(1990), Notes and Discussions W. T. Astbury, Rosie Franklin, and DNA… · 2007-09-20 · James...

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ANNALS OF SCIENCE, 47 (1990), 607-618 Notes and Discussions W. T. Astbury, Rosie Franklin, and DNA: A Memoir MANSEL DAVIE~ 14, Marine Terrace, Criccieth, LL52 0EF U.K. Received 10 April 1990 Summary Astbury's role in the X-ray study of DNA; his failure to continue his pioneering appraisal; surprising details of his MRC grant application; and his disinterest in Beighton's DNA photographs demand attention. Rosie Franklin's later involvementand behaviour receivecomments, which,as with Astbury,are based on personal knowledge. Introduction Science is so poorly presented in the United Kingdom that the public has an inadequate appreciation of how it proceeds: and that, perhaps, not so much in spite of, but because of, offerings to it of attractive accounts of outstanding achievements. In these there lies a disadvantage. The discovery of radium, the isolation of pencillin, the unravelling of the DNA structure are not typical of everyday science. Even these dramatic advances do have elements of the ordinary routine, but these are omitted in their telling. Everyday science is at so much lower a key as to lack the obvious attraction and the thrill inevitably present in major discoveries. The vast bulk of scientific activity, on which the great achievements are necessarily built, can appear pedestrian and boring except to those personally involved. An account of such normal, almost routine operations, would not long keep the reader's attention. However, there is an intermediate state between the excitement of Nobel-ranking work and the more usual unglamorous science. This includes the subsidiary work which leads up to, or represents failed attempts towards, the great prizes. This could satisfy the lay person as a good football match leading up to the Cup Final. The present theme is that of studies which were closely related to the dramatic aspects of the discovery of the DNA structure. They are not untypical of all that huge bulk of work which could have achieved great acclaim 'if only'. Jacques Monod, himself a Nobel prizewinner, went so far as to propose that the history of biology should include the errors and confusion out of which discoveries grew. This is a Baconian proposition. But it is reasonable to expose the normal trials and failures of research. Let me remind the reader that DNA is the acronym for the name of one of the most extraordinary constituents of the living wodd--deoxyribose nucleic acid. This is close to the magical chemical compound forming the chromosomes, and therefore the genes, present in almost all living cells. It is the many millions of genes which go to form the forty-six chromosomes in every human organic cell that define all the physical and physiological details of the whole individual. The total of our inherited character is ultimately dependent upon the structures of millions of DNA molecules. 0003-3790/90 $3-00 1990Taylor & Francis Ltd.

Transcript of (1990), Notes and Discussions W. T. Astbury, Rosie Franklin, and DNA… · 2007-09-20 · James...

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ANNALS OF SCIENCE, 47 (1990), 607-618

Notes and Discussions

W. T. Astbury, Rosie Franklin, and DNA: A Memoir

MANSEL DAVIE~

14, Marine Terrace, Criccieth, LL52 0EF U.K.

Received 10 April 1990

Summary Astbury's role in the X-ray study of DNA; his failure to continue his pioneering appraisal; surprising details of his MRC grant application; and his disinterest in Beighton's DNA photographs demand attention. Rosie Franklin's later involvement and behaviour receive comments, which, as with Astbury, are based on personal knowledge.

Introduction Science is so poorly presented in the United Kingdom that the public has an

inadequate appreciation of how it proceeds: and that, perhaps, not so much in spite of, but because of, offerings to it of attractive accounts of outstanding achievements. In these there lies a disadvantage. The discovery of radium, the isolation of pencillin, the unravelling of the DNA structure are not typical of everyday science. Even these dramatic advances do have elements of the ordinary routine, but these are omitted in their telling. Everyday science is at so much lower a key as to lack the obvious attraction and the thrill inevitably present in major discoveries.

The vast bulk of scientific activity, on which the great achievements are necessarily built, can appear pedestrian and boring except to those personally involved. An account of such normal, almost routine operations, would not long keep the reader's attention. However, there is an intermediate state between the excitement of Nobel-ranking work and the more usual unglamorous science. This includes the subsidiary work which leads up to, or represents failed attempts towards, the great prizes. This could satisfy the lay person as a good football match leading up to the Cup Final.

The present theme is that of studies which were closely related to the dramatic aspects of the discovery of the DNA structure. They are not untypical of all that huge bulk of work which could have achieved great acclaim 'if only'. Jacques Monod, himself a Nobel prizewinner, went so far as to propose that the history of biology should include the errors and confusion out of which discoveries grew. This is a Baconian proposition. But it is reasonable to expose the normal trials and failures of research.

