Rosalind Franklin

by Brenda Maddox

  Klug, a small neat quick man with an ironic smile, was then twenty-six. South African, the son of Jewish immigrants from Lithuania, a graduate of the University of Witwatersrand with a master’s degree from the University of Cape Town, he had taken a PhD from Cambridge in 1952 and come to Birkbeck the following year on a Nuffield Foundation fellowship to do X-ray analysis of biological molecules. His wife, Liebe, was a modern dancer and choreographer, and they had a small son. The couple rapidly became Rosalind’s personal friends — her new Luzzatis.

  Rosalind needed a new friend because she had a new enemy. She came back from America ready to write. After a year’s hiatus in 1954 when she had published nothing, she had accumulated enough information through a mass of excellent X-ray photographs for a number of papers on TMV. The first was to be for Nature on the virus’ structure and she sent a copy of the manuscript to the British virologist Norman W. Pirie.

  Pirie had a proprietary interest in plant viruses. He grew his own at the Rothamsted Experimental Station in Hertfordshire and had supplied Rosalind with specimens for her research. He and his colleague, Frederick Bawden, were the Gilbert and Sullivan of British plant virology, their names linked since their landmark paper in 1936 revealed that the virus was long and thin, like a pencil or a stick of cinnamon. Watching the pair in action, the young French geneticist François Jacob saw ‘old cronies who loved to play the buffoon, trading jokes and metaphysical aphorisms, all in a rapid choppy English which left me in a cold sweat’. Jim Watson, when he was working on TMV, witnessed their confident double-act dominating a meeting: ‘No one could match the smooth erudition of Bawden or the assured nihilism of Pirie, who strongly disliked the notion that some ‘phages have tails or that TMV is of fixed length.’

  But Rosalind had found, from X-ray photographs of a kind no one had taken before, that the TMV rods were all the same length (3,000 Angstroms). She said so in the opening line of her paper. She also said that protein subunits inside the rods were identical.

  Pirie would not hear of it. Among his colleagues he was known to be difficult and abrupt with younger people, and made no attempt to conceal this, least of all from a young woman researcher with no academic rank, whose new grant from the Agricultural Research Council he and Bawden had approved. He wrote an irate letter to ‘Dear Miss Franklin,’ as if she were a lazy student:

  As you probably expected I have all the usual objections to this paper. But in case the faults have slipped in through inadvertence I may as well itemise some of them.

  You start off with a bald erroneous statement. It is true that under certain conditions of testing, the number of lesions given by a constant weight of material is greater the greater the proportion of 300 mp particles in the prep. It is also true that preparations nearly free from 300 mp are infective to an extent that makes it unreasonable to assign all the infectivity to one length of particle. Defined biologically therefore you cannot say TMV is 300 mp long. Also no one has published data on any preparation in which 300 mp particles make up more than half the total weight; so the statement isn’t true physically either.

  This is all no doubt a pity for succinct writing but there it is.4

  The argument from amino acid composition to weight of the protein sub-units depends on knowledge of how many types of sub-unit there are. You, baseless, assume only one. I would be more cautious. If you want an argument in favour of such caution I would remind you of all the excitement that now accompanies the demolition of the old, baseless, tetranucleotide picture of RNA, etc. Only those who did not realise that nature should not be assumed to be simple ever swallowed the hypothesis. I suggest here that the idea of a single type of sub-unit is the least probable of all the possibilities . . .

  And there was much more. Rosalind sensed that Pirie was a dangerous enemy to have. With greatest respect and thanking him for his continued help, she defended her own findings. So she should have done. She was right and he was wrong. The TMV rods are of the same length, and the protein subunits — as her research proved — are identical. On 7 December 1954, she replied:

  Dear Dr Pirie,

  Many thanks for your letter and criticisms, which were as you suggest, not unexpected. In particular, I was afraid that you would disapprove of the first sentence. But the E.M. photographs (Williams et al.) of the ‘crystalline inclusions’ breaking up do seem to show a convincing uniformity of length, indicating a fundamental unit of length 3000 A, and the fact that such units are often aggregated end-to-end does not vitiate any of the argument.

