Authors: Brenda Maddox
With her photographs increasingly clear and sharp, Rosalind took a set to Oxford to show Dorothy Hodgkin. They spread them out on the big tables of the shabby museum laboratory where Dorothy worked. (âLike most British labs,' an American visitor commented, âit looks like the corner of a dusty old barn.') Hodgkin exclaimed that Rosalind's photographs were the best she had ever seen â so clear, in fact, that it might be possible to work out the space group of the crystal. (According to the
International X-ray Tables,
crystals are classified by their symmetry â that is, the shape of their unit cell â into 230 space groups. Prepared by W.T. Astbury of Leeds, with Kathleen Lonsdale, at the Royal Institution and published in 1924, the tables were, in Rosalind's time, the crystallographer's Bible.)
Rosalind volunteered that she had already narrowed the possibilities down to three space groups. But two of these, Hodgkin swiftly pointed out, were impossible. Only one had the correct âhandedness' for the sugars in DNA. Rosalind accepted the correction.
3
Rosalind never doubted that the B form of DNA was a helix. How could she have done? That was the general view at King's. It was what she said in her Turner and Newall report and it was what Randall reported to a meeting of the biophysics committee of the Medical Research Council on 14 March 1952. The MRC committee, formed in 1947, oversaw all biophysics research expenditure and met regularly at its recipient institutions.
That day the MRC committee gathered in London at the Department of Clinical Research of University College Hospital Medical School. Randall's progress report was one of two items on the agenda. At King's, he announced, the apparatus-building phase was over; now they were conducting a concentrated attack on cell structure. In sum, âFrom the X-ray evidence nucleic acid was now thought to have a helical structure.' Randall invited the committee to hold its next meeting at King's, where the new physics department was nearly finished. The visit was arranged for December.
For her Easter break in 1952 Rosalind went on yet another walking tour of North Wales. Her companion that year was Margaret Nance, who had accompanied her to the Italian Alps and who often, now that they were both back in London, joined Rosalind in long walks around London, to Windsor Great Park or the Berkshire Downs. Rosalind would ring up, and, according to Margaret, âwould not take no for an answer. If I refused, she wanted to know why.' But Margaret liked her, in spite of her occasional fierceness, for her vigour and her great love of the outdoors.
On I May 1952 the Royal Society held a meeting in London on proteins. Pauling, who was to have been the guest of honour, was absent. There was general astonishment that (even though the excesses of McCarthyism were well known) such an eminent scientist should be banned from leaving his own country. During the day Rosalind was approached by Pauline Cowan, a student of Dorothy Hodgkin's, who was wondering whether to accept an offer from King's. âDon't' was Rosalind's advice. King's was not a happy place, she said, and contrasted badly with Hodgkin's cheerful and productive lab in Oxford.
Jim Watson was also there. He was still at the Cavendish in Cambridge, his work now supported by the National Foundation for Infantile Paralysis. Thwarted in his DNA pursuit by Bragg's ban, he was working on ribonucleic acid, RNA, in the form found in the virus that mottles tobacco leaves: tobacco mosaic virus, or TMV.
Watson had not forgotten about DNA, however, and wrote to his mentor Max Delbruck that Maurice Wilkins at King's had obtained âextremely excellent' X-ray diffraction photographs of DNA, adding:
It is obvious that a great deal of work should go into elucidating this structure. However, the people at King's are involved in a fight among themselves and so at present no real effort is being made to solve the structure. We have attempted to interest them in attempting to build plausible models. However, we have temporarily stopped for the political reason of not working on the problem of a close friend. If, however, the King's people persist in doing nothing, we shall again try our luck.
After the Royal Society meeting, Rosalind showed some of her DNA photographs to Robert Corey, Pauling's colleague and an eminent protein chemist, who had attended in Pauling's place. Corey carried the news back to Caltech. Rosalind's photographs were superb. Pauling himself had taken a few unsatisfactory photographs of DNA that year and his interest was whetted by what Corey told him.