Let me remind the reader that DNA is the acronym for the name of one of the most extraordinary constituents of the living wodd--deoxyribose nucleic acid. This is close to the magical chemical compound forming the chromosomes, and therefore the genes, present in almost all living cells. It is the many millions of genes which go to form the forty-six chromosomes in every human organic cell that define all the physical and physiological details of the whole individual. The total of our inherited character is ultimately dependent upon the structures of millions of DNA molecules.

0003-3790/90 $3-00 �9 1990 Taylor & Francis Ltd.

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There is no single constituent in the living organism, plant or animal, of greater significance that its DNA molecules. This conclusion was first dearly advanced only in the 1940s. Accordingly, when in 1953 scientists at Cambridge, supported by colleagues in London, announced that they had determined the detailed pattern of the DNA molecular structure, it was quickly claimed as one of the most far-reaching scientific advances of the century. Crick and Watson at Cambridge, and Wilkins at London, duly shared a Nobel Prize.

It is a sober fact that even if the story of the DNA discovery is not itself of inherent, lasting significance, it is undoubtedly one of the most interesting chapters in science history. The dozen leading participants include individuals whose personal characters markedly influenced their contributions: that was because, unusually, success came less from careful experimental measurement, quantitative assessment, or mathematical analysis than from a conviction of the supreme importance of the problem. This conviction served to stimulate inspired guesswork. The solution was a triumph of imagination over a paucity of facts. Quite simply, the problem was to find the architecture of a long chain-like molecule. As the result was no more recondite or abstract than a meccano model, the widest possible public could appreciate its essence.

And the unity of science has rarely been better illustrated: a problem central to the whole of life processes was solved by a combination of chemical, physical, and mathematical appreciation. The arbitrariness of what may still be convenient divisions in science is reflected by the fact that the Nobel Prize awarded for the DNA structure determination was the Physiology Prize. This was entirely appropriate in that the enormous significance of DNA is centred on physiology.

The DNA structure was finally solved on the basis of X-ray diffraction studies. The lay reader can replace 'diffraction' by 'selective reflection'. This is where my story starts. Technical aspects need not concern us: the relevant point is that the X-ray diffraction pattern is not a shadow-graph such as is used in medicine to reveal broken bones, stomach ulcers, etc. The 'selective reflection' is that of a narrow beam of X-rays (about 1 mm or less in diameter) directed at the very small specimen being studied, e.g. of DNA, whose crystalline features 'reflect' the beam in a highly selective, and so revealing, way.

In their first, all-important account of the DNA structure, Crick and Watson1 state explicitly that they had used the X-ray patterns published by W. T. Astbury. To answer the question why did not Astbury deduce the structure of DNA is one of the aims of this account.

Let me emphasize that there are four well-known volumes detailing different aspects of the DNA story. They are:

James Watson, The Double Helix (London, 1968) Robert Olby, The Path to the Double Helix (London, 1974) H. F. Judson, The Eighth Day of Creation (London, 1979) Anne Sayre, Rosalind Franklin and DNA (New York, 1975).

Only the authors names will be used in later references to these sources. Watson's is a personal, idiosyncratic account and a highly acclaimed piece of writing. It does not

1 F. H. C. Crick and J. D. Watson, 'Molecular Structures of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid', Nature, 171 (1953), 737.

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attempt a scientific history, for which Olby and Judson must be consulted. Despite the thorough character of these two later accounts, such is the significance of the DNA story, that further aspects relating to Astbury and Franklin need to be added.

Astbory's laboratory My observations are based on my membership of Astbury's Laboratory (1942-

1947) when I took many DNA diffraction photographs, and on my knowing Rosie Franklin, firstly as a member of the Part II (i.e. Honours) Physical Chemistry Class in Cambridge, in which I acted as an assistant demonstrator. It is unlikely that I could be the last practising scientist to indicate how being in media res gives a light (and perhaps shadows) on events which the outsider cannot acquire. History is notoriously difficult to present accurately, and one can get the impression that, thanks to distance either in time or space, some history of science is published for historians of science. Crick makes one relevant comment: 'Unfortunately, people have forgotten what it was we did not know at the time' (Judson, p. 203).

Olby and Judson refer in their accounts, not surprisingly, to 'Astbury's diffraction patterns', and Watson in a letter written only some days after first arriving at the structure, tells Delbruck,' . . . we have no photographs of our own and like Pauling must use Astbury's photographs'. Astbury's was the only name on the essential paper they referred to. During my time, I never saw Astbury himself even get involved in the taking of a diffraction photograph. Astbury rightly ascribed the 1939 photographs that he published to Florence Bell, a research student who incorporated them in her Leeds University Ph.D. thesis (1939).

