Genome

somebody had suggested that the scrapie agent might have no D N A or R N A genes at all. It might be the only piece of life on the planet that did not use nucleic acid and had no genes of its own. Since Francis Crick had recently coined what he called, half-seriously, the

'central dogma of genetics' — that D N A makes R N A makes protein

- the suggestion that there was a living thing with no D N A was about as welcome in biology as Luther's principles in Rome.

In 1982 a geneticist named Stanley Prusiner proposed a resolution of the apparent paradox between a DNA-less creature and a disease that moved through human D N A . Prusiner had discovered a chunk P O L I T I C S 2 7 7

of protein that resisted digestion by normal protease enzymes and that was present in animals with scrapie-like diseases but not in healthy versions of the same species. It was comparatively straight-forward for him to work out the sequence of amino acids in this protein chunk, calculate the equivalent D N A sequence and search for such sequences in amongst the genes of mice and, later, people.

Prusiner thus found the gene, called PRP (for protease-resistant protein) and nailed his heresy to the church door of science. His theory, gradually elaborated over the next few years, went like this.

PRP is a normal gene in mice and people; it produces a normal protein. It is not the gene of a virus. But its product, known as a prion, is a protein with an unusual quality: it can suddenly change its shape into a tough and sticky form that resists all attempts to destroy it and that gathers together in aggregate lumps, disrupting the structure of the cell. All this would be unprecedented enough, but Prusiner proposed something even more exotic. He suggested that this new form of prion has the capacity to reshape normal prions into versions of itself. It does not alter the sequence — proteins, like genes, are made of long, digital sequences - but it does change the way they fold up.1

Prusiner's theory fell on stony ground. It failed entirely to explain some of the most basic features of scrapie and related diseases, in particular, the fact that the diseases came in different strains. As he puts it ruefully today, 'Such a hypothesis enjoyed little enthusiasm.'

I vividly remember the scorn with which scrapie experts greeted the Prusiner theory when I asked them for their views for an article I was writing about this time. But gradually, as the facts came in, it seemed as if he might have guessed right. It eventually became clear that a mouse with no prion genes cannot catch any of these diseases, whereas a dose of misshapen prion is sufficient to give the diseases to another mouse: the disease is both caused by prions and transmitted by them. But although the Prusiner theory has since felled a large forest of ignorance - and Prusiner duly followed Gajdusek to Stockholm to collect a Nobel prize - large woods remain. Prions retain deep mysteries, the foremost of which is what on earth they 278 G E N O M E

exist for. The PRP gene is not only present in every mammal so far examined, but it varies very little in sequence, which implies that it is doing some important job. That job almost certainly concerns the brain, which is where the gene is switched on. It may involve copper, which the prion seems to be fond of. But - and here's the mystery — a mouse in which both copies of the gene have been deliberately knocked out since before birth is a perfectly normal mouse. It seems that whatever function the prion serves, the mouse can grow to do without it. We are still no nearer to knowing why we have this potentially lethal gene.2

Meanwhile we live just a mutation or two away from catching the disease from our own prion genes. In human beings the gene has 253 'words' of three letters each, though the first twenty-two and the last twenty-three are cut off the protein as soon as it is manufactured. In just four places, a change of word can lead to prion disease — but to four different manifestations of the disease.

Changing the 102nd word from proline to leucine causes Gerstmann—Straiissler-Scheinker disease, an inherited version of the disease that takes a long time to kill. Changing the 200th word from glutamine to lysine causes the type of C J D typical of the Libyan Jews. Changing the 178th word from aspartic acid to aspara¬

gine causes typical C J D , unless the 129th word is also changed from valine to methionine, in which case possibly the most horrible of all the prion diseases results. This is a rare affliction, known as fatal familial insomnia, where death occurs after months of total insomnia. In this case, it is the thalamus (which is, among other things, the brain's sleep centre), which is eaten away by the disease.

It seems that the different symptoms of different prion diseases result from the erosion of different parts of the brain.

In the decade since these facts first became clear, science has been at its most magnificent in probing further into the mysteries of this one gene. Experiments of almost mind-boggling ingenuity have poured out of Prusiner's and others' laboratories, revealing a story of extraordinary determinism and specificity. The 'bad' prion changes shape by refolding its central chunk (words 108-121). A P O L I T I C S 2 7 9

mutation in this region that makes the shape-change more likely is fatal so early in the life of a mouse that prion disease strikes within weeks of birth. The mutations that we see, in the various pedigrees of inherited prion disease, are peripheral ones that only slightly change the odds of the change in shape. In this way science tells us more and more about prions, but each new piece of knowledge only exposes a greater depth of mystery.

How exactly is this shape change effected? Is there, as Prusiner suspects, an unidentified second protein involved, called protein X, and if so, why can we not find it? We do not know.

How can it be that the same gene, expressed in all parts of the brain, behaves differently in different parts of the brain depending on which mutation it has? In goats, the symptoms of the disease vary from sleepiness to hyperactivity depending on which of two strains of the disease they get. We do not know why this should be.

Why is there a species barrier, which makes it hard to transmit prion diseases between species, but easy within species? Why is it very difficult to transmit by the oral route, but comparatively easy by means of direct injection into the brain? We do not know.

Why is the onset of symptoms dose-dependent? The more prions a mouse ingests, the sooner it will show symptoms. The more copies of a prion gene that a mouse has, the more quickly it can get prion disease when injected with rogue prions. Why? We do not know.

Why is it safer to be heterozygous than homozygous? In other words, if you have, at word 129, a valine on one copy of the gene and a methionine on the other copy, why are you more resistant to prion diseases (except fatal familial insomnia) than somebody who has either two valines or two methionines? We do not know.

Why is the disease so picky? Mice cannot easily get hamster scrapie, nor vice versa. But a mouse deliberately equipped with a hamster prion gene will catch hamster scrapie from an injection of hamster brains. A mouse equipped with two different versions of human prion genes can catch two kinds of human disease, one like fatal familial insomnia and one like C J D . A mouse equipped with 2 8 0 G E N O M E

both human and mouse prion genes will be slower to get human C J D than a mouse with only a human prion gene: does this mean different prions compete? We do not know.

How does the gene change its strain as it moves through a new species? Mice cannnot easily catch hamster scrapie, but when they do, they pass it on with progressively greater ease to other mice.3

Why? We do not know.

Why does the disease spread from the site of injection slowly and progressively, as if bad prions can only convert good prions in their immediate vicinity? We know the disease moves through the B cells of the immune system, which somehow transmit it to the brain.4

But why them, and how? We do not know.

The truly baffling aspect of this proliferating knowledge of ignorance is that it strikes at the heart of an even more central genetic dogma than Francis Crick's. It undermines one of the messages I have been evangelising since the very first chapter of this book, that the core of biology is digital. Here, in the prion gene, we have respectable digital changes, substituting one word for another, yet causing changes that cannot be wholly predicted without other knowledge. The prion system is analogue, not digital. It is a change not of sequence but of shape and it depends on dose, location and whether the wind is in the west. That is not to say it lacks determinism. If anything, C J D is even more precise than Huntington's disease in the age at which it strikes. The record includes cases of siblings who caught it at exactly the same age despite living apart all their lives.

Prion diseases are caused by a sort of chain reaction in which one prion converts its neighbour to its own shape and they each then convert another, and so on, exponentially. It is just like the fateful image that Leo Szilard conjured in his brain one day in 1933, while waiting to cross a street in London: the image of an atom splitting and emitting two neutrons, which caused another atom to split and emit two neutrons, and so on — the image of the chain reaction that later exploded over Hiroshima. The prion chain reaction is of course much slower than the neutron one. But it is just P O L I T I C S 2 8 1

as capable of exponential explosion; the New Guinea kuru epidemic stood as proof of this possibility even as Prusiner began to tease out the details in the early 1980s. Yet already, much closer to home an even bigger epidemic of prion disease was just starting its chain reaction. This time the victims were cows.

Nobody knows exactly when, where or how — that damned mystery again — but at some time in the late 1970s or early 1980s the British manufacturers of processed cattle food began to incorporate misshapen prions into their product. It might have been because a change in the processes in rendering factories followed a fall in the price of tallow. It might have been because rising numbers of old sheep found their way into the factories thanks to generous lamb subsidies. Whichever was the cause, the wrong-shaped prions got into the system: all it took was one highly infectious animal, riddled with scrapified prions, rendered into cattle cake. No matter that the bones and offal from old cows and sheep were boiled to sterility as they were rendered into protein-rich supplements for dairy cattle.

Scrapified prions can survive boiling.

The chances of giving a cow prion disease would still have been very small, but with hundreds of thousands of cows it was enough.

As soon as the first cases of 'mad-cow disease' went back into the food chain to be made into feed for other cows, the chain reaction had begun. More and more prions came through into the cattle cake, giving larger and larger doses to new calves. The long incubation period meant that doomed animals took five years on average to show symptoms. When the first six cases were recognised as something unusual by the end of 1986, there were already roughly 50,000 doomed animals in Britain, though nobody could possibly have known it. Eventually about 180,000 cattle died of bovine spongiform encephalopathy (BSE) before the disease was almost eradicated in the late 1990s.

Within a year of the first reported case, skilful detective work by government vets had pinned down the source of the problem as contaminated feed. It was the only theory that fitted all the details and it accounted for strange anomalies such as the fact that the 2 8 2 G E N O M E

island of Guernsey had an epidemic long before Jersey: the two islands had two different feed suppliers, one of which used much meat and bonemeal, while the other used little. By July 1988 the Ruminant Feed Ban was law. It is hard to see how experts or ministers could have acted more quickly, except with perfect hindsight. By August 1988, the Southwood committee's recommendation that all BSE-infected cattle be destroyed and not allowed to enter the food chain had been enacted. This was when the first blunder was made: the decision to pay only fifty per cent of each animal's value in compensation, thus providing an incentive to farmers to ignore signs of the disease. But even this mistake may not have been as costly as people assume: when compensation was increased, there was no jump in the number of cases notified.

The Specified Bovine Offals Ban, preventing adult cows' brains from entering the human food chain, came into force a year later, and was only extended to calves in 1990. This might have happened sooner, but, given what was known about the difficulty other species had of catching sheep scrapie except by direct injection of brain into brain, at the time it seemed too cautious. It had proved impossible to infect monkeys with human prion diseases through their food, except by using huge doses: and the jump from cow to person is a much bigger jump than from person to monkey. (It has been estimated that intracerebral injection magnifies the risk 100 million times compared with ingestion.) To say anything other than that beef was 'safe'

to eat at this stage would have been the height of irresponsibility.

As far as scientists were concerned, the risk of cross-species transmission by the oral route was indeed vanishingly small: so small that it would be impossible to achieve a single case in an experiment without hundreds of thousands of experimental animals. But that was the point: the experiment was being conducted with fifty million experimental animals called Britons. In such a large sample, a few cases were inevitable. For the politician, safety was an absolute, not a relative matter. They did not want few human cases; they wanted no human cases. Besides, B S E , like every prion disease before it, was proving alarmingly good at springing surprises. Cats were catching it P O L I T I C S 2 8 3

from the same meat and bonemeal that cattle ate - more than seventy domestic cats, plus three cheetahs, a puma, an ocelot and even a tiger have since died of B S E . But no case of dog B S E has yet appeared. Were people going to be as resistant as dogs or as susceptible as cats?

By 1992, the cattle problem was effectively solved, although the peak of the epidemic was still to come because of the five-year lag between infection and symptoms. Very few cattle born since 1992

have caught or will catch B S E . Yet the human hysteria was only just beginning. It was now that the decisions taken by politicians started to grow steadily more lunatic. Thanks to the offals ban, beef was now safer to eat than at any time in ten years, yet it was only now that people began to boycott it.

In March 1996, the government announced that ten people had indeed died of a form of prion disease that looked suspiciously as if it had been transmitted from beef during the dangerous period: it resembled B S E in some symptoms and it had never been seen before. Public alarm, fanned by a willing press, became — briefly —

extreme. Wild predictions of millions of deaths in Britain alone were taken seriously. The folly of turning cattle into cannibals was widely portrayed as an argument for organic farming. Conspiracy theories abounded: that the disease was caused by pesticides; that scientists were being muzzled by politicians; that the true facts were being suppressed; that deregulation of the feed industry had caused the problem; that France, Ireland, Germany and other countries were suppressing news of epidemics just as large.

The government felt obliged to respond with a further useless ban, on the consumption of any cow over thirty months of age: a ban that further inflamed public alarm, ruined a whole industry and choked the system with doomed cattle. Later that year, at the insistence of European politicians, the government ordered the 'selective cull' of 100,000 more cattle, even though it knew this was a meaningless gesture that would further alienate farmers and consumers. It was no longer even shutting the stable door after the horse had bolted; it was sacrificing a goat outside the stable. Predictably, the 2 8 4 G E N O M E

new cull did not even have the effect of lifting the European Union's largely self-interested ban on all British beef exports. But worse was to follow with the ban on beef on the bone in 1997. Everybody agreed that the risk from beef on the bone was infinitesimal - likely to lead to at most one case of C J D every four years. The government's approach to risk was now so nationalising that the agriculture minister was not even prepared to let people make up their own minds about a risk smaller than that of being struck by lightning.

By taking such an absurd attitude to risk, indeed, the government predictably provoked riskier behaviour in its subjects. In some circles, almost a mood of civil disobedience obtained, and I found myself offered more oxtail stew as the ban loomed than I had ever done before.

Throughout 1996, Britain braced itself for an epidemic of human B S E . Yet in the year from March only six people died of the disease.

