The Mysterious World of the Human Genome. Frank Ryan

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СКАЧАТЬ 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 of molecules, extending this basic science to the complex organic molecules that are the chemical building blocks of life.

      The twentieth century has amazed us with its achievements in astronomy, in which scientists have plotted the stars and galaxies, and the forces, such as black holes, that govern the Universe. Equally important, though not so easily recognised as such by the ordinary man and woman, have been the achievements of the chemists and biochemists in exploring the micro-universe of atoms and molecules. Two forces in particular play a key role in the way that atoms bind to one another to make up life’s particular molecules. One of these is called the covalent bond; the other is called the hydrogen bond. Pauling applied the science of quantum mechanics to the forces involved in these two very different chemical bonds.

      We have no need to concern ourselves with the complex mathematics of the applied physics. We just need to grasp the basic mechanics. And where better to look than at the familiar molecule of water.

      Everybody knows that the chemical formula for water is H₂O. This tells us that a molecule of water comprises one atom of oxygen and two atoms of hydrogen. But how do they link with one another to form the stable compound that we handle and consume every day of our lives? The molecule of water might be compared to a planet, oxygen, with two encircling moons of hydrogen. In such a situation, we can readily imagine how the force of gravity would hold the hydrogen moons to their orbits around the oxygen planet. In molecular terms, the forces holding the two hydrogen atoms to the oxygen atom are called ‘covalent bonds’. At the ultramicroscopic level of atoms, the nucleus of each hydrogen atom contains a single positively charged proton while circling around the nucleus is a single negatively charged electron. Meanwhile, the oxygen atom has eight positively charged protons within its nucleus and eight balancing, negatively charged electrons in orbits around it. These electrons occupy two orbits – two electrons taking up an inner orbit and six taking up an outer orbit. In coming together to form a molecule of water, the two electrons in orbit around each of the two hydrogen nuclei have paired with two of the six electrons of the oxygen outer orbits. The paired electrons share their attraction to the protons of the two parent nuclei, so the paired electrons are now equally attracted to the oxygen nucleus and the hydrogen nuclei. This sharing of attraction creates a stable ‘covalent’ bond between the three atoms, just as gravity created stable orbits for the two moons rotating around our imaginary planet of oxygen.

      Hydrogen bonds are something else.

      Once again, we might take water as our example. But here we are looking at the chemical interactions between whole water molecules – the H₂Os reacting with one another. There are forces of attraction, albeit rather weaker and less stable than covalent СКАЧАТЬ