In July 1946, at an important symposium on nucleic acids held at Cambridge, Astbury reported: 2 'There is not a great deal that is recent in the experimental work reported in this paper for there has not been the opportunity to go on with the nucleic acids until the last few months'. This sentence would be more strictly correct were 'novel' to replace 'recent'. Nevertheless, Astbury then presented the most extended account which can be quoted of his views on their structure. Although later seen to be incorrect in essential respects, they were much more specific, and nearer the truth, on the all-important structure of the DNA molecular chains in the solid state than could be quoted from other sources.

All accounts agree that Astbury was the pioneer and his laboratory the sole source of DNA X-ray studies before 1950. There were good reasons for this. Since, the early 1930s, Astbury at Leeds had studied the structures of natural fibres, especially those of cellulose (cotton, jute, etc.), wool in all its forms, and other animal hairs, feathers, and quills. (Notice that no synthetic 'plastics' appear in this list.) The common feature in all these materials was their constitution from long, chain-like molecules, lying largely in the direction of the fibre length. In the spider's thread the molecular orientation was found to be enhanced by a stretching of the fibre as it was spun from the thick, glue-like protein, fibroin, prepared by the spider.

Leeds University had a specific interest in the woollen industry, whose activities were fostered by its Faculty of Textile Science, and in which Astbury held the position of Reader in Textile Physics. For some years after he started at Leeds, Astbury's laboratory and its equipment was supported by the University with a grant which

2 W. T. Astbury, 'X-ray Studies of Nucleic Acids', Symposium Society of Experimental Biology, 1 (1947), 66-76.

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could be only s per annum. No source in the U.K. backed his work to a tenth of the extent to which it was supported by the Rockfeller Foundation of New York. It was partly due to an initiative by Dr Joseph Needham of Cambridge, that the Rockefeller Foundation gave s for Astbury's work in 1935: between 1934 and 1938 Astbury received $71000 or s 18 000 from this source (Olby, pp. 253, 441). The princely nature of this support is clear when one notes that s 000 in 1938 was the equivalent of s 000 in 1990. It was thanks exclusively to the Rockefeller Foundation that Astbury had his apparatus and research assistants for DNA studies.

For three years from 1942 1 had been one of Astbury's assistants, but specifically devoted to the interests of a fibre-making company, Messrs British Celanese Ltd. In September 1945 I started in new position under Astbury with a Rockefeller research fellowship. The plan was for me to explore protein and related structures by infra-red spectroscopic methods: equipment for this was on order from the U.S.A. More of that later. Until the spectrometer arrived, Astbury gave me a new specimen of DNA he had received from Casperson (Copenhagen), possibly via Rockefeller contacts in New York. At that time Astbury was one of the very few physicists who well appreciated the unique significance of the DNA structure, as he had clearly grasped that structure must provide a means for the transmission of inherited charactereristics in all living things. Certainly I did not have that appreciation in my mind when I started examining DNA in 1945: Avery's indications from the transformations in pneumococcal types were only published in 1944 and their wide importance was not accepted for many years.

Chemists had shown that DNA was composed of long molecules and, to succeed in its X-ray study, an essential step was to orient those molecules so that their regular arrangement would give rise to a good quasi-crystalline pattern. My DNA specimen was a white fluffy material readily soluble in water. With a few drops of water on a glass slide, a small amount formed a viscous, almost gummy solution. This could be spread so that, with a little drying, a fairly uniform film was produced. Narrow strips could be cut, mounted as a bundle, then clamped and stretched, whilst still retaining moisture, in a small frame for X-ray examination. There were many variants or addenda to this basic operation, and many different X-ray diffraction photographs were taken.

These pictures showed no essentially new features beyond those in Bell's thesis, but there was an improved definition, if only because the DNA specimen was superior to hers. Smaller degradation led to smaller background scattering and probably contributed, apart from any improvement achieved in the manipulative preparation, to a slightly higher degree of crystallinity. All of which gave somewhat sharper diffraction features. Nevertheless, both Astbury and myself were disappointed that no new details of the structure were revealed. Subsequently, L. C. Spark, a graduate student starting on his own research course, took for Astbury some 'divided plate' photographs of new DNA complexes. These also received Crick and Watson's particular attention (Olby, Figure 11).

It is relevant to consider why these results at Leeds were so far inferior to those achieved by Rosie Franklin in 1952-1953. Four factors can be cited.

(1) We now know that the rich diffraction pattern first seen by Gosling and Wilkins in 1950, was given only by Signer's hugely improved DNA specimen. Far less degraded than previous preparations, it had a molecular weight of seven million.

(2) No attempt was made at Leeds to control the humidity of the DNA specimen when being photographed. Water readily dissolved the specimen, leading to complete dissorientation of the molecules. It was not realized that a substantial water content was essential to maintain what proved to be the all-revealing double helix structure.

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(3) Rosie Franklin's later photographs were taken with a fine-focus X- ray source (as also Beighton's: see later) and a specially designed micro-camera, refinements which clarified the detail in her beautiful patterns.

