by Andrew Brown
Although Caspar carried out his X-ray crystallography in Cambridge, the stimulus and the materials for it resulted from a visit to Birkbeck. He talked to Klug about spherical viruses and the two of them raided the laboratory refrigerator. There they found vials of TBSV and TYMV left over from Bernal’s own experiments, many years before. They agreed that Caspar should take the tomato virus while Klug and his research student, John Finch, would work with the turnip virus. The turnip yellow virus that Klug chose had a larger unit cell than did tomato bushy stunt virus and proved harder to solve. Eventually, both spherical plant viruses were shown to have icosahedral symmetry – with 180 sub-units symmetrically packed into a regular polyhedron.
Franklin’s group at Birkbeck was at the leading edge of biomolecular research as Bernal reminded their sponsor, the Agricultural Research Council. Writing to the ARC chairman, Lord Rothschild, Sage emphasized that the group’s ‘results which are beginning to show the precise relation of nucleic acid to the protein component are… at the very centre of interest of biological structure analysis and are already beginning to tie up with the structure of such components such as microsomes and chromosomes’.69 As a result of Sage’s intervention, the ARC (who had been niggardly in their support of Franklin) agreed to renew their grant for one more year. In an effort to secure future funding, Franklin took the novel step of applying to the US Public Health Service for support. Within months, she was rewarded with an annual grant of £10,000 – a sum so large that the London University Senate assumed it was to be spread over three years. If they had understood that the money was for one year, Klug was told that they would have refused the grant because it created unacceptable inequality between the different research groups at Birkbeck.70 Until now all the structural research in England had been carried out on plant viruses: in her application to the US Public Health Service, Franklin indicated that she wished to venture into field of animal viruses. She had spent time at various US laboratories in the summer of 1956, and two of her colleagues in Berkeley offered her samples of the newly crystallized polio virus to study. She approached Bernal about this new work and he wrote to the Master of Birkbeck, Lockwood, for his permission in July 1957, pointing out that ‘In view of the extremely small amounts of infective material with which she will be dealing, and the very careful precautions she will be taking, there could be no objection to the research being carried out.’71
Bernal was wrong in this assurance. Rosalind Franklin asked Stan Lenton to procure ‘20 lbs. of cotton wool, 20 gallons of formaldehyde and six empty biscuit tins’.72 When he asked her what this was all for, he was told ‘Live polio virus’. Although polio vaccination was available in England by this time, memories of summer polio epidemics were fresh, and the news that live polio virus was going to be brought into the dilapidated Birkbeck laboratories caused a great deal of alarm among the staff, especially those with children. There was also the presence of Werner Ehrenberg, the physicist who was crippled as a result of childhood polio, as a visible reminder of the danger. Bernal called a departmental meeting that lasted for four hours; although he thought the actual risk was negligible he arranged for the virus to be stored at the nearby London School of Hygiene and Tropical Medicine.
