Unravelling the Double Helix

by Gareth Williams

  He sent a nice thank-you telegram to Sir Henry Dale, President of the Royal Society, expressing regret that ‘compelling circumstances’ prevented him from travelling to London to receive the Copley Medal. Dale decided to present the medal to Avery himself, while on a trip to New York. He called in unannounced and knocked on the door of Avery’s inner sanctum, medal in hand. When there was no reply, Dale put his head around the door – and saw the back of a small, old man sitting at the laboratory bench, totally immersed in his own world. Dale quietly withdrew, murmuring ‘Now I understand’, and left a note with the medal.

  The swing doors of Avery’s personal lab closed behind him for the last time in spring 1948. In Nashville, family meant more to him than anything else; he rented a house on the same street as Roy’s, and his cousin Winnie moved in as housekeeper. The summer pilgrimages to Deer Isle continued, with gardening and painting in between.

  Avery completely stopped doing science, but did not turn his back on everything from his previous life. On his desk in Nashville was the same memento that he had made space for at the Rockefeller: the framed snapshot of a man who was a perfect stranger except in the pages of scientific journals, sitting in the sunshine with his dog on a hillside in the south of England.

  Avery never had the chance to appreciate fully how much his work changed the course of biology, and he might have been surprised to learn that scientists destined for great things had realised the importance of his discovery. Some were youngsters at the start of their careers, and others seniors at their peak. Harriett Taylor was so excited by the twenty-two pages in the Journal of Experimental Medicine that she abandoned the genetics of yeast and defected to Avery’s lab. She gave the paper to someone even younger and more impressionable: a nineteen-year-old medical student, who experienced such ‘excruciating pleasure’ on reading it that he stayed up all night to think it through, and then gave up medicine for pure science. His name was Joshua Lederberg, and he went on to win the 1958 Nobel Prize for Physiology or Medicine for his work on ‘the genetic material of bacteria’. The paper also knocked an established researcher off course. Erwin Chargaff, who ran a busy biochemistry research lab at Columbia University, diverted his entire research effort into DNA because it was suddenly the most exciting molecule on the horizon.

  Many years later, the first person to have heard Avery in full flow about DNA put it all in a nutshell. Macfarlane Burnet, by now Sir, FRS and Nobel laureate (Physiology or Medicine, 1960), looked back and said simply that Avery’s work ‘heralded the opening of the field of molecular biology’.

  Oh, to be in England

  One of the many letters that Avery never answered was dated 18 January 1945. It began, ‘Dear Professor Avery, I do not know if you remember me . . .’ and could have come from an awestruck junior.

  The writer had greatly enjoyed ‘a little talk with you about the pneumococcus and things’ several years earlier, was now ‘extremely thrilled’ by the work on ‘your factor’, and wondered if ‘you could possibly let me have some for X-ray examination’. This seemed ‘a wonderful chance to make an important step forward’; the writer had done ‘a fair amount of work on the structure of the nucleic acids’, but unfortunately the war had got in the way and some of it was still unpublished. The letter was postmarked Leeds, England and was signed by Dr William T. Astbury, FRS.

  During the war – which cruelly deprived Astbury of ‘my secretary, my personal assistant, and even my lab boy’ – most of his research had trod water. The only bright spot had been in 1940, with his election to Fellowship of the Royal Society. Now, at last, life was improving. Two days after he wrote to Avery, he received a letter from A.V. Hill, Secretary of the Royal Society, inviting him to give the annual Croonian Lecture. This considerable honour set him in the footsteps of Thomas Hunt Morgan, who had reported the 2,000 Drosophila mutations in his Croonian Lecture of twenty-three years earlier. Hill added that it was unusual for a physicist to give a lecture that had been ‘biological’ since 1684, but that Astbury’s skill in bridging the disciplines made him the ideal man for the job.

  The invitation, and the top-level approval of his research philosophy, galvanised Astbury to write to the Vice-Chancellor of Leeds on 6 February. Biology was entering a new ‘molecular structural phase’, he explained. Leeds ‘should be bold and lead the way’, by setting up the world’s first Department of Molecular Biology, to explore the interface between physics and biology.

