson. Wilkins was elected FRS in 1959, and was made Companion of the British Empire in 1962.

Alexander (‘Alec’) Stokes (1919-2003) obtained a PhD in X-ray crystallography at the Cavendish Laboratory under the supervision of Lawrence Bragg. He joined the Biophysics Unit at King’s in 1947, as someone who not only had extensive experience of the study of crystals by the X-ray method, but also understood the complex mathematics involved. “In his book The Double Helix (1968), Watson attributed the discovery of DNA’s essentially helical structure to Stokes. ‘Stokes had solved the problem on the train while going home one evening and had produced the theory on a small sheet of paper the next morning,’ Watson wrote. The diagram showed a remarkable likeness to the rather fuzzy X-ray diffraction patterns which Wilkins had been getting. Later on, Randall too was quoted as saying that ‘it was Alec Stokes who worked it out’. Stokes, though, always insisted his role had been secondary to that of Wilkins, who had come to him one day in 1950 and asked him to work out mathematically the sort of X-ray pattern that might be expected from a helical molecular structure. It was later suggested that Stokes should have shared in the Nobel prize; but he always modestly insisted that his contribution had not been important enough: ‘I sometimes think the result was worth perhaps one five thousandth of a Nobel Prize. But they do not divide out the Nobel Prize in that way – if they did, there would be a long queue of claimants’” (Obituary, Daily Telegraph, 28 February 2003).

Herbert Wilson (1929-2008) obtained a PhD on X-ray studies of metals at Bangor University in 1952, and that autumn joined the King’s group. “I asked him to develop further what we had done on sperm heads and to try other nucleoproteins – naturally occurring complexes of protein and DNA from which DNA could be extracted” (Wilkins, p. 196). He co-authored (with Wilkins and Stokes) ‘Molecular structure of deoxypentose nucleic acids’, one of the three famous DNA papers published in Nature in April 1953. In 1966 he published a landmark book, Diffractions of X-rays by Proteins, Nucleic Acids and Viruses. He was appointed Professor of Physics at the University of Stirling in 1983, a post he held until his retirement in 1991. Wilson’s contribution to the study of the structure of DNA was featured in a special issue of Nature published in January 2005.

William (‘Bill’) Seeds, “a rotund Irishman with Swiss connections on his mother’s side, was a graduate of Trinity College, Dublin, and engaged on the mechanical details of a reflecting microscope. Seeds was the Biophysics Unit’s joker, given to raucous remarks. He also loved running around the department, stirring things up, and coining nicknames: the quiet thinker Stokes was the ‘Archangel Gabriel’; the lean and taciturn Maurice was ‘Uncle’; … It did not take long for Seeds to turn Rosalind into ‘Rosy’. She could not stand him. He did not like her either” (Maddox, p. 160).

This offprint is, like the famous three-paper offprint of six months earlier, printed from the same type as the journal printing, but in a single column, the journal being printed in double columns. Unlike the three-paper offprint, however, the present offprint was issued in printed wrappers.

Klug, ‘The discovery of the DNA double helix,’ Journal of Molecular Biology 335 (2004), pp. 3-26. Maddox, Rosalind Franklin: The Dark Lady of DNA, 2002. Magill, The 20th Century O-Z: Dictionary of World Biography, 2013. Wilkins, The Third Man of the Double Helix, 2003.

8vo (210 x 141 mm), pp. [1], 2-7, [8], with two figures in text (one of an X-ray diffraction photograph). Original printed wrappers.

Item #5006

Price: $3,500.00