Rosalind Franklin (14 page)

She summed up her regrets in a strong letter to Colin and his new wife Charlotte (whom she liked very much), first thanking them for a copy of
Christ Stopped at Eboli
which she had read in Italian. Even her favourite brother, however, cannot have caught the subtle reference to the narrow and unsatisfactory relationship that told her she had no future in Paris:

 

... I still cannot believe that I'm leaving here next January — I can see no way out of it now, but I'm sure it was the biggest mistake of my life. At times I think seriously of just saying that I've changed my mind and will stay here. But at this stage it would mean upsetting such a lot of people that it's not worth doing unless I really decide to stay here indefinitely — and I'm just not quite sure enough for that. If only I had managed to meet more of the right people here and had a wider circle I shouldn't hesitate. Apart from that I far prefer here the place, the people, the life and the climate. I feel — and felt even before I came to France — far more European than English. National feeling, whether it be for England or any other country, is meaningless to me. However, I suppose my fate is decided and I ought to stop thinking about staying on here — though that is impossible. I am doomed to spend the next 3 months moaning about the future and a good many months after that moaning about the present.

 

Her intimation of trouble ahead was well-founded but she was very far from making the biggest mistake of her life. J.T. Randall, however, had just made his.

Part Two

EIGHT
What Is Life?

T
HE FIRST HALF OF
twentieth-century science belonged to physics, with the general theory of relativity, quantum mechanics and nuclear fission. The second half would belong to biology. In the post-war world, the secret of the gene - how hereditary characteristics pass from one generation to another - was the hottest topic in science.

For a number of physicists who had worked on the Manhattan Project to develop the atomic bomb, the post-war shift into biology was a stark exchange of the science of death for the science of life. But their conversion was as much intellectual as ideological. Biology was now where the action lay. The war had interrupted a line of investigation leading towards understanding the chemical basis of heredity.

That physical features are passed on by discrete units (later called genes) had been discovered in 1865 by the Austrian monk Gregor Mendel in his experiments with garden peas. Each gene determined a single characteristic, such as height or colour, in the next generation of plant. By 1905 it had been learned that within living cells the genes are strung together like beads on the chromosomes, which copy themselves and separate. But how does the genetic information get from the old chromosome to the new?

Protein was the obvious candidate. By the 1920s it was thought that genes were made of protein. The other main ingredient in the chromosome is deoxyribonucleic acid, or DNA. DNA, a substance of high molecular weight, was identified in 1871 by a young Swiss scientist, Friedrich Miescher. (There is, in fact, a second kind of nucleic acid in the cell, called RNA, with a slightly different chemical composition.) The ‘D' in DNA stands for ‘de- oxy' — a prefix often spelled as ‘des' in Rosalind's day, a usage now obsolete — which identifies it as the ribonucleic acid with one fewer hydroxyl group. But as RNA exists in cells mainly outside the nucleus, it was unlikely to be the genetic vehicle.

Protein was far more interesting to geneticists than DNA because there was a lot more of it and also because each protein molecule is a long chain of chemicals of which twenty kinds occur in living things. DNA, in contrast, contains only four kinds of the repeating units called nucleotides. Hence it seemed too simple to carry the complex instructions required to specify the distinct form of each of the infinite variety of cells that constitute living matter.

In 1936, at the Rockefeller Institute on the Upper East Side of Manhattan, a microbiologist called Oswald Avery wondered aloud if the ‘transforming principle' — that is, the carrier of the genetic information from old chromosomes to new — might not be the nucleic acid, DNA. No one took much notice. DNA seemed just a boring binding agent for the protein in the cell.

During the pre-war years, in Britain, J.D. Bernal at Cambridge and William Astbury at Leeds, both crystallographers, began using X-rays to determine the structure of molecules in crystals. Astbury, interested in very large biological molecules, had taken hundreds of X-ray diffraction pictures of fibres prepared from DNA. From the diffraction patterns obtained, Astbury tried building a model of DNA. With metal plates and rods, he put together a Meccano-like model suggesting how DNA's components — bases, sugars, phosphates — might fit together. Astbury concluded — correctly, as it turned out — that the bases lay flat, stacked on each other like a pile of pennies spaced 3.4 Ångströms apart. This ‘3.4 Ä' was no gratuitous detail. Published with other measurements in an Astbury paper in
Nature
in 1938, it was to remain constant throughout all the attempts to solve DNA's structure that were to come.