Far from growing, the numbers seemed to be steady or falling. As I write, it is still uncertain how many people will die of 'new-variant'

C J D . The figure has inched up past forty, each case an almost unimaginable family tragedy, but not yet an epidemic. At first, the victims of this new-variant C J D appeared, on investigation, to be particularly enthusiastic meat-eaters in the dangerous years, even though one of the first cases had turned vegetarian some years before. But this was an illusion: when scientists asked the relatives of those thought to have died of C J D (but who, post mortem, were proved to have died of something else) about their habits, they found the same meat-eating bias: the memories said more about the psychology of the relatives than reality.

The one thing the victims had in common was that almost all were of one genotype-homozygous for methionine at 'word' 129.

Perhaps the far more numerous heterozygotes and valine¬

homozygotes will prove simply to have a longer incubation period: B S E transmitted to monkeys by intracerebral injection has a much longer incubation period than most prion diseases. On the other hand, given that the vast majority of human infections from beef would have occurred before the end of 1988, and ten years is already P O L I T I C S 2 8 5

twice as long as the average incubation period in cattle, maybe the species barrier is as high as it seems in animal experiments and we have already seen the worst of the epidemic. Maybe, too, the new-variant C J D has nothing to do with beef-eating. Many now believe that the possibility that human vaccines and other medical products, made with beef products, posed a much greater danger was somewhat too hastily rejected by the authorities in the late 1980s.

C J D has killed lifelong vegetarians who had never had surgery, never left Britain and never worked on a farm or in a butcher's shop. The last and greatest mystery of the prion is that even today

- when forms of C J D have been caught by all sorts of known means, including cannibalism, surgery, hormone injections and possibly beef-eating - eighty-five per cent of all C J D cases are 'sporadic', meaning that they cannot at the moment be explained by anything other than random chance. This offends our natural determinism, in which diseases must have causes, but we do not live in a fully determined world. Perhaps C J D just happens spontaneously at the rate of about one case per million people.

Prions have humbled us with our ignorance. We did not suspect that there was a form of self-replication that did not use D N A -

did not indeed use digital information at all. We did not imagine that a disease of such profound mystery could emerge from such unlikely quarters and prove so deadly. We still do not quite see how changes in the folding of a peptide chain can cause such havoc, or how tiny changes in the composition of the chain can have such complicated implications. As two prion experts have written, 'Personal and family tragedies, ethnological catastrophes and economic disasters can all be traced back to the mischievous misfolding of one small molecule.'

C H R O M O S O M E 2 1

E u g e n i c s

I know no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise that control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion. Thomas Jefferson Chromosome 21 is the smallest human chromosome. It ought, as a result, to be called chromosome 22, but the chromosome that has that name was until recently thought to be smaller still and the name is now established. Perhaps because it is the smallest chromosome, with probably the fewest genes, chromosome 21 is the only chromosome that can be present in three copies rather than two in a healthy human body. In all other cases, having an extra copy of a whole chromosome so upsets the balance of the human genome that the body cannot properly develop at all. Children are occasionally born with an extra chromosome 13 or 18, but they never survive more than a few days. Children born with an extra chromosome 21 are healthy, conspicuously happy and destined to live for many years.

But they are not considered, in that pejorative word, 'normal'. They E U G E N I C S 287

have Down syndrome. Their characteristic appearance — short stature, plump bodies, narrow eyes, happy faces - is immediately familiar. So is the fact that they are mentally retarded, gentle and destined to age rapidly, often developing a form of Alzheimer's disease, and die before they reach the age of forty.

Down-syndrome babies are generally born to older mothers. The probability of having a Down-syndrome baby grows rapidly and exponentially as the age of the mother increases, from 1 in 2,300 at the age of twenty to 1 in 100 at forty. It is for this reason alone that Down embryos are the principal victims, or their mothers the principal users, of genetic screening. In most countries amniocentesis is now offered to - perhaps even imposed on - all older mothers, to check whether the foetus carries an extra chromosome. If it does, the mother is offered - or cajoled into - an abortion. The reason given is that, despite the happy demeanour of these children, most people would rather not be the parent of a Down child. If you are of one opinion, you see this as a manifestation of benign science, miraculously preventing the birth of cruelly incapacitated people at no suffering. If you are of another opinion you see the officially encouraged murder of a sacred human life in the dubious name of human perfection and to the disrespect of disability. You see, in effect, eugenics still in action, more than fifty years after it was grotesquely discredited by Nazi atrocities.

This chapter is about the dark side of genetics' past, the black sheep of the genetics family - the murder, sterilisation and abortion committed in the name of genetic purity.

The father of eugenics, Francis Galton, was in many ways the opposite of his first cousin, Charles Darwin. Where Darwin was methodical, patient, shy and conventional, Galton was an intellectual dilettante, a psychosexual mess and showman. He was also brilliant.

He explored southern Africa, studied twins, collected statistics and dreamed of Utopias. Today his fame is almost as great as his cousin's, though it is something more like notoriety than fame. Darwinism was always in danger of being turned into a political creed and Galton did so. The philosopher Herbert Spencer had enthusiastically 288 G E N O M E

embraced the idea of survival of the fittest, arguing that it buttressed the credibility of laissez-faire economics and justified the individualism of Victorian society: social darwinism, he called it. Galton's vision was more prosaic. If, as Darwin had argued, species had been altered by systematic selective breeding, like cattle and racing pigeons, then so could human beings be bred to improve the race.

In a sense Galton appealed to an older tradition than Darwinism: the eighteenth-century tradition of cattle breeding and the even older breeding of apple and corn varieties. His cry was: let us improve the stock of our own species as we have improved that of others.

Let us breed from the best and not from the worst specimens of humanity. In 1885 he coined the term 'eugenic' for such breeding.

But who was 'us'? In a Spencerian world of individualism, it was literally each one of us: eugenics meant that each individual strove to pick a good mate - somebody with a good mind and a healthy body. It was little more than being selective about our marriage partners — which we already were. In the Galtonian world, though,

'us' came to mean something more collective. Galton's first and most influential follower was Karl Pearson, a radical socialist Utopian and a brilliant statistician. Fascinated and frightened by the growing economic power of Germany, Pearson turned eugenics into a strand of jingoism. It was not the individual that must be eugenic; it was the nation. Only by selectively breeding among its citizens would Britain stay ahead of its continental rival. The state must have a say in who should breed and who should not. At its birth eugenics was not a politicised science; it was a science-ised political creed.

By 1900, eugenics had caught the popular imagination. The name Eugene was suddenly in vogue and there was a groundswell of popular fascination with the idea of planned breeding, as eugenics meetings popped up all over Britain. Pearson wrote to Galton in 1907: 'I hear most respectable middle-class matrons saying, if children are weakly, "Ah, but that was not a eugenic marriage!"' The poor condition of Boer War recruits to the army stimulated as much debate about better breeding as it did about better welfare.

Something similar was happening in Germany, where a mixture E U G E N I C S 2 8 9

of Friedrich Nietzsche's philosophy of the hero and Ernst Haeckel's doctrine of biological destiny produced an enthusiasm for evolutionary progress to go with economic and social progress. The easy gravitation to an authoritarian philosophy meant that in Germany, even more than in Britain, biology became enmeshed in nationalism.

But for the moment it remained largely ideological, not practical.1

So far, so benign. The focus soon shifted, however, from encouraging the 'eugenic' breeding of the best to halting the 'dysgenic'

breeding of the worst. And the 'worst' soon came to mean mainly the 'feeble-minded', which included alcoholics, epileptics and criminals as well as the mentally retarded. This was especially true in the United States, where in 1904 Charles Davenport, an admirer of Galton and Pearson, persuaded Andrew Carnegie to found for him the Cold Spring Harbor Laboratory to study eugenics. Davenport, a strait-laced conservative with immense energy, was more concerned with preventing dysgenic breeding than urging eugenic breeding. His science was simplistic to say the least; for example, he said that now that Mendelism had proved the particulate nature of inheritance, the American idea of a national 'melting pot' could be consigned to the past; he also suggested that a naval family had a gene for thalassophilia, or love of the sea. But in politics, Davenport was skilled and influential. Helped along by a successful book by Henry Goddard about a largely mythical, mentally deficient family called the Kallikaks, in which the case was strongly made that feeble-mindedness was inherited, Davenport and his allies gradually persuaded American political opinion that the race was in desperate danger of degeneracy. Said Theodore Roosevelt: 'Some day we will realise that the prime duty, the inescapable duty, of the good citizen of the right type is to leave his or her blood behind him in the world.' Wrong types need not apply.2

Much of the American enthusiasm for eugenics stemmed from anti-immigrant feeling. At a time of rapid immigration from eastern and southern Europe, it was easy to whip up paranoia that the

'better' Anglo-Saxon stock of the country was being diluted. Eugenic arguments provided a convenient cover for those who wished to 2 9 0 G E N O M E

restrict immigration for more traditional, racist reasons. The Immigration Restriction Act of 1924 was a direct result of eugenic campaigning. For the next twenty years it consigned many desperate European emigrants to a worse fate at home by denying them a new home in the United States, and it remained on the books unamended for forty years.

Restricting immigration was not the only legal success for the eugenists. By 1911 six states already had laws on their books to allow the forced sterilisation of the mentally unfit. Six years later another nine states had joined them. If the state could take the life of a criminal, so went the argument, then surely it could deny the right to reproduce (as if mental innocence were on a par with criminal guilt). 'It is the acme of stupidity . . . to talk in such cases of individual liberty, or the rights of the individual. Such individuals

. . . have no right to propagate their kind.' So wrote an American doctor named W. J. Robinson.

The Supreme Court threw out many sterilisation laws at first, but in 1927 it changed its line. In Buck v. Bell, the court ruled that the commonwealth of Virginia could sterilise Carrie Buck, a seventeen-year-old girl committed to a colony for epileptics and the feeble minded in Lynchburg, where she lived with her mother Emma and her daughter Vivian. After a cursory examination, Vivian, who was seven months old (!), was declared an imbecile and Carrie was ordered to be sterilised. As Justice Oliver Wendell Holmes famously put it in his judgment, 'Three generations of imbeciles are enough.'

Vivian died young, but Carrie survived into old age, a respectable woman of moderate intelligence who did crossword puzzles in her spare time. Her sister Doris, also sterilised, tried for many years to have babies before realising what had been done to her without her consent. Virginia continued to sterilise the mentally handicapped into the 1970s. America, bastion of individual liberty, sterilised more than 100,000 people for feeble-mindedness, under more than 30

state and federal laws passed between 1910 and 1935.

But although America was the pioneer, other countries followed.

Sweden sterilised 60,000. Canada, Norway, Finland, Estonia and E U G E N I C S 2 9 1

Iceland all put coercive sterilisation laws on their books and used them. Germany, most notoriously, first sterilised 400,000 people and then murdered many of them. In just eighteen months in the Second World War, 70,000 already-sterilised German psychiatric patients were gassed just to free hospital beds for wounded soldiers.

But Britain, almost alone among Protestant industrial countries, never passed a eugenic law: that is, it never passed a law allowing the government to interfere in the individual's right to breed. In particular, there was never a British law preventing marriage of the mentally deficient, and there was never a British law allowing compulsory sterilisation by the state on the grounds of feeble-mindedness. (This is not to deny that there has been individual

'freelance' practice of cajoled sterilisation by doctors or hospitals.) Britain was not unique; in countries where the influence of the Roman Catholic church was strong, there were no eugenic laws.

The Netherlands avoided passing such laws. The Soviet Union, more concerned about purging and killing clever people than dull ones, never put such a law on its books. But Britain stands out, because it was the source of much — indeed most — eugenic science and propaganda in the first forty years of the twentieth century. Rather than ask how so many countries could have followed such cruel practices, it is instructive to turn the question on its head: why did Britain resist the temptation? Who deserves the credit?

Not the scientists. Scientists like to tell themselves today that eugenics was always seen as a 'pseudoscience' and frowned on by true scientists, especially after the rediscovery of Mendelism (which reveals how many more silent carriers of mutations there are than frank mutants), but there is little in the written record to support this. Most scientists welcomed the flattery of being treated as experts in a new technocracy. They were perpetually urging immediate action by government. (In Germany, more than half of all academic biologists joined the Nazi party - a higher proportion than in any other professional group - and not one criticised eugenics. ) A case in point is Sir Ronald Fisher, yet another founder of modern statistics (although Galton, Pearson and Fisher were great 2 9 2 G E N O M E

statisticians, nobody has concluded that statistics is as dangerous as genetics). Fisher was a true Mendelian, but he was also vice president of the Eugenics Society. He was obsessed with what he called 'the redistribution of the incidence of reproduction' from the upper classes to the poor: the fact that poor people had more children than rich people. Even later critics of eugenics like Julian Huxley and J. B. S. Haldane were supporters before 1920; it was the crudity and bias with which eugenic policies came to be adopted in the United States that they complained about, not the principle.

Nor could the socialists claim credit for stopping eugenics.

Although the Labour party opposed eugenics by the 1930s, the socialist movement in general provided much of the intellectual ammunition for eugenics before that. You have to dig hard to find a prominent British socialist in the first thirty years of the century who expressed even faint opposition to eugenic policies. It is extra-ordinarily easy to find pro-eugenic quotes from Fabians of the day.

H. G. Wells, J. M. Keynes, George Bernard Shaw, Havelock Ellis, Harold Laski, Sidney and Beatrice Webb - all said creepy things about the urgent need to stop stupid or disabled people from breeding. A character in Shaw's Man and superman says: 'Being cowards, we defeat natural selection under cover of philanthropy: being slug-gards, we neglect artificial selection under cover of delicacy and morality.'

