Life's Greatest Secret (16 page)

At the time, Watson was based in Copenhagen, rather unsuccessfully studying phage duplication, having obtained his PhD on phage genetics with Salvador Luria a year earlier, at the remarkably young age of 22 years.
²⁴
Watson had become obsessed with how genes copied themselves, and Wilkins’s data seemed to suggest a way of attacking the problem. On his return to Copenhagen, Watson read Pauling’s slew of articles on the α-helix and became determined to use X-ray crystallography to study genes. After some squabbles with his funding agency, in autumn 1951 Watson moved to Cambridge and began work in Max Perutz’s group, which had world-leading expertise in X-ray crystallography. In Cambridge he shared an office with Francis Crick.
²⁵
One of the great scientific partnerships began. Watson described his new colleague in a letter to Delbrück:

The most interesting member in the group is a research student named Francis Crick. … He is no doubt the brightest person I have ever worked with and the nearest approach to Pauling I’ve ever seen. … He never stops talking or thinking and since I spend much of my time in his house (he has a very charming French wife who is an excellent cook) I find myself in a state of suspended stimulation.

Crick recalled he was ‘electrified’ by meeting Watson. ‘It was
remarkable
’, he said, because they had the same focus on understanding gene structure but they had entirely different skills – phage genetics and crystallography, respectively. In 1947, Crick had described his desire to unravel ‘the chemical physics of biology’.
²⁷
He was not initially particularly interested in genes or DNA – like most people, he assumed that the genetic material would be a protein. In 1950 he had teased Wilkins for his work on DNA, telling him, ‘What you ought to do is get yourself a good protein.’
²⁸

*

During the summer of 1951, Wilkins became increasingly convinced that the X-ray diffraction data showed that DNA had a helical structure. When Wilkins first presented this idea, Franklin’s response was to tell him to stop working on X-ray data from DNA and ‘go back to your microscopes’. Wilkins, who was the assistant director of the laboratory, was incredulous that a postdoctoral researcher should speak to him in such a fashion, but typically said nothing.
²⁹
Matters got worse when another member of the King’s group, Alex Stokes, found mathematical support for Wilkins’s intuition. When Wilkins told Franklin of their success, she responded furiously, saying, ‘How dare you interpret my data for me?’
³⁰

To overcome the tension between Wilkins and Franklin, Randall adopted the simplest solution: the two researchers would be kept apart. There was a ready justification for this. Franklin had shown that DNA came in two distinct forms, named A and B, depending on the degree of humidity. The A form, which could be seen under drier conditions, gave precise but highly complex images; the B form, which occurred at high humidity levels, was more blurry and less enticing. X-ray crystallography requires precise measurements from the diffraction images; if the photo is blurred, it will be impossible to come to an accurate description. Randall decided that Franklin should study the A form DNA using Signer’s samples, while Wilkins would investigate the B form using Chargaff’s less pure DNA. Randall could perhaps have resolved everything by being frank with the pair of them; but he was not, and matters got no better.

Shortly afterwards, on 21 November 1951, the King’s group organised a small meeting on DNA at which they all presented their latest findings. Jim Watson was in the audience and when Franklin spoke, his attention was torn between her results and idle musings about her looks. Franklin showed DNA images she had made with the lab’s new fine-focus X-ray tube, which had a very narrow beam, and she described the two forms, A and B, highlighting the fact that the A form produced clearer images, showing ‘evidence for spiral structure’. The next day, Watson and Crick excitedly discussed the details that Watson could recall – as was his habit, the cocky young American had taken no notes. Crick became convinced that only a few structures would fit Franklin’s data and within a week they had a model for DNA. This was accompanied by a rather pompous eight-page ‘memorandum’ by Crick that outlined their strategy, which was above all ‘to incorporate the
minimum
number of experimental facts’.
³¹
This was quite appropriate, as neither man had done a single experiment on DNA structure.