But Astbury made serious errors, his work was tentative, and he had no clear idea of the way forward. By the time of the Second World War, no one knew that genes were composed entirely of DNA.

In 1943 Avery, at sixty-seven, was too old for military service. Still working at the Rockefeller Institute and building on an experiment with pneumococcus (bacteria that cause pneumonia) done by the English physician Frederick Griffith in 1928, he made a revolutionary discovery. He found that when DNA was transferred from a dead strain of pneumoccous to a living strain, it brought with it the hereditary attributes of the donor.

Was the ‘transforming principle' so simple then — purely DNA? In science, where many grab for glory, there are some who thrust glory from them. Avery, a shy bachelor who wore a pince-nez, was one of those too modest for his own good. His discovery has been called worth two Nobel prizes, but he never got even one — perhaps because, rather than rushing into print, he put his findings in a letter to his brother Roy, a medical bacteriologist at Vanderbilt University Medical School in Nashville. ‘I have not published anything about it — indeed have discussed it only with a few,' he said, ‘because I am not yet convinced that we have (as yet) sufficient evidence.'

A year later, however, Avery, with two colleagues, wrote out their research. In what became a classic paper, they described an intricate series of experiments using the two forms of pneumococcus, virulent and non-virulent. When they freed a purified form of DNA from heat-killed virulent pneumoccocus bacteria and injected it into a live, non-virulent strain, they found that it produced a permanent heritable change in the DNA of the recipient cells. Thus the fact was established — at least for the readers of
The Journal of Experimental Medicine
— that the nucleic acid DNA and not the protein was the genetic message-carrier.

The essential mystery remained. How could a monotonous substance such as DNA, like an alphabet with only four letters, convey enough specific information to produce the enormous variety of living things, from daisies to dinosaurs? The answer must lie in the way the molecule was put together. Avery and his co-authors, Colin MacLeod and Maclyn McCarty could say no more than that ‘nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined'.

In 1943, another scientist at one remove from the world conflict (because he had been offered a haven in neutral Ireland) gave a series of lectures in Dublin, called provocatively ‘What Is Life?' An audience of 400 for every lecture suggested that his supposedly difficult subject was of great general interest.

Erwin Schrodinger, a Viennese, had shared the Nobel prize in physics in 1933 for laying the foundations of wave mechanics. That same year he left Berlin where he had been working because, although not himself Jewish, he would not remain in Germany when persecution of the Jews became national policy. A long odyssey through Europe brought him, in 1940, to Dublin at the invitation of Eamon de Valera, Ireland's premier. De Valera had been a mathematician before he became a revolutionary, then a politician; in 1940 he set up the Dublin Institute of Advanced Studies. Schro dinger found Ireland ‘paradise', not least because it allowed him the detachment to think about a very big question.

In his Dublin lectures, Schro dinger addressed what puzzled many students — why biology was treated as a subject completely separate from physics and chemistry: frogs, fruit flies and cells on one side, atoms and molecules, electricity and magnetism, on the other. The time had come, Schro dinger declared from his Irish platform, to think of living organisms in terms of their molecular and atomic structure. There was no great divide between the living and non-living; they all obey the same laws of physics and chemistry.

He put a physicist's question to biology. If entropy is (according to the second law of thermodynamics) things falling apart, the natural disintegration of order into disorder, why don't genes decay? Why are they instead passed intact from generation to generation?

He gave his own answer. ‘Life' is matter that is doing something. The technical term is metabolism — ‘eating, drinking, breathing, assimilating, replicating, avoiding entropy'. To Schro dinger, life could be defined as ‘negative entropy' — something
not
falling into chaos and approaching ‘the dangerous state of maximum entropy, which is death'. Genes preserve their structure because the chromosome that carries them is an irregular crystal. The arrangement of units within the crystal constitutes the hereditary code.

The lectures were published as a book the following year, ready for physicists to read as the war ended and they looked for new frontiers to explore. To the molecular biologist and scientific historian Gunther Stent of the University of California at Berkeley,
What Is Life?
was the
Uncle Tom's Cabin
of biology — a small book that started a revolution. For post-war physicists, suffering from professional malaise, ‘When one of the inventors of quantum mechanics [could] ask ‘‘What is life?'' ‘ Stent declared, ‘they were confronted with a fundamental problem worthy of their mettle.' Biological problems could now be tackled with their own language, physics.

