44. Discovery of DNA Structure 1945-1953

 

In September 1938, on the day Neville Chamberlain flew back to London from Munich with his little bit of paper, the 18 year old Rosalind Franklin had gone up to Cambridge to study mathematics, physics and chemistry. There were fewer new students than usual that year because of the war but despite that she had to endure a lot of abuse for being a woman and a jew. She had already built up a strong system of defense against the already frequent attacks from the establishment but the isolation made her quiet and prickly and she found it difficult to trust many others. She also developed an effective defense to these attacks and was more than able to give back as good as she got.

Scientists were deserting the softer side of evolutionary biology’s ship, expecting the next advance from The Synthesis to come from somewhere completely different. Tansley was busy writing up his life-time’s observations of The Ecology of the British Isles and specialists on different groups of animals and plants shut themselves away at the end of the many quiet corridors in museums. The future was also in projects that could help post-war economic growth, and several were funded for applications by the Medical and Agricultural Research Councils, and by the mining companies such as Turner & Newall.

For Rosalind Franklin, newly graduated in chemistry from Cambridge, Paris was an easier place than London to start her career in that hard and hopeful post-war world. There she was surrounded by young optimists who had been stripped of the heavy traditions and they celebrated as only existentialists could, with optimistic talk of the self and dreams that while “London mists are yellow, Paris’s are blue”. Her science looked though crystals with x-rays and showed the intimate chemical structures of hard substances such as coal. The rigor her work demanded became a set of rules that she easily applied to the rest of her life, and the clash between their subject and the object became close and painful. Curiously, just before the First World War only forty years earlier, Marie Stopes had also studied coal and also had difficult experiences fitting in to the man’s world.

One of the most important inventions made during the Second World War was a machine to emit radar beams, created by the Manchester physicist Lawrence Bragg’s student, John Randall. By 1951 Randall was using these techniques in his Biophysics Department at King’s College London and he went on to recruit Maurice Wilkins to look at the structure of DNA. They extracted this from the thymus glands of freshly slaughtered calves, for which they queued outside a butcher’s stall at Smithfield Market nearby.

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That year, Rosalind Franklin moved from Paris to become part of the King’s research group and used the techniques she had learnt in France to make her far superior preparations for x-ray studies.

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They soon revealed the “general principles on which the structure of DNA might be based” but once again there was a fight between a London group and another at Cambridge. There, Jim Watson and Frances Crick came up with the model of a three strand helix with the phosphate groups on the inside. Their boss John Kendrew invited Wilkins and Franklin and the others from King’s College London to see the Cambridge model, but Franklin was not impressed: the phosphate groups didn’t fit properly so as to link on to the water. She believed this to be essential for the molecule to hold together.

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The penny dropped in January 1953 when Jim Watson was accidentally shown Rosalind Franklin’s best x-ray photograph, number 51. “The instant I saw the picture my mouth fell open and my pulse began to race.” The Cambridge group realized that if the photograph was accurate it meant that the DNA molecule had two chains, not three. They could test that idea by building a three-dimensional model of the molecules to see if the phosphate groups and the water molecules fitted together. Though Watson and Crick’s famous work is still regarded as the greatest contribution to biology of the twentieth century, they are also remembered for not acknowledging all the evidence from the London group, and Franklin’s work in particular.

Despite having the best x-ray diffraction equipment that was available Franklin had never been happy in the King’s College laboratory. As a jewish woman she felt marginalized and her colleagues were mostly cold and focused on their own ambitions in ways that she hadn’t experienced during her four years in Paris. So she jumped at the chance of transferring her scholarship to JD Bernal’s crystallography laboratory just up the road at Birkbeck College in Bloomsbury. She got on well with Bernal and liked the eccentric atmosphere of the two decrepit Georgian terraced houses in Torrington Square where they all worked. The openness suited her own style. (And the wall in Bernal’s office suited the style of his visitor Pablo Picasso.)

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Even in Paris she had brushed aside formal routines in the excitement and rush of getting a new experiment underway and ready to yield some promising results. It was like picking up a new hand of cards at poker, ever hopeful of winning the next time. In Paris this enthusiasm made her overstay her time exposed to radiation, forcing her to stay away from work, and in the Torrington Square houses there was more danger. The two old houses had been damaged during the war and were falling apart, and they were overcrowded and badly organized. Inflammable and poisonous chemicals were kept under the wooden stairs, sinks didn’t drain properly, lavatories got blocked and people crashed into one another going up and down the rickety stairs with chemicals and delicate equipment. Bernal lived in a flat on the top floor where he often took his new girl-friends, not knowing that the floor-boards squeaked. At first, this shocked the prim Rosalind but her admiration for Bernal’s science were most important.

Having produced the brilliant photograph 51 from calf thymus DNA, at Birkbeck she was challenged to work out the structure of the different kind of nucleic acid thought to be in viruses. It seemed that there was an important connection between DNA and proteins, something to do with the DNA being made up of long chains of nucleotide bases and proteins with matching amino acids. To help with this research, in the room next door to Franklin was Aaron Klug had just arrived to use some of the same x-ray techniques to work out the structure of the first protein to be described as a chain of amino acids in a particular sequence, haemoglobin. It was work that eventually won Klug a Nobel Prize. Before then, in 1958 and at the age of 37, Rosalind Franklin died of ovarian cancer.

With the double helix structure of chromosomal DNA and a single helix for RNA both worked out, the way was clear to work out how genes on those long DNA molecules might relate to the structure of proteins such as haemoglobin. For many years organic chemists had known that nucleic acids were chains of four bases, adenine thymine guanine and cytosine, while proteins were long chains of about 20 different amino acids. The structure of DNA hinted that some mechanism linked these two kinds of big molecules. Crick called it “The Genetic Code” and his group at Cambridge worked out its meaning through the heady days of the early 1960s. They found that on each strand three of these bases coded for one amino acid. That made 64 possible codes for the 20 amino acids that were needed to make proteins, more than enough to go round.

What more was needed for a more complete understanding of how life is controlled inside a cell? More details were being worked out about the way the citric acid cycle caused respiration to convert oxygen and sugars into energy and a second set of pathways yielding energy were discovered by Melvin Calvin in 1946.

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This was photosynthesis, using light energy from the sun to drive the cyclic pathways of biochemical reactions to synthesise sugars and other useful organic compounds. It was work that once again was made possible from the war effort of the US Atomic Energy Commission, and Calvin’s large research group used radioisotopes of carbon to track the intermediates. Science has always been helped along in this way by new technology, the two systems depending on one another symbiotically. A major tool that the same culture developed during the 1940s was the electron microscope which began its own revolution in the way various disciplines could study cell structure.

 

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