(4) Perhaps, or, indeed probably, more immediately relevant than any of the above factors was the mode of preparation of the specimens for photographing. Here the stupidity factor comes into play. I had myself taken X-ray photographs of spiders' threads and established that most of the fibroin molecules lay within an angle of 7 ~ to the fibre axis, and I was well aware of how that high orientation had been produced. The orientation was better than Messrs Nylon Spinners could then produce in their fibre, but, as Astbury pointed out, nature had been on the operation for several million years. I had wound spiders' thread into bundles but failed to appreciate that a gummy DNA solution could give a similar thread. That essential observation was due to Wilkins in 1950.

In addition to taking the DNA photographs, Astbury asked me to construct a molecular model representing his proposed DNA structure. For this I had some adequate experience. Spectroscopic structural studies had given me a critical interest in bond lengths and angles, and I knew the immediate relevance in the solid state, where DNA was being studied, of the effective size of atoms, i.e. of their so-called van der Waals diameters. The first edition of H. A. Stuart's Molekfdstruktur 3 contained quantitative indications not available in my 1939 edition of Pauling's The Nature o f the Chemical Bond. a Model building had already shown me that the Meyer-Misch unit cell for cellulose was unlikely to be correct unless the central chain was inverted. More significantly, it was from models built in Astbury's laboratory that I found the different mode of linkage of pyranose units to be found in alginic acid and its derivatives: different, that is, from the linkage common to most cellulose-based structures. 5

Many accounts of the DNA discovery omit the essential chemical work (e.g. by Levene, Carter and Cohn, Gulland, et al.) without which no meaningful model or significant structure could be advanced. Not surprisingly, some of the previously accepted details of the DNA chain were corrected when the model was built. (Olby, pp. 324-6). The model was taken to the December 1945 meeting of the Institute of Physics, which gave me, apart from comments that I had used the Papal colours for the different atoms, the pleasure of demonstrating it, to G. F. C. Searle amongst others.

After spending four months on the DNA studies, in January 1946 1 switched my interests to infra-red work, as the Beckman IR2 spectrometer had arrived in Liverpool, and I now pursued aspects of simple molecules until I left Leeds in November 1947.

Such account as is otherwise available of my DNA activity appears in the Astbury 1947 paper 6 which provided guidance for Crick and Watson. It must be emphasized that the photo-prints in that paper are very poor reproductions of the original negatives, lacking all faint but real detail. The reader will accept this after comparing the 1947 figures with those better prints from the same source to be found in Olby's book. In that paper Astbury merely thanks me for constructing models, and Dr F. O. Bell and Mr L. C. Sharp (but not myself) for photographs. Maybe he did not use my

a H. A. Stuart, Molekiilstruktur (Berlin, 1934). L. Pauling, The Nature of the Chemical Bond (London, 1939).

5 W. T. Astbury and Mansel Davies, 'The Structure of Cellulose', Nature, 154 (1944), 84. See also W. T. Astbury, 'The Structure of Alginic Acid', Nature, 155 (1945), 667. In the first of these references my contribution was the cellulose model and the modified biose structure found in alginates: in the second I am, with four others, thanked, but no indication appears that the model given for alginic acid was my finding.

6 Footnote 2.

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photographs in the paper--a possibility which could be established if all the prints (apart from Figures 2a + 2b which are Sharp's) came from Bell's 1939 thesis, which he had already used in his 1938 paper. 7

The 1947 paper was Astbury's last serious contribution to the DNA problem. Olby, in his account of the Leeds work, rightly raises the question why it was not further pursued, seeing that some definite advances were to be seen despite the very small new effort. This question does pose a problem.

It is important to recall that the structure represented by my model, based as it was on an essentially linear chain manipulated to stack the bases at 3"4A apart, was very far indeed from the double helix. Olby rightly records (p. 325) that Astbury had considered a helical configuration, although I have no memory of his mentioning this in the discussions on the model. In 1946, when the significant work ceased, Astbury's was the only laboratory which had effectively pursued X-ray studies of DNA, and the benefit/effort ratio was undoubtedly high, certainly in my opinion, a There is no question that Astbury was fully committed to such biomolecular studies. He had just persuaded the Leeds University authorities to name his laboratory The Department of Biomolecular Structure when he was given professorial status in 1945.

Olby goes on to recount how Astbury had contacted Mellanby, the Secretary of the Medical Research Council, on a possible application he wished to make for research funds, and had received a very encouraging response. At least, the indications were that his proposals would be of immediate interest to the Council. Of this every member of Astbury's group was made aware, and we were each asked to write our own suggestions for future work in the areas of our particular competence, bearing in mind what the application was committed to, that is, studies in biomolecular structure. In addition to Astbury, the group consisted of H. J. Woods, mathematical physicist; I. MacArthur, X-ray diffraction specialist; K. M. Rudall, biologist and expert on epidermal and other animal membranes; R. Reed, electron microscopist; M. Davies, infra-red spectroscopist. MacArthur, Reed, and Davies were basically physical chemists. If small, the group's abilities were admirably distributed for the programme in Astbury's mind.