The first Watson and Crick model of DNA was a triple helix – there were three intertwined phosphate-sugar strands in the centre, with the bases sticking out like fingers. In triumph the pair invited Wilkins, Gosling and Franklin to come to Cambridge to view their creation. Franklin took one look at the model and dismissed it. Her X-ray data that had so entranced Watson had clearly shown that the phosphate-sugar groups were on the outside, not the inside, whereas the magnesium ions that held Watson and Crick’s triple helix together would be unable to fulfil this function because they would be surrounded by water molecules. If such a structure ever existed, it would instantly fly apart. All this had been explained in her talk at the King’s meeting, but Watson had not fully understood what she was saying and had not written anything down. Watson and Crick’s first venture into model-building ended in embarrassing failure.

Watson’s failure to pay attention was even more significant than he realised. According to Franklin’s notes, when she spoke at the November meeting she described the shape of the ‘unit cell’ (the shape of each molecule) of the DNA crystal as ‘monoclinic’. This crystallographic jargon meant that the molecule would show rotational symmetry, and that if there were chains of molecules wrapped around each other in the structure, they must run in opposite directions. This turned out to be a vital insight into the structure of DNA, but Watson did not understand enough crystallography to grasp its significance. Crick did, in an instant, when he eventually learned of it fifteen months later.

When Randall heard about the Cambridge duo’s attempt to muscle in on the structure of DNA, he furiously asked the head of the Cavendish Laboratory, Sir Lawrence Bragg, to tell the two upstarts to leave DNA alone. Bragg had a low opinion of Crick and probably no opinion of Watson, who was beneath his notice, so he willingly banned them from doing any further work on DNA. Crick returned to his PhD on haemoglobin structure, and Watson began studying the nucleic acids in the tobacco mosaic virus, learning elementary X-ray crystallography. The fiasco also reinforced Franklin’s prejudices against building speculative models. The data had to lead to the model, she felt. Watson and Crick, high on mathematics and fixated with Pauling the alpha-helix male, had been utterly confident that logic and ‘the
minimum
number of experimental facts’ would lead them to the answer. Instead it had led to ridicule.

Despite Franklin’s conviction that the results would speak for themselves, her data were confusing because she was looking at the precise and detailed images produced by the A form of DNA. She apparently assumed they were so sharp because the A form was an array of crystals that were all oriented in the same direction. In fact, the A form is made up of small crystalline blocks in which the crystals within a block have the same orientation, but where different blocks have different orientations, producing an image that is both clear and complex.
³²
Deducing the structure of DNA from the A form image was going to be extremely difficult. When Crick eventually saw the A form data, in 1954, he told Wilkins:

This is the first time I have had an opportunity for a detailed study of the picture of Structure A, and I must say I am glad I didn’t see it earlier, as it would have worried me considerably.

Eventually, putting too much faith in the sensitivity of her apparatus, Franklin concluded that the A form was not helical and sent round a spoof death notice, edged with black, to members of the laboratory:

It is with great regret that we have to announce the death, on Friday 18th July, 1952, of D.N.A. HELIX (crystalline).

By this time Franklin had already decided she had had enough of the terrible atmosphere at King’s; she agreed with Randall that at the end of the year she would move to Birkbeck College and would abandon her studies of DNA.

Despite the triple helix fiasco, Watson and Crick did not stop thinking about the structure of DNA. Crick asked a colleague to work out the chemical bonds that could exist between the bases and was delighted when he was told that A would bind with T, and C with G. In a flash, Crick realised that this provided the clue to gene replication, through what he called complementary replication. If A on one molecule bound with T on another, you would get a kind of mirror image of the original DNA; if the same process was then repeated with that ‘mirror’, a new strand of DNA, identical to the original one, would have been created. If there were two molecules of DNA bound together at the outset, replication would be even more straightforward – simply copy each strand and you would duplicate the original molecule.
³⁴