While she was at the Royal Society, her camera was on. The X-ray photographs she and Gosling were taking required long exposure â as much as 100 hours â of a single DNA fibre positioned at very close range â 15 millimetres. Sometimes during exposure, the fibre would change from the crystalline A form to the paracrystalline B form. Once this happened so abruptly that the fibre fell off the holder. The photograph taken between 1 and 2 May showed a stark x, formed of tigerish black stripes radiating out from the centre. The spaces between the arms of the x were completely blank. It was the clearest picture ever taken of the B form of DNA, unquestionably a helix. Rosalind numbered it Photograph 51 and put it aside, to return (as agreed with Randall) to the puzzle of the A form.
This decision, in the light of subsequent events, has been much criticised. But she had every reason to continue interpreting her A-form patterns, for these contained more of the information useful to crystallographers. She refused to see a helix in the A form without more proof. She had two serious papers in preparation announcing her discoveries and preferred to wait until she was sure. What was the rush?
Struck by the macroscopic (that is, visible to the naked eye) change in the fibres between the A and the B forms, she wondered whether the molecular structure could have been changed and that the helix of B could have come unwound. Her dilemma in July 1952 is described by Robert Olby in the
Dictionary of Scientific Biography:
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the cylindrical Patterson function obtained by Gosling strengthened her antihelical views, although the arrangement of peaks was consistent with a helix. She was misled, by what appeared to be clear evidence of a structural repeat at half the height of the unit cell, into ruling out helices for the A form, since no DNA chain could possibly be folded into a helix with a pitch equal to half the height of the unit cell
(14
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Everything in her education and background had taught her to be absolutely sure of her facts before she presented them to the world. No less than Dorothy Hodgkin in retrospect agreed with the soundness of Rosalind's approach. âAs Rosalind was necessarily involved in collecting the accurate data on DNA, it was natural of her to postpone model building until her data was complete, and until she had extracted all the information she could that would limit the kind of model she should build.'
For Rosalind the price of sticking to her guns was condescension. At a meeting at the Zoological Museum in Cambridge she ran into Francis Crick in a queue and told him about the asymmetries she was getting in the A form. Crick warned her that she was being misled into thinking that the A form was not a helix; that there were other explanations for what she was seeing which would accommodate a helical structure.
Crick had spoken condescendingly. Later he was to say, âI'm afraid we always used to adopt â let's say a
patronising
attitude towards her. When she told us DNA couldn't be a helix, we said, Nonsense. And when she said but her measurements showed that it couldn't, we said, ââWell, they're wrong.'' You see, that was our sort of attitude.' Crick, in this case, was right: the kind of asymmetry that Franklin was finding in the X-ray reflections could be accounted for. But she too was right in her defensiveness; she knew when she was not being taken seriously.
If she had felt very confident and supported, she might have been able to make outrageous leaps of imagination. âLack of intuition' does not begin to cover the lattice of emotions, warnings and sensitivity to a hostile environment that told her to be wary and proceed with caution.
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In May, her reputation in coal research brought her an invitation from an unexpected quarter, Yugoslavia. She went off happily, having heard from Bernal that he would take her at Birkbeck any time that Randall agreed. She thought it politic to postpone telling Randall that she was leaving until she got back from her month's travel.
To be abroad once more was bliss â apart from the large cities: âafter 2 days in Zagreb I shall be able to spot a Croat a mile off for the rest of my life'. As for Belgrade: âa pathetic place, where nothing is permanent and nobody knows whether they belong to east or west'. Otherwise, she encountered impressive research, kind people and spectacular scenery, marred on occasion by political proselytising.
In Zagreb, where she went to give a lecture on âSome aspects of the ultra fine structure of coals and cokes', arranged by two university professors, she met Katarina Kranjc, the first woman in Yugoslavia to use X-rays and the first to take a PhD in physics. Only five years older than Rosalind, Kranjc went to the station with a large bunch of red roses. âI do not know what I imagined a woman scientist should look like,' she wrote later, âbut I certainly did not expect her to be such a charming young girl: my astonishment was enormous.' Kranjc observed also that Rosalind was very concerned with her health and always peeled peaches before eating them.
