Unravelling the Double Helix

by Gareth Williams

  Wilkins’s method still failed to produce useful quantities of 235U, but California was a fair swap for the edgy grey austerity of Birmingham. Instead of grabbing lunch with Randall and Boot in the Students’ Union, Wilkins could now enjoy a sandwich while looking across to the Bay Bridge and talking philosophy with new friends. And there was a woman in his life – Ruth, an art student who was bright, witty and shared his political views. They quickly ‘became close’. So close that Ruth fell pregnant; that Wilkins said they must keep the baby and get married; and that she agreed.

  Summer 1945 was frantic for the Manhattan Project and life-changing for Wilkins. The first significant moment was when Harrie Massey, one of Oliphant’s team, gave him a book by Erwin Schrödinger, who had won the Nobel Prize for Physics in 1933 and escaped from the Nazis a few years later. The book was small, but its title posed a huge question: What is Life?

  It was the distillate of lectures that Schrödinger delivered in July 1944 at Trinity College in Dublin, where he was Director of Theoretical Physics. These lectures were a sensation: packed out every night with people off the streets as well as academics, dignitaries and the press. Schrödinger set out to demystify the processes of life by making them conform to the laws of quantum physics. His most famous sound-bite was the claim that genes are ‘aperiodic crystals’. Although he never explained what that meant, many believed that Schrödinger was a new messiah, bringing the hard clarity of physics to the anarchy of biology. Others found him unconvincing, like an oracle whose utterances had to be interpreted by the faithful.

  Maurice Wilkins was one of those immediately seduced by the beauty of the writing and the power of the intellect that lay behind it. Genes and chromosomes had never crossed his path before. Suddenly, he was captivated by the thought of guiding his kind of science into the messy biological arena of genes and heredity. Schrödinger’s ‘aperiodic crystals’ rang a strangely familiar bell; the concept seemed ‘remarkably like the luminescent crystals I had studied before the War’. For now, though, he had work to finish, and ‘aperiodic crystals’ and genes were pushed into hibernation.

  *

  Around this time, Wilkins heard from John Randall, whom he had left behind in Birmingham. Randall had been through a rough patch and was unhappy and bitter, because the magnetron had left its inventors high and dry. The Americans had made off with it, modifying the design so that it could be mass-produced by American companies. The Admiralty, which funded Randall’s part of the radar programme, did not apply for a patent until January 1943, by which time the US Patents Office had already challenged the claim that Randall and Boot had invented it.

  On top of that, Randall’s Royal Society Fellowship had run out, and even though he was the technological equivalent of a war hero, it was not extended. In desperation, he accepted an offer from Lawrence Bragg at the Cavendish Laboratory in Cambridge for ‘half-time employment as a temporary lecturer’, with an absurdly heavy teaching load, no time for research and half his Fellowship salary. But it was better than the dole, so he moved to Cambridge in October 1943.

  He and Harry Boot remained in touch while lawyers on both sides of the Atlantic continued wrangling over patents. In late summer 1944, Boot wrote with a pessimistic update, signing the letter ‘Harry (£££)’. He added a PS: ‘I’m afraid I haven’t yet got used to your new title’. Randall’s new title was ‘Professor’. He had escaped the menial teaching post at the Cavendish and moved north of the border, to the Chair of Natural Philosophy (Physics) at the University of St Andrew’s. He settled in quickly and started shaking the place up. And as soon as he had cobbled together enough money, he contacted his former PhD student, Maurice Wilkins, and offered him the post of lecturer.

  Over in California, Wilkins’s relationship with Ruth had flourished after its first real test – the discovery that she was expecting their child. The second test came when Randall’s offer arrived. Wilkins turned that one down, but not the one that followed, with an increased salary offer. The war in Europe had just ended, and Ruth seemed to welcome the prospect of moving to Scotland. ‘I like rain,’ she said, and Wilkins began looking forward to returning to Britain with his wife and new baby.

  Two bolts from the blue ruined his last few weeks in Berkeley. The first was a message from Ruth to go to a lawyer’s office, where he was presented with a $200 bill and their divorce papers, ready for him to sign. Wilkins was devastated and tortured himself with the thought that he should have ‘discussed the implications of marriage more thoroughly’. Ruth gave birth shortly after the divorce; her ex-husband saw his son once in hospital before she left Berkeley with the baby.

