by Andrew Brown
What Bernal failed to see, despite the fact that he was studying both at the same time, were the shared features of the sex hormones and the sterol molecules. His model for the sterols was a four-ringed head with a long tail of carbon atoms attached. He had correctly deduced that oestrogens also contained condensed carbon rings, but failed to consider that they were in essence the sterol ring system less the long tail. It was a surprising oversight since the evidence was literally under his nose – in his laboratory notebook there were observations for cholesterol and pregnandiol (a metabolite or chemical product derived from cholesterol and the sex hormones) on the same page.60 Had he only made this connection, it seems certain that he would have shared the 1939 Nobel Prize for Chemistry; as it was, there were those like Solly Zuckerman who believed that Bernal and Marrian were unfairly overlooked by the Nobel committee.
For Bernal the work on sterols and sex hormones, while satisfying, was only a small piece in an increasingly ambitious scheme that was taking shape in his generously sized cranium. He rehearsed his ideas in front of the select group of philosophically minded biologists and biochemists at the Dunn Laboratory. Foremost amongst these was Joseph Needham, who in 1931 had just completed a monumental three-volume work, Chemical Embryology. Like much of Needham’s output this was a wide-ranging book, encyclopedic in its treatment of the developing egg, but nevertheless subject to parody in the Dunn Laboratory magazine as Eggs; From Aristotle to the Present (in 27 volumes).61 The tomes of Chemical Embryology did in fact contain a good deal of history, and appropriately Needham was one of the organizers of the Second International Congress of the History of Science and Technology held in London during June and July 1931. As we shall see, the Congress had a lasting influence on Bernal and on the politics of British science. In the lecture he prepared for the meeting, Bernal was intent on making the case for modern physics holding the key to the solution of fundamental biological problems.
Bernal believed that from the physical point of view, the two central puzzles of life were that of activity, (e.g. muscle contraction or nerve conduction), and growth, which included both the building up of organized elements in the cell and the reproduction of cells. He stated that X-ray crystallography, for the first time, was allowing direct study of the structure of organic molecules, and he felt that scientists like him were ‘beginning to grasp the chemical and physical nature of the protein molecule’.62 He referred to Astbury’s demonstration that stretched and unstretched wool depended on two different forms of protein – a- and β-keratin. He thought that two different protein states would also account for the extension and contraction in muscle, where X-ray pictures looked very similar to those of hair. Bernal was convinced that the structure of proteins was the key to understanding the secret of life.
In 1931, genes were known to reside along chromosomes and were thought to consist of proteins – only the almost limitless variety of proteins with their vast number of possible amino acid sequences seemed to offer a physical basis for the biological specificity of cell function. When a cell divides into two identical daughters, Bernal stated: ‘The facts of genetics demand, as J.B.S. Haldane has pointed out, that… the individual [protein] molecules in a chromosome must be exactly duplicated.’63 In Bernal’s opinion, ‘only a supernatural agency, a divine copyist’, could exactly duplicate a three-dimensional solid molecule by entering its inner complexity. ‘If we prefer a natural solution,’ he continued, ‘we must imagine the molecule stretched out either in a plane or along a line. In either case the simpler constituent molecules have only to arrange themselves one by one on their identical partners in the original molecule, and then become linked to each other.’64
The analogy he had in mind was of a lacemaker’s frame, on which simple organic molecules would settle before being joined into larger aggregates. He then rejected the idea of two-dimensional replication because while each amino acid can exist in a right-handed or left-handed form (a classification based on the rotation of polarized light), only the left-handed form is found in nature: two-dimensional reproduction would lead to mirror image molecules which do not occur. ‘There remains then,’ he continued, ‘only one-dimensional reproduction. At the moment of reproduction, but not necessarily at any other time, the molecule of a protein must be imagined as pseudolinear, associating itself element by element with identical groups, related by an axis instead of a plane of symmetry…’65 He ended on a note that was at once cautionary and optimistic: ‘It is impossible to claim that these ideas are anything but preliminary guesses, but they have the advantage of being susceptible to experimental test.’66 Two decades later Crick and Watson would show that the genetic material in cells is the double helix of DNA (not a protein), and that the exact replication of genes depends on the linear sequence of bases along the DNA molecule. It is ironic that the Second International Congress was regarded by its delegates, especially Sage, as a political rather than a scientific milestone, for buried amongst all the bombast was the essence of the most powerful idea in twentieth-century biology.*
