Franklin had worked systematically on how water affected the structure of DNA. Increasing the relative humidity transformed ‘damp’ DNA into ‘wet’, and vice versa. She gave the name ‘A form’ to the damp fibres which had produced the beautiful crystalline photo for Wilkins and Gosling back in April 1950. Wet DNA, which she called the ‘B form’, yielded a different picture: the dramatic X-shape which, according to the calculations of both Stokes and Crick, was produced by a helical structure. This was the ‘helical cross’ pattern which she had shown Wilkins with her ‘air of cool superiority’, although that particular example – one of her earliest attempts – was not especially striking.
Franklin never hesitated to describe the B form as ‘helical’. The A pattern, which Wilkins and Gosling had discovered but which Randall had allocated to her to work on, was a much greater challenge. Initially, she believed that it too had a helical structure, with regular distortions introduced by the removal of water which somehow made it look crystalline. Her attempts to work out the A structure led her into territory where no crystallographer had gone before: dragging the already cumbersome Patterson analysis into three dimensions to try to cut through the confusion between helix and crystal. This was no mean feat – Max Perutz later described it as ‘one of the most difficult conceptions in crystallography’ – and it took months for any answer to emerge.
In the meantime, she and Gosling were feeling their way in the dark and with no obvious light at the end of the tunnel. Their tilting camera had at last been built and was producing good pictures from DNA fibres mounted on their bent paperclip. Recording the data was a tedious, two-person operation: Franklin standing at the front of the dimly lit room, measuring the position and intensity of each spot on the projected image of the X-ray film, and calling out the numbers to Gosling who wrote them down on filing cards. To outsiders, the impression they gave was of being ‘buried in papers for weeks, getting nowhere’.
Before long, the complexities of the Patterson analysis, compounded by some freak results, led them astray – so far that Franklin began to doubt her initial assumption that the A form was helical. In February 1952, she suggested in her fellowship report that the structure consisted of two or three helical strands, tightly intertwined around a common long axis. Two months later, while standing with Francis Crick in the lunch queue at a meeting in Cambridge, she admitted that she no longer believed in the helix. Crick told her that this was nonsense and that her calculations must be wrong.
A conference in Yugoslavia that spring must have been a welcome break, especially as she was invited to speak about certainties (the X-ray properties of coal) and then went on to a holiday on the Dalmatian coast. When she got back to King’s, the doubts returned. Her ‘anti-helical phase’ reached its climax on 15 July 1952, when Wilkins received a handwritten card from Franklin and Gosling. It was black-bordered, like an obituary notice, and announced ‘with great regret the death of DNA Helix (Crystalline)’. The cause was ‘a protracted illness which an intensive course of besselised injections had failed to relieve’. This epitaph for a working hypothesis seems to have been an accurate reflection of Franklin’s thinking at that time; she was at last closing in on the ‘unit cell’ – the basic building-block of every crystal – of DNA, from the morass of data generated by the Patterson analyses.
The A form was no longer his business, but Wilkins was not amused by the spoof death notice. Indeed, it unsettled him. There was no evidence that the ‘wet’ DNA he was working with – in the heads of cuttlefish and squid sperm – was anything but helical, but he still had not extracted a decent X-ray image from Chargaff’s DNA. Despite Franklin’s hostility, he respected her greater experience in X-ray crystallography, and her doubts about the helix eventually began to infect him. He later wrote that she put him ‘on the wrong track’ and for a while ‘fairly well convinced me that the structure might not be helical’.
His uncertainty came through in the report prepared for the annual visit of the MRC Biophysics Committee on 15 December 1952. Wilkins wrote the overview of the DNA work, referring to its helical structure but also mentioning that reservations had emerged about it. In her section, Franklin did not mention the word ‘helix’ at all, and instead laid out a classic crystallographer’s stall with her estimates of the dimensions of the ‘unit cell’ of the DNA ‘crystal’ – as it might have appeared in the International Tables for Crystallography that Astbury and Yardley had compiled back in 1924.
