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Authors: Brenda Maddox

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A more superstitious man might have interpreted the sacred portals shut in his face as a portent.

TWELVE
Eureka and Goodbye

(6 January-16 March )

‘Rosy, of course, did not directly give us her data. For that matter, no one at King's realised they were in our hands.'

 

James Watson,
The Double Helix

T
HE SECRET OF LIFE
, four billion years old, was unpicked in a drama that moved day by day, almost hour by hour, in the first seven weeks of 1953.

News that Linus Pauling and Robert Corey had solved the structure of DNA started the clock running. On 6 January Rosalind, who somehow had got wind of the news, wrote Corey at Caltech and asked for details. They had been in correspondence since May when he had marvelled at her ‘splendid X-ray photographs of nucleic acid fibres'.

Her notebooks show intense activity as January progressed. She herself had started to think of building a model of the A form based on her Patterson calculations. Might these represent a figure-eight shape - two coils crossed in the middle? Or paired rods? She knew of Chargaff's ratios and tried to squeeze the four bases of DNA into a structure with the phosphates on the outside. They would not fit. Still bemused by the discrepancies between the A form and the B form, she accepted that the B form was a two-chain helix but still had doubts about the other. As her later collaborator Aaron Klug was to comment, ‘The stage reached by Franklin at the time is a stage recognisable to many scientific workers, when there are apparently contradictory, or discordant, observations jostling for one's attention and one does not know which are the clues to select for solving the puzzle.'

 

She had been at work for a week when Peter Pauling returned to Cambridge from his winter break in Germany and Austria. On 13 January he wrote his father to ask for a copy of the Pauling-Corey paper on DNA, adding that the Cavendish's MRC Unit would like one too. He prefaced the request with a joke:

 

You know how children are threatened ‘You had better be good or the bad ogre will come get you.' Well, for more than a year, Francis and others have been saying to the nucleic acid people at King's, ‘You had better work hard or Pauling will get interested in nucleic acids.'

 

Pauling sent the paper, confident that he had scored another victory over Sir Lawrence Bragg, his old rival at the Cavendish. In fact, he sent two copies of ‘A Proposed Structure for the Nucleic Acids' to England, one to Peter and the other to Bragg. Peter replied, ‘We were all excited about the nucleic acid structure. Many thanks for the paper. Second sunny day since I have been in England.'

The paper appears to have arrived on 28 January, and there was indeed excitement at the Cavendish. When Peter brought the paper to the lab, Jim Watson had to restrain himself from grabbing it out of Peter's hand. He held back, impatiently listening to Peter's summary, until he yanked it out of Peter's outside pocket and read it for himself. Instantly he saw that Pauling's proposed structure — a triple-stranded helix with the phosphates at the centre — was much like the mistaken model that he and Francis Crick had built in November 1951. Worse — or better, from Watson's point of view — Pauling had made a fatal chemical error. The phosphates were not ionised — that is, Pauling had not built in the electrical charges phosphates acquire when in water. What he was proposing as a structure for nucleic acid was not an acid at all.

Pauling had made the silly mistake because he was in a hurry. But why? There has been much retrospective speculation on why one of the world's greatest chemists, the holder of the Presidential Medal for Science, the author of the classic textbook on the nature of the chemical bond, should have risked his reputation by rushing into print with a carelessly flawed proposal. One suggestion was that Pauling, having cracked the structure of protein, wanted credit for solving the other half of the cell's secrets. Another is that, for all his many honours, Pauling had never won the Nobel prize. Pauling later said that his wife once asked him why he hadn't cracked the problem and that, upon reflection, his answer was: ‘I guess that I always thought that the DNA structure was mine to solve, and therefore I didn't pursue it aggressively enough.'

Watson's delight in the error was tempered by the news that the Pauling paper would soon be published in February in the
Proceedings of the National Academy of Sciences.
The mistake would immediately be spotted and Pauling would be on the trail again. Watson felt he and Crick had about six weeks' breathing space.