Research into the new field of biophysics inched forward in the late 1940s. In 1949 another Austrian refugee scientist, Erwin Chargaff working at the Columbia College of Physicians and Surgeons in New York was one of the very few who took Avery's results to heart and changed his research programme in consequence. He analysed the proportions of the four bases of DNA and found a curious correspondence. The numbers of molecules present of the two bases, adenine and guanine, called purines were always equal to the total amount of thymine and cytosine, the other two bases, called pyrimidines. This neat ratio, found in all forms of DNA, cried out for explanation, but Chargaff could not think what it might be.

That is where things stood when Rosalind Franklin arrived at King's College London on 5 January 1951. Leaving coal research to work on DNA, moving from the crystal structure of inanimate substances to that of biological molecules, she had crossed the border between non-living and living. Coal does not make more coal, but genes make more genes.

NINE
Joining the Circus

(January - May 1951)

A
CELLAR IN THE
S
TRAND
was an unlikely place to look for the secret of life. But the subterranean setting was all too appropriate for what has been called one of the great personal quarrels in the history of science.

In 1951 the contrast between Paris, which had escaped the attentions of the Luftwaffe, and London which had not, was all too apparent. The main quadrangle at King's College London, stretched between the Aldwych and the Thames Embankment, was occupied by a bomb crater 58 feet long and 27 feet deep. The biophysics unit in the basement wound round the pit, which was being excavated to build the new physics department. The South Bank seen from across the Thames was simply piles of rubble. London was depressing, at its bleakest since the outbreak of war, with bomb sites used as car parks, cracked buildings propped up by wooden buttresses and makeshift housing everywhere. Six years after the war's end, food was still rationed, and sallow faces showed the effects of years of privation. Menus offering ‘meat and two veg' delivered a plate of beige mutton and two forms of overcooked potato. The Welfare State that Rosalind had so admired from France was fraying round the edges. An economic crisis brought on by the onset of the Korean War had, among other things, ended the free spectacles and false teeth offered by the new National Health Service, and in the general election of February 1950 the Labour government's post-war majority of 146 fell to a mere 5.

The contrasting genders often attributed to Paris and London were visibly true. London was a man's city, a place of furled umbrellas, bowler hats, men's clubs and gentlemen's tailors: to the expatriate writer Jean Rhys, it was ‘patriarchy personified'. So it was for Rosalind. In Paris she was confident, admired, independent. Now she was a daughter again. At first she lived at home with her parents at their new home in north London, then moved to the flat in South Kensington secured by Ellis Franklin's business connections. Dutifully but not unwillingly, she crossed London to her parents' Friday night dinners where the arguments flared as before. Rosalind's intolerance of her father's conservative views, her mother decided, stemmed from associates in France who had been in the French Resistance, ‘many of them politically embittered Communists'.

Rosalind was thus in a state of glum apprehension when a graduate student at King's, whose wife had worked with her at BCURA, volunteered to show her around the college. John Bradley found her tense and unbending, reluctant to be introduced. Clutching her aversion to things English around her like a cloak, she looked for, and found, mediocrity.

One element in English life unmentioned in her foreboding letters from France was class. At the start of the 1950s the social divisions were almost as pre-war. The Angry Young Men had not yet been heard from. Not until 1956 would
My Fair Lady
inform a popular audience that ‘every time an Englishman speaks, he makes another Englishman despise him'. Rosalind's quick, clipped voice carried a class label.

The impression she made on Dr Jean Hanson, for example, the biophysics unit's senior biologist was ‘typically upper-class — a product of the best girls' schools':

if you are English you feel it about another person. I always supposed her family was rich, though she never talked about it — she really stood out very much around here where most of the other people with very few exceptions came from ordinary backgrounds, middle-class or in some cases, I sup-pose, lower than that. Really, the word is aristocratic — she looked like an aristocrat and she acted like one . . . just the way she spoke, there were people at that time who sneered at the upper-class way of speaking, and really
hated
it.

The accent divide cut both ways. King's, part of the ill-coordinated University of London, was no Oxbridge college. Its corridors echoed with something less than Received Pronunciation. To Rosalind, the voices signalled that she had got herself among the intellectually second rate.

