I. Ultraviolet dichroism and molecular structure in living cells. II. Electron microscopy of nuclear membranes. Lecture given at the Symposium on Submicroscopical Structure of Protoplasm, May 22-25, 1951, at the Naples Zoological Station. Offprint from: Pubblicazioni della Stazione Zoologica di Napoli, Vol. XXIII, Supplemento.


First edition, extremely rare offprint, of this historic lecture by Wilkins which ignited the search by Crick and Watson for the structure of DNA. “The history of science is full of quirky minor accidents with major consequences. In 1951, Wilkins’s boss, Professor Randall, was invited to a conference on macromolecules in Naples. At short notice he asked Wilkins to take his place and, in doing so, precipitated a meeting of incalculable importance. Wilkins went to Naples armed with taut enthusiasm for the prospects of his new type of research and with the best X-ray picture of DNA that he had so far taken. Dr James Watson, at this time touring European laboratories to find the best place to settle to study the biology of genes, was at the meeting. He was more or less on holiday, but thought that Randall might have something interesting to say, for he was a physicist of some note as well as one of the world’s few experienced biophysicists. However, Watson was immediately and permanently fired by Wilkins’s talk on the investigation of DNA structure and by the beautiful X-ray diffraction patterns revealed by his single slide. Watson said later that this contribution ‘stood out from the rest like a beacon.’ Watson was a biologist, and the meeting did not bring him to London. But it concentrated his thoughts, took him to Cambridge, underpinned his eventual collaboration with Crick and led to a continuing exchange of ideas and information between the Cambridge group and Maurice Wilkins and Rosalind Franklin in the MRC unit at King’s College. The stage was set for great discoveries” (Wilkins Obituary, The Guardian, 7 October 2004). In his memoir What Mad Pursuit (pp. 67-68), Francis Crick writes: “One of the oddities of the whole episode is that neither Jim nor I were officially working on DNA at all. I was trying to write a thesis on the X-ray diffraction of polypeptides and proteins, while Jim had ostensibly come to Cambridge to help John Kendrew crystallize myoglobin. As a friend of Maurice Wilkins I had learned a lot about their work on DNA – which was officially recognized – while Jim had become intrigued by the diffraction problem after hearing Maurice talk in Naples.” And in Double Helix (pp. 21 et seq.), Watson writes: “It was Wilkins who had first excited me about X-ray work on DNA. This happened at Naples when a small scientific meeting was held on the structures of the large molecules found in living cells … His [Maurice’s] talk was far from vacuous and stood out sharply from the rest … Maurice’s X-ray diffraction picture of DNA was to the point. It was flicked on the screen near the end of his talk … he stated that the picture showed much more detail than previous pictures and could, in fact, be considered as arising from a crystalline substance. And when the structure of DNA was known, we might be in a better position to understand how genes work. Suddenly I was excited about chemistry.” Not on OCLC or COPAC, but there are two copies in the archives of King’s College, London. No copies in auction records.

In 1946 Wilkins moved, with John Randall (1905-84), to the new biophysics research unit at King’s College, London, which was funded by the Medical Research Council (a UK government agency). “By the time Wilkins went to King’s College, scientists at the Rockefeller Institute in New York had proved that genes were made of deoxyribonucleic acid (DNA). Wilkins became fascinated by this substance, and he started doing research on it, at first indirectly, by trying to cause mutations in fruit flies with ultrasonic vibrations, then directly, by developing a special microscope for studying the amount of DNA in cells … Wilkins decided to leave the analysis of DNA in intact cells to the biologists; he believed that he could contribute more effectively by using his specialized skills to study the DNA molecule in isolation, outside the cell.

“One of the techniques physicists had developed by that time was the analysis of dichroism patterns. Wilkins placed the specimen of DNA under the microscope and then subjected it to two colors of light simultaneously. One color was transmitted directly and the other was reflected. From the contrast of the colors, some information about the structure of DNA could be inferred.

“These optical studies of DNA molecules eventually convinced Wilkins that DNA fibers would be ideal material for X-ray diffraction studies. While examining DNA gels prepared for his dichroism work, Wilkins observed, through a microscope, that each time he touched the gel with a glass rod and then removed it, a thin fiber of DNA was drawn out and suspended between the rod and the gel. The uniformity of the fibers suggested that the DNA molecules were arranged in some kind of regular pattern, and therefore they might be suitable for analysis by X-ray diffraction …

“The first diffraction patterns of DNA obtained with their makeshift equipment were very encouraging. Before long, Wilkins and his colleagues got much sharper diffraction photographs of DNA. The sharpness showed that the DNA molecules were highly regular; the pattern indicated that they were helical. Wilkins had learned from John Bernal that it was important to keep the fibers moist to get good diffraction patters. This proved to be a key to obtaining experimental data that were useful in clarifying the structure of DNA … By 1951, then, Wilkins had come to realize that the X-ray diffraction pattern of DNA exhibited helical characteristics” (Magill, pp. 3995-6).

