Unravelling the Double Helix

by Gareth Williams

  Avery had been grooming MacLeod to take over as director of the pneumonia research lab at the Rockefeller, and the recent rush of papers on sulfapyridine should have made him a strong candidate. In February 1941, MacLeod received a gift from heaven: an invitation to become Professor of Microbiology at New York University. MacLeod decided to use the offer as a bargaining chip to get his dream job, and made the grave error of trying to haggle with Tom Rivers. Short of helping him to pack, Rivers did everything to push MacLeod into the Chair at New York – while reminding him that he only had six months of funding left at the Rockefeller. MacLeod had to accept the offer that he had intended to turn down. Soon after, Rivers announced that one of his own bright young virologists had been appointed to lead a new research programme on viral pneumonia, and would direct the pneumonia research lab when Avery retired.

  Doomed to leave in a few months, MacLeod settled back at the bench and worked fast and furiously to crack the identity of the transforming principle before his time ran out. In his haste, he forgot to follow up an odd result that he recorded on 28 January 1941. He had tested a sample of transforming principle with diphenylamine, which turns an attractive china blue colour in the presence of the sugar, deoxyribose. This prompted MacLeod to write: ‘Thus it would appear as though the transforming extracts may contain a little desoxyribose nucleic acid in addition to the large amounts of ribose nucleic acid present.’

  Colin McLeod was therefore the first to record the true nature of the substance that could alter the inherited characteristics of pneumococci in perpetuity – but there is no indication that he realised the significance of what he wrote. Within days of making that entry, MacLeod received the invitation from New York University which sealed his fate. This explains why the eureka moment – such as it was – was not witnessed by MacLeod, but by the man who took his place at the bench in Avery’s lab in September 1941.

  * Both men were murdered in prison.

  † Domagk eventually collected his Nobel Prize in December 1946.

  ‡ Dubos also discovered the Type III SSS-degrading enzyme, in bacteria from a peat-bog.

  15

  APPLICATIONS OF SCIENCE

  Wednesday, 28 August 1940.

  In Moscow, there was still no word from Nikolai Vavilov, now missing for three weeks, nor any hint about his fate. In New York, Colin MacLeod was coming to terms with failure; he had flogged himself as hard as he could, but was not going to crack the identity of the transforming principle during his last few days at the Rockefeller. And in Liverpool, certain products of British research were about to sail for America in a black metal deed box, under circumstances that could have been lifted from a spy thriller.

  The box was the size of a small suitcase, with an unusually sturdy lock and holes drilled in its sides. It belonged to Sir Henry Tizard, physicist and leader of the top-secret British Scientific and Technical Mission to America. Inside were blueprints for a revolutionary ‘jet’ aircraft engine, clever fuses for bombs, a device to detect distant aircraft and submarines – and a brief memorandum that predicted a bomb with unimaginable destructive power.

  Tizard was already in Washington, preparing the ground for a difficult meeting. America was still neutral, with powerful voices arguing against getting involved in the war in Europe. Tizard’s role was to persuade the US military that Britain would be an effective partner should America be sucked into the conflict.

  The box joined him two weeks later, having crossed the Atlantic with an armed escort ordered to sink it rather than let it fall into enemy hands.* When Tizard lifted its lid on 12 September 1940, the Americans were immediately bowled over by one of the treasures inside. This was a bulky tube several inches long, so astonishingly brilliant that the American scientists who took it away wished that they had thought of it first (and some later claimed that they had). The genius of the device lay in a squat copper cylinder with an array of circular holes drilled in one end, rather like the cylinder of a revolver. This was the ‘cavity resonator magnetron’, invented six months earlier by John T. Randall and Harry Boot of the Physics Department at Birmingham University.

  Harry Boot has only a brief, walk-on role in the story of DNA, but John Randall’s part is pivotal. Without him, the tangled saga of the double helix would have had a completely different ending.

