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Life through X-ray eyes

As cameras go, Ray Gosling’s might have appeared to be a snap or two short of a full album. His kit was no state-of-the-art Zeiss or Leica – but then Gosling was not in the paparazzi business. In the early 1950s, working as a graduate student with crystallographer Rosalind Franklin – aka the Dark Lady of DNA – his image-making relied on X-rays rather than light. His subjects were biological molecules; his ambition was not to flatter but to probe.

It was crystallography, as much a craft as a science in those days, that gave Francis Crick and James Watson the crucial insight to construct their model of DNA in February 1953. After decades in storage at King’s College London, the surviving cameras that took the key pictures have been dug out and dusted off, ready to join the 50th anniversary celebrations of the discovery of the double helix.

RAY GOSLING left school in the mid-1940s hoping to become a doctor. His family had other ideas. A training in medicine was lengthy. It would be too expensive, they told him. So he became a physicist instead. In the late 1940s, Gosling joined the Medical Research Council’s Biophysics Research Unit at King’s College London, and went on to play a supporting role in one of the greatest discoveries in biology.

Founded in 1946 by J. T. Randall, the biophysics unit – Randall’s Circus, as Gosling likes to refer to it – consisted of a mixed bunch of biologists and physicists, among them Maurice Wilkins, the third member of the trio destined to collect a Nobel prize for fathoming the structure of DNA. It was Wilkins who oversaw some of Gosling’s earlier work. But when Rosalind Franklin joined the department in 1951, Gosling became her assistant.

One of the techniques that staff in the biophysics unit had begun to use was X-ray crystallography. The technique allows the positions of the atoms in a crystal to be inferred from a study of the diffraction patterns produced when the crystal is illuminated by a beam of X-rays. The patterns are recorded using special cameras.

The instruments that Franklin and Gosling used consisted of a shallow backing plate roughly the size of a jam-jar lid fitted with a small frame for holding the specimen, and a piece of film. Both were kept in place and enclosed by a domed screw cap with a pinhole through which the X-ray beam was directed.

Cameras were expensive. The biophysics unit bought one, but needed more. The obvious, if not strictly legal, remedy was to copy it. Everyone in Randall’s unit was expected to have a modicum of craft skill as well as scientific knowledge, and PhD students might even do a spell in the workshop under the tutelage of its chief technician Len Pitches. It was his skill with a lathe and milling machine that made it possible to pirate half a dozen copies of the camera.

Then there was the matter of preparing samples to put in them. DNA can be drawn into slender fibrils: “like a filament of spider’s web”, as Wilkins described it in his Nobel prize lecture. This was not strictly true. Earlier, when instructing Gosling in the art of fibril making, his description was closer to the mark: the gooey threads of nucleic acid were, he said, “like snot”.

Wilkins and Gosling manipulated the filaments with the help of an opened paper clip and a tube of quick-setting cement from Woolworths. “Maurice would pull the fibres and I would wind them in a tight bunch round the paper clip. We glued the fibres to its ends.” By pulling apart the arms of the clip the bundle of DNA filaments could be tensioned before they were placed inside the camera.

At the time Gosling joined King’s College, the physics department had no X-ray source of its own. The chemists had an antiquated instrument, however, and arrangements were made to use it – but only out of hours. So it was that the young postgraduate came to pass his evenings sitting in a small, unventilated, lead-lined basement room somewhere below river level on the Thames Embankment.

To get the sharpest possible images, the interior of the camera had to be filled with a gas that would scatter the X-ray beam less than air. Hydrogen was ideal, and it was fed into the instrument via a tube. The older camera on which Gosling began the work required a rubber condom and a kind of sealing wax to make it reasonably gas-tight. Even so, Gosling knew that hydrogen was leaking into his ill-ventilated laboratory. “I think it fair to say I was scared stiff,” he recalls. “There was no circulation of air. I really did think back to those old Zeppelins that went poof!”

Gosling was fortunate: he did not blow himself up. And this was not his only piece of luck. DNA is now known to occur in two forms, A and B, depending on how wet it is. Earlier researchers had inadvertently been working with a mix of the two, resulting in poorly defined images. To see how much of the hazardous hydrogen he was feeding into his camera, Gosling bubbled it through a water trap. This humidified it, in some cases to the 75 per cent that switched all the DNA into its A form.

What he describes as his “eureka moment” came when he was working with one preparation containing some 35 DNA fibres. Crystallography was not a quick business, and this experiment had been running for five days. He removed the film, developed it, and peered at the results. Many of his previous images had been murky or smudged. Even in the dim light of the dark room he knew that this one was different. He had clear, sharp dots instead of a greyish fog.

“I just couldn’t believe my eyes when I saw this spotty pattern all over the film,” he says. “This was something that nobody had got before. I was excited because it meant that if we could measure the intensity of these spots and their positions, we would be able to get a handle on the structure of the molecule.” Wilkins took some of the pictures to a meeting on DNA in Naples. The clear patterns caused a stir.

Although Gosling had obtained good pictures, he still didn’t know why. However, just before Franklin joined King’s, the significance of the humidity began to dawn on Wilkins and Gosling. When Franklin arrived, she pointed out that by bubbling the hydrogen through salt solutions of set concentrations rather than pure water, you could alter the humidity of the gas at will. Raising it to some 95 per cent produced the B form of DNA, giving images that offered the vital clue to its structure.

With Franklin’s experience of crystallographythe images steadily improved. In the event, it was the quality of her pictures that allowed Crick and Watson to infer the helical form of the DNA molecule. When their paper appeared in Nature in April 1953, it was accompanied by a report from Franklin and Gosling that included their now famous photo 51 showing an image of the sodium salt of DNA from calf thymus.”Our general ideas,” they wrote, “are not inconsistent with the model proposed by Watson and Crick in the preceding communication.”

Gosling went on to spend time in the West Indies before returning to London, where he wound up as professor of physics applied to medicine at Guy’s Hospital. The man who had aimed to become a medic, but instead became a DNA cameraman, retired in 1991. The work he contributed to has already had a fundamental impact on human health. Much more, in all likelihood, than anything he would have achieved in the lifetime of routine doctoring he originally hankered after.

Topics: women in science

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