Matt Ridley

skeletons from before 1492, but not in European skeletons from before that date). People with the O version of the gene seem to be less susceptible to syphilis than those with other blood types.8

Now consider a bizarre discovery that would have made little sense before the discovery of the association between susceptibility to cholera and blood groups. If, as a professor, you ask four men and two women each to wear a cotton T-shirt, no deodorant and no perfume, for two nights, then hand these T-shirts to you, you will probably be humoured as a mite kinky. If you then ask a total of 121 men and women to sniff the armpits of these dirty T-shirts and rank them according to attractiveness of smell, you will be considered, to put it mildly, eccentric. But true scientists should not be embarrassable. The result of exactly such an experiment, by Claus Wederkind and Sandra Furi, was the discovery that men and women most prefer (or least dislike) the body odour of members of the opposite sex who are most different from them genetically. Wederkind and Furi looked at M H C genes on chromosome 6, which are the genes involved in the definition of self and the recognition of parasitic intruders by the immune system. They are immensely variable genes. Other things being equal, a female mouse will prefer to mate with a male that has maximally different M H C genes from herself, a fact she discerns by sniffing his urine. It was this discovery that alerted Wederkind and Furi to the possibility that we, too, might D I S E A S E 1 4 5

retain some such ability to choose our mates on the basis of their genes. Only women on the contraceptive pill failed to show a clear preference for different M H C genotypes in male-impregnated T-shirt armpits. But then the pill is known to affect the sense of smell. As Wedekind and Furi put it,9 'No one smells good to everybody; it depends on who is sniffing whom.'

The mouse experiment had always been interpreted in terms of outbreeding: the female mouse tries to find a male from a genetically different population, so that she can have offspring with varied genes and little risk of inbred diseases. But perhaps she - and T-shirt-sniffing people - are actually doing something that makes sense in terms of the blood-group story. Remember that, when making love in a time of cholera, an AA person is best off looking for a BB mate, so that all their children will be cholera-resistant ABs. If the same sort of system applies to other genes and their co-evolution with other diseases - and the M H C complex of genes seems to be the principal site of disease-resistance genes - then the advantage of being sexually attracted to a genetic opposite is obvious.

The Human Genome Project is founded upon a fallacy. There is no such thing as 'the human genome'. Neither in space nor in time can such a definite object be defined. At hundreds of different loci, scattered throughout the twenty-three chromosomes, there are genes that differ from person to person. Nobody can say that the blood group A is 'normal' and O, B and AB are 'abnormal'. So when the Human Genome Project publishes the sequence of the typical human being, what will it publish for the A B O gene on chromosome 9? The project's declared aim is to publish the average or

'consensus' sequence of 200 different people. But this would miss the point in the case of the A B O gene, because it is a crucial part of its function that it should not be the same in everybody. Variation is an inherent and integral part of the human - or indeed any —

genome.

Nor does it make sense to take a snapshot at this particular moment in 1999 and believe that the resulting picture somehow represents a stable and permanent image. Genomes change.

1 4 6 G E N O M E

Different versions of genes rise and fall in popularity driven often by the rise and fall of diseases. There is a regrettable human tendency to exaggerate stability, to believe in equilibrium. In fact the genome is a dynamic, changing scene. There was a time when ecologists believed in 'climax' vegetation - oak forests for England, fir forests for Norway. They have learnt better. Ecology, like genetics, is not about equilibrium states. It is about change, change and change.

Nothing stays the same forever.

The first person who half glimpsed this was probably J. B. S.

Haldane, who tried to find a reason for the abundance of human genetic variation. As early as 1949 he conjectured that genetic variation might owe a good deal to the pressures of parasites. But Haldane's Indian colleague, Suresh Jayakar, rocked the boat in 1970

by suggesting that there need be no stability, and that parasites could cause a perpetual cycling fluctuation in gene frequencies. By the 1980s the torch had passed to the Australian Robert May, who demonstrated that even in the simplest system of a parasite and its host, there might be no equilibrium outcome: that eternal chaotic motion could flow from a deterministic system. May thus became one of the fathers of chaos theory. The baton was picked up by the Briton William Hamilton, who developed mathematical models to explain the evolution of sexual reproduction, models that relied upon a genetic arms race between parasites and their hosts, and which resulted in what Hamilton called 'the permanent unrest of many [genes]'.10

Some time in the 1970s, as happened in physics half a century before, the old world of certainty, stability and determinism in biology fell. In its place we must build a world of fluctuation, change and unpredictability. The genome that we decipher in this generation is but a snapshot of an ever-changing document. There is no definitive edition.

C H R O M O S O M E 1 0

S t r e s s

This is the excellent foppery of the world, that, when we are sick in fortune — often the surfeit of our own behaviour, — we make guilty of our disasters the sun, the moon, and the stars; as if we were villains by necess-ity, fools by heavenly compulsion . . . an admirable eva-sion of whoremaster man, to lay his goatish disposition to the charge of a star. William Shakespeare, King Lear The genome is a scripture in which is written the past history of plagues. The long struggles of our ancestors with malaria and dysentery are recorded in the patterns of human genetic variation. Your chances of avoiding death from malaria are pre-programmed in your genes, and in the genes of the malaria organism. You send out your team of genes to play the match, and so does the malaria parasite.

If their attackers are better than your defenders, they win. Bad luck.

No substitutes allowed.

But it is not like that, is it? Genetic resistance to disease is the last resort. There are all sorts of simpler ways of defeating disease.

Sleep under a mosquito net, drain the swamps, take a pill, spray 1 4 8 G E N O M E

D D T around the village. Eat well, sleep well, avoid stress, keep your immune system in good health and generally maintain a sunny disposition. All of these things are relevant to whether you catch an infection. The genome is not the only battlefield. In the last few chapters I have fallen into the habit of reductionism. I have taken the organism apart to isolate its genes and discern their particular interests. But no gene is an island. Each one exists as part of an enormous confederation called the body. It is time to put the organism back together again. It is time to visit a much more social gene, a gene whose whole function is to integrate some of the many different