  Power and glory

  John Randall (Figure 15.1) was born in 1905, halfway between Liverpool and Manchester. He was seven years younger than Bill Astbury, with whom he shared his working-class origins, grammar-school education, and a career shaped by the Bragg dynasty. Randall studied physics at Manchester and graduated in 1922 with the best First of the year. He turned down the chance to do a Master’s with Lawrence Bragg because the Nobel laureate overawed him. Instead, he tackled a mundane aspect of X-ray crystallography that gave him no opportunity to shine. He failed to impress and later wrote, ‘They did not think well enough of me to keep me on.’ More bluntly, Bragg told Randall that his future lay in industry, not academia – a put-down which permanently clouded their relationship.

  In 1926, aged twenty-one, Randall signed up with the General Electric Company in Wembley. His marriage to Doris Duckworth a couple of years later helped him to adapt to the ‘smooth South’ and to working in an ‘unusually talented group’ where rudeness and belligerence flowed as freely as clever ideas. He became an expert in ‘phosphors’ – luminescent powders that boost the light emitted by fluorescent tubes – and wrote a 300-page book about ‘X-ray and electron diffraction of amorphous solids’, which included rubber and wool.

  Figure 15.1 John Randall.

  All this enabled him to be rehabilitated into academia. J.D. Bernal wanted him in Cambridge, but could only pay half the going rate. In 1937, Randall won a Royal Society Fellowship and took it to the Physics Department at Birmingham under Mark Oliphant, an Australian nuclear physicist who had trained with Rutherford. Randall’s lab was a room with a sloping ceiling because it was tucked in under a raked lecture theatre; delicate instruments had to be recalibrated whenever the students overhead became restive and stamped their feet.

  In 1938, Randall acquired a research assistant who wanted to do a PhD on luminescence. The applicant had rung Oliphant, who had supervised him as an undergraduate in Cambridge, to ask if there were any jobs going. Oliphant believed that he had potential, even though there was no hard evidence; the applicant had left Cambridge with a 2:2 in Physics. The newcomer was a tall, bespectacled, rather earnest twenty-five-year-old man called Maurice Wilkins (Figure 15.2). Oliphant told him that Randall was doing ‘interesting things’ with luminescence, and made the introductions. Randall was persuaded, and Wilkins signed up for a PhD in the Luminescence Lab.

  They found each other engaging and stimulating company, but the PhD got off to a slow start which exposed Randall’s ruthless streak. Randall gave Wilkins a long list of photographs to prepare – for a backlog of papers that Randall was writing – and then told him to build his own apparatus for measuring luminescence. Then, just as Wilkins was getting into his stride during the last weeks of peace in summer 1939, Randall was called away urgently and left his new PhD student to cope on his own.

  Figure 15.2 Maurice Wilkins (left), in discussion with Nobel Laureate Renato Dulbecco.

  Randall’s new project was funded by a massive government grant which Oliphant had won against Lawrence Bragg, recently installed as Director of the Cavendish Laboratory in Cambridge. It was classified top secret. The aim was to make a powerful, accurate radar system small enough to fit in an aeroplane; a stroke of genius was required, as the existing equipment weighed a couple of tons and filled a large room.

  Oliphant was impressed by Randall’s ability to think unconventionally and put him on the case, assisted by Harry Boot, a research student who, as a schoolboy, had built a Van der Graaf generator in his bedroom. The inspiration for the cavity resonance magnetron came from a second-hand book about the invention of radio, which Randall read while on holiday in Wales. The mag
netron works on the same principle as an acoustic guitar, which is also a cavity resonator; substitute surges of electrons for the vibrations of the strings, and the holes drilled in the copper cylinder for the sound-box, and you have the basic concept for the ‘valve’ which Randall and Boot put together during the winter of 1939–40. The prototype was first tested on 20 February 1940, and immediately showed promise. A brilliant arc appeared around the business end; neon tubes several feet away burst into light without being switched on; a cigarette could be lit by bringing it close to the invisible beam; and the hand holding the cigarette became worryingly warm. Hundreds of prototypes later, they had a magnetron which blasted out microwave radiation that was 500 times more powerful than existing radar valves. It could see through cloud at night and pick out an aircraft over 200 miles away, a battleship at 60 miles and a surfaced U-boat at 30 miles – and it could fit into a night fighter.