  Then, on 6 August 1945, the news broke that Hiroshima had been destroyed by the atomic bomb nicknamed ‘Little Boy’. Like everyone else outside the Manhattan ‘Executive Board’, Wilkins had been kept perfectly in the dark. He did not know that the prototype – ‘Trinity’ – had been tested successfully in the deserts of New Mexico on 16 July. The news blackout was impressive, given that the flash was bright enough to be noticed by a woman 150 miles away, who happened to be blind. Initially, Wilkins was infected by the ‘joyful sense of achievement’ that swept through Berkeley – until a philosopher friend, who ‘did not look very happy’, confessed that he had always hoped that the bomb would fail. Wilkins wrote later, ‘I felt rather small, and gradually the penny dropped. I said, “Yes, you’re right.”’

  A few days after that, Wilkins was on the boat for England, alone.

  War work

  The stock question, ‘What did you do during the war?’, would have received strikingly different responses from the three fledglings who, back in 1928, had flown Sir William Bragg’s nest at the Royal Institution.

  J.D. Bernal lived up to his polymathic reputation, enlivened by his sense of adventure and a total disregard for his own safety. During the Blitz, he worked out how to distinguish a dud bomb from one with a delayed-action fuse that was still ticking – stimulating J.B.S. Haldane to write (on the back of a menu), ‘Desmond Bernal / Is not eternal / He may not escape from / The next bomb’. Bernal went on to model the impact of an intensive air-raid on an English industrial city, choosing Coventry (with its cathedral as the primary aiming-point) some five months before it all happened for real. Later came a rough crossing to the Normandy beaches in a motor torpedo boat on the afternoon of D-Day, and a particularly close encounter with a bomb on D+l; and, via Babylon, experiments with depth-charges in the jungles of Ceylon.

  Kathleen Lonsdale had a much quieter time. As a pacifist and conscientious objector, she refused to report for Civil Defence duties and spent some months detained at His Majesty’s pleasure in Holloway Prison – a valuable experience, she claimed, because it helped her communication skills.

  Bill Astbury found the war irksome. His main contribution to the war effort was teaching navigation to trainee RAF pilots. His research suffered two direct hits in January 1941, when the Ministry of Labour and National Service wrote to him requiring Florence Bell and his lab assistant Elwyn Beighton to report for military service. Astbury replied robustly, insisting that both were engaged on work of national importance and were ‘irreplaceable’, but the Man from the Ministry (a certain C.P. Snow) was unmoved. Both were plucked out of X-ray crystallography and retrained as radio operators; even worse, Bell then married a US Army lieutenant who later carried her off to Washington. Astbury managed to continue some experimental work, including a heroic labour of love by Miss A.M. Melland, working in Cambridge, who spent thirty days stringing up a microscopic array of over 1,250 giant chromosomes from the salivary glands of midge larvae. The array was rushed to Leeds, X-rayed by Astbury during an air-raid – and yielded nothing of interest.

  On 11 March 1942, the three received bad news. Their patriarch, the Old Man’, had died quietly in his flat above the Royal Institution. Sir William Bragg was still ‘in his full mental vigour’, although there had been mutterings because ‘his kindliness had led him to welcome certain ambiguous advances fro
m learned bodies in Nazi Germany . . . which, in his goodness of heart, he took at face value’. A curious situation for a man who had refused to collect his Nobel Prize in person because ‘Germans would be there’.

  Blast from the past

  Back in July 1942, the Journal of Heredity had printed an unusual paper, which would have lifted the spirits of its readers. It was based on what a sprightly eighty-six-year-old man could remember about ‘a unique summer afternoon of two-thirds of a century ago’. The interviewee was C.W. Eichling, still sporting the neat beard and moustache that he had first grown for the special horticultural mission of his youth, and the article was entitled ‘I talked with Mendel’.

  Eichling had gone on to much greater things following the nine-month trip through Germany and Austria which brought him to Brünn and the Abbey of St Thomas in the summer of 1878. After working as a travelling salesman for Roempler, the exotic plantsman of Nancy, he moved to New Orleans and set up his own business. Roempler withered on the vine, but Eichling flourished; his Illustrated Plant and Seed Catalogue ran to over 100 pages, and ‘Eichling’s Superior Flat Dutch Cabbage’ and his ‘First and Best Peas’ were second to none.