  What the crystallographic data show is that the units are sufficiently similar to enable them to occupy structurally equivalent positions . . . One of the merits of the Watson and Crick DNA structure is that it explains how different bases can occupy structurally equivalent sites, and it seems that something of the same kind must happen in the virus protein. But the nature of the X-ray diagram shows that there is a high degree of repetition in the structure.

  In my paper I am now referring to the units as ‘structurally equivalent’.

  It is never a good idea to let your opponent know your worst fears, as Rosalind did when she concluded, ‘I hope that you do not disapprove so strongly of what I have written that you will never again be willing to provide me with material to work on.’

  A vain hope. Pirie was so annoyed with her for the paper that appeared in Nature that he stopped sending her viruses. From then on she and Klug had to grow their own. What they could not grow for themselves was Pirie’s influence with the Agricultural Research Council (ARC) and its powerful secretary, Sir William Slater.

  Far friendlier eyes on the same Nature manuscript were cast by Jim Watson. He had proposed the basic shape of TMV in a paper in Biochimica et Biophysica Acta, and Rosalind was building on his idea, correcting it with the help of her unique X-ray photographs. Watson wrote Rosalind from Caltech in December that he and his colleagues, Leslie Orgel and Don Caspar, had all read her draft and liked it. ‘Thus the following criticisms are only of 2nd degree importance.’ There followed a long list of technical points (along the lines of ‘Size of subunit 5 x 102 95% = 4.5 x 10 7/37 x 3,000 over 68 = 35,000’). Watson ended, ‘In spite of these criticisms, a very nice summary of TMV status . . . We are naturally curious as to what you are doing.’

  Whatever impression Watson’s flopping shirt-tails and laceless canvas shoes had made at Cambridge, there was nothing untidy about his science. His notes to Rosalind were in tiny writing as precise as a typewriter’s, with clear diagrams and formulae: the marks of a man who saves neatness for where it counts.

  Rosalind’s second TMV appearance in Nature followed a few months later in a joint paper written with Barry Commoner of Washington University in St Louis, who had sent her a preparation of his abnormal protein called B8 associated with tobacco mosaic virus after their meeting in St Louis the previous summer. Commoner (later the well-known ecologist) had the advantage of equipment she lacked. ‘There not being an ultracentrifuge anywhere in this college,’ she wrote him, ‘I concentrated the solution you sent me simply by allowing it to evaporate slowly through the dialysis bag.’

  Frequently she went to Cambridge to talk with Francis Crick, who had returned from Brooklyn. Like Watson, he was deep into RNA and virus structure. For Rosalind, Crick had moved into the ‘brilliant’ class that stirred her hero-worshipping tendency. In him she saw the gravitas, demeanour and acute reasoning she expected of a great scientist. ‘She would do nothing without clearing it with Francis,’ Klug observed. Yet Rosalind could scold even Crick, and was heard lecturing him, ‘Facts are facts, Francis.’

  (When another of Rosalind’s heroes, Linus Pauling, was awarded the Nobel prize for chemistry in late 1954, Rosalind was horrified that the BBC news report concentrated on Pauling’s politics rather than his achievements as the greatest chemist of the time. She got her Birkbeck colleague Wolfie Traub to call someone he knew at the BBC and ask them to rewrite the bulletin.)

  She and Klug were hard at work on two jo
int TMV papers. Between them they agreed that Rosalind would concentrate on the rod-shaped viruses such as TMV, while Klug would move to the spherical viruses affecting other plants. (Plant viruses appear as rods or spheres.) They needed assistance, and with advertisements in Nature struck gold. Two future Fellows of the Royal Society joined them as research assistants, registered for a PhD and threw themselves into the work. John Finch joined in January 1955, from King’s College London (where he had heard vaguely of some difficulty between Rosalind and Maurice Wilkins, but nothing more). Kenneth Holmes, from St John’s College, Cambridge, joined in July. Rosalind decided the division of labour: Holmes would work with her, taking rod-shaped viruses as his thesis topic; Finch would tackle spherical viruses with Klug, with Rosalind in overall charge.

