Matt Ridley

the press can be very misleading. Yet anybody who gets evidence of a link between a disease and a gene has a duty to publish it. If it proves an illusion, little harm is done. Arguably, more damage has been done by false negatives (true genes that have been prematurely ruled out on inadequate data) than by false positives (suspicions of a link that later prove unfounded).

Cookson and his colleagues eventually got their gene and pinned down a mutation within it that the asthmatics in their sample had more often than others did. It was an asthma gene of sorts. But it only accounted for fifteen per cent of the explanation of asthma and it has proved remarkably hard to replicate the finding in other subjects, a maddening feature of asthma-gene hunting that has recurred with distressing frequency. By 1994 one of Cookson's rivals, David Marsh, was suggesting a strong link between asthma and the gene for interleukin 4, on chromosome 5, based on a study of eleven Amish families. That, too, proved hard to replicate. By 1997 a group of Finns was comprehensively ruling out a connection between asthma and the same gene. That same year a study of a mixed- race population in America concluded that eleven chromosomal regions could be linked to susceptibility to asthma, of which ten were unique to only one racial or ethnic group. In other words, the gene that most defined susceptiblity to asthma in blacks was not the same gene that most defined susceptibility to asthma in whites, which was different again from the gene that most defined susceptibility to asthma in Hispanics.3

Gender differences are just as pronounced as racial ones. According to research by the American Lung Association, whereas ozone from petrol-burning cars triggers asthma in men, particulates from 7 4 G E N O M E

diesel engines are more likely to trigger asthma in women. As a rule, males seem to have an early bout of allergy and to outgrow it, while females develop allergies in their mid or late twenties and do not outgrow them (though rules have exceptions, of course, including the rule that rules have exceptions). This could explain something peculiar about asthma inheritance: people often appear to inherit it from allergic mothers, but rarely from their fathers. This could just mean that the father's asthma was long ago in his youth and has been largely forgotten.

The trouble seems to be that there are so many ways of altering the sensitivity of the body to asthma triggers, all along the chain of reactions that leads to the symptoms, that all sorts of genes can be

'asthma genes', yet no single one can explain more than a handful of cases. ADRB2, for example, lies on the long arm of chromosome 5. It is the recipe for a protein called the beta- 2-adrenergic receptor, which controls bronchodilation and bronchoconstriction - the actual, direct symptom of asthma in the tightening of the windpipe.

The commonest anti-asthma drugs work by attacking this receptor.

So surely a mutation in ADRB2 would be a prime 'asthma gene'?

The gene was pinned down first in cells derived from the Chinese hamster: a fairly routine 1,239-letter long recipe of D N A . Sure enough a promising spelling difference between some severe nocturnal asthmatics and some non-nocturnal asthmatics soon emerged: letter number 46 was G instead of A. But the result was far from conclusive. Approximately eighty per cent of the nocturnal asthmatics had a G, while fifty-two per cent of the non- nocturnal asthmatics had G. The scientists suggested that this difference was sufficient to prevent the damping down of the allergic system that usually occurs at night.4

But nocturnal asthmatics are a small minority. To muddy the waters still further, the very same spelling difference has since been linked to a different asthmatic problem: resistance to asthma drugs.

Those with the letter G at the same forty-sixth position in the same gene on both copies of chromosome 5 are more likely to find that their asthma drugs, such as formoterol, gradually become ineffective E N V I R O N M E N T 7 5

over a period of weeks or months than those with a letter A on both copies.

'More likely' . . . 'probably' . . . 'in some of: this is hardly the language of determinism I used for Huntington's disease on chromosome 4. The A to G change at position 46 on the ADRB2 gene plainly has something to do with asthma susceptibility, but it cannot be called the 'asthma gene', nor used to explain why asthma strikes some people and not others. It is at best a tiny part of the tale, applicable in a small minority or having a small influence easily overridden by other factors. You had better get used to such indeterminacy. The more we delve into the genome the less fatalistic it will seem. Grey indeterminacy, variable causality and vague predisposition are the hallmarks of the system. This is not because what I said in previous chapters about simple, particulate inheritance is wrong, but because simplicity piled upon simplicity creates complexity. The genome is as complicated and indeterminate as ordinary life, because it is ordinary life. This should come as a relief. Simple determinism, whether of the genetic or environmental kind, is a depressing prospect for those with a fondness for free will.

C H R O M O S O M E 6

I n t e l l i g e n c e

The hereditarian fallacy is not the simple claim that IQ is to some degree 'heritable' [but] the equation of

'heritable' with 'inevitable'. Stephen Jay Gould I have been misleading you, and breaking my own rule into the bargain. I ought to write it out a hundred times as punishment: G E N E S A R E N O T T H E R E T O C A U S E D I S E A S E S .

Even if a gene causes a disease by being 'broken', most genes are not 'broken' in any of us, they just come in different flavours. The blue-eyed gene is not a broken version of the brown-eyed gene, or the red-haired gene a broken version of the brown-haired gene.

They are, in the jargon, different alleles - alternative versions of the same genetic 'paragraph', all equally fit, valid and legitimate. They are all normal; there is no single definition of normality.

Time to stop beating about the bush. Time to plunge headlong into the most tangled briar of the lot, the roughest, scratchiest, most impenetrable and least easy of all the brambles in the genetic forest: the inheritance of intelligence.

Chromosome 6 is the best place to find such a thicket. It was on I N T E L L I G E N C E 7 7

chromosome 6, towards the end of 1997, that a brave or perhaps foolhardy scientist first announced to the world that he had found a gene 'for intelligence'. Brave, indeed, for however good his evidence, there are plenty of people out there who refuse to admit that such things could exist, let alone do. Their grounds for scepticism are not only a weary suspicion, bred by politically tainted research over many decades, of anybody who even touches the subject of hereditary intelligence, but also a hefty dose of common sense.

Mother Nature has plainly not entrusted the determination,of our intellectual capacities to the blind fate of a gene or genes; she gave us parents, learning, language, culture and education to program ourselves with.

Yet this is what Robert Plomin announced that he and his colleagues had discovered. A group of especially