Stockholm in June, back among her like-minded, cosmopolitan peers, must have been a blessed release from Rosalind Franklin’s basement office in King’s. The trip started auspiciously, as she shared a cabin on the North Sea crossing with a brilliant and entertaining woman, who although badly seasick, was an emerging superstar of X-ray crystallography. Dorothy Crowfoot (now Mrs Hodgkin) was on her way to report the structure of vitamin B12, a discovery that her former PhD supervisor, J.D. Bernal, thought worthy of a Nobel Prize.
The Second International Crystallography Congress, under the patronage of the King of Sweden, did not disappoint. The congress attracted 350 scientists and 70 ‘passive members’ (their other halves), with a four-day programme which included 150 papers, review lectures, masterclasses, a geological excursion, a boat trip around the Stockholm Archipelago and dinner in Uppsala Castle. The topics included materials that formed crystals, from metals to viruses, and others that did not. Franklin presented two papers on the forms of carbon in coal; other talks were given by her friends from Mering’s group and by Adrienne Weill (on crystals in ‘an Egyptian object’). Snapshots taken during the meeting caught Franklin looking relaxed and happy, exploring an island in Stockholm Harbour.
The big guns of X-ray crystallography turned out in force, with Sir Lawrence Bragg proposing the vote of thanks to the organisers. The star of the show, however, was someone who was not even there: a man had just transformed the understanding of the structure of proteins – and in the process had hurled Bragg into a pit of furious despair. Two years after first thinking of it, Linus Pauling had finally told the world about his alpha-helix. He submitted the paper announcing its discovery on his fiftieth birthday, 28 February 1951, and it had been published in the venerable Proceedings of the National Academy of Science (PNAS) in March. The paper was short and brilliant, and the alpha-helix made perfect sense from the moment it was unveiled. Pauling’s paper was also a splendid example of scientific schadenfreude. He revelled in pointing out that everyone else trying to solve the three-dimensional structure of proteins had been wrong – notably the Cambridge trio of Bragg, Perutz and Kendrew, who a year earlier had published a paper full of fatally flawed assumptions and ‘rough approximations’.
Bragg and everyone else had barely absorbed this bombshell when Pauling stormed back into PNAS with a slab of evidence so weighty that it crushed any last vestige of doubt. This was a string of seven papers, filling over fifty of PNAS’s close-printed pages, describing another basic configuration that protein chains adopt (the ‘beta-sheet’), and proving that it and the alpha-helix occurred in a miscellany of proteins. These papers were also submitted on a significant date: the day on which Pauling had been identified by Senator Joseph McCarthy’s Unamerican Activities Committee as a leading Soviet sympathiser and security risk.
Pauling’s papers totally wrecked the spring of 1951 for the Cambridge trio. Pauling was entirely correct about all the errors in their ideas about how a chain of amino acids could form a spiral; afterwards, he twisted the knife by saying that they might have got closer if they had paid closer attention to his book, The Nature of the Chemical Bond. Bragg later said that publishing their ‘ill-judged and abortive’ paper was ‘the worst mistake in my career’. Max Perutz was also furious. Although transfixed by the intuitive ‘beauty’ of the alpha-helix – ‘it just had to be dead right’ – he was gripped with a blind rage at his own stupidity for not having thought of it himself.
A major theme of the congress was number-crunching: how to make sense of all the spots and smears on X-ray photographs of complicated materials, especially large proteins and substances which did not form tidy crystals. Top-flight mathematics had been pulled in, with automatic calculating machines that riffled through punched cards and a ‘high-speed digital electronic computer’ which John Kendrew was using to peer into the heart of myoglobin.
The workshop on ‘Advanced techniques in structure determination’ was essential listening for Rosalind Franklin, preparing herself to do battle with the complex X-ray patterns of DNA. The top attraction was Lindo Patterson, an English physicist who had used X-rays to probe the structure of cellulose fibres and had given his name to a widely used mathematical analysis. The ‘Patterson function’, published in 1934, turned the pattern of spots on an X-ray diffraction photograph into a contour map of electron density that indicated the position of individual atoms inside complex molecules. Patterson’s admirers included Vittorio Luzzati, one of Franklin’s closest friends in Paris, who also spoke in the session.