The works of H. G. Wells are especially rich in juicy quotes: 'The children people bring into the world can be no more their private concern entirely than the disease germs they disseminate or the noises a man makes in a thin-floored flat.' Or 'The swarms of black, and brown, and dirty white, and yellow people . . . will have to go.'

Or 'It has become apparent that whole masses of human population are, as a whole, inferior in their claim upon the future . . . to give them equality is to sink to their level, to protect and cherish them is to be swamped in their fecundity.' He added, reassuringly, 'All such killing will be done with an opiate.' (It wasn't.)4

Socialists, with their belief in planning and their readiness to put the state in a position of power over the individual, were ready-made E U G E N I C S 293

for the eugenic message. Breeding, too, was ripe for nationalisation.

It was among Pearson's friends in the Fabian Society that eugenics first took root as a popular theme. Eugenics was grist to the mill of their socialism. Eugenics was a progressive philosophy, and called for a role for the state.

Soon the Conservatives and Liberals were just as enthusiastic.

Arthur Balfour, ex-prime minister, chaired the first International Eugenics Conference in London in 1912 and the sponsoring vice-presidents included the Lord Chief Justice and Winston Churchill.

The Oxford Union approved the principles of eugenics by nearly two to one in 1911. As Churchill put it, 'the multiplication of the feeble-minded' was 'a very terrible danger to the race'.

To be sure, there were a few lone voices of dissent. One or two intellectuals remained suspicious, among them Hilaire Belloc and G. K. Chesterton, who wrote that 'eugenicists had discovered how to combine hardening of the heart with softening of the head'. But be in no doubt that most Britons were in favour of eugenic laws.

There were two moments when Britain very nearly did pass eugenic laws: in 1913 and 1934. In the first case, the attempt was thwarted by brave and often lonely opponents swimming against the tide of conventional wisdom. In 1904 the government set up a Royal Commission under the Earl of Radnor on the 'care and control of the feeble-minded'. When it reported in 1908, it took a strongly hereditarian view of mental deficiency, which was not surprising given that many of its members were paid-up eugenists. As Gerry Anderson has demonstrated in a recent Cambridge thesis,5 there followed a period of sustained lobbying by pressure groups to try to persuade the government to act. The Home Office received hundreds of resolutions from county and borough councils and from education committees, urging the passage of a bill that would restrict reproduction by the 'unfit'. The new Eugenics Education Society bombarded M P s and had meetings with the Home Secretary to further the cause.

For a while nothing happened. The Home Secretary, Herbert Gladstone, was unsympathetic. But when he was replaced by 2 9 4 G E N O M E

Winston Churchill in 1910, eugenics at last had an ardent champion at the cabinet table. Churchill had already in 1909 circulated as a cabinet paper a pro-eugenics speech by Alfred Tredgold. In December 1910, installed in the Home Office, Churchill wrote to the Prime Minister, Herbert Asquith, advocating urgent eugenic legislation and concluding: 'I feel that the source from which the stream of madness is fed should be cut off and sealed up before another year has passed.'

He wanted for mental patients that their 'curse would die with them'.

In case there is any doubt of what he meant, Wilfrid Scawen Blunt wrote that Churchill was already privately advocating the use of X-rays and operations to sterilise the mentally unfit.

The constitutional crises of 1910 and 1911 prevented Churchill introducing a bill and he moved on to the Admiralty. But by 1912

the clamour for legislation had revived and a Tory backbencher, Gershom Stewart, eventually forced the government's hand by introducing his own private member's bill on the matter. In 1912 the new Home Secretary, Reginald McKenna, somewhat reluctantly brought in a government bill, the Mental Deficiency Bill. The bill would restrict procreation by feebled-minded people and would punish those who married mental defectives. It was an open secret that it could be amended to allow compulsory sterilisation as soon as practicable.

One man deserves to be singled out for mounting opposition to this bill: a radical libertarian MP with the famous - indeed relevant

- name of Josiah Wedgwood. Scion of the famous industrial family that had repeatedly intermarried with the Darwin family — Charles Darwin had a grandfather, a father-in-law and a brother-in-law (twice over) each called Josiah Wedgwood — the latest Josiah was a naval architect by profession. He had been elected to Parliament in the Liberal landslide of 1906, but later joined the Labour party and retired to the House of Lords in 1942. (Darwin's son, Leonard, was at the time president of the Eugenics Society.) Wedgwood disliked eugenics intensely. He charged that the Eugenics Society was trying 'to breed up the working class as though they were cattle' and he asserted that the laws of heredity were 'too E U G E N I C S 295

undetermined for one to pin faith on any doctrine, much less to legislate according to it'. But his main objection was on the grounds of individual liberty. He was appalled at a bill that gave the state powers to take a child from its own home by force, by clauses that granted policemen the duty to act upon reports from members of the public that somebody was 'feeble-minded'. His motive was not social justice, but individual liberty: he was joined by Tory libertarians such as Lord Robert Cecil. Their common cause was that of the individual against the state.

The clause that really stuck in Wedgwood's throat was the one that stated it to be 'desirable in the interests of the community that [the feeble-minded] should be deprived of the opportunity of procreating children.' This was, in Wedgwood's words, 'the most abominable thing ever suggested' and not 'the care for the liberty of the subject and for the protection of the individual against the state that we have a right to expect from a Liberal Administration'.6

Wedgwood's attack was so effective that the government withdrew the bill and presented it again the next year in much watered-down form. Crucially, it now omitted 'any reference to what might be regarded as the eugenic idea' (in McKenna's words), and the offensive clauses regulating marriage and preventing procreation were dropped. Wedgwood still opposed the bill and for two whole nights, fuelled by bars of chocolate, he sustained his attack by tabling more than 200 amendments. But when his support had dwindled to four members, he gave up and the bill passed into law.

Wedgwood probably thought he had failed. The forcible committal of mental patients became a feature of British life and this in practice did make it harder for them to breed. But in truth he had not only prevented eugenic measures being adopted; he had also sent a warning shot across the bows of any future government that eugenic legislation could be contentious. And he had identified the central flaw in the whole eugenic project. This was not that it was based on faulty science, nor that it was impractical, but that it was fundamentally oppressive and cruel, because it required the full power of the state to be asserted over the rights of the individual.

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In the early 1930s, as unemployment rose during the depression, eugenics experienced a marked revival. In Britain the membership of eugenic societies reached record levels, as people began, absurdly, to blame high unemployment and poverty on the very racial degeneration that had been predicted by the first eugenists. It was now that most countries passed their eugenic laws. Sweden, for instance, imple-mented its compulsory sterilisation law in 1934, as did Germany.

Pressure for a British sterilisation law had again been building for some years, aided by a government report on mental deficiency known as the Wood report, which concluded that mental problems were on the increase and that this was partly due to the high fertility of mental defectives (this was the committee which carefully defined three categories of mental defectives: idiots, imbeciles and the feeble-minded). But when a private member's eugenics bill, introduced to the House of Commons by a Labour M P , was blocked, the eugenics pressure group changed tack and turned its attention to the civil service. The Department of Health was persuaded to appoint a committee under Sir Laurence Brock to examine the case for sterilis-ing the mentally unfit.

The Brock committee, despite its bureaucratic origins, was parti-san from the outset. Most of its members were, according to a modern historian, 'not even in a weak sense actuated by a desire to consider dispassionately the contradictory and inconclusive evidence'. The committee accepted a hereditarian view of mental deficiency, ignoring the evidence against this and 'padding' (its word) the evidence in favour. It accepted the notion of a fast-breeding mental underclass, despite inconclusive evidence, and it 'rejected'

compulsory sterilisation only to help assuage critics - it glossed over the problem of obtaining consent from mentally defective people.

A quotation from a popular book about biology published in 1931

gives the game away: 'Many of these low types might be bribed or otherwise persuaded to accept voluntary sterilization.'7

The Brock report was the purest propaganda, dressed up as a dispassionate and expert assessment of the issues. As has been pointed out recently, in the way it created a synthetic crisis, endorsed E U G E N I C S 297

by a consensus of 'experts' and requiring urgent action, it was a harbinger of the way international civil servants would behave much later in the century over global warming.8

The report was intended to lead to a sterilisation bill, but such a bill never saw the light of day. This time it was not so much because of a determined contrarian like Wedgwood, but because of a changing climate of opinion throughout society. Many scientists had changed their minds, notably J. B. S. Haldane, partly because of the growing influence of environmental explanations of human nature promulgated by people like Margaret Mead and the behaviourists in psychology. The Labour party was now firmly against eugenics, which it saw as a form of class war on the working class. The opposition of the Catholic Church was also influential in some quarters.9

Surprisingly, it was not until 1938 that reports filtered through from Germany of what compulsory sterilisation meant in practice.

The Brock committee had been unwise enough to praise the Nazi sterilisation law, which came into force in January 1934. It was now clear that this law was an intolerable infringement of personal liberty and an excuse for persecution. In Britain, good sense prevailed.10

This brief history of eugenics leads me to one firm conclusion.

What is wrong with eugenics is not the science, but the coercion.

Eugenics is like any other programme that puts the social benefit before the individual's rights. It is a humanitarian, not a scientific crime. There is little doubt that eugenic breeding would 'work' for human beings just as it works for dogs and dairy cattle. It would be possible to reduce the incidence of many mental disorders and improve the health of the population by selective breeding. But there is also little doubt that it could only be done very slowly at a gigantic cost in cruelty, injustice and oppression. Karl Pearson once said, in answer to Wedgwood: 'What is social is right, and there is no definition of right beyond that.' That dreadful statement should be the epitaph of eugenics.

Yet, as we read in our newspapers of genes for intelligence, of germline gene therapy, of prenatal diagnosis and screening, we can-298 G E N O M E

not but feel in our bones that eugenics is not dead. As I argued in the chapter on chromosome 6, Galton's conviction that much of human nature has a hereditary element is back in fashion, this time with better — though not conclusive — empirical evidence. Increasingly, today, genetic screening allows parents to choose the genes of their children. The philosopher Philip Kitcher, for instance, calls genetic screening 'laissez-faire eugenics': 'Everyone is to be his (or her) own eugenicist, taking advantage of the available genetic tests to make the reproductive decisions she (he) thinks correct.'11

By this standard, eugenics happens every day in hospitals all over the world and by far its most common victims are embryos equipped with an extra chromosome 21, who would otherwise be born with Down syndrome. In most cases, had they been born, they would have led short, but largely happy lives — that is the nature of their disposition. In most cases, had they been born, they would have been loved by parents and siblings. But for a dependent, non-sentient embryo, not being born is not necessarily the same as being killed.

We are back, in short order, to the debate on abortion and whether the mother has the right to abort a child, or the state the right to stop her: an old debate. Genetic knowledge gives her more reasons for wanting an abortion. The possibility of choosing among embryos for special ability, rather than against lack of ability, may not be too far away. Choosing boys and aborting girls is already a rampant abuse of amniocentesis in the Indian subcontinent in particular.

Have we rejected government eugenics merely to fall into the trap of allowing private eugenics? Parents may come under all sorts of pressures to adopt voluntary eugenics, from doctors, from health-insurance companies and from the culture at large. Stories abound of women as late as the 1970s being cajoled by their doctors into sterilisation because they carried a gene for a genetic disease. Yet if government were to ban genetic screening on the grounds that it might be abused, it would risk increasing the load of suffering in the world: it would be just as cruel to outlaw screening as to make it compulsory. It is an individual decision, not one that can be left to technocrats. Kitcher certainly thinks so: 'As for the traits that E U G E N I C S 2 9 9

people attempt to promote or avoid, that is surely their own business.' So does James Watson: 'These things should be kept away from people who think they know b e s t . . . I am trying to see genetic decisions put in the hand of users, which governments aren't.'12

Although there are still a few fringe scientists worried about the genetic deterioration of races and populations,13 most scientists now recognise that the well-being of individuals should take priority over that of groups. There is a world of difference between genetic screening and what the eugenists wanted in their heyday — and it lies in this: genetic screening is about giving private individuals private choices on private criteria. Eugenics was about nationalising that decision to make people breed not for themselves but for the state. It is a distinction frequently overlooked in the rush to define what 'we' must allow in the new genetic world. Who is 'we'? We as individuals, or we as the collective interest of the state or the race?

Compare two modern examples of 'eugenics' as actually practised today. In the United States, as I discussed in the chapter on chromosome 13, the Committee for the Prevention of Jewish Genetic Disease tests schoolchildren's blood and advises against later marriages in which both parties carry the same disease-causing version of a particular gene. This is an entirely voluntary policy. Although it has been criticised as eugenic, there is no coercion involved at all.14

The other example comes from China, where the government continues to sterilise and abort on eugenic grounds. Chen Mingzhang, minister of public health, recently expostulated that births of inferior quality are serious among 'the old revolutionary base, ethnic minorities, the frontier, and economically poor areas'. The Maternal and Infant Health Care Law, which came into effect only in 1994, makes premarital check-ups compulsory and gives to doctors, not parents, the decision to abort a child. Nearly ninety per cent of Chinese geneticists approve of this compared with five per cent of American geneticists; by contrast eighty-five per cent of the American geneticists think an abortion decision should be made by the woman, compared with forty-four per cent of the Chinese. As 3 0 0 G E N O M E

Xin Mao, who conducted the Chinese part of this poll, put it, echoing Karl Pearson: 'The Chinese culture is quite different, and things are focused on the good of society, not the good of the individual.'15

Many modern accounts of the history of eugenics present it as an example of the dangers of letting science, genetics especially, out of control. It is much more an example of the danger of letting government out of control.

C H R O M O S O M E 2 2

F r e e W i l l

Hume's fork: Either our actions are determined, in which case we are not responsible for them, or they are the result of random events, in which case we are not responsible for them.