  The University Council agreed that Dr Astbury would be promoted to professor to head his new department, but there were two snags. Firstly, no money. Secondly, ‘Molecular Biology’ was too revolutionary. The wise men of the university saw only hard frontiers between physics and biology and thought that Astbury was not quite biological enough. He had to settle for a ‘rather ridiculous mouthful’ – the ‘Department of Biomolecular Structure’.

  Astbury delivered his showcase Croonian Lecture ‘On the structure of biological fibres and the problem of muscle’ on 13 July 1945, a couple of months after victory in Europe. It sparkled with his usual erudition and wit, and provided a wonderful propaganda opportunity. Astbury closed with ‘a plea for still closer co-operation between the biological and physical sciences’, adding that ‘we are at the dawn of the new era of “molecular biology”, as I like to call it.’

  The notion appeared to excite the interest of the Medical Research Council, which invited Astbury to put in a proposal to fund his new department. This was like manna from heaven and initially, the omens looked good. Unfortunately, his hopes were dashed early in 1946 by a regretful letter from the MRC’s chairman, saying that he personally liked Astbury’s vision of molecular biology, but that both of them would be ‘living in a fool’s paradise’ if they continued to believe that the MRC could spirit up anything more than ‘little or no help’. A badly dispirited Astbury returned to the treadmill of grant-writing and fund-raising.

  The first anniversary of his letter to Avery came and went in January 1946, with no reply from New York. By now, DNA was losing ground. He barely mentioned it in his Croonian Lecture, and his butterfly-like attention had been snared by ‘flagella’, the molecular whips which propel bacteria. And now he had someone to do the experimental work. Elwyn Beighton, the ‘lab boy’ turned technician who had been snaffled by the military in 1941, had recently contacted him to ask if he could do research in Astbury’s new department. Astbury signed Beighton up to do a PhD on ‘X-ray studies of bacterial flagella’.

  In July 1946, Astbury attended a meeting that signalled the return of normality to the scientific world: a symposium on nucleic acids, organised in Cambridge by the Society for Experimental Biology. Unembarrassed by the lack of new data, he recycled Florence Bell’s X-ray photographs of seven years earlier. The DNA molecule was still the same stack of pennies, and the 3.4 A spacing was ‘a stereochemical correlation of deep significance’. His thinking had moved on in only one regard. The long shadow of the late Phoebus Levene had now fallen on him; Astbury’s proposed DNA polymer consisted of repeating units of tetranucleotides, glued end to end.

  While he spoke, Astbury may or may not have noticed a face in the audience that was new to meetings about ‘molecular biology’ or nucleic acids: Professor John Randall, from the University of St Andrew’s.

  Homecoming

  Spring 1946 was particularly kind to John Randall. He had recently been elected to Fellowship of the Royal Society and was looking forward to the admission ceremony in mid-May. And everything was going well at St Andrew’s, where he had been Professor of Natural Philosophy for eighteen months.

  Maurice Wilkins had watched his boss ‘putting new life’ into the department, which had been ‘virtually devoid of research facilities’. Randall interpreted ‘Natural Philosophy’ more liberally than his predecessors, adding a distinctly biological flavour to physics. His own biological research had been limited to X-ray crystallography of cellulose fibres while at GEC, and an odd experiment with magnets and frozen horse blood in
Birmingham. Now, with Wilkins’s help, new ideas were tumbling out: what pulled chromosomes through the cytoplasm when a cell divided; novel ways of damaging chromosomes to produce mutations (Wilkins wanted to try ultrasound); and X-ray and microscopic studies of the nuclear material in the heads of cuttlefish sperm. In all, an ambitious research programme in territory that Astbury would instantly have identified as ‘molecular biology’.