“We can gather some clues as to the state of Wilkins’ work on DNA and nucleoproteins in early 1951 from the paper he gave during a four-day meeting on ‘Submicroscopical Structure of Protoplasm’ (May 22-25, 1951) at the Naples Zoological Station. His paper opened with the following statement of aims:

‘The properties of crystals reflect the properties of the molecules of which they are composed. Hence, when living matter is to be found in the crystalline state, the possibility is increased of molecular interpretation of biological structure and processes. In particular, the study of crystalline nucleoproteins in living cells may help one to approach more closely the problem of gene structure’ [p. 105].

“In the audience was the young post-doctoral American J. D. Watson. No wonder he pricked up his ears! Wilkins described how his group at King’s were concentrating on two aspects of nucleic acids: their structure and their molecular orientation in sperm heads. His message was that extracted DNA and cellular DNA were the same, since their properties were so similar. No X-ray patterns from Sepia [a type of cuttlefish] sperm heads had yet been taken, but optical studies revealed striking parallels in the arrangement of the nucleic acid molecules in the sperm head and in the fiber, the orientation of the bases and the presence of an extensible molecular chain structure … What is clear from this meeting is the fact that Wilkins did not discuss helical molecules. He did discuss the helical packing of molecules. Both in the TMV [Tobacco mosaic virus] crystals which he studied in vitro, and in hydrated DNA fibers (after extension), he noted banding when viewing them between crossed nicols [a device used to measure the rotation of the plane of polarization of light transmitted through the crystal]. This pattern indicated a regular change in the optic axis along the crystal and the fibre, suggestive of either a zig-zag or a helical packing of the long-chain molecules.

“For Watson the real excitement came when the X-ray picture of DNA – of the crystalline or A form – ‘was flicked on the screen near the end of his talk’. Although Wilkins’ ‘dry English form’ obscured any enthusiasm, his statement that ‘the picture showed much more detail than previous pictures and could, in fact, be considered as arising from a crystalline substance’ caused Watson to make a volte face and get

‘excited about chemistry. Before Maurice’s talk I had worried about the possibility that the gene might be fantastically irregular. Now, however, I knew that genes could crystallize; hence they must have a regular structure that could be solved in a straightforward fashion’” (Olby, pp. 338-340).

“Before Watson heard [Wilkins’ talk] in Naples, his attitude to nucleic acids seems to have been somewhat ill-defined. He wrote of his daydreams ‘about discovering the secret of the gene, but not once did I have the faintest trace of a respectable idea’ (Double Helix, p. 30). To be sure, he had come to Copenhagen to learn nucleic acid chemistry, DNA looked like the stuff of the gene, but whether DNA held the key to the duplication of the gene remained to be seen. The immediate problem was how to get at the structure of the genetic material. Chromosomes were no good. Nucleoproteins were messy, but Wilkins taught Watson in Naples that the approach to the structure of the gene could be made through the structure of oriented fibres of the sodium salt of DNA” (ibid., p. 355).

“On his return [to King’s], Wilkins found that [Rosalind] Franklin and [Raymond] Gosling, using more advanced X-ray equipment with which they were able to attain higher humidities than previously, had made much progress. Since collaboration was no longer possible [because Franklin believed the DNA problem was hers while Wilkins believed she worked for him], the work was divided, and Wilkins and Franklin studied different problems. Wilkins was able to show the existence of helical DNA in certain living cells. He also showed that DNAs from different biological sources were basically the same; this was important evidence for the generality of the DNA structure” (Magill, p. 3996).

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 war-time 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 first concerned with genetic effects of ultrasonics; after one or two years, he changed his research to development of reflecting microscopes for ultraviolet microspectrophotometric study of nucleic acids in cells. He also studied the orientation of purines and pyrimidines in TMV and in nucleic acids, by measuring the ultraviolet dichroism of oriented specimens, and he studied, with the visible-light polarizing microscope, the arrangement of virus particles in crystals of TMV and measured dry mass in cells with interference microscopes. He then began X-ray diffraction studies of DNA and sperm heads. The discovery of well-defined patterns led to the derivation of the molecular structure of DNA. Further X-ray studies established the correctness of the Watson–Crick proposal for DNA structure. Wilkins was elected FRS in 1959, was made Companion of the British Empire in 1962, and in the same year awarded the Nobel Prize in Physiology or Medicine (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.”

The Stazione Zoologica in Naples was founded in 1872 by the prominent German Darwinist Anton Dohrn (1840-1909). The majority of the initial funding for the Station came from Dohrn himself, who also donated his personal library. Other funds came from Charles Darwin, Thomas Huxley, and Rudolf Virchow, among others. To raise additional income, Dohrn constructed a large portion of the Station as a public aquarium. The Station was the first independent research institute for marine biology. It did not have an independent research program, but instead it supported the interests of the scholars working there. To disseminate information about the work conducted at the Station, Dohrn founded the journal Mittheilungen aus der Zoologischen station zu Neapel (1879-1915), which became Pubblicazioni della Stazione Zoologica di Napoli (1924–1978).

Magill, The 20th Century O-Z: Dictionary of World Biography, 2013. Olby, The Path to the Double Helix, 1974.

Large 8vo (245 x 172 mm), pp. [105], 106-115, [1, blank], with two photographic plates (numbered IX & X) protected by tissue guards. Original printed wrappers.

Item #5007

Price: $3,500.00