The Mysterious World of the Human Genome. Frank Ryan
Office in Washington, informing them of his change of plans. Ten days after he had returned to Cambridge he received a bombshell in the post: he was instructed, by a new director, to forgo his plans. The Fellowship had decided he was unqualified to do crystallography work. He should transfer to a laboratory working on physiology of the cell in Stockholm. Watson appealed once more to Luria.
As far as Watson was concerned it was out of the question to follow these new instructions. If the worst came to the worst, he would survive for at least a year on the $1,000 still left to him from the previous year’s stipend. Kendrew helped him out when his landlady chucked him out of his digs. It was just another indignity when he ended up occupying a tiny room at Kendrew’s home, which was unbelievably damp and heated only by an aged electric heater. Though it looked like an open invitation to tuberculosis, living with friends was preferable to the sort of digs he might be able to afford in his impecunious state. And there was a comfort to be had:
‘I had discovered the fun of talking to Francis Crick.’
And talk they did.
In Crick’s own memory: ‘Jim and I hit it off immediately, partly because our interests were astonishingly similar and partly, I suspect, because a certain youthful arrogance, a ruthlessness, and an impatience with sloppy thinking came naturally to us both.’ That conversation, lasting for two or three hours just about every day for two years, would unravel the most important mystery ever in the history of biology – the molecular basis of heredity.
We need to grasp a few fundamentals to understand how this happened. Firstly, we have two young and ambitious men – in Watson’s case aged just 23, in Crick’s, aged 35 – who were both exceptionally intelligent and surrounded by the ambience of high scientific endeavour and achievement. We need to grasp that Watson’s interest, intense and obsessive, was the structure of DNA in its potential to explain the mystery of the workings of the gene, and thus the storing of heredity. We also need to grasp the slight, but important, difference with Crick’s interest, which was not DNA, or even the gene in itself, but the potential of DNA to explain how Schrödinger’s mysterious molecular codes – his aperiodic crystals – had the potential not only for coding heredity but for translating from one code to another, from the gene to the second aperiodic crystal that must determine the structure of proteins.
Crick would subsequently recall Watson’s arrival in early October 1951. Odile, his French second wife, and he were living in a tiny ramshackle apartment with a green door that they had inherited from the Perutzes. Conveniently situated for the centre of Cambridge and only a few minutes’ walk from the Cavendish Laboratory, it was all they could afford on Crick’s research stipend. The ‘Green Door’, as it was thereafter called, consisted of an attic over a tobacconist’s house, with ‘two and a half rooms’ and a small kitchen that was reached by climbing a steep staircase off the back of the tobacconist’s house. The two rooms served as living room and bedroom for Crick and Odile, with the half room providing a bedroom for Crick’s son, Michael – born to his first wife, Ruth Doreen – when Michael was home from boarding school. The wash-room and lavatory opened halfway up the stairs and the bath, covered with a hinged board, was a feature of the tiny kitchen.
One day, out of the blue, Perutz brought Watson to the flat. Crick was out. But he would recall Odile remarking that Max had come round with a young American who ‘had no hair’. The newly arrived Watson was sporting a crew-cut – a hairstyle uncommon in England at the time. They met within a day or two … ‘I remember the chats we had over those first two or three days in a broad sort of way.’
Both men were impecunious, but it hardly mattered since they were uninterested in money. What mattered was that the deeply personal, deeply intellectual, symbiosis had begun. Crick brought a rowdy enjoyment of problem solving, together with the hubris, born out of his background in physics, to believe that the big problem facing them – the mystery of the gene – was indeed solvable. Watson, who had little knowledge of physics or X-ray crystallography, brought a mine of knowledge about the way in which genes worked – the fruits of the bacteriophage researches of Luria and Delbrück. Perutz would subsequently confirm that the arrival of Watson, at that particular moment of time, was opportune for the workings of the Cavendish Lab, where his enthusiastic personality appeared to have galvanised Crick, and where his knowledge of the field of genetics added an exotic aspect to the structural physics and chemistry that otherwise prevailed. Moreover, different as their backgrounds were, Crick and Watson shared a deep, insatiable level of curiosity about the puzzle that lay at the very root of biology: they were determined, almost from their first meeting, that they would solve the mysterious nature of the gene.
The first creative step was to realise that the answer lay with DNA. To be more accurate, they realised that somehow chemical structure must parallel function: so the answer to the great conundrum lay in the three-dimensional chemical structure of DNA. But nobody really knew what shape or form this structure took. To the minds of Crick and Watson at that particular moment in time, it would have seemed nothing more than a ghost in the mist.
New discoveries in science will usually involve a lengthy period of laboratory labour, with knowledge growing by hard-won increments, often involving contributions from several, or a good deal more than several, different sources. In many ways the struggle to get to grips with the mysteries of heredity followed exactly such a course. But the mundane sweat of the laboratory aspects, the growth of knowledge by hard-won increments, would not fall to Watson and Crick. These would be left to others. The Crick–Watson symbiosis would be founded on a second, equally important ingredient of scientific advance, and one that has commonalities with the advances in the arts and humanities: this is the quintessentially human gift we call ‘creativity’.
Within the hierarchy of the lab, Crick and Watson were the lowest contributing level. In Crick’s words, ‘I was just a research student and Jim was just a visitor.’ They read very widely, imbibing the fruits of the hard work of others. They talked and talked, thinking out loud, probing one another’s ideas and knowledge, often with Crick playing devil’s advocate. In fact they gossiped and argued so much they were given a room to themselves – to avoid their interrupting the thoughts of their more senior colleagues – within the crowded structure of the old Cavendish Laboratory. The X-ray laboratory, with its heavy machinery and radiation dangers, was located in the basement. Jim and Francis would also share a cheap and cheerful lunch, of shepherd’s pie or sausage and beans, at the local pub, the Eagle – a grubby establishment in a cobblestoned courtyard – where the creative debate would simply continue.
What little they knew about DNA was made even more uncertain by the fact that Crick believed that much of what was generally assumed to be the case with DNA and heredity was almost certainly wrong. It had been this attitude that had got him into trouble with Bragg. It meant that he didn’t even trust the work of his seniors here in the lab. But the real reason behind Bragg’s anger was his resentment of the fact that the chemist, Pauling, had discovered the alpha helix of protein. Meanwhile, Crick was convinced that the reason why the Cavendish had missed out on this was because they were assuming the accuracy of some earlier experimentation on the X-ray interpretation of the skin protein, keratin, which is the main ingredient of our human nails and a raptor’s claws. The way in which Crick’s mind worked can be gleaned from a remembered conversation:
‘The point is [so-called] evidence can be unreliable, and therefore you should use as little of it as you can. We have three or four bits of data, we don’t know which one is reliable … [What if] we discard that one … then we can look at the rest and see if we can make sense of that.’
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Watson joined the Cavendish in the same year, 1951, in which Linus Pauling published his paper on the protein ‘alpha helix’. This discovery so rattled Watson that all of the time he was working with Crick on the structure of DNA, he was looking over his shoulder in Pauling’s direction.
He had good reason for seeing Pauling as the supreme rival in such an exploration; awarded the Nobel Prize in Chemistry in 1954, Pauling was already being hailed by scientific historians as one of the most influential chemists in history. His master work, though he contributed a great deal more, was to apply a quantum theory perspective to the chemical bonds that bind atoms within the structure