The lecture was a great success. Visits by foreign scientists were rare and Rosalind's talk was their first direct information about crystallographic laboratories in Britain and France. Afterwards Kranjc and another chemist working on X-ray structure analysis, Dr. Drago Grdenic, took Rosalind to the opera and a theatre café. Returning to her hotel, she gave them small packages of tea and coffee as presents. They all spoke French together and her new acquaintances thought they had never heard any English person speak it better.
The trip included two days' walking and a night in a hut in the Julian Alps, and a week, which she took as holiday, on the Dalmatian coast. Dubrovnik was lovely; at Split the local scientific institute took her on a boat trip to a nearby island, with experts to expound on everything from microbiology to the economics of fishing. âThey reckon that they have already succeeded in increasing the fertility of the sea 40-fold in certain regions.' At Kricula, âthe loveliest of all', she enjoyed the company of a young Italian schoolmaster who had been asked to show her around:
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we wandered round a series of deep blue coves amid rich tropical vegetation, and bathed in the sea. When I told him that in England if the sea was more than a few metres deep you couldn't see the bottom he thought it the greatest joke. He said he really must go there one day, just to see â which I thought was very broad-minded of him. I'm sure if I lived in Kricula I should have no urge to travel. Then we talked politics, and he produced the most preposterous communist propaganda statements about England, which my Italian was utterly unable to answer adequately.
After passing through Venice, then stopping for two days in Paris, she was home. It was, she wrote the Sayres, âall too good to be true â I imagine I shall have to wait a long time for such a thing to happen again'.
In June 1952 the hole in King's courtyard was filled at last. The new Physics and Engineering laboratories were opened, dedicated on 27 June by Lord Cherwell, Churchill's scientific adviser. For the occasion, the Wheatstone Physics Laboratory issued a pamphlet relating its long history, plus an account of the current research activities of the department. These included the work of the group on âMolecular Structure of Nucleic Acids and Nucleoprotein in Cells', whose members were listed as âM.F.H. Wilkins, R.E. Franklin, A.R. Stokes and R.G. Gosling' and their work summarised:
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The pure sodium salt of desoxyribose nucleic acid may be extracted from cells and crystallised, and X-ray diffraction shows the crystal to consist of a parallel arrangement of helical polymer chains. A very similar arrangement of chains also exists in nucleoproteins in living cells.
The research, it was hoped, might cast light on the biological function of nucleic acid and even on specific molecular structures which may be associated with gene action.
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King's got little credit for getting this far, because it did not go on to discover what linked the parallel chains or indeed to offer any clue to âgene action' â how the DNA molecule replicated.
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While Rosalind was in Yugoslavia, Watson and Crick in Cambridge met Erwin Chargaff from Columbia University in New York City, whom they knew to be one of the world's experts on DNA. It was Chargaff who in 1950 had discovered that in DNA, the number of adenine molecules is always nearly the same as the number of thymine molecules, and a similar correspondence is found with cytosine and guanine. In other words, there are equal numbers of purine and pyrimidine molecules. Chargaff analysed the proportions of the four bases of DNA and found a curious correspondence. The numbers of molecules present in the two bases called purines were always equal to the total amount of thymine and cytosine, the other two bases, called pyrimidines.
At Cambridge Watson was an object of curiosity for his untidiness. He went about in tennis shoes with untied laces, wore shorts even in the winter and stared at people with his mouth open, snorting with laughter. Yet all the passion Rosalind felt for France, Watson felt for England: the colleges seen from the Backs of the River Cam were for him âthe most beautiful buildings in the world'.
He had instantly judged Cambridge as a whole âthe most attractive site for science in Britain, if not the world'. Thwarted in his DNA pursuit by Sir Lawrence Bragg's ban, and determined to remain in Cambridge, he was applying himself to the related nucleic acid, RNA. He expected the RNA molecule to be in the shape of a helix â that is, a spiral, like Pauling's alpha helix of protein.