Another speaker at the Congress who would have been impressed by Bernal’s thesis that understanding the reproduction of protein molecules was a necessary first step to a complete description of the behaviour of whole organisms was Joseph Henry Woodger, Reader in Biology at the Middlesex Hospital Medical School. Woodger’s ambition as a philosopher of science was to invent a symbolic logic for biology, which would allow diverse phenomena to be integrated into an ordered theory. He and Needham had been corresponding about this question for some years, and after the Second International Congress they felt that the time had come to expand the discussion to include other original scientists in a ‘Biotheoretical Gathering’ or informal club. Needham proposed Sage as a member, referring to him as ‘perhaps the most acute mind of my acquaintances here and particularly interested in biological problems’.67 So it was, paying six shillings a day to his hosts to defray the cost of food, that Bernal found himself staying at Woodger’s house on Epsom Down for three days in August 1932, with about half-a-dozen others.
The meeting meandered through Woodger’s house and out into the garden; meals were served but did not interrupt the flow of ideas. Some attempt was made to keep embryology in mind as the centre ground; it was a field that was energetically ploughed with a variety of tools from mathematics and logic as well as chemistry and biology. Bernal’s set contribution was an exploration of the junction between biology and chemistry, beginning at the sub-atomic level of quantum mechanics, passing through his own territory of crystals, colloids and polymers, and on to life forms such as viruses and protozoa before arriving at multi-cellular organisms. Of all the speakers, Bernal had the strongest background in the physical sciences, but he was not inhibited in joining arguments about embryology with the biologists present. Needham left an image of how Bernal typically reacted to a setback or a perplexing scientific problem: ‘He would long look down and away from you while discussing it, but then would suddenly turn and look you straight in the eye, propounding with his dazzling smile some remedy for the trouble, some unseen aspect of the facts, some unimaginable new theory, or some amusingly paradoxical truth.’68
Shortly after the inaugural Biotheoretical Gathering, Bernal left Cambridge for a lecture tour to Russia in the company of a number of other scientists and physicians, led by Lawrence Bragg. The main purpose of the trip was a meeting with Russian scientists at the School of Physical Chemistry in Moscow. After the meeting, the British party was supposed to fly out from the new Moscow airport and assembled there at 4 o’clock in the morning only to find that the countryside was enveloped by a thick autumn fog. Facilities at the airport were non-existent, and all Bernal could do to pass the time was to pace up and down. He was joined by Ralph Fowler, a Cambridge mathematician and Rutherford’s son-in-law, who limped as a result of wounds sustained in the war, but managed to keep pace with the voluble, long-haired Sage. Naturally the fog became the major topic of conversation. Bernal began to muse on
the water droplets, about 1 micron in diameter, that comprised the mist. He wondered why they did not coalesce to form raindrops. Fowler asked him what his ideas were on the structure of water, and in doing so unleashed a flood.
The first mystery to Bernal was why water existed at all – other heavier molecules such as hydrogen sulphide were gases and yet here was ‘the lightest of small molecules, which was sufficiently held together at ordinary temperatures to form a liquid’.69 There were other anomalies too, notably the fact that ice is less dense than water, and while these were commonplace observations, Bernal found the conventional explanations to be vague and unsatisfactory. And while the phenomena were commonplace, they were of immense significance for the Earth (where lakes and seas would be permanently frozen if ice were heavier than water and therefore unexposed to the warming of the sun) and for the evolution of life in an aqueous environment. As he was talking to Fowler, Bernal thought about the molecular structure of water and began to consider novel solutions such as the two hydrogen atoms being buried inside the oxygen atom. He came to the realization that just as with a crystal, the physical properties of a liquid must depend on the geometrical and physical relations between its constituent molecules, atoms or ions. The conversation lasted about twelve hours until the fog lifted, and on the aeroplane Fowler suggested to Sage that he write up the new theory.