There was nothing second rate about King's tradition in laboratory science. The college had appointed its first professor of natural and experimental philosophy in 1831, long before Oxford established the Clarendon Laboratory or Cambridge the Cavendish. In 1834 Charles Wheatstone, King's first professor of experimental philosophy, laid down iron and copper wires in the vaults for experiments in electricity. In 1860, James Clerk Maxwell was appointed professor of natural philosophy and proved that electricity and magnetism are aspects of the same phenomenon.

But science at King's had always breathed ecclesiastical air. Theology was its biggest department. With 400 students training for the Anglican priesthood, there were swirling cassocks and dog collars everywhere. The college was established in 1829 by the Church of England as a protest against the opening of University College London, the ‘Godless Institute of Gower Street'. UCL, founded by dissenters, was denied a royal charter because it admitted Roman Catholics, Jews and other non-Anglicans. King's, in conspicuous contrast, boasted a large chapel with vaulted ceiling (and later designs by George Gilbert Scott), the only consecrated building in the University of London. The sound of hymns from morning service rang in the ears of the scientists as they made their way along the flagged passages and down the stone stairways, past a door marked ‘Professor of Dogmatic Theology', to their labs in the basement.

Rosalind soon was informed that women were not allowed in the King's senior common room where some of the staff ate lunch.

With happy memories of the Labo Central's disputatious
déjeuners
at Chez Solange, she felt angry and excluded. It seemed as if her work was not going to be taken seriously. But she ought not to have been surprised. It was hardly a unique arrangement in London at the time, certainly not in a bastion of the Established Church. Women were still not employed at Keyser's bank. Even free-thinking University College, the first to admit women with full status, had one common room for men only, and a separate, joint, common room — for men and women; known familiarly as ‘the joint', it survived well into the 1960s; UCL women, when polled, chose to retain the status quo.

Like UCL, King's had two dining rooms, one for men and women, the other for men only, both served from the same kitchen. Many of the men preferred to eat in the communal dining room, overlooking the Thames, and some of the scientists refused to go at all into the male preserve because of the preponderance of ‘hooded crows' (clerics).

There was yet another element at King's foreign to Rosalind. The biophysics unit included a number of ex-military men who had come to King's for an intensive two-year undergraduate course, and who remained on, working together as a team. They had a tough, ferocious approach to work and play — a barracks- room, beer-drinking camaraderie that spilled over after hours into Finch's pub on the Strand.

In short, an upper-middle-class Anglo-Jewish woman with French tastes in serious discourse suddenly found herself in an environment friendly to everything she was not. Adjustment was not helped by a mournful postcard from the Faculté des Sciences de l'Universite de Paris, Laboratoire de Minéralogie:
‘Chère Mademoiselle, Nous regrettons tous à Paris votre départ.'

On 8 January 1951, J.T. Randall, FRS, called a meeting in his office to introduce Rosalind and discuss the way ahead. Present were three of the people he had mentioned in his letter changing Rosalind's direction of research. Most important to her was Raymond Gosling, a young doctoral student, the only one at King's using X-ray diffraction, and now assigned to assist her. Gosling joked that he was ‘the PhD slave boy handed over in chains'.

Gosling liked jokes. Young, endomorphic, good-natured, he referred to Randall as ‘JT', ‘the Old Man' or ‘King John'. Nonetheless, he saw the boss as a visionary genius and considered himself lucky, a product of University College Medical School, to get into Randall's sought-after biophysics unit. Gosling had heard that Rosalind was pretty high-powered. Now he could see that she had ‘beautiful dark eyes, shining black hair, an intensity about her, and an awkwardness in conversation'.

Also present was the physicist and mathematician Alec Stokes who Randall had said wished ‘to concern himself almost entirely with theoretical problems'. There too was the ‘graduate from Syracuse, Mrs Heller'. Louise Heller was working as a volunteer at King's while her husband studied in London on a Fulbright scholarship. She too formed a strong impression of the new arrival: ‘very attractive, very bright, very impatient and very opinionated'.