It could be assumed that Astbury would himself expound the general range of the studies--including those of DNA--which would be pursued, also with research students responsible for preparative and general supportive work. My contribution outlined infra-red studies as a means of exploring the structure and, more particularly, the interactions of chemical groups characteristic of biomolecnlar structures. In the proteins, the amide group was a key feature, but there was no significant assignment of its frequencies or of their behaviour on interaction in the solid state. This was, of course, one of the motives in Astbury's acquiring the infra-red spectrometer, and, after 1947, this work was pursued at Aberystwyth.

The other members of the team contributed their own proposals. These all went to Astbury, who, it was natural to presume, constructed an inclusive presentation of the total prospects. It must be confessed that I never saw such an overall statement which could have been quite impressive, but that was not too surprising as Astbury did not indulge in open collaboration.

W. T. Astbury and Florence O. Bell, 'Some Recent Developments in the X-ray Study of Proteins and Related Structures', Cold Spring Harbor Symposium on Quantitative Biology, 6 (1938), 109-18.

a R. Olby, The Path to the Double Helix (London, 1974), p. 326.

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What is surprising, not to say astonishing, is to find a later Secretary of the Medical Research Council, Himsworth, writing in 1968 (after Astbury's death), that there appeared no reference in the MRC records of a 'a memorandum setting out his scientific proposals and requirements.., ever having been asked for, or Astbury having volunteered one'. And a further comment I find incredible: 'From the correspondence it seems that Astbury managed to convey the impression to the Council that his real interest was in structures like cellulose and artificial fibres' (Olby, p. 237). How could anyone of Astbury's scientific status make such an approach to the Medical Research Council? No-one who knew him at the time, or who reads his published articles, or considers the developments in his Biomolecular Department, can find Himsworth's comments other than a bizarre misrepresentation of Astbury's interests.

Perhaps one clue to this apparent mystery is given by Astbury's poor opinion of medical science. In talks he had given to medical research groups, he had encountered what seemed extraordinary ignorance of the molecular world, and he was inclined to write-off the whole medical profession. If the MRC panel in 1946 had not appreciated Astbury's commitment to biomolecular polymers rather than synthetic plastics, they could at least be illustrating his assessment of the then medical insights in science.

The question is further twisted by the choice of Randall to lead a group on biomolecular structure. Olby explains what may be called the 'academic politics' aspect of this decision. The reader must grasp that Randall's pre-war interests and reputation had been centred on studies of silicates, glasses, and ceramics, and that he then made a major contribution by helping to design the magnetron valve for radar war work. These scientific concerns are distinctly further from biomolecules than even synthetic plastics.

I well remember Astbury coming into the laboratory tea one afternoon (it must have been in March 1947) and announcing that 'Randall has been given the MRC grant'. He was a picture of depression. I never heard him discuss the Department's total submission, but he was explicit in one suggestion for its failure. He had never been able to hit it off with the younger Bragg, Sir William Lawrence ('Bill') Bragg, and (thought Astbury) MRC had leant on or been bent by W. L. B.'s opinions. I have no evidence to support this, but it was Astbury's expressed conclusion. It is a fact that at this same time MRC also awarded a research grant to Bragg's Cavendish Laboratory, but it was for the X-ray study of the haemoglobin structure, established there before Bragg had become its Director.

The relevance of these details is that, having been the pioneer, having a clear, perhaps too emotional an appreciation of the importance of the DNA problem, Astbury made no further contribution to its solution. And now comes the final puzzle.

A final puzzle When I left Leeds in 1947, a young man, later Dr Elwyn Beighton, was a laboratory

photographic technician. He subsequently advanced his status, taking up research activities. Olby first reported that in 1951 he achieved almost ideal conditions and obtained truly excellent diffraction patterns for DNA in its B-form. (Olby, p. 379, Figures 16 and 17). Chargaff, the eminent biochemist at Berkeley, had sent Astbury an improved DNA preparation--although it still proved to be inferior to the Signer material used by Wilkins and later by Franklin. Bcighton obtained these dramatically improved results in May 1951, and it is difficult to believe that Astbury did not immediately respond to their significance. Olby writes: 'Strangely enough, Astbury was disappointed by these results...' (Olby, p. 379). To me, this is amazing, as a schoolchild

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can see the remarkable differences between the photographs published in 1947 and those of 1951. To the merest tyro in X-ray diffraction studies, the sharpness of the spots and the simplicity of the patterns now instantly suggest that some well-defined and highly regular structure was present in the specimen.