  The only missing ingredient was money – and then, in February 1946, a round-robin letter arrived from the Royal Society, inviting ideas for ‘extraordinary expenditure’ to get British science back on its feet after the war. Randall sent in a draft proposal for his biological-physical research – and received a response that is the stuff of scientists’ dreams. His ‘unnecessarily modest’ application was not fundable, but only because he had not asked for enough. A.V. Hill, Secretary of the Royal Society, encouraged him to ‘open your mouth a bit wider’ and helpfully listed all the posts and equipment (‘pretty expensive’) that he should have requested. Would Randall care to resubmit something ‘more adventurous’? Randall did as he was told. His proposal for ‘a bigger scheme for biophysics research’ at St Andrew’s went back in record time. It featured the indispensable Maurice Wilkins, ‘back from Berkeley, full of enthusiasm for biophysics’, and already working on ultrasound and chromosomes.

  In his covering letter, Randall admitted that the expanded proposal might be ‘bigger than you hoped I would make it’, and he was right. It bust the Royal Society’s budget so comprehensively that the Treasury got involved and transferred the bid to the Medical Research Council, who had more money for this kind of thing. The MRC was also hugely impressed, but ‘biophysics’ was so revolutionary that they had to convene an expert committee which would consider the bid and reach a verdict by Christmas. Those experts included a man who had recently tried and failed to thrill the MRC with his own vision of biophysics, or ‘molecular biology’ as he preferred to call it: Professor William Astbury FRS, of Leeds University.

  One other niggling concern was mentioned discreetly to Randall. If funded, his new programme would really be too big for a provincial outfit like St Andrew’s; somewhere in London would work better. The same thought had already occurred to both Randall and Wilkins. In a flattering light, the Gothic buildings of St Andrew’s could pass for Oxbridge, but it was a long way from the centre of gravity of top-quality science in the golden triangle of London-Oxford-Cambridge. Wilkins was finding ‘the isolation oppressive’ and had begun looking for a post in London. And thanks to an off-scene twist of fate that turned into an amazing stroke of luck, London was about to enter the frame.

  This is where Detective-Inspector Whitehead of Special Branch comes into the story – only for an hour or so, but with lasting impact. On 28 February 1946, Whitehead was briefed to wait outside the main physics lecture theatre at King’s College, London; trouble was not expected but several other officers came too, just in case. After the end of the twelve o’clock lecture, the policemen closed in and arrested the lecturer. Dr Allen Nunn May, Reader in Theoretical Physics, was charged with having passed to the Russians information ‘likely to be of use to an enemy’. The information was all about how to make an atom bomb. Nunn May had worked on the Tube Alloys project in Canada; he was also was a devout Communist who detested fascism. Under questioning, he admitted handing on secrets to the Russians, whom he saw as friends and allies. Being a principled man who despised squealers, he refused to identify any of his contacts.

  By extraordinary coincidence, Maurice Wilkins had lodged with Nunn May’s parents in Birmingham for several weeks in 1943, but never met their son because he was away on confidential ‘war work’. Of greater relevance to this story, Nunn May was also a brilliant academic and at the time of his arrest was the favoured candidate for the prestigious Wheatstone Chair of Physics at King’s, which was about to become vacant. As Nunn May was now facing charges of treason, it seemed unlikely that he would be able to attend for interview, so an alternative candidate had to be sought.

  In April 1946, John Randall and Harry Boot spent three weeks at the Radiation Laboratory at MIT, whose creation had been inspired by their invention, the cavity magnetron. Its work now done, the ‘Rad Lab’ was being wound up and its activities dispersed to various American electronics companies. To mark the event, a history of the lab was being compiled, and Randall and Boot were asked to write up the origins of the magnetron. It seemed a fitting tribute to their role in the evolution of radar. And the protracted wrangling over patents had recently crawled to a happy ending, with an exceptional award of £36,000 (equivalent to £1.5 million in 2018), split between Randall, Boot and their colleague Jim Sayers, who had refined the design.