Bernal and Fowler both worked on the problem after returning to Cambridge, and in April 1933 presented their results at a conference on ‘Liquid crystals and anisotropic melts’ that Bernal helped to organize at the Royal Institution. Bernal had obtained X-ray diffraction curves for water that showed that it differed from the close atomic packing of an ideal liquid. They also stated that water is not a linear molecule, H–O–H, but shaped like a boomerang, with oxygen at its centre and hydrogen atoms at the tips. The oxygen atom has a far higher affinity for electrons than the hydrogen atoms do so that each O–H bond has a small negative charge at one end and a positive at the other – it is a dipole. In the paper, they made the first accurate estimate of the distance along an O–H bond, 0.96 Å. The dipolar nature means that there is a weak attraction, a hydrogen bond, between adjacent molecules, and Bernal and Fowler deduced that the molecules would orientate themselves so that each limb of a boomerang molecule would point towards the negatively charged oxygen atom at the centre of an adjacent molecule. This meant that the molecules would be arranged in a tetrahedral pattern. In ice, the tetrahedral pattern is regular and gives an open structure of low density: the key hypothesis forwarded by Bernal and Fowler was that to a large extent the hydrogen bonding between molecules largely persists in liquid water providing its remarkable internal cohesiveness. At low temperatures, the X-ray diffraction curve of water ‘approaches the ice-like arrangement’ while at high temperatures it resembles that of an ideal liquid: ‘the nature of water is determined by different geometrical arrangements of the same molecules in small regions of the liquid due to different amounts of molecular movement imposed by the temperature. In each small region, containing a few hundreds to a few tens of molecules at different temperatures, the arrangement is pseudo-crystalline.’70 This was not only a landmark paper in the history of physical chemistry, it would have a huge bearing on the subsequent understanding of living systems, whose cellular components exist in an aqueous environment.
The presentation on the pseudo-crystalline nature of water at the Royal Insitution was the second paper at the meeting with Bernal’s name on it. The first was given by his new doctoral student – a shy, dreamy, twenty-two year old Oxford chemistry graduate, Dorothy Crowfoot. She had spent her fourth year as an undergraduate working on X-ray crystallography and had arrived in Cambridge in October 1932 to work with Sage. Although Miss Crowfoot presented the paper71 on organic liquid crystals and undoubtedly did the lion’s share of the experimentation, the work bore Bernal’s unmistakable style. First, great stress was laid on the optical properties of the crystals as well as the results of X-ray photographs. Bernal always made a point of carefully examining any new crystal under a polarizing microscope before subjecting it to X-ray analysis. The second feature was the confident tone of the conclusion, where the authors enquired ‘as to the nature of the molecules required to form liquid crystals’ and made some suggestions which were both detailed and comprehensive. There were 150 scientists at the meeting, with a strong international contingent, but the name Mr Bernal (Cambridge) dominated the discussion after nearly every paper, with penetrating and often lengthy comments. Although many of his remarks addressed arcane physical theory, Bernal was particularly excited by the role that liquid crystals might play in cellular components such as the myelin sheaths around nerves.