By this time, Franklin was seriously ill with ovarian cancer and had undergone surgery. She did start work with the polio crystals, but was frustrated because when she mounted them in capillary tubes for X-ray study, the crystals would rapidly disappear. The crystals were in a very dilute salt solution and Franklin came to the conclusion that the crystals were interacting with metal ions that leached from the glass of the capillary tube.73 She wrote to glass specialists in Sheffield requesting neutral glass, free of any metal, but before this could be supplied she became too ill to work. She died in April 1958 at the age of thirty-seven, and Sage wrote a heartfelt obituary in The Times, calling ‘her early and tragic death… a great loss to science’. Drawing on his characteristic ability to make scientific subjects understandable to the layman, Bernal gave a masterly summary of her career. In a later obituary in Nature, he referred to the ‘extreme clarity and perfection’ of her work. At a time when there was little public awareness of DNA and no controversy about the discovery of its structure, Bernal thought it worthwhile to attempt to ‘disentangle’ her contribution to the work. He credited her with ‘the technique of preparing and taking X-ray photographs of the two hydrated forms of deoxyribonucleic acid and by applying the methods of Patterson function analysis to show that the structure was best accounted for by a double spiral of nucleotides, in which the phosphorus atoms lay on the outside’.74 Paying tribute to her qualities as a scientist and a human being, Sage wrote:
Her photographs are among the most beautiful X-ray photographs of any substance ever taken. Their excellence was the fruit of extreme care in preparation and mounting of the specimen as well as in the taking of the photographs. She did nearly all this work with her own hands. At the same time, she proved to be an admirable director of a research team and inspired those who worked with her to reach the same high standard. Her devotion to research showed itself at its finest in the last months of her life. Although stricken with an illness which she knew would be fatal, she continued to work right up to the end.75
Franklin’s legacy to Birkbeck was the talented research group of Klug, Finch and Holmes who, thanks to her, were now financially secure for the next few years. With the generous US funding, they were able to buy better X-ray sets and a powerful centrifuge for spinning down virus particles into concentrated solutions (Franklin’s technique had been to hang the virus solutions from the ceilings in bags and rely on evaporation and gravity to do their slow work).76 In California, scientists had succeeded in preparing better quality crystals of polio virus and offered some to Klug. The offer came from Carlton Schwerdt and when Klug accepted, Schwerdt said he and his wife were coming to London and would bring the crystals with them. Patsy Schwerdt was an attractive woman, ‘one of these marvellous, bubbly, American extraverts who could disarm anybody’.77 On their arrival at Heathrow airport, Schwerdt gave his wife the Dewar flask to carry. When she was asked by a Customs Officer what she had in the flask, she said ‘Some polio virus.’ The Officer responded in panic, ‘You can’t bring that in here.’ Smiling demurely, she reassured him that the contents were safe because they were only crystals, and he waved her through!
Again the crystals were kept at the School of Hygiene and Tropical Medicine. Klug thought of an alternative to the glass capillary problem that plagued Franklin, when she first attempted to work with polio crystals. He noticed that researchers in Jeffery’s group at Birkbeck enclosed cement powders in capillaries made of quartz to withstand high temperatures. He decided to try quartz for the polio crystals and found that the crystals remained intact. There was still resistance at Birkbeck to working on polio and the most powerful rotating anode X-ray tube was at the Royal Institution, where Sir Lawrence Bragg was now president. Klug decided that the best X-ray photographs would be obtained at the RI, but this meant carrying the virus crystals across central London. Working with Finch, he mounted the crystals into quartz capillaries, which were then placed on a platform and covered with a dome. Quartz is tougher than glass, and thin glass tubes containing formalin were also placed on the platform so that if the sealed container were dropped, the glass would shatter and the formalin would kill any free virus. Klug demonstrated this apparatus to the Chief Medical Officer who approved it. Klug decided that the safest way to travel the short distance from Bloomsbury to Piccadilly was on the Underground.