More important was who was not there. Maurice Wilkins, Randall's deputy, assistant director of the biophysics unit, was on holiday. Wilkins had been working intensively on nucleic acids at King's for several years. If Gosling was anybody's slave, it was his. Together they had mounted a bundle of nucleic acid fibres on a wire frame (the ‘frame' being a bent paperclip stuck in a holder), then kept the sample moist by passing saturated hydrogen through their Raymax tube and Unicam camera. When warned by Randall that air might leak into the camera (spoiling the vacuum necessary to prevent the X-ray beam diffusing), they sealed it with a condom. The result was what Randall had described to Rosalind in the crucial letter:

Gosling, working in conjunction with Wilkins, has already found that fibres of desoxyribose nucleic acid derived from material provided by Professor Signer of Berne give remarkably good fibre diagrams.

Gosling's photographs were more than remarkable, they were unique. The spots forming an x-shape were the first clear indication that deoxyribonucleic acid — DNA — had a crystalline structure. When Wilkins showed Gosling's measurement of the spots to Stokes, what struck Stokes were the blank spaces along the length of the ‘x'. Might the molecule, he speculated, have the shape of a helix?

Wilkins believed he was instrumental in getting Rosalind assigned to DNA. When he heard from Randall that she was coming to work on proteins in solution, he thought it a waste as they were getting such good results on nucleic acids. Considering her X-ray expertise, why not, he suggested, ‘grab her and get her in on the DNA work'? To his surprise, Randall readily agreed. Randall usually hemmed and hawed over such decisions. With new equipment on the way, Maurice had looked forward to her joining his team.

King's had been using an X-ray machine loaned by the British Admiralty. When the Admiralty wanted it back, Wilkins and Gosling went to Birkbeck and asked to buy the new fine-focus tube that Werner Ehrenberg and Walter Spear had invented to concentrate X-rays into a very narrow beam. Ehrenberg generously gave them the prototype instead. This tube, when fitted with a very small camera, made it easier to control the humidity inside the camera. The way was now open to photographing a single DNA fibre one-tenth of a millimetre across.

 

Rosalind's first task was to complete and try out the new apparatus and to order more. With brisk know-how and an array of smart-looking catalogues, she ordered equipment from Paris, adeptly haggling in French about price and specifications, and an English-made vacuum pump to extract air from the camera. With Gosling she set about designing a tilting microcamera to be made by King's workshops.

At the same time Randall encouraged her to write up her Paris work. Within a few weeks an extensive paper was on its way to the
Proceedings of the Royal Society,
with his endorsement: ‘communicated by J.T. Randall, FRS'. Publication in this distinguished journal was another first for Rosalind. It gave her the opportunity to expound on the subject on which she was now a world authority: the two distinct classes of carbons and the way that each formed crystals. With two more papers on their way to publication in
Acta Crystallographica,
she had, at the age of thirty, an impressive representation in what the scientific profession respects as ‘peer-reviewed journals'.

 

If anyone at King's was class-conscious, it was John Turton Randall. A short, bald, dapper Lancastrian, the son of a market gardener, he was a grammar-school boy who had worked his way from a county school to the University of Manchester where he led his year and took a first-class degree in crystal physics. When, somewhat to his dismay, he was steered by the Nobel Laureate Lawrence Bragg, then head of physics at Manchester, into industry rather than pursuit of a doctorate, he rose to become head of research at the General Electric Company based in Wembley. Yet he remained self-conscious about the ‘rough edges' of his northern ways and the difficulties in becoming ‘fully acceptable in the smoother south'. In 1937 he was given a fellowship and invited to the University of Birmingham where he set up a luminescence laboratory. In 1939 he shifted to the problem of increasing the power of radar.

Randall was — and knew he was — something of a war hero. His invention (with H.A.H. Boot) of the cavity magnetron, a device to create a powerful beam of low frequency electromagnetic waves which made possible the detection of distant objects. This invention was an invaluable aid to bombing at night and in overcast conditions, and was critically important in hunting down German submarines in the Battle of the Atlantic. President Franklin Roosevelt called the cavity magnetron ‘the most valuable cargo ever to reach these shores'.

It was certainly valuable for Randall. Well before the war was won, he put in his claim to the Royal Commission on Rewards for Inventors for inventions which had served the national good. He pursued his bounty assiduously over the next few years as he moved from Birmingham to St Andrews in Scotland, where he held the chair of Natural Philosophy. He even managed to secure tax relief and compensation for legal expenses incurred before finally collecting, in 1949, his one-third share of £36,000. (J. Sayres, another Birmingham researcher, and H.A.H. Boot each also got a third.) Randall thus became financially independent beyond dreams of ordinary academics.