  Holmes and Finch saw at once that Klug and Franklin had harmonising skills and temperaments. Both could be aggressive when science was at stake — Klug so much that Rosalind had to restrain him. ‘Don’t bully, Aaron,’ she would chide. Klug, for his part, a theoretician, in no way saw Rosalind as a mere experimentalist, an unequal partner. ‘It takes imagination and intellect to know precisely what experiments to do, to design them, prepare the specimens and then to observe the results,’ he said retrospectively. ‘She worked beautifully. Her single-mindedness made her a first-class experimentalist, with the sort of skill that blends intelligence and determination.’ It was not, he emphasised, ‘just good needlework’.

  Holmes, who worked closely with Rosalind, got to know her well, and before long, in his words, ‘would have gone through fire and water for her. She was prickly and difficult, especially at first, unable to put people at their ease. There was a forcefulness about her manner . . . a barrier to be overcome if you wanted to get to know her.’ His fiancée, Mary Scurby, who worked in the Birkbeck research library, found Rosalind hard to talk to. She was surprised to learn Rosalind had much admired the circular red felt skirt she had worn to a concert to which Bernal invited them all as a staff outing. John Finch did not work as closely with Rosalind and remained a bit wary of her, but admired how she nursed her viruses as they grew in their gels; he saw fine work, beautifully done.

  With Holmes, as with the others, Rosalind was very insistent that the work be done the way she wanted it done. One day, very proud of himself, Holmes cured a problem with the Beaudouin X-ray camera she had brought from France. Cleaning its tubes to get a vacuum was difficult, and after struggling, he devised a vacuum gauge to be fitted to the X-ray tube. To Klug’s and Finch’s amusement, Rosalind was not impressed. ‘We want to make X-rays, not measure vacuum!’ she scolded Holmes.

  Holmes thought she was beautiful. Looking back, he believed that, of course, Bernal would have made a pass at her — ‘a woman that attractive’ — if he had dared. It was an office sport to watch, when there was a new secretary, how Bernal would keep finding excuses to come into the office. But Rosalind’s formidable facade held off even this most intrepid of womanisers. She knew his weakness, however. Everybody who worked in the Torrington buildings noticed the creaking floorboards from Bernal’s flat and the strange women coming downstairs in the morning. There was an embarrassing incident when Bernal’s car was stolen from a street in Soho. Vittorio Luzzati was visiting at the time (Bernal had great respect for Luzzati’s abilities at X-ray analysis), and Rosalind tried to explain to him why Bernal’s car should have been parked in London’s red-light district. ‘C’est un endroit où sont les femmes!’ she said. ‘She didn’t know the French word putain [prostitute],’ Luzzati recalled. ‘She was very puritanical.’

  With Klug, Finch and Holmes, and another research assistant, James Watt, subsidised by the National Coal Board, who worked with her on coal, she had a quasi-family. She proudly added to her curriculum vitae ‘Leader of ‘‘ARC Group’’ at Birkbeck’. One of their unofficial functions was to act as buffers in her relationships with the rest of Birkbeck.

  Buffers were needed. When Rosalind’s technician, Bryon Wilson, told her he intended to take advantage of Birkbeck’s scheme of offering staff a week off for education — he wanted to work towards an O-level certificate — she questioned his intellectual abilities in words that stung. When he persisted, she transferred him to her coal research assistant and ignored him after that. (Wilson eventually got a doctorate and became a lecturer in microbiology at St Mary’s Hospital Medical School.)

  The same qualities of abruptness, reserve and suspicion that had been noticed at King’s College were noticed at Birkbeck too. Bernal’s people saw themselves as a family into which Rosalind didn’t fit. According to Wilson, ‘Everybody called her ‘‘Rosy’’ behind her back. She didn’t like it!’ She tended to pass people on the staircase and not say hello. She did not come to tea in the lab as the rest did. Holmes, one of her great admirers, acknowledged, ‘She was not a great communicator.’ He attributed it to her shyness. The clerk to the college, A.J. Caraffi, on the other hand, blamed her lack of academic status. This left her, Caraffi thought (although personally he saw her as a woman of wit and sparkle), with a feeling of ‘not quite belonging’ to the staff.