Thus in May 1951 the key to the DNA structure was available to Astbury in Leeds and he did nothing about it. A similar but less remarkable blankness occurred in Randall's group at King's College, London. Already in 1950, Wilkins had had Gosling take diffraction patterns of DNA fibres. They also produced highly revealing photographs very much richer in information than any published at the time, or for more than two years later. What is perhaps most extraordinary is that Wilkins showed these photographs at a conference in Naples (22-5 May, 1951) at which Astbury was present, and Astbury even commented (but not very significantly) on them in remarks reported by Olby. Beighton's study is timed as 'in the spring of 1951'. Astbury was thus aware that Beighton's photographs were closely paralleled elsewhere. Olby in his very carefully detailed account makes clear why Wilkins did not in 1951 proceed to any major insight, but he can only comment of Beighton's and Astbury's disregard of their photos that 'they did not appreciate their significance'. Although this seems to be confirmed by Beighton, 9 it approximates to the suggestion that the manager of a football team does not appreciate it when his side scores a goal. I can say that such photographs were exactly what Astbury was anxious to have in 1946. I have failed in the past to understand why he did not at least publish Beighton's photographs, even if, surprisingly, he did not grasp the helical structure revealed by the striking cross- pattern. (I desist from pursuing an almost equally difficult question: why was the diffraction result shown by Wilkins in 1951 not seized upon by Watson and Crick before Watson saw one very similar in 1953, which confirmed the helical model?)

Professor North, currently (1990) Director of the Astbury Department of Biophysics at Leeds University, was in Randalrs group at University College London in the early 1950s, and he has given me valuable comments, some based on Beighton's recall. 1 o

(1) 'This [Beighton's] pattern seemed to Astbury to be inferior to the one taken some years previously . . . . '. So Astbury did not publish what 'was not as good as an earlier one'. This contrasts with my comparison of the 1947-1951 photographs (above): and the 'earlier one' has disappeared, if it was ever published.

(2) 'The theory of helical diffraction had of course not yet been derived in 1951.' Agreed; but no mathematical treatment would be needed by Astbury, whose grasp of the diffraction process would have suggested the remarkable cross-pattern as symptomatic of the cross-chain segments (between front and back) present throughout a helical structure. H. R. Wilson confirms this view when he writes: 11 'Mere inspection of the paracrystalline (B-DNA) X-ray diffraction pattern suggested a helical structure'.

(3) Astbury 'was not over-depressed by the DNA 'failure'--what excited him was the success of the structural approach that he had pioneered, no matter who was responsible for its application'. This is a worthy generous outlook, but does it arise from a pioneer who has failed to keep up with the leaders in the race?

9A. C. T. North, letter to Mansel Davies, 4 December 1989. 10 Ibid. 11H. R. Wilson, 'The Double Helix and All That', TIBS, 13 (1988), 275-8.

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One acceptable possibility is that, having seen the dramatically improved diffraction pattern shown by Wilkins at Naples, Astbury accepted that the drive to the all-important DNA structure was already in harness in the group whose funding he had missed, and so he would now continue with his own even more biological studies--the structure of bacterial flagella, etc. 12 This view would seem to cover most of what would otherwise appear as marked inconsistencies in the appraisal of Astbury's role in the DNA saga.

There remain some other aspects of interest. Notice firstly that MRC awarded research grants for biomolecular studies to Bragg in Cambridge, and to Randall in London, when Astbury was passed over. The former was to promote the work that led to Nobel Prizes for Perutz and for Kendrew; Crick and Watson were neither at, nor was DNA work contemplated at, Cambridge in 1947. The support for Randall's group led to Wilkin's Nobel Prize. This highly satisfactory outcome seems fully to justify the MRC decisions. What would have happened had Astbury been supported becomes pure speculation.

Aspects of Astbury's character The reader will accept that, at this end of the discussion, as throughout much of the

DNA story, our understanding of events turns upon the personality of a leading participant. As one who much appreciated the abilities and insights of William Thomas Astbury, what may be relevant comments on his personality as seen by one young colleague may be added. Here, as in so many other aspects of his detailed account, there arc Olby's percipient, factually supported, observations on Astbury, the man. (Olby, pp. 45-9).

Astbury was an individualist, justifiably sure in his relation with colleagues of his role as a leader. When, in 1927, as a young man he was interviewed for the post of crystallographer in Cambridge, he was asked if he would be prepared to collaborate with others. His reply is quoted: 'I am not prepared to be anybody's lackey'. Bernal got the post. Of some twenty-two scientific publications listed by Olby under his name, only for three are there co-authors with Astbury. Olby himself misses one. Astbury was largely a loner, and he was liable to pass over specific contributions by others when publishing results.