The Californian workers had observed that polio crystals started to deteriorate after an hour at room temperature, so Klug and Finch made sure that theirs were always kept cold. They kept a jet of freezing dry air playing on the crystal during the X-ray exposures of 20 hours or more so that the crystal temperature never rose above 5°C. By this technique and with the use of the rotating anode X-ray tube, they were rewarded with photographs of exquisite detail, showin
g a greater degree of crystal perfection than had been previously observed with any other virus. Klug took the photographs to show Sage whose immediate reaction surprised him: ‘These photographs are worth ten thousand pounds’, he said. Klug then realized that Bernal needed to raise money constantly to keep the Biomolecular Laboratory running, and the photographs would be valuable tokens for that purpose. Finch and Klug published their findings in June 1959, announcing that the polio virus is constructed with icosahedral symmetry, (just like turnip yellow mosaic virus). In their 1956 paper, Crick and Watson had set out the advantage for the protein coat of a virus to be constructed from a large number of small protein molecules (the simpler the protein sub-unit, the less genetic coding information required to produce it). Finch and Klug now took this evolutionary argument a step further, suggesting that perhaps all spherical viruses would prove to have icosahedral symmetry. This was because an icosahedral arrangement ‘allows the use of the greatest possible number, namely, 60, of identical structural units in building the framework’ of the virus. Assuming the purpose of the protein coat is just to protect the genetic material within the virus, there is another way in which the icosahedral shape delivers the greatest bang for the virus’s buck. Finch and Klug pointed out: ‘If it is required to “enclose” a space around a point by a symmetrical arrangement of small identical units, it can be shown that the ratio of the number of sub-units to the volume enclosed is smallest if icosahedral symmetry is employed.’78
The icosahedron is one of five regular polyhedra,* described by Plato and sometimes known as the Platonic bodies. Despite their great antiquity, their shapes have never lost their fascination; in the twentieth century, their most prominent exponent was perhaps Buckminster Fuller – the self-taught, American designer, inventor and architect of the geodesic dome. In the late 1950s, Klug read a biography of Buckminster Fuller and wrote to him about the similarities between the icosahedral structure of viruses and geodesic domes. The next time he was in London, Buckminster Fuller visited Birkbeck and had a long conversation with Klug. Inspired by the American’s thoughts, Klug applied the architectural principles to viral structure – a fusion of art and science that must have delighted Sage. In what has become a classic paper in molecular biology, Caspar and Klug wrote:
The solution we have found was, in fact, inspired by the geometrical principles applied by Buckminster Fuller in the construction of geodesic domes. The resemblance of the designs of geodesic domes to icosahedral viruses had attracted our attention at the time of the poliomyelitis work. Fuller has pioneered in the development of a physically orientated geometry based on the principles of efficient design. Considering the structure of the virus shells in terms of these principles, we have found that with plausible assumptions on the degree of quasi-equivalence required, there is only one general way in which iso-dimensional shells may be constructed from a large number of identical protein sub-units, and this necessarily leads to icosahedral symmetry. Moreover, virus sub-units organized on this scheme would have the property of self-assembly into a shell of definite size.
The basic assumption is that the shell is held together by the same type of bonds throughout, but that these bonds may be deformed in slightly different ways in the different, non-symmetry related environments. Molecular structures are not built to conform to exact mathematical concepts, but, rather, to satisfy the condition that the system be in a minimum energy configuration.79
The Torrington Square houses were meant to provide temporary accommodation for about five years, but the crystallography group would be trapped there for nearly twenty. More than a decade after any bombs had fallen on London, the war’s greatest expert on structural damage was in receipt of the following message from the Clerk of Birkbeck College: ‘I feel sure that you will be relieved to learn that there are no immediate prospects of the spontaneous collapse of the northern external wall of 22 Torrington Sq.’80 Bernal first wrote to John Lockwood, Master of Birkbeck, in 1951 suggesting that X-ray crystallography be spun off from physics as a separate department. Five years later, he was still pressing the point, with no success; he also wanted to set up a separate department of computing under Booth. He pointed out to Lockwood that ‘the very existence of crystallography teaching and research [in the University of London] is dependent on me personally’.81 Sage was not seeking to magnify his own importance, but warning the Master that crystallography and computing were vital support services for other branches of science and if they were not formally organized, there could be a resulting financial burden on Birkbeck.
Faster progress was made in Cambridge, the country’s other major molecular biology centre, where the laboratories were as scattered and poorly housed as at Birkbeck. The Medical Research Council was persuaded by the remarkable accomplishments of Watson and Crick, Perutz and Kendrew to build a new facility, away from the mediaeval colleges in the heart of the city. The elements of X-ray crystallography, electron microscopy, biochemistry and virology were to be housed in new purpose-built laboratories, under one roof. The MRC Laboratory of Molecular Biology opened in 1962 under Perutz’s chairmanship. The MRC offered Klug and his Birkbeck virology group space in the new Cambridge facility. The American grant that Franklin had secured for them in 1957 ran out in 1961. The move was supported by Bernal, although as the pioneer in the field of virus structure, he must have been sad to see them go. Klug, who went on to win the Nobel Prize for Chemistry in 1982 and to become President of the Royal Society, still regards Bernal as the godfather of the MRC Laboratory of Molecular Biology and the man who virtually invented the subject.