After the congress, Franklin took back to London happy memories of an excellent meeting and a working knowledge of the Patterson analysis, ready to begin translating X-ray photographs into a molecular structure for DNA. However, the session in Stockholm had glossed over some ambiguities that were embedded in the method. Patterson himself demonstrated its potential weakness by proving that several different arrangements of atoms within a molecule could produce the same map. Bragg’s eventual verdict was that ‘Patterson synthesis was a guiding star . . . As events turned out, it was a false star.’ But for now, the Patterson function was in vogue, and Franklin put all her faith in it.
Fallout
In mid-July 1951, Max Perutz ran his second meeting on protein structure at the MRC Unit in Cambridge. The setting was grand – the auditorium which had once rung to the sound of Rutherford’s voice – and the programme was an interesting amalgam of research in Cambridge and the sister MRC unit at King’s.
Randall was unable to attend, so Wilkins led the dozen-strong London delegation. As well as his own work, Wilkins had been given dispensation to present new data from the sperm studies which Randall had reclaimed. Rosalind Franklin was there, observing and finding her feet, and not yet with anything to present from her seven months at King’s.
Wilkins again showed the photograph of the ‘crystalline’ structure of Signer’s DNA, which had been hot off the press at the meeting the previous year. This was the first time that Franklin had seen Wilkins in action – and talking about a photograph taken by Ray Gosling, whom Randall had reassigned to her for her DNA project.
Next, Wilkins showed two more recent X-ray photographs, both taken by Gosling since Franklin had arrived at King’s. One was of the threads of cuttlefish sperm which Wilkins had painstakingly prepared from the sperm sacs of Sepia while he was in Naples in May. This showed only a vague image. The second photo, from a film of herring sperm, was clearer and revealed a blurry four-lobed pattern centred on the X-ray beam. Wilkins had thought hard about what this picture was trying to tell him and had a hunch about the vertical gap between the ‘lobes’. The gap fell on the ‘meridian’ which portrayed the long axis of the fibre molecule, and made him wonder if they were looking along something that had a relatively hollow core – perhaps because it had a helical shape.
Wilkins felt moved to be speaking in the very spot where Rutherford had lectured, but his talk had a mixed reception. Most people applauded briskly, even though it was nothing to do with proteins; Perutz remarked that it was ‘interesting’. At the back, Francis Crick had been chatting loudly to someone all the way through, which might explain why he retained no memory of the talk. Franklin said nothing, until she got outside and confronted Wilkins as he left the lecture theatre. He later wrote: ‘I found a surprise waiting for me. Rosalind Franklin came up to me and announced, quietly and firmly, that I should stop doing X-ray work. She concluded with the instruction: “Go back to your microscopes!”’
Wilkins was ‘shocked and upset’. Until that moment, he had found Franklin ‘friendly enough, apart from sometimes being a little sharp of tongue . . . She seemed a high-principled, civilised person.’ He was still troubled later that afternoon, when they all went out on the river in punts. Wilkins looked up at one point and saw another boat bearing down on them, with Franklin on the back, punt-pole raised. ‘Now she’s trying to drown me,’ he muttered to his companions. Whether or not the others found that funny, his own memories o
f the meeting were permanently soured.
Numbers games
Over the summer, Wilkins thought more about the bizarre four-lobed X-ray pattern and the possibility that the DNA in sperm heads was helical. So he asked Alec Stokes, the ‘theoretical’ crystallographer, to predict the X-ray image that would be produced by a helical molecule.
Mathematically, this was virgin territory, but Stokes came up with the answer in a couple of days; he did the key calculation one evening while on the commuter train home to Welwyn Garden City. Stokes did not bother with the Patterson analysis which had been all the rage at the Crystallography Congress in Stockholm, and which Rosalind Franklin had taken to heart. Instead, salvation came from the heavens, thanks to a German mathematician-astronomer who won a competition to measure the distance from the Sun to another star. This was the work of Friedrich Bessel (1784–1846), who published his calculations in 1833, the same year in which Robert Brown reported a curious structure in orchid cells which he called the nucleus.