In the event, the MRC visit went well, with no awkward questions about helices. Afterwards, the annual report of the King’s Biophysics Unit, including the detailed contributions by Wilkins and Franklin, was circulated to all members of the MRC Biophysics Committee. The contents were not confidential and would never have been withheld from colleagues in the sister MRC unit in Cambridge. However, they were not routinely sent to junior researchers such as Francis Crick and Jim Watson.
Franklin’s fellowship still had over a year to run, but the MRC report of December 1952 was her last at King’s – because she was leaving. News of her departure had broken in November; the most obvious reaction was from Ray Gosling, who was saddened and distressed.
Franklin had been desperate to quit King’s for many months. Her trip to Paris at Christmas, just after the fiasco in Cambridge, had drawn a blank; Mering had no job for her. On returning to London, and without telling Randall, she contacted J.D. Bernal about transferring the last two years of her fellowship to his lab at Birkbeck. Unlike the ‘repulsive’, second-class brains at King’s, Franklin thought that Bernal was ‘brilliant’, and he was willing to take her. However, the moment was not quite right to tell Randall. She dithered through the spring and then decided to wait until after her trip to Yugoslavia.
Exactly what happened was never made clear. Years later, Gosling – who was closer to Franklin than anyone else – told Wilkins that Randall had asked her to leave. This was news to Wilkins, who wrote ‘we did not know what she had done’. From Randall’s viewpoint, there were plenty of possibilities. He might have decided that Franklin was causing too much friction, even though his original decision to set her up against Wilkins was partly to blame; or that she had not published anything on her work at King’s, especially after using eight months of her fellowship to write up her papers from Paris; or perhaps he had heard that she was plotting behind his back to take her fellowship elsewhere.
Franklin’s transfer to Birkbeck was agreed in June 1952, with effect from early January 1953. Randall made it crystal clear that this would be a complete and irreversible break, severing all her connections with King’s, DNA research and Ray Gosling. Franklin used her remaining time at King’s to finish off the Patterson analyses and write up her and Gosling’s work on the structure of DNA. And although Randall had assigned her to the crystalline and capricious A form, one of her draft papers included a stunning picture of a bold black cross that she described as ‘a very good wet photo’ of the B form. In her index of X-ray images, it was catalogued as Photograph 51.
In suspension
Shortly before Christmas 1951, Crick had drafted a reply to the two letters, formal and informal, which Wilkins sent him after the model fiasco. This was ‘a brief note . . . to try to cheer you up’ and to remind Wilkins about his ‘fortunate position’ in being close to solving ‘one of the key problems in biomolecular structure’. Crick apologised for having kicked Wilkins in the pants (‘it was between friends’) and hoped that ‘our burglary will at least produce a united front in your group’. Wilkins might well have been cheered up to receive the letter, but it was never sent.
When Watson and Crick returned to the Cavendish after New Year 1952, they appeared to be observing Bragg’s moratorium on DNA research. However, helices were still hovering in the air. On returning to proteins, Crick wondered whether cylindrical lengths of alpha-helix might themselves be twisted into a spiral. He wrote up this ‘supercoiled’ structure and infuriated Linus Pauling, who had hit on the same idea, by beating
him into print.
Watson was put to work on the tobacco mosaic virus (TMV) which, according to the terms of his fellowship, was what he should have been doing anyway. To the ‘unconcealed amusement’ of colleagues, he had to get his hands dirty doing X-ray crystallography of the virus particles. TMV was known to be a cylinder consisting of hundreds of protein subunits, stuck together like the kernels on a cob of corn, with RNA (rather than DNA) somehow woven into the structure. Despite his practical inexperience, Watson made rapid progress and in June 1952 was able to show Crick the X-ray that revealed the ‘tell-tale features of a helix’. The protein subunits were arranged in a tight spiral that formed the cylindrical surface of the virus.