Oxford Dictionary of Philosophy

As this book is being completed, a few months before the end of a millennium, there comes news of a momentous announcement. At the Sanger Centre, near Cambridge - the laboratory which leads the world in reading the human genome - the complete sequence of chromosome 22 is finished. All 15.5 million 'words' (or so - the exact length depends on the repeat sequences, which vary greatly) in the twenty-second chapter of the human autobiography have been read and written down in English letters: 47 million As, Cs, Gs and Ts.

Near the tip of the long arm of chromosome 22 there lies a massive and complicated gene, pregnant with significance, known as HFW. It has fourteen exons, which together spell out a text more than 6,000 letters long. That text is severely edited after transcription by the strange process of R N A splicing to produce a 3 0 2 G E N O M E

highly complicated protein that is expressed only in a small part of the prefrontal cortex of the brain. The function of the protein is, generalising horribly, to endow human beings with free will. Without HFW, we would have no free will.

The preceding paragraph is fictional. There is no HFW gene on chromosome 22 nor on any other. After twenty-two chapters of relentless truth, I just felt like deceiving you. I cracked under the strain of being a non-fiction writer and could no longer resist the temptation to make something up.

But who am 'I'? The I who, overcome by a silly impulse, decided to write a fictional paragraph? I am a biological creature put together by my genes. They prescribed my shape, gave me five fingers on each hand and thirty-two teeth in my mouth, laid down my capacity for language, and defined about half of my intellectual capacity.

When I remember something, it is they that do it for me, switching on the C R E B system to store the memory. They built me a brain and delegated responsibility for day-to-day duties to it. They also gave me the distinct impression that I am free to make up my own mind about how to behave. Simple introspection tells me there is nothing that I 'cannot help myself doing. There is equally nothing that says that I must do one thing and not something else. I am quite capable of jumping in my car and driving to Edinburgh right now and for no other reason than that I want to, or of making up a whole paragraph of fiction. I am a free agent, equipped with free will.

Where did this free will come from? It plainly could not have come from my genes, or else it would not be free will. The answer, according to many, is that it came from society, culture and nurture.

According to this reasoning, freedom equals the parts of our natures not determined by our genes, a sort of flower that blooms after our genes have done their tyrannical worst. We can rise above our genetic determinism and grasp that mystic flower, freedom.

There has been a long tradition among a certain kind of science writer to say that the world of biology is divided into people who believe in genetic determinism and people who believe in freedom.

Yet these same writers have rejected genetic determinism only by F R E E W I L L 3 0 3

establishing other forms of biological determinism in its place - the determinism of parental influence or social conditioning. It is odd that so many writers who defend human dignity against the tyranny of our genes seem happy to accept the tyranny of our surroundings.

I was once criticised in print for allegedly saying (which I had not) that all behaviour is genetically determined. The writer went on to give an example of how behaviour was not genetic: it was well known that child abusers were generally abused themselves as children and this was the cause of their later behaviour. It did not seem to occur to him that this was just as deterministic and a far more heartless and prejudicial condemnation of people who had suffered enough than anything I had said. He was arguing that the children of child abusers were likely to become child abusers and there was little they could do about it. It did not occur to him that he was applying a double standard: demanding rigorous proof for genetic explanations of behaviour while easily accepting social ones.

The crude distinction between genes as implacable programmers of a Calvinist predestination and the environment as the home of liberal free will is a fallacy. One of the most powerful environmental sculptors of character and ability is the sum of conditions in the womb, about which you can do nothing. As I argued in the chapter on chromosome 6, some of the genes for intellectual ability are probably genes for appetite rather than aptitude: they set their possessor on a course of willing learning. The same result can be achieved by an inspiring teacher. Nature, in other words, can be much more malleable than nurture.

Aldous Huxley's Brave new world, written at the height of eugenic enthusiasm in the 1920s, presents a terrifying world of uniform, coerced control in which there is no individuality. Each person meekly and willingly accepts his or her place in a caste system -

alphas to epsilons - and obediently does the tasks and enjoys the recreations that society expects of him or her. The very phrase brave new world' has come to mean such a dystopia brought into being by central control and advanced science working hand-in-hand.

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It therefore comes as something of a surprise to read the book and discover that there is virtually nothing about eugenics in it.

Alphas and epsilons are not bred, but are produced by chemical adjustment in artificial wombs followed by Pavlovian conditioning and brainwashing, then sustained in adulthood by opiate-like drugs.

In other words, this dystopia owes nothing to nature and everything to nurture. It is an environmental, not a genetic, hell. Everybody's fate is determined, but by their controlled environment, not their genes. It is indeed biological determinism, but not genetic determinism. Aldous Huxley's genius was to recognise how hellish a world in which nurture prevailed would actually be. Indeed, it is hard to tell whether the extreme genetic determinists who ruled Germany in the 1930s caused more suffering than the extreme environmental determinists who ruled Russia at the same time. All we can be sure of is that both extremes were horrible.

Fortunately we are spectacularly resistant to brainwashing. No matter how hard their parents or their politicians tell them that smoking is bad for them, young people still take it up. Indeed, it is precisely because grown-ups lecture them about it that it seems so appealing. We are genetically endowed with a tendency to be bloody-minded towards authority, especially in our teens, to guard our own innate character against dictators, teachers, abusing step-parents or government advertising campaigns.

Besides, we now know that virtually all the evidence purporting to show how parental influences shape our character is deeply flawed.

There is indeed a correlation between abusing children and having been abused as a child, but it can be entirely accounted for by inherited personality traits. The children of abusers inherit their persecutor's characteristics. Properly controlled for this effect, studies leave no room for nurture determinism at all. The step-children of abusers, for instance, do not become abusers.1

The same, remarkably, is true of virtually every standard social nostrum you have ever heard. Criminals rear criminals. Divorcees rear divorcers. Problem parents rear problem children. Obese parents rear obese children. Having subscribed to all of these F R E E W I L L 3 0 5

assertions during a long career of writing psychology textbooks, Judith Rich Harris suddenly began questioning them a few years ago. What she discovered appalled her. Because virtually no studies had controlled for heritability, there was no proof of causation at all in any study. Not even lip service was being paid to this omission: correlation was being routinely presented as causation. Yet in each case, from behaviour genetics studies, there was new, strong evidence against what Rich Harris calls 'the nurture assumption'. Studies of the divorce rate of twins, for example, reveal that genetics accounts for about half of the variation in divorce rate, non-shared environmental factors for another half and shared home environment for nothing at all.1 In other words, you are no more likely to divorce if reared in a broken home than the average - unless your biological parents divorced. Studies of criminal records of adoptees in Denmark revealed a strong correlation with the criminal record of the biological parent and a very small correlation with the criminal record of the adopting parent — and even that vanished when controlled for peer-group effects, whereby the adopting parents were found to live in more, or less, criminal neighbourhoods according to whether they themselves were criminals.

Indeed, it is now clear that children probably have more non-genetic effect on parents than vice versa. As I argued in the chapter on chromosomes X and Y, it used to be conventional wisdom that distant fathers and over-protective mothers turn sons gay. It is now considered much more likely to be the reverse: perceiving that a son is not fully interested in masculine concerns, the father retreats; the mother compensates by being overprotective. Likewise, it is true that autistic children often have cold mothers; but this is an effect, not a cause: the mother, exhausted and dispirited by years of unre-warding attempts to break through to an autistic child, eventually gives up trying.

Rich Harris has systematically demolished the dogma that has lain, unchallenged, beneath twentieth-century social science: the assumption that parents shape the personality and culture of their children.

In Sigmund Freud's psychology, John Watson's behaviourism and 3 0 6 G E N O M E

Margaret Mead's anthropology, nurture-determinism by parents was never tested, only assumed. Yet the evidence, from twin studies, from the children of immigrants and from adoption studies, is now staring us in the face: people get their personalities from their genes and from their peers, not from their parents.1

In the 1970s, after the publication of E . O . Wilson's book Sociobiology, there was a vigorous counter-attack against the idea of genetic influences on behaviour led by Wilson's Harvard colleagues, Richard Lewontin and Stephen Jay Gould. Their favourite slogan, used as a tide for one of Lewontin's books, was uncompromisingly dogmatic:

'Not in our genes!' It was at the time still just a plausible hypothesis to assert that genetic influences on behaviour were slight or non-existent. After twenty-five years of studies in behavioural genetics, that view is no longer tenable. Genes do influence behaviour.

Yet even after these discoveries, environment is still massively important - probably in total more important than genes in nearly all behaviours. But a remarkably small part in environmental influence is played by parental influence. This is not to deny that parents matter, or that children could do without them. Indeed, as Rich Harris observes, it is absurd to argue otherwise. Parents shape the home environment and a happy home environment is a good thing in its own right. You do not have to believe that happiness determines personality to agree that it is a good thing to have. But children do not seem to let the home environment influence their personality outside the home, nor to let it influence their personality in later life as an adult. Rich Harris makes the vital observation that we all keep the public and private zones of our lives separate and we do not necessarily take the lessons or the personality from one to the other. We easily 'code-switch' between them. Thus we acquire the language (in the case of immigrants) or accent of our peers, not our parents, for use in the rest of our lives. Culture is transmitted autonomously from each children's peer group to the next and not from parent to child - which is why, for example, the move towards greater adult sexual equality has had zero effect on willing sexual segregation in the playground. As every parent knows, children preF R E E W I L L 3 0 7

fer to imitate peers than parents. Psychology, like sociology and anthropology, has been dominated by those with a strong antipathy to genetic explanations; it can no longer sustain such ignorance.2

My point is not to rehearse the nature-nurture debate, which I explored in the chapter on chromosome 6, but to draw attention to the fact that even if the nurture assumption had proved true, it would not have reduced determinism one iota. As it is, by stressing the powerful influence that conformity to a peer group can have on personality, Rich Harris lays bare just how much more alarming social determinism is than genetic. It is brainwashing. Far from leaving room for free will, it rather diminishes it. A child who expresses her own (partly genetic) personality in defiance of her parents' or her siblings' pressures is at least obeying endogenous causality, not somebody else's.

So there is no escape from determinism by appealing to socialisa-tion. Either effects have causes or they do not. If I am timid because of something that happened to me when I was young, that event is no less deterministic than a gene for timidity. The greater mistake is not to equate determinism with genes, but to mistake determinism for inevitability. Said the three authors of Not in our genes, Steven Rose, Leon Kamin and Richard Lewontin, 'To the biological determinists the old credo "You can't change human nature" is the alpha and omega of the human condition.' But this equation - determinism equals fatalism — is so well understood to be a fallacy that it is hard to find the straw men that the three critics indict.3

The reason the equation of determinism with fatalism is a fallacy is as follows. Suppose you are ill, but you reason that there is no point in calling the doctor because either you will recover, or you won't: in either case, a doctor is superfluous. But this overlooks the possibility that your recovery or lack thereof could be caused by your calling the doctor, or failure to do so. It follows that determinism implies nothing about what you can or cannot do. Determinism looks backwards to the causes of the present state, not forward to the consequences.

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Yet the myth persists that genetic determinism is a more implacable kind of fate than social determinism. As James Watson has put it, 'We talk about gene therapy as if it can change someone's fate, but you can also change someone's fate if you pay off their credit card.' The whole point of genetic knowledge is to remedy genetic defects with (mostly non-genetic) interventions. Far from the discoveries of genetic mutations leading to fatalism, I have already cited many examples where they have led to redoubled efforts to ameliorate their effects. As I pointed out in the chapter on chromosome 6, when dyslexia was belatedly recognised as a real, and possibly genetic, condition, the response of parents, teachers and governments was not fatalistic. Nobody said that because it was a genetic condition dyslexia was therefore incurable and from now on children diagnosed with dyslexia would be allowed to remain illiterate. Quite the reverse happened: remedial education for dyslexics was developed, with impressive results. Likewise, as I argued in the chapter on chromosome 11, even psychotherapists have found genetic explanations of shyness helpful in curing it. By reassuring shy people that their shyness is innate and 'real', it somehow helps them overcome it.

Nor does it make sense to argue that biological determinism threatens the case for political freedom. As Sam Brittan has argued,

'the opposite of freedom is coercion, not determinism.'4 We cherish political freedom because it allows us freedom of personal self-determination, not the other way around. Though we pay lip service to our love of free will, when the chips are down we cling to determinism to save us. In February 1994 an American named Stephen Mobley was convicted of the murder of a pizza-shop manager, John Collins, and sentenced to death. Appealing to have the sentence reduced to life imprisonment, his lawyers offered a genetic defence. Mobley came, they said, from a long pedigree of crooks and criminals. He probably killed Collins because his genes made him do it. 'He' was not responsible; he was a genetically determined automaton.

Mobley was happy to surrender his illusion of free will; he wanted F R E E W I L L 3 0 9

it to be thought that he had none. So does every criminal who uses the defence of insanity or diminished responsibility. So does every jealous spouse who uses the defence of temporary insanity or justifiable rage after murdering an unfaithful partner. So does the unfaithful partner when justifying the infidelity. So does every tycoon who uses the excuse of Alzheimer's disease when accused of fraud against his shareholders. So indeed does a child in the playground who says that his friend made him do it. So does each one of us when we willingly go along with a subtle suggestion from the therapist that we should blame our parents for our present unhappiness. So does a politician who blames social conditions for the crime rate in an area. So does an economist when he asserts that consumers are utility maximisers. So does a biographer when he tries to explain how his subject's character was forged by formative experiences. So does everybody who consults a horoscope. In every case there is a willing, happy and grateful embracing of determinism. Far from loving free will, we seem to be a species that positively leaps to surrender it whenever we can.5

Full responsibility for one's actions is a necessary fiction without which the law would flounder, but it is a fiction all the same. To the extent that you act in character you are responsible for your actions; yet acting in character is merely expressing the many determinisms that caused your character. David Hume found himself impaled on this dilemma, subsequently named Hume's fork. Either our actions are determined, in which case we are not responsible for them, or they are random, in which case we are not responsible for them. In either case, common sense is outraged and society impossible to organise.