  She was notorious as a non-conversationalist. At lunch in the faculty dining room (where she had at first trouble gaining admittance because she was considered non-faculty or ‘external staff’), one day she plucked up courage to comment, ‘It’s a fine year for mushrooms,’ and lapsed into silence again.

  She had an outright clash with Stan Lenton, the college’s much-admired steward in charge of technical services. Lenton grew very irritated with the curt way in which Rosalind would ask for new equipment. Things came to a head when she ordered a massive transformer from Paris. The monster gadget turned up at a Customs freight department in south London. From long experience, Lenton knew the forms and procedures necessary to get things through Customs without being charged duty, but Rosalind declared she was ‘quite capable’ of dealing with it herself. A week later she knocked on his door and acknowledged defeat. He solved the problem for her and, ‘We never looked back after that.’

  One reason to hold herself aloof was that so many of Bernal’s staff were extremely left-wing or even outright members of the Communist Party. The social divide between her and them was real. People at Birkbeck were aware that there was money behind her. As someone put it, ‘She lived in Kensington and she travelled.’ One evening a big car drove up to 21 Torrington Square; from the back a woman in evening dress asked for Rosalind. The porter who went up to call her found her in her lab coat and was told she would be down in ten minutes. In exactly ten minutes, she emerged, elegant, transformed, and was driven away.

  If Rosalind made much the same impression at Birkbeck as at King’s, the great difference was that at Birkbeck, she was leader of a team doing superb work; she was neither isolated nor unappreciated nor unprotected. Bernal thought the world of her and saw that her firmness inspired those around her to reach the same high standard.

  If she had lacked a collaborator at King’s, she now had three, and in mid-1955 acquired a fourth. The American biophysicist Don Caspar, whom Watson knew at Caltech, held a PhD from Yale, with a thesis on TMV. In mid-1955 he left Caltech to spend a year at Cambridge as a postdoctoral fellow in molecular biology, and asked Rosalind (with many friendly references to ‘Jim’) if he might work with her for a time. Rosalind replied that she was interested but had no funds and also had two new people to look after, but ‘if that doesn’t put you off we shall be very glad to have you’.

  Caspar was an ebullient twenty-seven. Having known Rosalind only through correspondence, when he finally met her in the summer of 1955, he was taken aback. He had expected a dour English bluestocking, ‘and she turned out to be an attractive vivacious young woman’. The ingredients for compatibility were there: Caspar was foreign, very bright, with a Jewish background and an intense preoccupation with their mutual special subject. He was unmarried and had a disarming friendliness. One day when he arrived to see her, Rosalind was outside on the steps, with Ken Holmes and James Wat
t. When the small moustached smiling figure hailed her, ‘Hey, Ros!’ her companions waited for the explosion. There was none. Somehow the young American got away with it. ‘I had no hang-ups with her at all,’ Caspar said, and was astonished that others did.

  Caspar’s work and Rosalind’s meshed perfectly. At Yale he had discovered, as she had heard from Jim Watson when she was at Caltech, that the tobacco mosaic virus has a hole straight through the middle. The hole came as a surprise because the virus’s centre had been thought to be full of the nucleic acid, RNA.

  Rosalind was on her way to an answer to the related question: where is the RNA, if not in the central cavity? From her X-ray pictures which gave her better data than had been available to Caspar and Watson, she discovered that the RNA is deeply embedded between the protein subunits, winding around its inner groove like a twisting thread. She found also that the protein surface of the TMV is like a knobbly screw.

  Summary of the first analysis of the structure of TMV shows the protein subunits ranged around the hole at the core, with the RNA embedded between the protein subunits, winding around its inner groove like a twisting thread. This diagram was published by Klug and Caspar in 1960.

  Caspar was employing, just as Rosalind, Klug and Holmes had in their own research, the very new technique, developed by Max Perutz, of isomorphous replacement, or heavy atom substitution. That is, they introduced some atoms of a heavy element such as mercury or lead into the virus protein. The difference between the X-ray patterns produced by crystals of the molecules with and without the heavy atoms then reveals the structure. Revealingly, the graphs plotted by Caspar and Rosalind, when superimposed, showed the exact distance of the RNA from the centre of the virus.