Genome: The Autobiography of a Species in 23 Chapters. Matt Ridley
Yet the problem of mutation remained. Darwinism demanded variety upon which to feed. Mendelism supplied stability instead. If genes were the atoms of biology, then changing them was as heretical as alchemy. The breakthrough came with the first artificial induction of mutation by somebody as different from Garrod and Mendel as could be imagined. Alongside an Edwardian doctor and an Augustinian friar we must place the pugnacious Hermann Joe Muller. Muller was typical of the many brilliant, Jewish scientific refugees crossing the Atlantic in the 1930s in every way except one: he was heading east. A native New Yorker, son of the owner of a small metal-casting business, he had been drawn to genetics at Columbia University, but fell out with his mentor, Morgan, and moved to the University of Texas in 1920. There is a whiff of anti-semitism about Morgan’s attitude to the brilliant Muller, but the pattern was all too typical. Muller fought with everybody all his life. In 1932, his marriage on the rocks and his colleagues stealing his ideas (so he said), he attempted suicide, then left Texas for Europe.
Muller’s great discovery, for which he was to win the Nobel prize, was that genes are artificially mutable. It was like Ernest Rutherford’s discovery a few years before that atomic elements were transmutable and that the word ‘atom’, meaning in Greek uncuttable, was inappropriate. In 1926, he asked himself, ‘[Is] mutation unique among biological processes in being itself outside the reach of modification or control, – that it occupies a position similar to that till recently characteristic of atomic transmutation in physical science?’
The following year he answered the question. By bombarding fruit flies with X-rays, Muller caused their genes to mutate so that their offspring sported new deformities. Mutation, he wrote, ‘does not stand as an unreachable god playing its pranks upon us from some impregnable citadel in the germplasm.’ Like atoms, Mendel’s particles must have some internal structure, too. They could be changed by X-rays. They were still genes after mutation, but not the same genes.
Artificial mutation kick-started modern genetics. Using Muller’s X-rays, in 1940 two scientists named George Beadle and Edward Tatum created mutant versions of a bread mould called Neurospora. They then worked out that the mutants failed to make a certain chemical because they lacked the working version of a certain enzyme. They proposed a law of biology, which caught on and has proved to be more or less correct: one gene specifies one enzyme. Geneticists began to chant it under their breath: one gene, one enzyme. It was Garrod’s old conjecture in modern, biochemical detail. Three years later came Linus Pauling’s remarkable deduction that a nasty form of anaemia afflicting mostly black people, in which the red cells turned into sickle shapes, was caused by a fault in the gene for the protein haemoglobin. That fault behaved like a true Mendelian mutation. Things were gradually falling into place: genes were recipes for proteins; mutations were altered proteins made by altered genes.
Muller, meanwhile, was out of the picture. In 1932 his fervent socialism and his equally fervent belief in the selective breeding of human beings, eugenics (he wanted to see children carefully bred with the character of Marx or Lenin, though in later editions of his book he judiciously altered this to Lincoln and Descartes), led him across the Atlantic to Europe. He arrived in Berlin just a few months before Hitler came to power. He watched, horrified, as the Nazis smashed the laboratories of his boss, Oscar Vogt, for not expelling the Jews under his charge.
Muller went east once more, to Leningrad, arriving in the laboratory of Nikolay Vavilov just before the anti-Mendelist Trofim Lysenko caught the ear of Stalin and began his persecution of Mendelian geneticists in support of his own crackpot theories that wheat plants, like Russian souls, could be trained rather than bred to new regimes; and that those who believed otherwise should not be persuaded, but shot. Vavilov died in prison. Ever hopeful, Muller sent Stalin a copy of his latest eugenic book, but hearing it had not gone down well, found an excuse to get out of the country just in time. He went to the Spanish Civil War, where he worked in the blood bank of the International Brigade, and thence to Edinburgh, arriving with his usual ill luck just in time for the outbreak of the Second World War. He found it hard to do science in a blacked-out Scottish winter wearing gloves in the laboratory and he tried desperately to return to America. But nobody wanted a belligerent, prickly socialist who lectured ineptly and had been living in Soviet Russia. Eventually Indiana University gave him a job. The following year he won the Nobel prize for his discovery of artificial mutation.
But still the gene itself remained an inaccessible and mysterious thing, its ability to specify precise recipes for proteins made all the more baffling by the fact that it must itself be made of protein; nothing else in the cell seemed complicated enough to qualify. True, there was something else in chromosomes: that dull little nucleic acid called DNA. It had first been isolated, from the pus-soaked bandages of wounded soldiers, in the German town of Tübingen in 1869 by a Swiss doctor named Friedrich Miescher. Miescher himself guessed that DNA might be the key to heredity, writing to his uncle in 1892 with amazing prescience that DNA might convey the hereditary message ‘just as the words and concepts of all languages can find expression in 24–30 letters of the alphabet’. But DNA had few fans; it was known to be a comparatively monotonous substance: how could it convey a message in just four varieties?5
Drawn by the presence of Muller, there arrived in Bloomington, Indiana, a precocious and confident nineteen-year-old, already equipped with a bachelor’s degree, named James Watson. He must have seemed an unlikely solution to the gene problem, but the solution he was. Trained at Indiana University by the Italian émigré Salvador Luria (predictably, Watson did not hit it off with Muller), Watson developed an obsessive conviction that genes were made of DNA, not protein. In search of vindication, he went to Denmark, then, dissatisfied with the colleagues he found there, to Cambridge in October 1951. Chance threw him together in the Cavendish laboratory with a mind of equal brilliance captivated by the same conviction about the importance of DNA, Francis Crick.
The rest is history. Crick was the opposite of precocious. Already thirty-five, he still had no PhD (a German bomb had destroyed the apparatus at University College, London, with which he was supposed to have measured the viscosity of hot water under pressure – to his great relief), and his sideways lurch into biology from a stalled career in physics was not, so far, a conspicuous success. He had already fled from the tedium of one Cambridge laboratory where he was employed to measure the viscosity of cells forced to ingest particles, and was busy learning crystallography at the Cavendish. But he did not have the patience to stick to his own problems, or the humility to stick to small questions. His laugh, his confident intelligence and his knack of telling people the answers to their own scientific questions were getting on nerves at the Cavendish. Crick was also vaguely dissatisfied with the prevailing obsession with proteins. The structure of the gene was the big question and DNA, he suspected, was a part of the answer. Lured by Watson, he played truant from his own research to indulge in DNA games. So was born one of the great, amicably competitive and therefore productive collaborations in the history of science: the young, ambitious, suppleminded American who knew some biology and the effortlessly brilliant but unfocused older Briton who knew some physics. It was an exothermic reaction.
Within a few short months, using other people’s laboriously gathered but under-analysed facts, they had made possibly the greatest scientific discovery of all time, the structure of DNA. Not even Archimedes leaping from his bath had been granted greater reason to boast, as Francis Crick did in the Eagle pub on 28 February 1953, ‘We’ve discovered the secret of life.’ Watson was mortified; he still feared that they might have made a mistake.
But they had not. All was suddenly clear: DNA contained a code written along the length of an elegant, intertwined staircase of a double helix, of potentially infinite length. That code copied itself by means of chemical affinities between its letters and spelt out the recipes for proteins by means of an as yet unknown phrasebook linking DNA to protein. The stunning significance of the structure of DNA was how simple it made everything seem and yet how beautiful. As Richard Dawkins has put it,6 ‘What is truly revolutionary about molecular biology in the post-Watson–Crick era is that it has become digital…the machine code of the genes is uncannily computer-like.’
A month after the Watson–Crick structure was published, Britain