Christianity has wrestled with these issues for two millennia and theologians of other stripes for much longer. God, almost by definition, seems to deny free will or He would not be omnipotent. Yet Christianity in particular has striven to preserve a concept of free will because, without it, human beings cannot be held accountable for their actions. Without accountability, sin is a mockery and Hell a damnable injustice from a just God. The modern Christian consensus is that 3 1 0 G E N O M E

God has implanted free will in us, so that we have a choice of living virtuously or in sin.

Several prominent evolutionary biologists have recently argued that religious belief is an expression of a universal human instinct

— that there is in some sense a group of genes for believing in God or gods. (One neuroscientist even claims to have found a dedicated neural module in the temporal lobes of the brain that is bigger or more active in religious believers; hyper-religiosity is a feature of some types of temporal-lobe epilepsy.) A religious instinct may be no more than a by-product of an instinctive superstition to assume that all events, even thunderstorms, have wilful causes. Such a superstition could have been useful in the Stone Age. When a boulder rolls down the hill and nearly crushes you, it is less dangerous to subscribe to the conspiracy theory that it was pushed by somebody than to assume it was an accident. Our very language is larded with intentionality. I wrote earlier that my genes built me and delegated responsibility to my brain. My genes did nothing of the sort. It all just happened.

E. O. Wilson even argues, in his book Consilience,6 that morality is the codified expression of our instincts, and that what is right is indeed - despite the naturalistic fallacy — derived from what comes naturally. This leads to the paradoxical conclusion that belief in a god, being natural, is therefore correct. Yet Wilson himself was reared a devout Baptist and is now an agnostic, so he has rebelled against a deterministic instinct. Likewise, Steven Pinker, by remaining childless while subscribing to the theory of the selfish gene, has told his selfish genes to 'go jump in a lake'.

So even determinists can escape determinism. We have a paradox.

Unless our behaviour is random, then it is determined. If it is determined, then it is not free. And yet we feel, and demonstrably are, free. Charles Darwin described free will as a delusion caused by our inability to analyse our own motives. Modern Darwinists such as Robert Trivers have even argued that deceiving ourselves about such matters is itself an evolved adaptation. Pinker has called free will 'an idealisation of human beings that makes the ethics game F R E E W I L L 3 1 1

playable'. The writer Rita Carter calls it an illusion hard-wired into the mind. The philosopher Tony Ingram calls free will something that we assume other people have — we seem to have an inbuilt bias to ascribe free will to everybody and everything about us, from recalcitrant outboard motors to recalcitrant children equipped with our genes.7

I would like to think that we can get a little closer to resolving the paradox than that. Recall that, when discussing chromosome 10, I described how the stress response consists of genes at the whim of the social environment, not vice versa. If genes can affect behaviour and behaviour can affect genes, then the causality is circular. And in a system of circular feedbacks, hugely unpredictable results can follow from simple deterministic processes.

This kind of notion goes under the name of chaos theory. Much as I hate to admit it, the physicists have got there first. Pierre-Simon de LaPlace, the great French mathematician of the eighteenth century, once mused that if, as a good Newtonian, he could know the positions and the motions of every atom in the universe, he could predict the future. Or rather, he suspected that he could not know the future, but he wondered why not. It is fashionable to say that the answer lies at the subatomic level, where we now know that there are quantum-mechanical events that are only statistically predictable and the world is not made of Newtonian billiard balls. But that is not much help because Newtonian physics is actually a pretty good description of events at the scale at which we live and nobody seriously believes that we rely, for our free will, on the probabilistic scaffolding of Heisenberg's uncertainty principle. To put the reason bluntly: in deciding to write this chapter this afternoon, my brain did not play dice. To act randomly is not the same thing as to act freely — in fact, quite the reverse.8

Chaos theory provides a better answer to LaPlace. Unlike quantum physics, it does not rest on chance. Chaotic systems, as defined by mathematicians, are determined, not random. But the theory holds that even if you know all the determining factors in a system, you may not be able to predict the course it will take, because of the 3 1 2 G E N O M E

way different causes can interact with each other. Even simply determined systems can behave chaotically. They do so partly because of reflexivity, whereby one action affects the starting conditions of the next action, so small effects become larger causes. The trajectory of the stock market index, the future of the weather and the 'fractal geometry' of a coastline are all chaotic systems: in each case, the broad outline or course of events is predictable, but the precise details are not. We know it will be colder in winter than summer, but we cannot tell whether it will snow next Christmas Day.

Human behaviour shares these characteristics. Stress can alter the expression of genes, which can affect the response to stress and so on. Human behaviour is therefore unpredictable in the short term, but broadly predictable in the long term. Thus at any instant in the day, I can choose not to consume a meal. I am free not to eat. But over the course of the day it is almost a certainty that I will eat.

The timing of my meal may depend on many things — my hunger (partly dictated by my genes), the weather (chaotically determined by myriad external factors), or somebody else's decision to ask me out to lunch (he being a deterministic being over whom I have no control). This interaction of genetic and external influences makes my behaviour unpredictable, but not undetermined. In the gap between those words lies freedom.

We can never escape from determinism, but we can make a distinction between good determinisms and bad ones - free ones and unfree ones. Suppose that I am sitting in the laboratory of Shin Shimojo at the California Institute of Technology and he is at this very moment prodding with an electrode a part of my brain somewhere close to the anterior cingulate sulcus. Since the control of

'voluntary' movement is in this general area, he might be responsible for me making a movement that would, to me, have all the appearance of volition. Asked why I had moved my arm, I would almost certainly reply with conviction that it was a voluntary decision.

Professor Shimojo would know better (I hasten to add that this is still a thought experiment suggested to me by Shimojo, not a real one). It was not the fact that my movement was determined that F R E E W I L L 313

contradicted my illusion of freedom; it was the fact that it was determined from outside by somebody else.

The philosopher A. J. Ayer put it this way:9

If I suffered from a compulsive neurosis, so that I got up and walked across the room, whether I wanted to or not, or if I did so because somebody else compelled me, then I should not be acting freely. But if I do it now, I shall be acting freely, just because these conditions do not obtain; and the fact that my action may nevertheless have a cause is, from this point of view, irrelevant.

A psychologist of twins, Lyndon Eaves, has made a similar point:10

Freedom is the ability to stand up and transcend the limitations of the environment. That capacity is something that natural selection has placed in us, because it's adaptive . . . If you're going to be pushed around, would you rather be pushed around by your environment, which is not you, or by your genes, which in some sense is who you are.

Freedom lies in expressing your own determinism, not somebody else's. It is not the determinism that makes a difference, but the ownership. If freedom is what we prefer, then it is preferable to be determined by forces that originate in ourselves and not in others.

Part of our revulsion at cloning originates in the fear that what is uniquely ours could be shared by another. The single-minded obsession of the genes to do the determining in their own body is our strongest bulwark against loss of freedom to external causes. Do you begin to see why I facetiously flirted with the idea of a gene for free will? A gene for free will would not be such a paradox because it would locate the source of our behaviour inside us, where others cannot get at it. Of course, there is no single gene, but instead there is something infinitely more uplifting and magnificent: a whole human nature, flexibly preordained in our chromosomes and idio-syncratic to each of us. Everybody has a unique and different, endogenous nature. A self.

B I B L I O G R A P H Y A N D

N O T E S

The literature of genetics and molecular biology is gargantuan and out of date. As it is published, each book, article or scientific paper requires updat-ing or revising, so fast is new knowledge being minted (the same applies to my book). So many scientists are now working in the field that it is almost impossible even for many of them to keep up with each other's work. When writing this book, I found that frequent trips to the library and conversations with scientists were not enough. The new way to keep abreast was to surf the Net.

The best repository of genetic knowledge is found at Victor McCusick's incomparable website known as OMIM, for Online Mendelian Inheritance in Man. Found at http://www.ncbi.nlm.gov/omim/, it includes a separate essay with sources on every human gene that has been mapped or sequenced, and it is updated very regularly — an almost overwhelming task. The Weizmann Institute in Israel has another excellent website with 'gene-cards'

summarising what is known about each gene and links to other relevant websites: bioinformatics.weizmann.ac.il/cards.

But these websites give only summaries of knowledge and they are not for the faint-hearted: there is much jargon and assumed knowledge, which will defeat many amateurs. They also concentrate on the relevance of each gene for inherited disorders, thus compounding the problem that I have tried to combat in this book: the impression that the main function of genes is to cause diseases.

B I B L I O G R A P H Y A N D N O T E S 3 1 5

I have relied heavily on textbooks, therefore, to supplement and explain the latest knowledge. Some of the best are Tom Strachan and Andrew Read's Human molecular genetics (Bios Scientific Publishers, 1996), Robert Weaver and Philip Hedrick's Basic genetics (William C. Brown, 1995), David Micklos and Greg Freyer's DNA science (Cold Spring Harbor Laboratory Press, 1990) and Benjamin Lewin's Genes VI (Oxford University Press, 1997).

As for more popular books about the genome in general, I recommend Christopher Wills's Exons, introns and talking genes (Oxford University Press, 1991), Walter Bodmer and Robin McKie's The book of man (Little, Brown, 1994) and Steve Jones's The language of the genes (Harper Collins, 1993). Also Tom Strachan's The human genome (Bios, 1992). All of these are inevitably showing their age, though.

In each chapter of this book, I have usually relied on one or two main sources, plus a variety of individual scientific papers. The notes that follow are intended to direct the interested reader, who wishes to follow up the subjects, to these sources.

C H R O M O S O M E I

The idea that the gene and indeed life itself consists of digital information is found in Richard Dawkins's River out of Eden (Weidenfeld and Nicolson, 1995) and in Jeremy Campbell's Grammatical man (Allen Lane, 1983). An excellent account of the debates that still rage about the origin of life is found in Paul Davies's The fifth miracle (Penguin, 1998). For more detailed information on the RNA world, see Gesteland, R. F. and Atkins, J. F. (eds) (1993). The RNA world. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.

1. Darwin, E. (1794). Zoonomia: or the laws of organic life. Vol. II, p. 244. Third edition (1801). J. Johnson, London.

2. Campbell, J. (1983). Grammatical man: information, entropy, language and life.

Allen Lane, London.

3. Schrodinger, E. (1967). What is life? Mind and matter. Cambridge University Press, Cambridge.

4. Quoted in Judson, H. F. (1979). The eighth day of creation. Jonathan Cape, London.

3 1 6 G E N O M E

5. Hodges, A. (1997). Turing. Phoenix, London.

6. Campbell, J. (1983). Grammatical man: information, entropy, language and life.

Allen Lane, London.

7. Joyce, G. F. (1989). RNA evolution and the origins of life. Nature 338: 217-24; Unrau, P. J. and Bartel, D. P. (1998). RNA-catalysed nucleotide synthesis. Nature 395: 260—63.

8. Gesteland, R. F. and Atkins, J. F. (eds) (1993). The RNA world. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.

9. Gold, T. (1992). The deep, hot biosphere. Proceedings of the National Academy of Sciences of the USA 89: 6045—49; Gold, T. (1997). An unexplored habitat for life in the universe? American Scientist 85: 408—11.

10. Woese, C. (1998). The universal ancestor. Proceedings of the National Academy of Sciences of the USA 95: 6854—9.

11. Poole, A. M., Jeffares, D.C and Penny, D. (1998). The path from the RNA world. Journal of Molecular Evolution 46: 1 —17; Jeffares, D. C, Poole, A. M. and Penny, D. (1998). Relics from the RNA world. Journal of 'Molecular Evolution 46: 18—36.

C H R O M O S O M E 2

The story of human evolution from an ape ancestor has been told and retold many times. Good recent accounts include: N. T. Boa2's Eco homo (Basic Books, 1997), Alan Walker and Pat Shipman's The wisdom of bones (Phoenix, 1996), Richard Leakey and Roger Lewin's Origins reconsidered (Little, Brown, 1992) and Don Johanson and Blake Edgar's magnificently illustrated From Lucy to language (Weidenfeld and Nicolson, 1996).

1. Kottler, M.J. (1974). From 48 to 46: cytological technique, preconception, and the counting of human chromosomes. Bulletin of the History of Medicine 48: 465 — 502.

2. Young, J. Z. (1950). The life of vertebrates. Oxford University Press, Oxford.

3. Arnason, U., Gullberg, A. and Janke, A. (1998). Molecular timing of primate divergences as estimated by two non-primate calibration points.

Journal of Molecular Evolution 47: 718—27.

4. Huxley, T. H. (1863/1901). Man's place in nature and other anthropological essays, p. 153. Macmillan, London.

B I B L I O G R A P H Y A N D N O T E S 3 1 7

5. Rogers, A. and Jorde, R. B. (1995). Genetic evidence and modern human origins. Human Biology 67: 1—36.

6. Boaz, N. T. (1997). Eco homo. Basic Books, New York.

7. Walker, A. and Shipman, P. (1996). The wisdom of bones. Phoenix, London.

8. Ridley, M. (1996). The origins of virtue. Viking, London.

C H R O M O S O M E 3

There are many accounts of the history of genetics, of which the best is Horace Judson's The eighth day of creation (Jonathan Cape, London, 1979; reprinted by Penguin, 1995). A good account of Mendel's life is found in a novel by Simon Mawer: Mendel's dwarf (Doubleday, 1997).