  Of all the tricks in Tizard’s black box, it was the Randall-Boot magnetron which captivated the Americans at that crucial moment in September 1940. During the war, American factories made over a million magnetrons for ships, aircraft and artillery. The device was decisive in winning the battles in the skies above Britain and Europe. No wonder that the Director of the US Office of Strategic Services described the magnetron as ‘the most valuable cargo ever to reach our shores’.

  Meanwhile, back in Birmingham, Randall’s abandoned PhD student was having to manage by himself and was discovering that he thrived on neglect.

  Lost soul

  Maurice Wilkins was the middle of three children and a New Zealander by birth. His parents were Dubliners, with academics on his father’s side and a grandparental marriage which disintegrated so spectacularly that it was mentioned in Ulysses. New Zealand beckoned because his father, a school doctor, became bored with Ireland. He took his family to Pongoroa, set in rolling hills on the North Island, where Maurice was born ten days before Christmas 1916. The new baby was christened in a large silver bowl which his father had won as a cycling trophy.

  Maurice enjoyed seven colourful years in the ‘Garden of Eden’ before his father fell out with ‘the authorities’ and took the family on a year-long ‘world cruise’ which ended with a new job in Birmingham. This was within striking distance of the Welsh mountains, where father and son continued their ‘Worship of the Hills’, walking and climbing at weekends. There were early hints of where Maurice’s curiosity might eventually take him. Aged twelve, he sketched the imaginary Radium Island, in the middle of the South Pacific and rich in uranium ore. Two things that he held dear were ingrained in childhood: an ‘almost religious’ reverence for science, and anger, inherited from his father, over the ‘poverty in the midst of plenty’ which the Depression was laying bare. He was also fascinated by optics, and hand-ground the lenses for his home-built but professional-quality astronomical telescope.

  He won a scholarship to the local High School and nobody was surprised when, in 1935, he carried off an Entrance Scholarship at St John’s College, Cambridge to read Physics. Cambridge was more of a culture shock than he had expected – ‘great big buildings like citadels’ and a paranoid fear of ‘many clever people’. His first two years went smoothly, if not brilliantly. Best of all were the tutorials with Mark Oliphant, Rutherford’s right-hand man at the Cavendish who was about to be poached to the Chair in Physics at Birmingham. A major disappointment was J.D. Bernal, crystallographer extraordinaire, who relied on his ‘awesome charisma’ to carry him through his lectures; he would arrive late and stand enigmatically at the front for some minutes, reading a book.

  Wilkins had been looking forward to the third year and Crystal Physics, but it was a catastrophe. The first dozen pages of his notebook show no hint of trouble; then several pages are torn out and the rest are blank. Wilkins’s melt-down was due to politics, ‘the most significant aspect of my Cambridge experience’. He had joined the Communists, led locally by Bernal who had often been a VIP visitor to the Soviet Union before the war. Disguised as ‘John J. Johns’ (in case university apparatchiks did not share his views on public engagement), Wilkins wrote a regular science feature for the Young Communist League’s magazine. He took to the streets in London under the banner, ‘Scholarships, not battleships’, and was the only undergraduate to join the Cambridge Scientists Anti-War Group. This group, also led by Bernal, was genuinely underground; they met in the basement of a café on King’s Parade, while the corrupt bourgeoisie enjoyed lunch above their heads.

  Wilkins realised too late that Crystal Physics demanded more effort than ‘The secrets of the stars’ by John J. Johns, especially when he was summoned to explain why he had been writing ‘popular science for a left-wing youth paper’. What he called ‘my breakdown’ was diagnosed as a bout of depression. The result was the ‘very big shock’ of his 2:2 in Physics, which dashed any hope of doing research in Cambridge. The previously friendly Bernal now conspicuously kept his distance. As Wilkins later said, ‘I had to leave.’