Bessel also devised a shockingly clever method for working out the interplay of gravitational forces between multiple celestial bodies. The ‘Bessel function’ turned out to have applications that went beyond space, such as untying knotty problems in quantum mechanics. And Stokes discovered that it could be adapted to show how X-rays would be diffracted by molecules that were twisted into a regular spiral. The product of his stroke of brilliance was a hand-drawn diagram that looked like a child’s picture of an ocean swell, which he christened ‘Waves at Bessel-on-Sea’.* Wilkins was excited, and pinned the diagram up on the noticeboard in their lab.
Stokes’s drawing showed a series of undulating waves, stacked one above the other, each marching left to right and offset from the one below. Each wave represented the intensity of the X-rays that would be deflected off a regular helix, at a particular level within the structure. Stokes found that the peak of the wave moved out at progressively higher levels; because the diffraction pattern was symmetrical, this created four diverging arms which would appear like a heavy capital ‘X’. From the angles at which the arms of the X intersected, he could work out the dimensions of the helix.
Wilkins saw immediately that this fitted with his intuition that the four-lobed pattern from sperm DNA was helical. The four ‘lobes’ represented the arms of the cross, blurred because the DNA molecules in the sperm preparation were not perfectly aligned.
At the end of August 1951, the Biophysics Unit was mostly in a quiescent phase. Franklin was on holiday in France, and Wilkins had flown to America to stand in for Randall at the prestigious Gordon Conference. Before leaving, Wilkins had left Franklin a note about DNA.
The confrontation in Cambridge appeared to have blown over, and he assumed that she would find his suggestions helpful and constructive. He explained that there were problems with the Patterson analysis because it gave ‘the wrong symmetry’, and said that Stokes had used a different method to calculate the vital statistics of the DNA molecule. This appeared to be a helix, with a pitch of about 34 Å and a diameter of 20 Å. Wilkins added that this was still ‘all conjecture’ and that Franklin’s experiments with the new X-ray camera were ‘the only way to clear this up’. He ended, ‘I hope you had a good holiday, Yours, MW’.
While everyone else was away from Randall’s Circus, the ringmaster was still at his desk, agonising over a letter that was both helpful and threatening. The Secretary of the Royal Society wanted to meet him because knives were out: the MRC was split over whether to continue funding the Biophysics Unit, ‘a venture that so far had been more physical than biological’. Randall fired off a robust reply but agreed to meet, and was given some wisdom about how best to dress his Unit’s window to secure another five years’ money. One hint, which he passed on straight away, was that Dr Wilkins had drifted away from his excellent microscopical work on living cells, and should be put back on course.
Wilkins received Randall’s letter about this while at the Gordon Conference, and did not reply immediately. He was revelling in the trip: his first flight on an airliner, a lovely setting in the hills of New Hampshire, three days of ‘free and informal exchange of ideas’ about nucleic acids and proteins, and the chance to meet real DNA experts like Erwin Chargaff. Wilkins’s talk on the X-ray patterns of DNA was well received and Chargaff invited him to visit his lab in New York on the way home. Wilkins flew back to London in early September, with another gift of thymus DNA prepared by Chargaff.
From London, he went straight to Berlin and the family of his German girlfriend. Then it was a few days in Munich, followed by a biophysics conference in Stockholm, where he and Randall presented the Unit’s work. As instructed by Randall, Wilkins focused on his microscope studies – only to discover that his lifelong ‘passion for optics’ had deserted him. By the time he got back to King’s in early October, he was determined to concentrate full-time on solving the mysteries of DNA.
This decision came at an interesting time for Randall. He had heard on the grapevine that the MRC were prepared to pump a further five years’ money into the Unit, as long as they became more obviously biological. But he had received another worrying letter out of the blue, this time from America. Linus Pauling was bored with proteins and was looking for the next target worthy of his attention. He wanted Randall to send him Wilkins’s X-ray photos of DNA, as he understood from a friend that Wilkins was ‘not planning to interpret them’.
Randall’s response was a steely ‘hands off’. ‘Wilkins and others are busily engaged in interpreting the photographs . . . it would not be fair to them, or to the efforts of the lab as a whole, to hand them over to you.’ For the moment, Wilkins’s continuing work on DNA would be tolerated – at least by John Randall.