1. Beam, A. G. and Miller, E. D. (1979). Archibald Garrod and the development of the concept of inborn errors of metabolism. Bulletin of the History of Medicine 53: 315—28; Childs, B. (1970). Sir Archibald Garrod's conception of chemical individuality: a modern appreciation. New England Journal of Medicine 282: 71—7; Garrod, A. (1909). Inborn errors of metabolism. Oxford University Press, Oxford.

2. Mendel, G. (1865). Versuche uber Pflanzen-Hybriden. Verhandlungen des naturforschenden Vereines in Brunn 4: 3—47. English translation published in the Journal of 'the Royal Horticultural Society, V ol. 26 (1901).

3. Quoted in Fisher, R. A. (1930). The genetical theory of natural selection. Oxford University Press, Oxford.

4. Bateson, W. (1909). Mendel's principles of heredity. Cambridge University Press, Cambridge.

5. Miescher is quoted in Bodmer, W. and McKie, R. (1994). The book of man.

Little, Brown, London.

6. Dawkins, R. (1995). River out of Eden. Weidenfeld and Nicolson, London.

7. Hayes, B. (1998). The invention of the genetic code. American Scientist 86: 8-14.

8. Scazzocchio, C. (1997). Alkaptonuria: from humans to moulds and back.

Trends in Genetics 13: 125-7; Fernandez-Canon, J. M. and Penalva, M. A.

(1995). Homogentisate dioxygenase gene cloned in Aspergillus. Proceedings of the National Academy of Sciences of the USA 92: 9132-6.

3 I 8 G E N O M E

C H R O M O S O M E 4

For those concerned about inherited disorders such as Huntington's disease, the writings of Nancy and Alice Wexler, detailed in the notes below, are essential reading. Stephen Thomas's Genetic risk (Pelican, 1986) is a very accessible guide.

1. Thomas, S. (1986). Genetic risk. Pelican, London.

2. Gusella, J. F., McNeil, S., Persichetti, F., Srinidhi, J., Novelletto, A., Bird, E., Faber, P., Vonsattel, J . P . , Myers, R. H. and MacDonald, M. E. (1996).

Huntington's disease. Cold Spring Harbor Symposia on Quantitative Biology 61: 615—26.

3. Huntington, G. (1872). On chorea. Medical and Surgical Reporter 26: 3 1 7 - 2 1 .

4. Wexler, N. (1992). Clairvoyance and caution: repercussions from the Human Genome Project. In The code of codes (ed. D. Kevles and L. Hood), pp. 211-43. Harvard University Press.

5. Huntington's Disease Collaborative Research Group (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971—83.

6. Goldberg, Y. P. et al. (1996). Cleavage of huntingtin by apopain, a proapop-totic cysteine protease, is modulated by the polyglutamine tract. Nature Genetics 13: 442-9; DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J. P. and Aronin, N. (1997). Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277: 1990-93.

7. Kakiuza, A. (1998). Protein precipitation: a common etiology in neurodegenerative disorders? Trends in genetics 14: 398—402.

8. Bat, O., Kimmel, M. and Axelrod, D. E. (1997). Computer simulation of expansions of DNA triplet repeats in the fragile-X syndrome and Huntington's disease. Journal of Theoretical Biology 188: 53—67.

9. Schweitzer, J. K. and Livingston, D. M. (1997). Destabilisation of CAG

trinucleotide repeat tracts by mismatch repair mutations in yeast. Human Molecular Genetics 6: 349—55.

10. Mangiarini, L. (1997). Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. Nature Genetics 15: 197-200; Bates, G. P., Mangiarini, L., Mahal, A. and Davies, S. W. (1997).

B I B L I O G R A P H Y A N D N O T E S 3 1 9

Transgenic models of Huntington's disease. Human Molecular Genetics 6: 1633-7.

11. Chong, S. S. et al. (1997). Contribution of DNA sequence and CAG

si2e to mutation frequencies of intermediate alleles for Huntington's disease: evidence from single sperm analyses. Human Molecular Genetics 6: 301 — 10.

12. Wexler, N. S. (1992). The Tiresias complex: Huntington's disease as a paradigm of testing for late-onset disorders. FASEB Journal 6: 2820-25.

13. Wexler, A. (1995). Mapping fate. University of California Press, Los Angeles.

C H R O M O S O M E 5

One of the best books about gene hunting is William Cookson's The gene hunters: adventures in the genome jungle (Aurum Press, 1994). Cookson is one of my main sources of information on asthma genes.

1. Hamilton, G. (1998). Let them eat dirt. New Scientist, 18 July 1998: 26—

31; Rook, G. A. W. and Stanford, J. L. (1998). Give us this day our daily germs. Immunology Today 19: 113—16.

2. Cookson, W. (1994). The gene hunters: adventures in the genome jungle. Aurum Press, London.

3. Marsh, D. G. et al. (1994). Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin-E concentrations. Science 264: 1152—6.

4. Martinez, F. D. et al. (1997). Association between genetic polymorphism of the beta-2-adrenoceptor and response to albuterol in children with or without a history of wheezing. Journal of Clinical Investigation 100: 3184-8.

C H R O M O S O M E 6

The story of Robert Plomin's search for genes that influence intelligence will be told in a forthcoming book by Rosalind Arden. Plomin's textbook on Behavioral genetics is an especially readable introduction to the field (third edition, W. H. Freeman, 1997). Stephen Jay Gould's Mismeasure of man 3 2 0 G E N O M E

(Norton, 1981) is a good account of the early history of eugenics and IQ.

Lawrence Wright's Twins: genes, environment and the mystery of identity (Weidenfeld and Nicolson, 1997) is a delightful read.

1. Chorney, M. J., Chorney, K., Seese, N., Owen, M. J., Daniels, J., McGuffin, P., Thompson, L. A., Detterman, D. K., Benbow, C, Lubinski, D., Eley, T. and Plomin, R. (1998). A quantitative trait locus associated with cognitive ability in children. Psychological Science 9: 1-8.

2. Galton, F. (1883). Inquiries into human faculty. Macmillan, London.

3. Goddard, H. H. (1920), quoted in Gould, S. J. (1981). The mismeasure of man. Norton, New York.

4. Neisser, U. et al. (1996). Intelligence: knowns and unknowns. American Psychologist 51: 77—101.

5. Philpott, M. (1996). Genetic determinism. In Tam, H. (ed.), Punishment, excuses and moral development. Avebury, Aldershot.

6. Wright, L. (1997). Twins: genes, environment and the mystery of identity. Weidenfeld and Nicolson, London.

7. Scarr, S. (1992). Developmental theories for the 1990s: development and individual differences. Child Development 63: 1 —19.

8. Daniels, M., Devlin, B. and Roeder, K. (1997). Of genes and IQ. In Devlin, B., Fienberg, S. E., Resnick, D. P. and Roeder, K. (eds), Intelligence, genes and success. Copernicus, New York.

9. Herrnstein, R. J. and Murray, C. (1994). The bell curve. The Free Press, New York.

10. Haier, R. et al. (1992). Intelligence and changes in regional cerebral glucose metabolic rate following learning. Intelligence 16: 415—26.

11. Gould, S. J. (1981). The mismeasure of man. Norton, New York.

12. Furlow, F. B., Armijo-Prewitt, T., Gangestead, S. W. and Thornhill, R.

(1997). Fluctuating asymmetry and psychometric intelligence. Proceedings of the Royal Society of London, Series B 264: 823—9.

13. Neisser, U. (1997). Rising scores on intelligence tests. American Scientist 85: 440-47-B I B L I O G R A P H Y A N D N O T E S 3 2 1

C H R O M O S O M E 7

Evolutionary psychology, the theme of this chapter, is explored in several books, including Jerome Barkow, Leda Cosmides and John Tooby's The adapted mind (Oxford University Press, 1992), Robert Wright's The moral animal(Pantheon, 1994), Steven Pinker's How the mind works (Penguin, 1998) and my own The red queen (Viking, 1993). The origin of human language is explored in Steven Pinker's The language instinct (Penguin, 1994) and Terence Deacon's The symbolic species (Penguin, 1997).

1. For the death of Freudianism: Wolf, T. (1997). Sorry but your soul just died. The Independent on Sunday, 2 February 1997. For the death of Meadism: Freeman, D. (1983). Margaret Mead and Samoa: the making and unmaking of an anthropological myth. Harvard University Press, Cambridge, MA; Freeman, D. (1997). Frans Boas and 'The flower of heaven'. Penguin, London.

For the death of behaviourism: Harlow, H. F., Harlow, M. K. and Suomi, S. J. (1971). From thought to therapy: lessons from a primate laboratory.

American Scientist 59: 538-49.

2. Pinker, S. (1994). The language instinct the new science of language and mind.

Penguin, London.

3. Dale, P. S., Simonoff, E., Bishop, D. V. M., Eley, T. C, Oliver, B., Price, T. S., Purcell, S., Stevenson, J. and Plomin, R. (1998). Genetic influence on language delay in two-year-old children. Nature Neuroscience 1: 324—8; Paulesu, E. and Mehler, J. (1998). Right on in sign language. Nature 392: 233~4-4. Carter, R. (1998). Mapping the mind. Weidenfeld and Nicolson, London.

5. Bishop, D. V. M., North, T. and Donlan, C. (1995). Genetic basis of specific language impairment: evidence from a twin study. Developmental Medicine and Child Neurology 37: 56—71.

6. Fisher, S. E., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. and Pembrey, M. E. (1998). Localisation of a gene implicated in a severe speech and language disorder. Nature Genetics 18: 168—70.

7. Gopnik, M. (1990). Feature-blind grammar and dysphasia. Nature 344: 715.

8. Fletcher, P. (1990). Speech and language deficits. Nature 346: 226; Vargha-Khadem, F. and Passingham, R. E. (1990). Speech and language deficits.

Nature 346: 226.

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9. Gopnik, M., Dalakis, J., Fukuda, S. E., Fukuda, S. and Kehayia, E.

(1996). Genetic language impairment: unruly grammars. In Runciman, W. G., Maynard Smith, J. and Dunbar, R. I. M. (eds), Evolution of social behaviour patterns in primates and man, pp. 223—49. Oxford University Press, Oxford; Gopnik, M. (ed.) (1997). The inheritance and innateness of grammars. Oxford University Press, Oxford.

10. Gopnik, M. and Goad, H. (1997). What underlies inflectional error patterns in genetic dysphasia? Journal of Neurolinguistics 10: 109—38; Gopnik, M. (1999)- Familial language impairment: more English evidence. Folia Pho-netica et Logopaedia 51: in press. Myrna Gopnik, e-mail correspondence with the author, 1998.

11. Associated Press, 8 May 1997; Pinker, S. (1994). The language instinct: the new science of language and mind. Penguin, London.

12. Mineka, S. and Cook, M. (1993). Mechanisms involved in the observa-tional conditioning of fear. Journal of Experimental Psychology, General 122: 23-38.

13. Dawkins, R. (1986). The blind watchmaker. Longman, Essex.

C H R O M O S O M E S X A N D Y

The best place to find out more about intragenomic conflict is in Michael Majerus, Bill Amos and Gregory Hurst's textbook Evolution: the four billion year war (Longman, 1996) and W. D. Hamilton's Narrow roads of gene land (W. H. Freeman, 1995). For the studies that led to the conclusion that homosexuality was partly genetic, see Dean Hamer and Peter Copeland's The science of desire (Simon and Schuster, 1995) and Chandler Burr's A separate creation: how biology makes us gay (Bantam Press, 1996).

1. Amos, W. and Harwood, J. (1998). Factors affecting levels of genetic diversity in natural populations. Philosophical Transactions of the Royal Society of London, Series B 353: 177—86.

2. Rice, W. R. and Holland, B. (1997). The enemies within: intergenomic conflict, interlocus contest evolution (ICE), and the intraspecific Red Queen.

Behavioral Ecology and Sociobiology 41: 1 —10.

3. Majerus, M., Amos, W. and Hurst, G. (1996). Evolution: the four billion year war. Longman, Essex.

B I B L I O G R A P H Y A N D N O T E S 3 2 3

4. Swain, A., Narvaez, V., Burgoyne, P., Camerino, G. and Lovell-Badge, R. (1998). Daxi antagonises sry action in mammalian sex determination.

Nature 391: 761—7.

5. Hamilton, W. D. (1967). Extraordinary sex ratios. Science 156: 477—88.

6. Amos, W. and Harwood, J. (1998). Factors affecting levels of genetic diversity in natural populations. Philosophical Transactions of the Royal Society of London, Series B 353: 177—86.

7. Rice, W. R. (1992). Sexually antagonistic genes: experimental evidence.

Science 256: 1436—9.

8. Haig, D. (1993). Genetic conflicts in human pregnancy. Quarterly Review of Biology 68: 495 — 531.

9. Holland, B. and Rice, W. R. (1998). Chase-away sexual selection: antagonistic seduction versus resistance. Evolution 52: 1—7.

10. Rice, W. R. and Holland, B. (1997). The enemies within: intergenomic conflict, interlocus contest evolution (ICE), and the intraspecific Red Queen.

Behavioral Ecology and Sociobiology 41: 1 —10.

11. Hamer, D. H., Hu, S., Magnuson, V. L., Hu, N. et al (1993). A linkage between DNA markers on the X chromosome and male sexual orientation.

Science 261:321-7; Pillard, R. C. and Weinrich, J. D. (1986). Evidence of familial nature of male homosexuality. Archives of General Psychiatry 43: 808—12.

12. Bailey, J. M. and Pillard, R. C. (1991). A genetic study of male sexual orientation. Archives of General Psychiatry 48: 1089—96; Bailey, J. M. and Pillard, R. C. (1995). Genetics of human sexual orientation. Annual Review of Sex Research 6: 126—50.