Also on 28 January Rosalind gave her leaving seminar at King's. Maurice Wilkins thought she was long-winded; he strained to hear the word ‘helix' and did not. Neither did Herbert Wilson, who took notes. She did not refer to the B form of DNA, nor show the superb Photo 51, but concentrated instead on the recent experimental work of herself and Gosling that suggested that the A form of the molecule was not helical.

For J.T. Randall, an unwelcome sight at the end ofthat month was Jim Watson. The gawky young American from the Cavendish seemed always to be turning up at King's College London. One morning Randall went in to the coffee club that met daily in Angela Brown's room and there was Watson, grinning. ‘Here's the Dean of St Paul's!' he wisecracked. Randall's pompous Christmas letter to
The Times
had been the subject of general mirth in the lab.

No one else talked to the inventor of the cavity magnetron like that. Randall was furious. Once Watson was gone, he boomed out, ‘Never let that man in my sight again!' Out of sight, however, was not out of mind.

Rosalind did not like the sight of Watson either. On 30 January the door to her office opened and in he came. The only published account of what ensued is his: a pivotal scene in
The Double Helix:

 

Since the door was already ajar, I pushed it open to see her bending over a lighted box upon which lay an X-ray photograph she was measuring. Momentarily startled by my entry, she quickly regained her composure and, looking straight at my face, let her eyes tell me that uninvited guests should have the courtesy to knock.

 

Watson asked her whether she wanted a look at Pauling's manuscript, and getting little response, rushed on to point out where Pauling had gone astray. She countered with her own evidence that a helical structure was by no means proven. But Watson had heard from Wilkins that Rosalind was ‘definitely anti-helical' — neither of them having seen her evidence. (The Birkbeck crystallographer, Harry Carlisle, wrote in his memoirs, ‘I am convinced from Rosalind's excellent X-ray studies on both the A and the B forms of DNA that she was not in the least ‘‘anti-helical'' at that time as suggested by Watson in
The Double Helix.')
He felt that Rosalind was more concerned with extracting positive arguments from her X-ray data.' For his part, Watson decided that she did not know what she was talking about:

 

I was more aware of her data than she realised. Several months earlier Maurice had told me the nature of her so-called anti-helical results. Since Francis had assured me that they were a red herring, I decided to risk a full explosion. Without further hesitation I implied that she was incompetent in interpreting X-ray pictures. If only she would learn some theory, she would understand how her supposed anti-helical features arose from the minor distortions needed to pack regular helices into a crystallising lattice.

Suddenly Rosy came from behind the lab bench that separated us and began moving towards me. Fearing that in her hot anger she might strike me, I grabbed up the Pauling manuscript and hastily retreated to the open door.

 

‘Fearing that in her hot anger she might strike me': the patent absurdity of this remark has caused much scorn. Rosalind was of slim build and medium height, Watson a stringy six feet plus. But the male fear of the female has always been absurd — the stronger afraid of the weaker — but no less real for that. To dismiss it is to dismiss the Medusa, the Loathly Lady, the Wicked Witch of the West and all the other guises for whatever the male resents and recoils from in the female; that led even the mild-mannered graduate student John Cadogan to say of Rosalind, ‘She nearly terrified the living daylights out of me.'

Watson's own bewilderment with women is well chronicled in
The Double Helix.
He could not approach them unselfconsciously: they were either prey — ‘popsies' or ‘au pairs' — or goddesses such as his aristocratic Scottish hostess Naomi Mitchison or his sister Elizabeth. Rosalind was neither; worse, she was an angry woman. And she had reason to be angry. Courtesy might have demanded that Corey send a copy of their DNA paper to her, not to the Cavendish.

Watson portrays Rosalind's ‘hot anger' as entirely unmotivated. There is another possible explanation for her rage — indeed of the whole incident. Early in 1953, very upset, she complained to a friend at King's that she had come back to her room one day and found her notebooks being read. If Randall and Wilkins saw themselves as her bosses, she stormed to her confidant, they should have protected her work better. Instead, she knew Wilkins to be in open and frequent communication with the Cavendish pair. She voiced her fears also to an old colleague from BCURA.