In September, while Wilkins was still away, Franklin and Gosling had finally started photographing fibres of Signer’s DNA, which they stretched across a bent paper clip. They confirmed that damp DNA fibres produced a geometric array of spots – the crystalline pattern which Wilkins had shown in Cambridge. However, they found a completely different result when the DNA fibres were made wetter. Even though their first photographs were underexposed, it was clear that the spots had disappeared and were replaced by a symmetrical X-shaped pattern.
When Wilkins returned, Franklin came to find him and showed him the photographs of ‘wet’ DNA. She did this with ‘a cold superiority’ that he found unsettling. The images were vague, but Wilkins could make out the ‘X’ that Stokes had predicted with the Bessel analysis that was now pinned up on their lab noticeboard, a few doors away.
It seemed the right moment to share the new intelligence with Franklin – but if Wilkins had assumed that she would be grateful, he was badly mistaken. He was ‘stumped’ by her reaction when he and Stokes took her the diagram of ‘Waves at Bessel-on-Sea’ and began to explain what it all meant. She listened for a moment, then snapped, ‘How dare you interpret my data for me!’
That was the moment when their relationship began to spiral out of control. Wilkins had no idea how to cope with her personality or her temper. He could handle spats between men, such as the self-limiting rows with Randall, but somehow, Franklin ‘made it impossible to have a civilised discussion’. For her part, Franklin enjoyed a good shouting match, whether with the ‘stupid’ Professor Ronald Norrish FRS or the Parisian shop-owner who tried to sell her defective shoes. She also respected those who fought back; unfortunately, Wilkins merely retreated when faced with Franklin in a temper.
In his awkward way, Wilkins tried to smooth things over. He bought her chocolates, without obvious effect. His psychotherapist suggested inviting her out to dinner, but that failed too. When he went to ask her, it was a stiflingly hot afternoon and he found her grubby and sweating heavily (‘in the days before deodorants’) from repairing some equipment; he could not bring himself to do it.
Maurice Wilkins and Rosalind Franklin could have done great things together. Instead, they progressively parted company, each unaware of how wretched they were making
life for the other.
* A reference to Bexhill-on-Sea, a holiday town on the south coast of England where, coincidentally, Rosalind Franklin had gone to boarding school.
22
WHIZZ KID
With the rift deepening between himself and Franklin, the arrival of a note inviting Wilkins to spend a weekend in Cambridge with the Cricks was even more welcome than usual. The weekend in question was 9–11 November 1951, beginning on the Friday evening at the Hardy Club (which brought together biologists and physicists), where Crick was going to talk about the alpha-helix.
Crick also wanted to introduce Wilkins to a young American graduate who had recently joined the Cavendish. In fact, the American had already met Wilkins – and claimed that the encounter had transformed his life. Wilkins did not need to be reminded about when and where: May, on the bus from the Stazione Zoologica for the conference excursion to the Greek temples of Paestum. The American – an intense, persistent young man – had buttonholed him with a barrage of questions, and then stalked him through the ruins; one of Astbury’s team watched Wilkins hiding from the American behind other delegates. Wilkins’s impression was of a ‘very excited’ man who talked about viruses and genes, but without making much sense. He did not mention him in his five-page letter home to Randall but on returning to King’s, he told Gosling that if a ‘young, gangly American’ turned up looking for him, he was to be told that Wilkins was out of the country.
Now the American had bounced back from nowhere and for some reason was in Cambridge with Crick. His name was James Watson (Figure 22.1).
Chicago born and bred, Watson was known to millions of Americans soon after his fifteenth birthday. He was one of the juvenile masterminds who appeared in academic gowns and mortar boards on Quiz Kids, a prime-time television show and a national institution in America during the 1940s. The Quiz Kids were selected for their ‘quick minds, good looks and appealing personalities’, although ‘Jack’ was thought to ‘lack audience appeal’ and was ‘not a startling success’. His downfall was his patchy knowledge of the Bible, in which he was outclassed by an eight-year-old girl.
Unravelling the Double Helix Page 32