13. Hamer, D. H., Hu, S., Magnuson, V. L., Hu, N. et al. (1993). A linkage between DNA markers on the X chromosome and male sexual orientation.

Science 261: 321—7.

14. Bailey, J. M., Pillard, R. C, Dawood, K., Miller, M. B., Trivedi, S., Farrer, L. A. and Murphy, R. L.; in press. A family history study of male sexual orientation: no evidence for X-linked transmission. Behaviour Genetics.

15. Blanchard, R. (1997). Birth order and sibling sex ratio in homosexual versus heterosexual males and females. Annual Review of Sex Research 8: 27-67.

16. Blanchard, R. and Klassen, P. (1997). H-Y antigen and homosexuality in men. Journal of Theoretical Biology 185:373-8; Arthur, B. I., Jallon, J.-M., Caflisch, B., Choffat, Y. and Nothiger, R. (1998). Sexual behaviour in Drosophila is irreversibly programmed during a critical period. Current Biology 8: 1187-90.

17. Hamilton, W. D. (1995). Narrow roads of gene land, Vol. 1. W. H. Freeman, Basingstoke.

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C H R O M O S O M E 8

Again, one of the best sources on mobile genetic elements is the textbook by Michael Majerus, Bill Amos and Gregory Hurst: Evolution: the jour billion year war (Longman, 1996). A good account of the invention of genetic fingerprinting is in Walter Bodmer and Robin McKie's The book of man (Little, Brown, 1994). Sperm competition theory is explored in Tim Birkhead and Anders Moller's Sperm competition in birds (Academic Press, 1992).

1. Susan Blackmore explained this trick in her article "The power of the meme meme' in the Skeptic, Vol. 5 no. 2, p. 45.

2. Kazazian, H. H. and Moran, J. V. (1998). The impact of Li retrotransposons on the human genome. Nature Genetics 19: 19—24.

3. Casane, D., Boissinot, S., Chang, B. H. J., Shimmin, L. C. and Li, W. H.

(1997). Mutation pattern variation among regions of the primate genome.

Journal of Molecular Evolution 45: 216—26.

4. Doolittle, W. F. and Sapienza, C. (1980). Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601—3; Orgel, L. E. and Crick, F. H. C. (1980). Selfish DNA: the ultimate parasite. Nature 284: 604-7.

5. McClintock, B. (1951). Chromosome organisation and genie expression.

Cold Spring Harbor Symposia on Quantitative Biology 16: 13—47.

6. Yoder, J. A., Walsh, C. P. and Bestor, T. H. (1997). Cytosine methylation and the ecology of intragenomic parasites. Trends in Genetics 13: 335—40; Garrick, D., Fiering, S., Martin, D. I. K. and Whitelaw, E. (1998). Repeat-induced gene silencing in mammals. Nature Genetics 18: 56-9.

7. Jeffreys, A. J., Wilson, V. and Thein, S. L. (198 5). Hypervariable 'minisatellite' regions in human DNA. Nature 314: 67—73.

8. Reilly, P. R. and Page, D. C. (1998). We're off to see the genome. Nature Genetics 20: 15 — 17; New Scientist, 28 February 1998, p. 20.

9. See Daily Telegraph, 14 July 1998, and Sunday Times, 19 July 1998.

10. Ridley, M. (1993). The Red Queen: sex and the evolution of human nature.

Viking, London.

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C H R O M O S O M E 9

Randy Nesse and George Williams's Evolution and healing (Weidenfeld and Nicolson, 1995) is the best introduction to Darwinian medicine and the interplay between genes and pathogens.

1. Crow, J. F. (1993). Felix Bernstein and the first human marker locus.

Genetics 133: 4—7.

2. Yamomoto, F., Clausen, H., White, T., Marken, S. and Hakomori, S.

(1990). Molecular genetic basis of the histo-blood group ABO system. Nature 345: 229-33.

3. Dean, A. M. (1998). The molecular anatomy of an ancient adaptive event.

American Scientist 86: 26—37.

4. Gilbert, S. C, Plebanski, M., Gupta, S., Morris, J., Cox, M., Aidoo, M., Kwiatowski, D., Greenwood, B. M., Whittle, H. C. and Hill, A. V. S. (1998).

Association of malaria parasite population structure, HLA and immunological antagonism. Science 279: 1173-7; also A Hill, personal communication.

5. Pier, G. B. et al. (1998). Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 393: 79—82.

6. Hill, A. V. S. (1996). Genetics of infectious disease resistance. Current Opinion in Genetics and Development 6: 348—53.

7. Ridley, M. (1997). Disease. Phoenix, London.

8. Cavalli-Sforza, L. L. and Cavalli-Sforza, F. (1995). The great human diasporas.

Addison Wesley, Reading, Massachusetts.

9. Wederkind, C. and Furi, S. (1997). Body odour preferences in men and women: do they aim for specific MHC combinations or simple hetero-geneity? Proceedings of the Royal Society of London, Series B 264: 1471-9.

10. Hamilton, W. D. (1990). Memes of Haldane and Jayakar in a theory of sex. Journal of Genetics 69: 17—32.

3 2 6 G E N O M E

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

The tricky subject of psychoneuroimmunology is explored by Paul Martin's The sickening mind (Harper Collins, 1997).

1. Martin, P. (1997)- The sickening mind: brain, behaviour, immunity and disease.

Harper Collins, London.

2. Becker, J. B., Breedlove, M. S. and Crews, D. (1992). Behavioral endocrinology.

MIT Press, Cambridge, Massachusetts.

3. Marmot, M. G., Davey Smith, G., Stansfield, S., Patel, C, North, F. and Head, J. (1991). Health inequalities among British civil servants: the Whitehall II study. Lancet 337: 1387—93.

4. Sapolsky, R. M. (1997). The trouble with testosterone and other essays on the biology of the human predicament. Touchstone Press, New York.

5. Folstad, I. and Karter, A. J. (1992). Parasites, bright males and the immunocompetence handicap. American Naturalist 139: 603—22.

6. Zuk, M. (1992). The role of parasites in sexual selection: current evidence and future directions. Advances in the Study of Behavior 21: 39—68.

C H R O M O S O M E I I

Dean Hamer has both done the research and written the books on personality genetics and the search for genetic markers that correlate with personality differences. His book, with Peter Copeland, is Living with our genes (Doubleday, 1998).

1. Hamer, D. and Copeland, P. (1998). Living with our genes. Doubleday, New York.

2. Efran, J. S., Greene, M. A. and Gordon, D. E. (1998). Lessons of the new genetics. Family Therapy Networker 22 (March/April 1998): 26—41.

3. Kagan, J. (1994). Galen's prophecy: temperament in human nature. Basic Books, New York.

4. Wurtman, R.J. and Wurtman,J. J. (1994). Carbohydrates and depression.

In Masters, R. D. and McGuire, M. T. (eds), The neurotransmitter revolution, pp.96-109. Southern Illinois University Press, Carbondale and Edwardsville.

B I B L I O G R A P H Y A N D N O T E S 3 2 7

5. Kaplan, J. R., Fontenot, M. B., Manuck, S. B. and Muldoon, M. F. (1996).

Influence of dietary lipids on agonistic and affiliative behavior in Macaca fascicularis. American Journal of Primatology 38: 333 —47.

6. Raleigh, M. J. and McGuire, M. T. (1994). Serotonin, aggression and violence in vervet monkeys. In Masters, R. D. and McGuire, M. T. (eds), The neurotransmitter revolution, pp. 129-45. Southern Illinois University Press, Carbondale and Edwardsville.

C H R O M O S O M E 1 2

The story of homeotic genes and the way in which they have opened up the study of embryology is told in two recent textbooks: Principles of development by Lewis Wolpert (with Rosa Beddington, Jeremy Brockes, Thomas Jessell, Peter Lawrence and Elliot Meyerowitz) (Oxford University Press, 1998), and Cells, embryos and evolution by John Gerhart and Marc Kirschner (

Blackwell, 1997).

1. Bateson, W. (1894). Materials for the study of variation. Macmillan, London.

2. Tautz, D. and Schmid, K.J. (1998). From genes to individuals: developmental genes and the generation of the phenotype. Philosophical Transactions of the Royal Society of London, Series B 353: 231—40.

3. Niisslein-Volhard, C. and Wieschaus, E. (1980). Mutations affecting segment number and polarity in Drosophila. Nature 287: 795—801.

4. McGinnis, W., Garber, R. L., Wirz, J., Kuriowa, A. and Gehring, W. J.

(1984). A homologous protein coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 37: 403—8; Scott, M. and Weiner, A.J. (1984). Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax and fushi tarazu loci of Drosophila. Proceedings of the National Academy of Sciences of the USA 81: 4115-9.

5. Arendt, D. and Nubler-Jung, K. (1994). Inversion of the dorso-ventral axis? Nature 371: 26.

6. Sharman, A. C. and Brand, M. (1998). Evolution and homology of the nervous system: cross-phylum rescues of otd/Otx genes. Trends in Genetics 14: 211 —14.

7. Duboule, D. (1995). Vertebrate hox genes and proliferation — an alternative 3 2 8 G E N O M E

pathway to homeosis. Current Opinion in Genetics and Development 5: 525—8; Krumlauf, R. (1995). Hoxgenes invertebrate development. Cell 78: 191—201.

8. Zimmer, C. (1998). At the water's edge. Free Press, New York.

C H R O M O S O M E I 3

The geography of genes is explored in Luigi Luca Cavalli-Sforza and Fran-cesco Cavalli-Sforza's The great human diasporas (Addison Wesley, 1995); some of the same material is also covered in Jared Diamond's Guns, germs and steel (Jonathan Cape, 1997).

1. Cavalli-Sforza, L. (1998). The DNA revolution in population genetics.

Trends in Genetics 14: 60—65.

2. Intriguingly, the genetic evidence generally points to a far more rapid migration rate for women's genes than men's (comparing maternally inherited mitochondria with paternally inherited Y chromosomes) — perhaps eight times as high. This is partly because in human beings, as in other apes, it is generally females that leave, or are abducted from, their native group when they mate.

Jensen, M. (1998). All about Adam. New Scientist, 11 July 1998: 35—9.

3. Reported in HMS Beagle: The Biomednet Magazine (www.biomednet.com/

hmsbeagle), issue 20, November 1997.

4. Holden, C. and Mace, R. (1997). Phylogenetic analysis of the evolution of lactose digestion in adults. Human Biology 69: 605—28.

C H R O M O S O M E I 4

Two good books on ageing are Steven Austad's Why we age (John Wiley and Sons, 1997) and Tom Kirkwood's Time of our lives (Weidenfeld and Nicolson, 1999).

1. Slagboom, P. E., Droog, S. and Boomsma, D. I. (1994). Genetic determination of telomere size in humans: a twin study of three age groups. American Journal of Human Genetics 55: 876—82.

2. Lingner, J., Hughes, T. R., Shevchenko, A., Mann, M., Lundblad, V. and B I B L I O G R A P H Y A N D N O T E S 3 2 9

Cech, T. R. (1997). Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276: 561—7.

3. Clark, M. S. and Wall, W. J. (1996). Chromosomes: the complex code. Chapman and Hall, London.

4. Harrington, L., McPhail, T., Mar, V., Zhou, W., Oulton, R, Bass, M. B., Aruda, I. and Robinson, M. O. (1997). A mammalian telomerase-associated protein. Science 275: 973-7; Saito, T., Matsuda, Y., Suzuki, T., Hayashi, A., Yuan, X., Saito, M., Nakayama, J., Hori, T. and Ishikawa, F. (1997). Comparative gene-mapping of the human and mouse TEP-1 genes, which encode one protein component of telomerases. Genomics 46: 46—50.

5. Bodnar, A. G. et al. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349—52.

6. Niida, H., Matsumoto, T., Satoh, H., Shiwa, M., Tokutake, Y., Furuichi, Y. and Shinkai, Y. (1998). Severe growth defect in mouse cells lacking the telomerase RNA component. Nature Genetics 19: 203—6.

7. Chang, E. and Harley, C. B. (1995). Telomere length and replicative aging in human vascular tissues. Proceedings of the National Academy of Sciences of the USA 92: 11190—94.

8. Austad, S. (1997). Why we age. John Wiley, New York.

9. Slagboom, P. E., Droog, S. and Boomsma, D. I. (1994). Genetic determination of telomere size in humans: a twin study of three age groups. American Journal of Human Genetics 55: 876—82.

10. Ivanova, R et al. (1998). HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity. Human Molecular Genetics 7: 187—94.

11. The figure of 7,000 genes is given by George Martin, quoted in Austad, S. (1997). Why we age. John Wiley, New York.

12. Feng, J. et al. (1995). The RNA component of human telomerase. Science 269: 1236—41.

C H R O M O S O M E 1 5

Wolf Reik and Azim Surani's Genomic imprinting (Oxford University Press, 1997) is a good collection of essays on the topic of imprinting. Many books explore gender differences including my own The Red Queen (Viking, 3 3 0 G E N O M E

1. Holm, V. et al. (1993). Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 91: 398—401.

2. Angelman, H. (1965). 'Puppet' children. Developmental Medicine and Child Neurology 7: 681—8.

3. McGrath, J. and Solter, D. (1984). Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37: 179—83; Barton, S. C, Surami, M. A. H. and Norris, M. L. (1984). Role of paternal and maternal genomes in mouse development. Nature 311: 374—6.

4. Haig, D. and Westoby, M. (1989). Parent-specific gene expression and the triploid endosperm. American Naturalist 134: 147—55.

5. Haig, D. and Graham, C. (1991). Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell 64: 1045—6.

6. Dawson, W. (1965). Fertility and size inheritance in a Peromyscus species cross. Evolution 19: 44—5 5; Mestel, R. (1998). The genetic battle of the sexes.

