Science of Discworld III

the population. Perhaps twenty genes might be changing in this way if they were not very different in ‘fitness’ from the regular alleles. This picture of the population implied that almost all organisms in a given species must have pretty much the same genetic make-up, except for a few which carried the good alleles coming in, and winning, or the bad alleles on the way out. 1 These exceptions were mutants, famously and stupidly portrayed in many SF films.
    However, in the early 1960s Richard Lewontin’s group exploited a new way to investigate the genetics of wild (or indeed any) organisms. They looked at how many versions of common proteins they could find in the blood, or in cell extracts. If there was just one version, the organism had received the same allele from both of its parents: the technical term here is ‘homozygous’. If there were two versions, it had received different ones from each parent, and so was ‘heterozygous’.
    What they found was totally incompatible with the Fisher-Haldane picture.
    They found, and this has been amply confirmed in thousands of wild populations since, that in most organisms, about ten per cent ofgenes are heterozygous. We now know, thanks to the Human Genome Project, that human beings have about 34,000 genes. So about 3400 are heterozygous, in any individual, instead of the ten or so predicted by Haldane and Fisher.
    Furthermore, if many different organisms are sampled, it turns out that about one-third of all genes have variant alleles. Some are rare, but many of them occur in more than one per cent of the population.
    There is no way that this real-world picture of the genetic structure of populations can be reconciled with the classical view of population genetics. Nearly all current natural selection must be discriminating between different combinations of ancient mutations. It’s not a matter of a new mutation arriving and the result being immediately subjected to selection: instead, that mutation must typically hang around, for millions of years, until eventually it ends up playing a role that makes enough of a difference for natural selection to notice, and react.
    With hindsight, it is now obvious that all currently existing breeds of dog must have been ‘available’ – in the sense that the necessary alleles already existed, somewhere in the population – in the original domesticated wolves. There simply hasn’t been time to accumulate the necessary mutations purely in modern dogs. Darwin knew about the amount of cryptic and overt variation in pigeons, too. But his successors, hot on the trail of the molecular basis of life, forgot about wolves and pigeons. They pretty much forgot about cells. DNA was complicated enough: cell biology was impossible, and as for understanding an organism …
    Lewontin’s discovery was a significant turning point in our understanding of heredity and evolution. It was at least as radical as the much better publicised revolution that replaced Newton’s physics with Einstein’s, and it was arguably more important. We will see that in the last year or so there has been another, even more radical, revision of our thinking about the control of cell biology anddevelopment by the genes. The whole dogma about DNA, messenger RNA, and proteins has been given a reality check, and science’s internal ‘auditors’ have rendered it as archaic as Fisher’s population genetics.
    It is commonly assumed – not only by the average television producer of pop science half-hours, but also by most popular science book authors – that now we know about DNA, the ‘secret of life’, evolution and its mechanisms are an open book. Soon after the discovery of DNA’s structure and mechanism of replication by James Watson and Francis Crick, in the late 1950s, the media – and biology textbooks at all levels – were beginning to refer to it as the ‘Blueprint for Life’. Many books, culminating with Dawkins’s The Selfish Gene in the 1970s, promoted the view that by knowing about the mechanism of heredity, we had found the key to all of the important puzzles of biology and medicine, especially evolution.
    There was soon to be a major tragedy, resulting from a medical application of that mistaken view. The sedative thalidomide was increasingly being prescribed, and bought over the counter, to treat nausea and other minor discomforts of the early weeks of pregnancy. Only later was it discovered that in a small proportion of cases,