By now, Crick had settled down somewhat, with a baby daughter and a city-centre house in Portugal Place that was well known for its lively parties and its bath, decorated internally with a painting (by Odile) of a lady reclining in her birthday suit. Jim Watson was also thoroughly embedded in Cambridge, where he felt at home socially and intellectually. His life was not all science; he described being swept along by parties, tennis and conference trips, all densely populated by ‘popsies’ with whom he did not record any notable successes. Watson still cut an odd figure: a tall and awkward ‘unkempt youth’ who ‘dressed like a tramp’, with a disconcertingly direct stare, an overly wide grin and a snorting laugh. He had gone native by growing his hair and affecting Anglicisms when he spoke; even when not wearing tennis shorts, he was never going to be a fashion icon.
DNA had crept back into the frame in spring 1952, when Crick went to hear a lecture on cosmology and had a beer afterwards with John Griffith, a brilliant mathematician who was the same age (twenty-three) as Watson. Griffith was born in the same year that his uncle, a government microbiologist, published a peculiar paper about pneumococci switching their identity; his sister, along with the uncle’s dog, had a lucky escape from the bomb that killed the uncle and his best friend during the Blitz. Griffith had been trying to model how genes might replicate themselves, by applying quantum theory to the forces operating between atoms and molecules. Crick had been thinking about the same problem, and whether the nucleotide sequence of a gene could copy itself by each base attracting an identical one. He asked Griffith to calculate whether this ‘like-for-like’ pairing could operate through attractive forces that pulled together the flat surfaces of bases stacked on top of each other.
Griffith revealed his results to Crick some weeks later in the tea queue at the Cavendish. Due to a misunderstanding, he had not worked out the forces of attraction between the bases’ flat surfaces, but between their edges, as if the base molecules were being pushed together across a tabletop. And his answer was not what Crick had expected. Guanine did not attract guanine, for example. Instead, like attracted unlike – a pyrimidine to a purine – and in specific pairs: adenine (A) with thymine (T), and cytosine (C) with guanine (G).
Alert readers will remember A = T and C = G as the pairings which Erwin Chargaff found when analysing the base composition of DNA from different sources. However, if Crick had ever known this, he had forgotten – and his ignorance stood revealed with awful clarity soon afterwards. In late May 1952, John Kendrew told Crick and Watson that Chargaff was to visit Cambridge, and arranged for them to meet the great man over lunch at Peterhouse, Kendrew’s College. The encounter went badly. Chargaff began by ribbing Watson about his long, un-American hair and peculiar semi-Anglicised accent. Crick then weighed in with an account of Griffith’s finding that each base had a specific partner, only for Chargaff to demand if Crick had read his papers. Which papers? Crick wanted to know. Chargaff told him about the matching base compositions, which had an ‘electric’ effect on Crick. Unfortunately, Crick then sank himself irretrievably by not being able to remember the differences between the four bases, let alone which ones Griffith had identified as being mutually attractive.
Afterwards, Crick went to Griffith to check what he had found; by then, he had forgotten what Chargaff had told him. It was only when he dug out Chargaff’s papers in the library that the ‘electric’ result was fully confirmed. Chargaff and Griffith, by two completely different routes, had reached the same conclusion, namely that A goes with T, and C with G. For now, though, how that fitted into the structure and function of DNA remained on the list of tantalising but possibly unhelpful hints.
Erwin Chargaff’s recollection of lunch at Peterhouse with Crick and Watson was detailed and merciless. He wrote later that ‘they impressed me by their extreme ignorance’. Crick had ‘the look of a faded racing tout . . . an incessant falsetto, with occasional nuggets glistening in the turbid stream of prattle’. Watson was ‘quite undeveloped, with a grin more sly than sheepish, saying nothing of consequence’. Chargaff was well known as a caustic observer of the life scientific (and prided himself as such), but even for him, the caricatures of Crick and Watson were unusually cruel. However, timing is everything. Chargaff wrote those words years later, when – in his eyes at least – he had good cause to hate them both.
DNA reared its head again in Cambridge in late May, when Crick received the newsy four-page update from Wilkins, written on the train to Zurich. If Wilkins had assumed that its content would remain between him and his old friend, he was wrong. Crick leaked like a sieve, as Watson revealed in a long letter which he sent to Max Delbrück some days later.