Dorothy Crowfoot’s background was quite exotic – she was born in Cairo, where her father worked in the Egyptian Education Service – but in many ways she was a very innocent young woman. Apart from science, her major passion was archaeology (her father later became Director of the British School of Archaeology in Jerusalem), and although it was never difficult to find a topic for conversation with Sage, this interest provided an instant connection between them. Dorothy blossomed in the informal atmosphere of Bernal’s small, dilapidated department, where her skill and determination soon won her the admiration of all. She particularly looked forward to lunchtimes when, with coffee percolating on a gas ring on a laboratory bench, Sage would initiate conversations that one day might be ‘about anaerobic bacteria at the bottom of a lake in Russia and the origin of life, another, about Romanesque architecture in French villages, or Leonardo da Vinci’s engines of war or about poetry or painting. We never knew to what enchanted land we would next be taken.’72 Dorothy joined two other women, Helen Megaw and Nora Wooster, who were already carrying out research under Bernal’s supervision. They had both studied mineralogy as undergraduates at Cambridge and were working on inorganic crystals. Nora married Peter Wooster shortly after arriving in the laboratory. Unlike Dorothy, Helen and Nora believed that Sage was fallible, and one lunchtime they jointly decided to test his erudition. They asked him to talk about Mexican architecture, believing that he would not be prepared. He merely paused to ask whether they were interested in periods before or after the Spanish conquest and then launched into an enthralling account.73
Helen Megaw, a young woman from Belfast, began her PhD research under Professor Hutchinson in 1930. Bernal suggested to her that she should measure the thermal expansion of ice crystals along different axes. This was technically very demanding work which Megaw undertook with a modified gas X-ray tube, in which she could change the anti-cathode easily in order to obtain X-rays of different wavelengths. The tube needed to have its gas leak carefully controlled or otherwise it would blow a fuse or stop working. Helen had to sit by the tube, hour after hour, with one ear cocked, making the necessary valve adjustments in order to obtain any data.74
In 1934, Rutherford accepted administrative responsibility for the crystallography group under the aegis of the Cavendish, and Bernal was appointed the Assistant Director of Research. Perhaps as a goodwill gesture, Rutherford gave Bernal a small sample of heavy water, from which Megaw was able to grow crystals and compare their structure with that of ordinary ice. For her next project, Bernal suggested that she make a detailed X-ray analysis of hydrargillite crystals, an hydroxide of aluminium, for which the American Linus Pauling had already suggested an octahedral structure. Megaw broadly confirmed Pauling’s structure, but found an interesting irregularity in that the OH groups were drawn closely together. This finding was analogous to the observations made by Bernal and Fowler for water, and lead to a comprehensive review article by Bernal and Megaw on ‘The function of hydrogen in intermolecular forces’.75
Sage, preoccupied with the structure of proteins, believed that a revolution in biology was at hand, a feeling he likened to ‘looking through a hole in a wall at a new kingdom beyond’.76 In 1934, Bernal and Crowfoot joined forces on a piece of research that would breach the wall. Their achievement involve
d the interplay of serendipity and mental preparedness that characterizes so many great scientific discoveries. The accidental starting point of this story involved a visit by a friend of Bernal’s, Glenn Millikan, to a laboratory in Sweden. Millikan, the son of the 1923 Nobel Laureate in Physics, was a peripatetic physiologist, based at Trinity College, who loved to travel around Europe with a small rucksack as his only luggage. During the spring of 1934 he had been on an expedition to Lapland and on his way back to England, Millikan visited Svedberg’s laboratory in Uppsala. There he found John Philpot, an English biochemist who was learning the ultracentrifuge techniques in order to work on proteins. Philpot had left a beaker of pepsin in solution standing while he had gone away on a skiing trip for two weeks. Pepsin is an enzyme secreted by glands in the stomach to digest protein. On his return, Philpot found that some unusually large pepsin crystals, up to 2 mm in length, had appeared in the beaker. He showed these to Millikan who thought of Sage, always on the lookout for interesting crystals, and Millikan said ‘I know a man in Cambridge who would give his eyes for those crystals.’77 Philpot knew Bernal because he had been on the team at the National Institute for Medical Research in London working on vitamin D, and he was happy to send some crystals to him.