  Now, Eichling ‘looked back over 64 years to give us a glimpse of the first geneticist’. His account of his day in the sun with the genial bespectacled priest was an enthralling read for anyone with the faintest interest in genetics. The old man had two regrets: that he had failed to entice the ‘Founder of Genetics’ to break his vow of silence about the ‘little trick’ to perfect the abbey’s peas; and that ‘other plans’ had prevented him from fulfilling his promise to visit Mendel again.

  ‘I talked with Mendel’ was published to coincide with the 120th anniversary of Mendel’s birth on 22 July 1822. It would have delighted Nikolai Vavilov, but it is very unlikely that he ever saw that issue of the Journal of Heredity. Almost two years since his disappearance, there was still no news about his fate.

  Shortly after Eichling’s paper appeared, it was announced in London that Nikolai Ivanovich Vavilov had been elected a Foreign Member of the Royal Society. This rare honour was intended not only to recognise Vavilov’s achievements and to give him succour, but also to remind the Soviet authorities that the eyes of the global scientific community were on them. It was impossible to tell whether the message reached either of its targets; the Society later admitted that Vavilov ‘probably did not know’ of his election.

  Strangely, Vavilov’s plight failed to excite one of the few Fellows of the Royal Society who might have been able to pull strings inside Russia. J.D. ‘Sage’ Bernal, elected FRS in 1937, had kept in contact with top-level Soviet scientists, and in his 500-page book, The Social Function of Science (1939), praised ‘the beautiful example’ of Vavilov’s ‘bureau of plant industry’ and his ‘very thorough development of genetic principles’.

  But, being a loyal Communist, Bernal was careful not to rock the Stalinist boat. The ‘controversy on the foundations of genetics’ which engaged Vavilov and Lysenko was relegated to a footnote in his book. It was nothing to get upset about; just a minor spat that had been ‘magnified out of all proportion’ by the capitalists who wished to discredit Soviet science.

  * The armed escort arrived too late to prevent the box from being carried away by a well-meaning porter at Euston Station in London.

  16

  DREAMS OF GENETICISTS

  Through the summer of 1941, many Americans came to realise that peace was living on borrowed time. The Rockefeller Institute for Medical Research, now badged the ‘US Navy Reserve Research Unit’, was already responding to the threat of war in ways that did not necessarily remain faithful to its mission statement, ‘The application of science for the good of humanity’. John Northrop, renowned protein chemist and enzymologist, was perfecting his ‘titrimeter’ for detecting mustard gas, a loathsome toxin (banned under the 1927 Geneva Protocol) which kills its victims by drowning them in the secretions of their own lungs. Down the corridor, Northrop’s colleagues were also working on mustard gas – ensuring that it would stick better to skin and clothing after being sprayed from aircraft. Elsewhere, Rockefeller researchers were locked down in a top-secret programme to purify 235U, a product which had only one use.

  Work in Oswald Avery’s lab was unaffected. In early September, while Avery was on his long summer break in Maine, Colin MacLeod left reluctantly to become Chief of Microbiology at New York University. His replacement was Dr Maclyn McCarty, a thirty-year-old paediatrician whose boss had told him that his scientific talents would be wasted at the coalface of clinical medicine.

  Like Avery and MacLeod, McCarty had endured a peripatetic childhood, thanks to his father’s job in the motor industry. When he started medical school at Johns Hopkins, he already had a healthy respect for bacteria; an aunt, about to become a doctor, had died from septicaemia after cutting her finger during a post-mortem. His fascination with bacteria grew while he was a paediatrics intern in Baltimore and tried to save two children gravely ill with streptococcal meningitis. The first case, in 1936, obeyed the textbook ruling of 100 per cent mortality. The second, just a year later, made a full recovery. The difference, in a word, was sulfanilamide.