 

She herself was engaged in a race against time. Due to move to Birkbeck in the middle of March, she was rushing to finish up as much as possible of the Patterson interpretation of the A form of DNA before she left King's. She was working hard on three papers (to be published jointly with Gosling) so as to hand them to Randall before she left; his permission was needed before anything was sent out to other readers, let alone for publication. Two papers were for
Acta Crystallographica.
In them she was formally announcing to the scientific world what she had discovered at King's: the existence of DNA in two forms, and the conditions for readily and rapidly changing from one to the other. She described the DNA molecule. Its phosphates were on the outside, thus exposed and ready to take up water: making hydration, and therefore stretching, easy. Thus shielded in a sheath of water, the DNA was ‘relatively free from the influence of neighbouring molecules'. She appended to the first paper the startlingly clear X-ray photographs she and Gosling had taken of both forms. The second paper gave the measurements on the x-ray pattern of the A form on which she and Gosling had concentrated in the past six months: full of the kind of information that crystallographers would appreciate. The third, a shorter paper, was a more general summary of their findings on the B form.

 

As Watson retreated from Rosalind's wrath, he was rescued from his fantasised assault by Maurice Wilkins, who had put his head round the door. Wilkins consoled him that some months earlier, ‘she had made a similar lunge at him' and had blocked the door when he wanted to escape. As Wilkins poured out his ‘see what I'm up against' tale of woe, he reiterated what Rosalind had said in her 1951 colloquium about the two forms of DNA and complained that he had been left to use only samples given him by Erwin Chargaff in New York, which would not produce the A to B transition. Rosalind's Signer fibres had produced much better patterns. ‘She's got a very good B,' said Wilkins.

Wilkins had not known of Rosalind's excellent diffraction photograph numbered 51, taken eight months earlier, until Gosling brought it to him sometime that January. Gosling, preparing to complete his thesis without Rosalind's supervision, had every reason to show what was also his own current work to the assistant head of the department. ‘Maurice had a perfect right to that information,' Gosling said, looking back. ‘There was so much going on at King's before Rosalind came.' Both he and Wilkins knew the DNA research would continue after she left.

Unguardedly, Wilkins showed Watson Photo 51. There were many diffraction photographs of DNA around the lab; this one was simply the best. As the information in it was not new to Wilkins — Rosalind had related many of the details in her symposium in 1951 — he had no idea it would strike Watson with the force of revelation. Nor did he have any idea that Watson was about to make a new stab at building a model of DNA.

But Watson was now wiser than in late 1951 when he had botched his first model. A year of working on the tobacco mosaic virus had educated him, as had reading the Cochran—Crick—Vand paper on helices. He was now able to sweep up at a glance the meaning of Rosalind's photographic image: unbelievably clear evidence of a helix, with detectable parameters of tilting and spacing. It was with little exaggeration that he wrote in
The Double Helix:
‘The instant I saw the picture my mouth fell open and my pulse began to race.'

The two men had dinner that night in Soho. What Wilkins wanted to talk about was Chargaff's ratios and the possibility that they might hold the key to DNA's structure. Watson, however, pressed for numbers to go with the pattern he had just seen. He extracted a few. The repeat (the length of one turn of the helix) of the B form was 34.4 Ångströms — ten times the spacing between the bases stacked 3.4 Ångströms apart. On the train back to Cambridge, Watson drew the pattern from memory on the only paper available, the margin of his newspaper. It was stark enough to fit in the small space. In his mind there still lurked the possibility that the molecule might have three helical chains. As he cycled home from the train, mulling over Rosalind's photograph with its dark cross, he decided on two. ‘Francis would have to agree,' he later wrote. ‘Even though he was a physicist, he knew that important biological objects come in pairs.' (According to Crick, the argument was more complicated than that.)

 

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