  While at MIT, Randall was thinking about the future as well as the past. En route to America on the SS Aquitania, he had received a cryptic radio telegram which read: ‘APPLETON REQUESTS YOU CONTACT HALLIDAY AT KINGS COLLEGE IMMEDIATELY.’ Further information soon caught up with him in a handwritten letter from Edward Appleton FRS, discoverer of the ionosphere and formerly scientific administrator of Tube Alloys. Appleton got straight to the point. The Wheatstone Chair at King’s, which Appleton himself had occupied for twelve ‘very very happy’ years, was coming up. ‘I should like to see you there,’ wrote Appleton. He added that the decision was not in his hands, but ‘I would help if I knew you were interested’.

  Randall was, and Sir William Halliday, Principal of King’s College, took him to dinner at the Athenaeum on the evening of 16 May 1946. It was a good day; that morning, Randall had signed the Register of the Royal Society, below names such as Newton, Faraday, Darwin, Rutherford and a brace of Braggs.

  St Andrew’s were dismayed to lose Professor Randall after barely two years, especially as he took Maurice Wilkins and two other physicists with him – but then all’s fair in love, war and academia. John Randall began as Professor of Physics at King’s College in September 1946. His welcome package included a large hole in the ground which, if the MRC played ball, he would fill with enough money to put biophysics on the map.

  Grand tour

  To round off this chapter and to set the scene for the one that follows, we should briefly revisit some places of significance in the story so far. This is a highly selective tour – just a few lines of fine print dug out of the vast catalogue of devastation and misery that described post-war Europe. But it reminds us that science, like warfare, is all about winners and losers; and that those categories do not necessarily correlate with either achievement or justice.

  Tübingen, the logical place to start, came through the war with its medieval buildings virtually intact, but its reputation tarnished. As well as the thousands of forced sterilisations, the university had prospered by promoting the ‘science’ of the Reich. Its research specialities included neuroanatomy, based on a vast collection of human brains collected from people ‘unworthy of living’, Jews and others.

  Beautiful Heidelberg, where delegates at the Seventh International Physiology Conference in 1907 had admired the fireworks in the night sky above the castle, was also left miraculously unscathed. To keep warm during a cold snap in early April 1945, the American troops billeted in the university burned wooden filing cabinets and their contents. One contained all the personal papers and laboratory records of Albrecht Kossel, Nobel laureate and non-signatory of the Manifesto of the Ninety-Three.

  Kiel, university city and the strategic Baltic port which housed the U-boat ‘Wolf Pack’, lost 80 per cent of its buildings in over a hundred Allied air-raids. Items salvaged from a room in the ruins of the university’s Anatomy Institute included a brass microscope, heavily used, and a collection of over 4,200 European butterflies, mostly from the Alps. These were all that remained of the personal possessions of Walther Flemming.

  The Robert Koch Institute was located in an outer suburb of Berlin that was heavily pounded by Russian artillery during the battle to take the city. As the food ran out and the Russians closed in, Fred Neufeld kep
t himself going by jotting down his life story. His Recollections from my 50-year career as a bacteriologist was published in 1946, over a year after the war ended. There was just one irregularity in the paper: the symbol ‘ߙ’, as if referring to a footnote, beside Neufeld’s name on the title page. ‘ߙ’ signified ‘deceased’. Neufeld had died on 18 April 1945, a couple of weeks after his seventy-sixth birthday and just twelve days before Hitler shot himself a few miles to the south. His ‘autobiographical’ article had been reconstructed for him by his friends from the papers he left behind. The death certificate, issued without the nicety of a post-mortem, stated that Neufeld died of ‘Entkräftung’ (wasting). But in an old man weakened by starvation, it would not have been surprising if the coup de grace was delivered by the ‘old man’s friend’: a pneumococcus, slipping respectfully into Fred Neufeld’s lungs and carrying him off gently to a better place.

  Next, to Stockholm for the Nobel Prize Ceremony on 10 December 1946. Herman Muller, recipient of the Prize for Physiology or Medicine, was praised for his ‘amazing discovery . . . using roentgen radiation [X-rays] to increase enormously the number of mutations’ in fruit flies. The speaker threw in a ‘playful question’. Could ‘a kind of cosmic ray’ be found to induce a specific mutation that would make people ‘peace-loving and happy’?