  McCarty was interested in research from the start and co-wrote a paper on sulfapyridine, which was published in 1939, the same year as Colin MacLeod’s debut in the subject. His other early achievements included marriage (frowned upon, as he was still a student), the birth of two sons (ditto), and his accidental discovery that sulfapyridine prevented benzene, a common industrial chemical, from killing off white blood cells. This produced another paper and stimulated his boss to tell him that ‘it would be splendid if you could spend one year at the Rockefeller Institute’. By chance, McCarty had recently met Avery at a dinner party, and had found him a ‘charming and a fascinating raconteur’. One thing led to another and then to a two-year fellowship with Avery. McCarty’s boss pointed out that Avery’s intellect was in ‘the extreme upper stratosphere’, and hoped that McCarty would ‘not develop “Bends” on making the ascent’.

  McCarty visited Avery in spring 1941, several months before starting his fellowship. He was treated to ‘the Avery process of orientation’ but was surprised that the Red Seal discourse omitted something that had fascinated him when it was mentioned at medical school: the transformation of pneumococcal type. McCarty assumed that this research had withered on the vine, because Avery’s lab had not published anything on it in seven years. And on that first meeting, Avery made no effort to introduce him to Colin MacLeod, still working flat out in the lab to nail the elusive transforming principle before his time ran out.

  Enter McCarty

  McCarty’s induction began properly in mid-September, when Avery returned from holiday. This time, the Red Seal session was all about transformation and covered MacLeod’s work, left hanging tantalisingly in mid-air and crying out for a lucky break. This was what McCarty had been waiting for: ‘It captured my imagination from the start.’

  Avery had assumed that Colin MacLeod would dream up his own research programme when he left the Rockefeller; in fact, the new professor was refitting his lab at New York University to continue chasing the transforming principle. He called in soon after Avery got back and joined the discussion about what his successor would do. MacLeod had done his homework on McCarty and ‘enthusiastically’ encouraged him to dig further into sulfapyridine and benzene toxicity. For McCarty, his sights now firmly fixed on transformation, ‘nothing could have been further from my mind’. At the time, he did not spot the significance of MacLeod’s polite but definite ‘Hands off’, because he was ‘not sufficiently sensitive’ to his predecessor’s feelings. MacLeod came across as ‘generous and helpful’, even though it must have been galling to watch Avery handing over his hard-won project to the usurper.

  Many years later, when the two men shared digs at a conference, MacLeod confided to McCarty just how traumatic his departure from the Rockefeller had been. And it was only after MacLe
od’s death that the easy-going McCarty, who had only picked up vague hints of ‘mixed feelings’, discovered what the man he replaced had really thought about him.

  It took several weeks for MacLeod to realise that the transforming principle could poison his new job as well as the old one. In late October, he came back to Avery’s lab and symbolically handed ownership of the project to McCarty by showing him how to operate the Sharples Separator. McCarty’s first experiment was to strip away the Type III SSS from the transforming extract with the special enzyme, to confirm that this did not damage the transforming principle. He discovered afterwards that this had already been done, but it was useful experience and proved to Avery that the newcomer was gifted at bench work. As a spin-off, McCarty wondered about other ways of eliminating SSS, and found that depriving Type III S pneumococci of glucose reduced SSS levels without impairing transforming potency.

  Sunday 7 December began unremarkably, with McCarty going into the lab as usual to check his experiments. On the way home, he switched on the car radio and was shaken to hear that Japanese warplanes had attacked the American fleet in Pearl Harbor. The next morning, President Franklin D. Roosevelt delivered his ‘Hour of Infamy’ speech. By midday, America was at war with Japan, and two days later, with Germany and Italy.

  For several months, McCarty was protected from active service by being married and in possession of children. When the draft notice eventually arrived, Tom Rivers (now a commodore in the US Naval Reserve) pulled rank to keep Lieutenant McCarty working as before, but in naval uniform. Rivers also quashed McCarty’s guilt about not doing more for the war effort, telling him bluntly to forget it and get on with his research. So he did. By Christmas, he had got rid of the last traces of SSS and ribose nucleic acid, by thoroughly washing the heat-killed Type III S (which nobody had thought of doing before) and clearing out any residues with the SSS-splitting enzyme and RNase. Soon after New Year 1942, he purified the transforming principle further, using the alcohol extraction that Lionel Alloway had stumbled upon eight years earlier – and with even more dramatic results. On adding alcohol, a ‘stringy mass of fibrous precipitate’ appeared. Alloway’s precipitate had been contaminated by SSS and RNA; with these removed, McCarty’s white fibres now contained 99.9 per cent of the total transforming activity. Whatever it was, this was the real stuff.