18
History and the Origins of Life
Bernal’s friends were among the most important science writers of their time. Restricting the group to those who worked in England, and leaving aside C.P. Snow and J.G. Crowther who lived by their pens, they were remarkable for the range, quality and volume of their collective output. Haldane inherited H.G. Wells’ mantle as the best popular writer about science, but even he could not match the sales of Lancelot Hogben whose Mathematics for the Million: A Popular Self-Educator is estimated to have sold over half a million copies during its four editions.1 The doyen of the set was Joseph Needham, who abandoned his own career as an embryologist during the Second World War and devoted the remainder of his life to a landmark study of China, concentrating on the history of scientific development and the influence played by Chinese religion, politics and customs. Over a period of forty years, Needham published successive volumes of Science and Civilization in China, the early numbers of which were eagerly read, and often reviewed, by Sage. Needham came to believe that the predominance of Chinese science and technology for fifteen hundred years and its subsequent eclipse by European science from the seventeenth century onwards could be understood only in terms of differences between the social and economic systems of China and the West – an historical approach stimulated by his conversations with Bernal in Cambridge before the war.2
The first volume of Needham’s monumental work appeared in 1954, coinciding with Bernal’s own Science in History. Bernal’s was also an encyclopaedic book, in which he examined the interplay of science and society from prehistoric man to the present; it had its origins in a series of lectures on ‘Science in social history’ that he had given in 1948 at Ruskin College, Oxford. He started by considering the character of science and its emergence from evolving techniques such as hunting, agriculture, and pottery – ‘the mystery of the craftsmen’ – and from theory such as ‘the lore of the priest’.3 The first five hundred pages were taken up with the development of science from the Stone Age through the early centres of commercial and cultural activity such as Babylon, India and Egypt, to ancient Greece, and then back to the Middle East, where during the barbarian age of Europe, new discoveries were made in ‘a brilliant synthesis under the banner of Islam’. The new knowledge and techniques spread to mediaeval Europe, giving rise to what he saw as four major periods of advance: the Renaissance in Italy, the inte
llectual ferment leading to the Enlightenment (starting with Galileo and ending in Newton), the Industrial Revolution in Britain and the Revolution in Paris, and finally the accelerating pace of twentieth-century discoveries. At each stage of the story, Sage reminded his reader of the way in which social and economic change shaped science, and how science in turn altered human history.
The task of writing the book enthralled and, at times, threatened to overwhelm Sage. Much of it was dictated from his prodigious memory, and it was left to Francis Aprahamian to check and supply extra facts. The whole manuscript was rewritten half a dozen times, with Anita Rimel typing each new version and providing the index. Even for Sage, it was an ambitious undertaking that he justified in part as ‘a first attempt to sketch out the field, if only to stimulate, through its omissions and errors, others more leisured and better qualified to produce a more authoritative picture’.4 He did think though that his experience as a busy scientist, who had participated in some critically important work, gave him an advantage over a professional historian. Klug remembers how consumed Sage was by the preparation of the book – a project that he regarded as equal in importance to any of the experimental research going on at Birkbeck at the time.5
The first part of the book, in addition to being an historical account of science, was meant to buttress the Marxist view of the world that would then be used in a prescriptive way in the second part. Much of this was material, familiar from his previous writings, on the impending divorce of science from worn-out capitalism and the hope of a happier second marriage to socialism. The planning of science would go hand in hand with the central control of society, to the mutual benefit of both. In 1954, he still stoutly supported the baseless ideas of Lysenko (who would enjoy the enthusiastic patronage of Khrushchev in the USSR for another decade) against the genetic theories of Mendel. As details of the genetic code became irrefutable facts in the late 1950s, Bernal became more interested in the molecular approach to genetics and evolution, and Lysenko’s name disappeared from later editions of the book.