At the end of May 1952, Chargaff visited Cambridge and had a meal with Watson and Crick at which they talked about DNA. It did not go well. Chargaff – a notoriously prickly character – poured scorn on them because of their ignorance of chemistry and of his work. He later recalled that his first impression was ‘far from favorable; it was not improved by the many farcical elements that enlivened the ensuing conversation … So far as I could make out, they wanted, unencumbered by any knowledge of the chemistry involved, to fit DNA into a helix. The main reason seemed to be Pauling’s alpha-helix model of a protein.’
³⁵

Despite his evident irritation, Chargaff told Watson and Crick of the enigma of the apparent 1:1 ratios of A:T and C:G. As Crick later recalled:

Well, the effect was electric … I suddenly realized, by God, if you have complementary replication, you can

to get one-to-one ratios.

In a rare foray into the laboratory, Crick spent the next week trying to get bases to pair spontaneously in the test tube. It did not work, and Crick’s flash of insight led nowhere, for the moment.

*

King’s and Cambridge were not the only places where scientists were trying to understand the structure of DNA. On 28 May and 1 June 1951, Elwyn Beighton in Bill Astbury’s laboratory in Leeds took some of Chargaff’s DNA and made several X-ray images. They had the classic X-shape which we now know reveals the presence of a helix. Astbury was not impressed, and did not encourage Beighton to continue his work; he was not able to interpret the images correctly because Crick had not yet published his papers that described the diffraction pattern produced by a helix.
³⁷
Astbury may have felt that the material was less pure than the extracts he had worked with before the war, or he may have merely been frustrated that the image seemed too simple at a time when all the lines of argument were suggesting that DNA was the genetic material, the carrier of specificity. At around this time, the Medical Research Council (MRC) rejected Astbury’s proposal to create a new department, and the arrival on the scene of the well-funded group at King’s College may also have discouraged him from pursuing the structure of DNA. Whatever the case, the Leeds images became a historical dead-end, an enigmatic curiosity, and Astbury’s direct involvement in the determination of the structure of DNA was over.
³⁸

At about the same time, Edward Ronwin of the University of California produced a model of DNA. This was superficially similar to Astbury’s 1947 model – it had the phosphate-sugar backbone in the centre, with the bases fanning out. However, Ronwin had made some basic biochemical errors and his model contained too much phosphorus. Linus Pauling was outraged, and wrote a letter to the editor of the
Journal of the American Chemical Society
criticising the ‘foolishness’ of publishing Ronwin’s model, and complaining about ‘the irresponsible publication of unsupported hypotheses.’
³⁹

More seriously, in the first half of 1952, John Rowen at the National Cancer Institute in Maryland studied the molecule using light-scattering electron microscopy and viscometry. In 1953 he published an article describing its configuration as ‘intermediate between a rod and a coil’ before concluding that one of ‘its most striking properties is its tendency to spiral, twist and intertwine with neighbouring molecules’.
⁴⁰

*

Beginning in the second half of August 1952, Franklin took X-ray photos of her DNA samples every day, using a heavy disc-shaped metal camera that was about the width of an orange. Her PhD student, Raymond Gosling, recalled that she bounced ideas off him – they had what he called ‘pretty hot discussions’ in which she played the role of devil’s advocate and which he found enormously stimulating.
⁴¹
She never had that kind of discussion with Wilkins. Together with Gosling, Franklin began to calculate the Patterson function, the difficult mathematical procedure used by Sven Furberg at Birkbeck. This involved projecting the X-ray photos in a dark room, measuring the position and intensity of the various blobs on the pictures and then spending hours doing complex calculations. In November 1952, Franklin summarised the data she had obtained with Gosling as part of a brief report by Randall for the Biophysics Committee of the MRC. There was nothing in Franklin’s few paragraphs that had not been presented at the King’s symposium the previous year, but this time the data – including the different sizes of the repeating patterns in the A and B forms and above all the dimensions of the monoclinic unit cell, were written out clearly and slightly more precisely.
⁴²
In the middle of December, members of the Biophysics Committee made an official tour of the King’s lab and were each given a copy of the informal document. One of the visitors was Max Perutz from Cambridge.