Perhaps more significantly, he was the most Celtic Englishman I have encountered. 'Celtic' may be too broad: he was the most Welsh-like Englishman I have known. What do I mean? If he did not live on, he was motivated by, enthusiasms. This element was to be seen not only in an imaginative, almost romantic approach in his scientific activities, but also in his irrepressible interests in music, literature and poetry. I feel sure he would have said he could not have lived without music, and in that context Mozart was the Prince. His daughter, Mrs Maureen Astbury-Pereson has written to me 13 that her father thought of himself, from his great love of the sea, as a Norseman and, if Mozart was the Prince, then Beethoven was the King.

No scientist I have known was so prepared to spend time rewriting, 'polishing' a paper, so as to ensure its literary style came up to expectations. And if a poetic quotation could be worked in, as frequently it was, then so much the better.

Astbury was a native of Longton in the Potteries, Staffordshire, and was never forgetful that he had made his way, via scholarships, to Cambridge. His brother also

12 Footnote 9. 13 Mrs Maureen Astbury-Pereson, letter to Mansel Davies, 2 December 1989.

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achieved much distinction in a scientific career." Staffordshire is one of the areas in England with the largest of Celtic elements in the natives. Bill Astbury could be taken to conform to this statistical finding.

Is it too much to suggest that after his entirely reasonable expectations took a very heavy blow from the MRC, Astbury's enthusiasm deserted him and he lost heart for further demanding effort? Certainly his periods of ebullience were accompanied by spasms of depression. Perhaps I am in a minority amongst his colleagues in feeling that some such special explanation is needed for so bright a light in the DNA field to have gone out so suddenly.

Rosie Franklin With Rosie Franklin my contact was much more more limited than with Astbury.

The Part II (Honours) practical Physical Chemistry Class at Cambridge was, for 1936- 1940, the responsibility of Drs E. A. Moelwyn-Hughes and W. C. Price. I was one of their part time assistants. Naturally this led to the class being described as 'run by the Taffia'. Rosie Franklin was a regular member of the class one year. My memory is that, whilst she made no special impression, she was entirely competent in her work and that she showed a fully serious interest in it.

At Cambridge, mine was a minor degree of contact, but Fred (now Lord) Dainton was her supervisor for tutorial work in Physical Chemistry. When I asked him how had he evaluated her I received, as I might have expected, a most significant reply 14. He referred to the appearance of Watson's book, The Double Helix, in 1968:

... It also caused me a great deal of irritation not least in its reference to Rosalin Franklin whom I remembered well because I supervised her in Physical Chemistry for the whole of her Part II year. She than did a year's so-called research with Norrish, which she could not bear, before going to BCURA. Happily I still have my supervision notes and a very clear recollection of her. My report to Newnham JR. F's College, which would have arranged her supervision] in the third term was to the effect that Miss Franklin was certainly capable of getting a First because she had qualities of pertinacity and penetration which were rather exceptional. But I did not expect her to do so because she was very selective in the use of her time, going to depth in the things which interested her and neglecting the other parts of the subject. In the event this is exactly what happened in the Tripos Examination with the result that she only got a 2:1.

Both Barbara and I found her a very nice person indeed, though terribly shy and somewhat withdrawn from social contact. For example she gave us, very perceptively, just the wedding present she knew we would like. I was also much touched when about eighteen months before she died she turned up to a lecture I was giving at Birkbeck College and I noticed that she had changed into a charming and almost gracious woman though with none of her sharpness of criticism diminished. I was very glad to see Mrs Sayre's book about her which has put the record straight. Nothing need be added to this statement.

After the practical class, my next meaningful encounter with Rosie Franklin was in 1952. I was visiting the colleague already mentioned, now Professor W. C. Price of King's College Physics Department, London, essentially on spectroscopic interests. He

14 Lord Dainton, letter to Mansel Davies, 10 March 1982.

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knew of my association with Astbury's laboratory, and, in that context, told me that 'Randall's group was down the corridor'. I must have said that I would be interested to know what they were doing, but that I did not know Randall. 'Oh', he said, 'don't worry: go to see Rosie Franklin, she's there'. I straight away found her working in a typical basement room. No explanation on my part was needed for my interrrupting her. On thinking of it, I have concluded that she had clearly digested Astbury's 1947 paper, and knew that I had made some study of DNA. She was immediately pleased to tell me what she was doing and what she had found. When she showed me her photographs I was truly astonished at the detail they contained. I have never forgotten how my pulse raced. It did not need my telling her how vastly superior her photographs were to the ones I had taken. I realized she was showing me a key to the solution of the DNA problem.