  Luckily, his prospects picked up after his phone call to Mark Oliphant in Birmingham. Wilkins’s first impressions of John Randall were strongly positive – ‘a small, upright man with clear, bright eyes and a lively energetic personality . . . full of interesting ideas about research . . . informal and ready to talk freely, even gossip, even about personal problems’. And Oliphant’s department, humming with both science and intrigue, was a thrilling place to be. When Wilkins called in to see Oliphant, he stubbed his toe on something heavy that had been dumped on the floor. It was a sack of uranium oxide.

  And there was light

  With Randall now working full-time and in secret on the magnetron, Wilkins was left to push ahead with his PhD unsupervised. He found the working conditions ideal: a compelling problem, the excitement of breaking completely new ground, a blank instruction sheet and nobody breathing down his neck. He made remarkably quick progress.

  The Ministry of Home Security had moved on from its original bright ideas about applications for phosphors (e.g. making luminous collars to facilitate dog-walking during the blackout). Wilkins’s task, classified top secret, was to enhance the shining dot that marked the position of enemy aircraft on radar screens. Along the way, he wrote three masterly papers which killed off the current theory of phosphorescence and provided a convincing alternative. His work was described as ‘brilliant’ by one of the world’s leading theoretical physicists. With Oliphant’s approval, Wilkins added a punchy introduction and submitted the papers as his PhD thesis, a year early.

  The PhD also taught him valuable lessons about life in general and John Randall in particular. Wilkins included Randall as co-author on one paper but not the other two, because he had nothing to do with them. Randall insisted that his name must be on all three. Wilkins was ‘very disturbed’ by the injustice – and took himself on ‘a long, slow wartime rail journey’ back to Cambridge, to consult the psychologist who had helped him through his depression. He was advised to let the boss have his way, as his career might later depend on Randall’s goodwill. Learning point for Wilkins: ‘I could not take it for granted that Randall would always act in my best interest.’

  Apart from the friction over authorship, Wilkins’s relationship with Randall remained cordial. They and Henry Boot – who had been in the year below Wilkins at school – used to meet for lunch at the Students’ Union. The Official Secrets Act prevented discussion about the magnetron, but Wilkins had a rough idea of what was going on and could not help noticing the large horn-shaped structure which appeared on the roof above Randall’s lab.

  After his PhD, Wilkins found himself at a loose end and on the receiving end of night bombing raids. His growing hatred of the Nazis caused a transformation that would have been unthinkable to the idealistic and naive ‘John J. Johns’ back in the ‘small world’ of the Cambridge Scientists Anti-War Group. Maurice Wilkins went to ask Oliphant about joining another project, even more secret and infinitely more destructive.

  New World

 
; Oliphant’s top project was cloaked in the camouflage of ordinariness. It was called ‘Tube Alloys’, a name chosen to be ‘meaningless, but with a specious feasibility’. Its origin was an eight-page document – the ‘Frisch-Peierls memorandum’ – that went to America in Tizard’s black box. Otto Frisch and Rudolf Peierls were both Jewish physicists who fled Germany in 1939 and came to Birmingham to work on nuclear fission. They theorised that fission could ‘go critical’ with just a few kilograms of a rare isotope of uranium that had an atomic weight of 235 (235U). Accordingly, the Tube Alloys project was set up to make the world’s first nuclear bomb.

  Wilkins joined Tube Alloys in 1941. Oliphant set him working on the make-or-break problem of how to separate 235U from the non-explosive 238U, which makes up over 99 per cent of natural uranium. Wilkins’s brief was to turn uranium, normally a silvery metal as dense as gold, into a gas and to concentrate 235U using a diffusion barrier perforated with millions of tiny holes. He tried hard, with an array of bright steel tubes that passed through the ceiling of his lab and up one wall of the lecture theatre above, but two years later had got nowhere. In October 1944, it was decided on high that Oliphant’s team should move to the Radiation Laboratory at Berkeley, California, where facilities were better and time was not wasted by air-raids and power cuts. The ‘Manhattan Project’, as the American atom bomb programme was called, was a vast operation employing 130,000 people, all carefully parcelled up in ‘the greatest secrecy’.