Watson wrote that DNA still excited him the most but was out of his reach, at least for now. He and Crick had ‘temporarily’ pulled out ‘for the political reason of not working on the problem of a close friend’ – even though ‘the people at King’s’ were making ‘no real effort to solve the structure’ because they were ‘involved in a fight among themselves’. Watson could see that the people at King’s were sitting on a gold mine. They believed that the nucleotides of DNA were arranged ‘in a helical manner’, and Wilkins had recently taken ‘extremely excellent X-ray diffraction photos of orientated DNA’ – and had found, astonishingly, that living DNA in intact squid sperm showed ‘the same pattern as purified DNA!!!’
Those exclamation marks signified frustration as well as amazement. Meanwhile, the templates for making molecular models of the bases and sugars, which Crick and Watson had kindly given to Wilkins before Christmas, were still sitting unused at King’s. Watson warned, ‘If the King’s people persist in doing nothing, we shall again try our luck.’ For now, though, they held back.
End of year
In September 1952, two young American research fellows joined the Cavendish and were given space in the office occupied by Crick and Watson. One was Jerry Donohue, an experienced crystallographer and an expert on hydrogen bonding, who had trained at Caltech with Linus Pauling. The other had an even closer connection with the discoverer of the alpha-helix – he was Pauling’s son, Peter, who had come to do a PhD on myoglobin with John Kendrew. Neither suspected it when they arrived, but both were to play key roles – one direct and the other facilitatory – in the climax of the story of the double helix.
Although they are as yet superfluous to the plot, the arrival of Donohue and Pauling Junior completes the cast for the last act. In Cambridge, Crick and Watson are still notionally following Bragg’s moratorium, but ready to break ranks and run off with DNA if the opportunity arises. Down at King’s, Maurice Wilkins is working on DNA, seeing helices but troubled by the notion that they might turn out to be spurious. Rosalind Franklin is still there, dutifully assisted by Ray Gosling, working against the clock to finish her papers and make sense of the nightmarish analyses of the A form, before her time in Randall’s Circus runs out in January 1953.
And now there is a third entrant, who has not yet declared his intention to run but is catching up fast: Linus Pauling, of Caltech in Pasadena, California.
24
PHOTO FINISH
Maurice Wilkins spent most of January 1953 in limbo. Rosalind Franklin and Ray Gosling were still shut away incommunicado. The date had been fixed for Franklin’s farewell seminar – 28 January – bu
t an attack of flu had delayed her departure and nobody knew when she would finally leave. Wilkins planned to re-form his DNA group as soon as she had gone, but to avoid trouble in the meantime, was keeping well away from X-ray crystallography. Instead, he had gone back to his microscopes. And while using them to measure the DNA content in individual chromosomes, he rediscovered why living things had lured him away from physics, and experienced again the forgotten pleasure of talking science with friends.
Something ‘extraordinary’ happened in late January. Without warning, Ray Gosling came to find Wilkins and presented him with an X-ray diffraction photograph from Rosalind Franklin. The image was as extraordinary as the act of being given it: a beautifully clear, capital X of the B form of DNA (Figure 24.1). Gosling insisted that it was for Wilkins, and that it was his to do with as he wished. He left Wilkins stunned.
The photograph had an intriguing provenance. It had been taken almost nine months earlier, with a sixty-hour exposure that began on the evening of 1 May 1952 when Gosling mounted some wet DNA fibres on the bent paperclip. This date should have been a red-letter day for British science. Bill Astbury had organised a one-day symposium on protein structure at the Royal Society, built around an eminent speaker from the USA. Unfortunately, the US State Department believed that it was not in America’s interest for the speaker, who had Communist leanings and was a security threat, to leave the country. They therefore refused Dr Linus Pauling’s application for a visa, leaving a massive hole in Astbury’s conference programme.
In retrospect, that day was also fascinating for a more parochial reason. Rosalind Franklin had been there, assailed by doubts about the A structure, and told Wilkins that DNA could not possibly be helical. Yet this photograph, taken that same evening, was shouting ‘Look at me – I’m helical!’ just as loudly as Wilkins’s original A image had declared its crystallinity.
Unravelling the Double Helix Page 35