After my enthusiastic acclaim, I was anxious to learn how she had achieved this success. She explained how she produced the thin threads by drawing them out from a drop of gummy DNA solution, forming them into bundles, and controlling the humidity whilst recording the diffraction pattern. I have no memory of discussing the structural interpretation of the photograph. Having learned with Astbury how much could be deduced from the details of a fibre photograph, I probably had little doubt that systematic evaluation of her patterns would lead to major insights into the DNA structure.

Again, there are unusual aspects to note. Firstly, the Wilkins-Gosling-Franklin photographs, and more particularly Rosie Franklin's of 1952-53, provided the incontrovertible evidence for the DNA double helix. But more startling is the fact that Crick and Watson--as far as X-ray results were concerned--had almost completed their brilliant delineation of the structure merely on the guidance of details in photographs of degraded, excessively dehydrated, poorly crystalline Leeds DNA preparations. Final confirmation was given to Watson when as late as 1953, he briefly saw a Franklin photograph of the B-form of DNA which showed the immediately recognizable features of a helical structure.

This is an aspect of the Crick-Watson success which must make it almost unique in the history of modern science. One is inclined to emphasize that their solution was only dependent on hard evidence to a subsidiary degree. It was primarily the result of motivation arising from the conviction that the DNA structure was of supreme significance: because the transmission of the genetic code must arise from some clear, if not in fact (as it proved to be) simple structural features in the molecule. It was a triumph for intuitive insight.

In the presentation of Rosie Franklin's role, Watson was unfairly dismissive, but Olby carefully plots the situation. There was the occasion when Watson sought out Franklin at King's College on 30 January 1953. Watson describes how, as the advocate of a helical structure which, at that particular time Franklin decried: 'I decided to risk a full explosion. Without further hesitation I implied that she was incompetent in interpreting X-ray pictures' (Watson, p. 147). Of course, he was not risking, he was asking for an explosion. Watson did not realize that in terms of X-ray crystallography, Rosie Franklin was looking down her nose at this tyro: her almost violent reaction led to his moving quickly out of the room.

This is easily understood. Rosie Franklin was an experienced X-ray crystallographer. Watson was an American biologist who had picked up some understanding of X-ray patterns incidentally to his interest in DNA. But Rosie Franklin almost certainly made a mistake; Watson, for all his rudeness, could well have

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given her clues to the solution of the DNA structure. However, they were of such different characters: one soberly conscientious, with an unbending professional attitude to her work; the other a bright spark, with a devil-may-care attitude. Only if Rosie had been an angel could they have hit it off to indulge in useful exchanges.

I offer this opinion as it seems unjustified to write of Rosie Franklin as 'difficult'. The epithet has arisen because she was an individual orientated by her own scientific interests, and happiest pursuing them without unnecessary interference. The ease, if not in fact pleasure, with which she accepted my queries suggests that some element of understanding was all that was needed at least to ensure smooth initial relations.

Klug, who worked more closely with Franklin than anyone else, and who has had access to her notebooks, has made explicit how detailed was her appraisal of the photographs she had taken, is Determined, or, as it did not aid her progress, one must say grimly determined to make no avoidable assumptions, she pressed forward with her formal analysis. This was not a very intelligent modus operandi. To unravel a major problem of nature, it is reasonable to use all possible honest stratagems, including the making of working assumptions. By the nature of the case, it seems to me that any truly novel scientific advance can only be achieved on the basis of initial assumptions.

One final aside on the DNA saga. There is a very revealing account by Chargaff of his meeting with Crick and Watson at Cambridge in 1952. 'They impressed me by their extreme ignorance. I never met two men who knew so little and aspired to so much. They were going about it in a roguish, jocular manner: very bright young people who didn't know much . . . . It struck me as a typically British intellectual atmosphere, little work and lots of talk' (Judson, p. 142).

This is the impression that two of the younger and distinctly liberated members of the post-war generation could make on a senior colleague. He had, at least, spotted that they were 'bright'. The emphasis on their 'ignorance' is significant, and not atypical of continental colleagues when they meet young British scientists. An established German scientist having spent a week in one of our most prestigious research institutes in the thirties was known to say (I paraphrase): 'I could not have believed that such active participants in major scientific research could be so ignorant of their subjects'. Two reasons were (and are), the shorter period of pre-research instruction in Britain, and the fact that British scientists are often unable to read any foreign language literatures in their subjects. In the Crick-Watson case, it was their failure to have read the American journals carrying accounts of highly relevant work by Chargaffand his contemporaries which led to his dismissive assessment of them.

Acknowledgments The draft of this account has been read by a number of colleagues and I wish to

thank Professor R. Olby, Professor A. F. C. North, the late Dr R. Reed, Dr K. M. Rudall, Dr R. Lumley Jones, Mrs M. Astbury-Pereson, and Lord Dainton for their interest and help.

15 A. Klug, 'Rosalind Franklin and the Discovery of the Structure of DNA', Nature, 219 (1968), 808-10 and 843-4.