Natural History 107: 44—9.

7. Hurst, L. D. and McVean, G. T. (1997). Growth effects of uniparental disomies and the conflict theory of genomic imprinting. Trends in Genetics 13: 436—43; Hurst, L. D. (1997). Evolutionary theories of genomic imprinting. In Reik, W. and Surani, A. (eds), Genomic imprinting, pp. 211-37. Oxford University Press, Oxford.

8. Horsthemke, B. (1997). Imprinting in the Prader-Willi/Angelman syndrome region on human chromosome 15. In Reik, W. and Surani, A. (eds), Genomic imprinting, pp. 177-90. Oxford University Press, Oxford.

9. Reik, W. and Constancia, M. (1997). Making sense or antisense? Nature 389: 669—71.

10. McGrath, J. and Solter, D. (1984). Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37: 179-83.

11. Jaenisch, R. (1997). DNA methylation and imprinting: why bother?

Trends in Genetics 13: 323—9.

12. Cassidy, S. B. (1995). Uniparental disomy and genomic imprinting as causes of human genetic disease. Environmental and Molecular Mutagenesis 25, Suppl. 26: 13-20; Kishino, T. and Wagstaff, J. (1998). Genomic organisation of the UBE3A/E6-AP gene and related pseudogenes. Genomics 47: 101—7.

13. Jiang, Y., Tsai, T.-F., Bressler, J. and Beaudet, A. L. (1998). Imprinting in Angelman and Prader-Willi syndromes. Current Opinion in Genetics and Development 8: 334—42.

14. Allen, N. D., Logan, K., Lally, G., Drage, D. J., Norris, M. and Keverne, B I B L I O G R A P H Y A N D N O T E S 3 3 1

E. B. (1995). Distribution of pathenogenetic cells in the mouse brain and their influence on brain development and behaviour. Proceedings of the National Academy of Sciences of the USA 92: 10782—6; Trivers, R. and Burt, A. (in preparation), Kinship and genomic imprinting.

15. Vines, G. (1997). Where did you get your brains? New Scientist, 3 May 1997: 34-9; Lefebvre, L., Viville, S., Barton, S. C, Ishino, F., Keverne, E. B. and Surani, M. A. (1998). Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest. Nature Genetics 20: 163—9.

16. Pagel, M. (1999). Mother and father in surprise genetic agreement. Nature 397: 19-20.

17. Skuse, D. H. et al. (1997). Evidence from Turner's syndrome of an imprinted locus affecting cognitive function. Nature 387: 705—8.

18. Diamond, M. and Sigmundson, H. K. (1997). Sex assignment at birth: long-term review and clinical implications. Archives of Pediatric and Adolescent Medicine 151: 298-304.

C H R O M O S O M E 1 6

There are no good popular books on the genetics of learning mechanisms.

A good textbook is: M. F. Bear, B. W. Connors and M. A. Paradiso's Neuroscience: exploring the brain (Williams and Wilkins, 1996).

1. Baldwin, J. M. (1896). A new factor in evolution. American Naturalist 30: 441-51, 536-53.

2. Schacher, S., Castelluci, V. F. and Kandel, E. R. (1988). cAMP evokes long-term facilitation in Aplysia neurons that requires new protein synthesis.

Science 240: 1667—9.

3. Bailey, C. H., Bartsch, D. and Kandel, E. R. (1996). Towards a molecular definition of long-term memory storage. Proceedings of the National Academy of Sciences of the USA 93: 12445 — 52.

4. Tully, T., Preat, T., Boynton, S. C. and Del Vecchio, M. (1994). Genetic dissection of consolidated memory in Drosophila. Cell 79: 39-47; Dubnau, J. and Tully, T. (1998). Gene discovery in Drosophila: new insights for learning and memory. Annual Review of Neuroscience 21: 407—44.

5. Silva, A. J., Smith, A. M. and Giese, K. P. (1997). Gene targeting and 3 3 2 G E N O M E

the biology of learning and memory. Annual Review of Genetics 31: 527—46.

6. Davis, R. L. (1993). Mushroom bodies and Drosophila learning.

Neuron 11: 1-14; Grotewiel, M. S., Beck, C. D. O., Wu, K. H., Zhu, X.-R.

and Davis, R. L. (1998). Integrin-mediated short-term memory in Drosophila.

Nature 391: 455—60.

7. Vargha-Khadem, F., Gadian, D. G., Watkins, K. E., Connelly, A., Van-Paesschen, W. and Mishkin, M. (1997). Differential effects of early hippo¬

campal pathology on episodic and semantic memory. Science 277: 376—80.

C H R O M O S O M E 1 7

The best recent account of cancer research is Robert Weinberg's One renegade cell (Weidenfeld and Nicolson, 1998).

1. Hakem, R. et al. (1998). Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94: 339—52.

2. Ridley, M. (1996). The origins of virtue. Viking, London; Raff, M. (1998).

Cell suicide for beginners. Nature 396: 119-22.

3. Cookson, W. (1994). The gene hunters: adventures in the genome jungle. Aurum Press, London.

4. Sunday Telegraph, 3 May 1998, p. 25.

5. Weinberg, R. (1998). One renegade cell. Weidenfeld and Nicolson, London.

6. Levine, A. J. (1997). P53, the cellular gatekeeper for growth and division.

Cell 88: 323-31.

7. Lowe, S. W. (1995). Cancer therapy and p53. Current Opinion in Oncology 7: 547-53.

8. Huber, A . O . and Evan, G. I. (1998). Traps to catch unwary oncogenes.

Trends in Genetics 14: 364—7.

9. Cook-Deegan, R. (1994). The gene wars: science, politics and the human genome.

W. W. Norton, New York.

10. Krakauer, D. C. and Payne, R. J. H. (1997). The evolution of virus-induced apoptosis. Proceedings of the Royal Society of London, Series B 264: 1757-62.

11.. Le Grand, E. K. (1997). An adaptationist view of apoptosis. Quarterly Review of Biology 72: 135—47.

B I B L I O G R A P H Y A N D N O T E S 333

C H R O M O S O M E 1 8

Geoff Lyon and Peter G o r n e r ' s blow-by-blow account of the development of gene therapy, Altered fates ( N o r t o n , 1996) is a g o o d place to start. Eat your genes by Stephen Nottingham (Zed Books, 1998) details the history of plant genetic engineering. Lee Silver's Remaking Eden (Weidenfeld and Nicolson, 1997) explores the implications of reproductive technologies and genetic engineering in h u m a n beings.

1. Verma, I. M. and Somia, N. (1997). G e n e t h e r a p y - promises, problems and prospects. Nature 389: 239—42.

2. Carter, M. H. (1996). Pioneer Hi-Bred: testing for gene transfers. Harvard Business School Case Study N 9 - 5 9 7 - 0 5 5 .

3. Capecchi, M. R. (1989). Altering the g e n o m e by homologous recombination. Science 244: 1288—92.

4. First, N. and T h o m s o n , J. (1998). F r o m cows stem therapies? Nature Biotechnology 16: 620—21.

C H R O M O S O M E 1 9

T h e promises and perils of genetic screening have been discussed at great length in many books, articles and reports, but few stand out as essential sources of wisdom. Chandler Burr's A separate creation: how biology makes us gay (Bantam Press, 1996) is one.

1. Lyon, J. and G o r n e r , P. (1996). Altered fates. N o r t o n , N e w York.

2. E t o , M., Watanabe, K. and Makino, I. (1989). Increased frequencies of apolipoprotein E2 and E4 alleles in patients with ischemic heart disease.

Clinical Genetics 36: 183—8.

3. Lucotte, G., Loirat, F. and Hazout, S. (1997). Patterns of gradient of apolipoprotein E allele *4 frequencies in western E u r o p e . Human Biology 69: 2 5 3 - 6 2 .

4. K a m b o h , M. I. (1995). Apolipoprotein E polymorphism and susceptibility to Alzheimer's disease. Human Biology 67: 195—215; Flannery, T. (1998).

Throwim way leg. Weidenfeld and Nicolson, L o n d o n .

3 3 4 G E N O M E

5. Cook-Degan, R. (1995). The gene wars: science, politics and the human genome.

Norton, New York.

6. Kamboh, M. I. (1995). Apolipoprotein E polymorphism and susceptibility to Alzheimer's disease. Human Biology 67: 195—215; Corder, E. H. et al.

(1994). Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nature Genetics 7: 180—84.

7. Bickeboller, H. et al. (1997). Apolipoprotein E and Alzheimer disease: genotypic-specific risks by age and sex. American Journal of Human Genetics 60: 439—46; Payami, H. et al. (1996). Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. American Journal of Human Genetics 58: 803 — 11; Tang, M.-X. et al. (1996). Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians and Hispanics in New York City. American Journal of Human Genetics 58: 574—84.

8. Caldicott, F. et al. (1998). Mental disorders and genetics: the ethical context.

Nuffield Council on Bioethics, London.

9. Bickeboller, H. et al. (1997). Apolipoprotein E and Alzheimer disease: genotypic-specific risks by age and sex. American Journal of Human Genetics 60: 439—46.

10. Maddox, J. (1998). What remains to be discovered. Macmillan, London.

11. Cookson, C. (1998). Markers on the road to avoiding illness. Financial Times, 3 March 1998, p. 18; Schmidt, K. (1998). Just for you. New Scientist, 14 November 1998, p. 32.

12. Wilkie, T. (1996). The people who want to look inside your genes.

Guardian, 3 October 1996.

C H R O M O S O M E 2 0

The story of prions is exceptionally well told in Rosalind Ridley and Harry Baker's Fatal protein (Oxford University Press, 1998). I have also drawn on Richard Rhodes's Deadly feasts (Simon and Schuster, 1997) and Robert Klitzman's The trembling mountain (Plenum, 1998).

1. Prusiner, S. B. and Scott, M. R. (1997). Genetics of prions. Annual Review of Genetics 31: 139—75.

B I B L I O G R A P H Y A N D N O T E S 3 3 5

2. Brown, D. R. et al. (1997). The cellular prion protein binds copper in vivo.

Nature 390: 684—7.

3. Prusiner, S. B., Scott, M. R., DeArmand, S. J. and Cohen, F. E. (1998).

Prion protein biology. Cell 93: 337—49.

4. Klein, M. A. et al. (1997). A crucial role for B cells in neuroinvasive scrapie. Nature 390: 687—90.

5. Ridley, R. M. and Baker H. F. (1998). Fatal protein. Oxford University Press, Oxford.

C H R O M O S O M E 2 1

The most thorough history of the eugenics movement, Dan Kevles's In the name of eugenics (Harvard University Press, 1985) concentrates mostly on America. For the European scene, John Carey's The intellectuals and the masses (Faber and Faber, 1992) is eye-opening.

1. Hawkins, M. (1997). Social Darwinism in European and American thought.

Cambridge University Press, Cambridge.

2. Kevles, D. (1985). In the name of eugenics. Harvard University Press, Cambridge, Massachusetts.

3. Paul, D. B. and Spencer, H. G. (1995). The hidden science of eugenics.

Nature 374: 302-5.

4. Carey, J. (1992). The intellectuals and the masses. Faber and Faber, London.

5. Anderson, G. (1994). The politics of the mental deficiency act. M.Phil, dissertation, University of Cambridge.

6. Hansard, 29 May 1913.

7. Wells, H. G., Huxley, J. S. and Wells, G. P. (1931). The science of life.

Cassell, London.

8. Kealey, T., personal communication; Lindzen, R. (1996). Science and politics: global warming and eugenics. In Hahn, R. W. (ed.), Risks, costs and lives saved, pp. 85 — 103. Oxford University Press, Oxford.

9. King, D. and Hansen, R. (1999). Experts at work: state autonomy, social learning and eugenic sterilisation in 1930s Britain. British Journal of Political Science 29: 77—107.

10. Searle, G. R. (1979). Eugenics and politics in Britain in the 1930s. Annals of Political Science 36: 159—69.

336 G E N O M E

11. Kitcher, P. (1996). The lives to come. Simon and Schuster, New York.

12. Quoted in an interview in the Sunday Telegraph, 8 February 1997.

13. Lynn, R. (1996). Dysgenics: genetic deterioration in modern populations. Praeger, Westport, Connecticut.

14. Reported in HMS Beagle: The Biomednet Magazine (www.biomednet.com/

hmsbeagle), issue 20, November 1997.

15. Morton, N. (1998). Hippocratic or hypocritic: birthpangs of an ethical code. Nature Genetics 18: 18; Coghlan, A. (1998). Perfect people's republic.

New Scientist, 24 October 1998, p. 24.

C H R O M O S O M E 2 2

The most intelligent book on determinism is Judith Rich Harris's The nurture assumption (Bloomsbury, 1998). Steven Rose's Lifelines (Penguin, 1998) makes the opposing case. Dorothy Nelkin and Susan Lindee's The DNA mystique (Freeman, 1995) is worth a look.

1. Rich Harris, J. (1998). The nurture assumption. Bloomsbury, London.

2. Ehrenreich, B. and McIntosh, J. (1997). The new creationism. Nation, 9

June 1997.

3. Rose, S., Kamin, L. J. and Lewontin, R. C. (1984). Not in our genes.

Pantheon, London.

4. Brittan, S. (1998). Essays, moral, political and economic. Hume Papers on Public Policy, Vol. 6, no. 4. Edinburgh University Press, Edinburgh.

5. Reznek, L. (1997). Evil or ill? Justifying the insanity defence. Routledge, London.

6. Wilson, E. O. (1998). Consilience. Little, Brown, New York.

7. Darwin's views on free will are quoted in Wright, R. (1994). The moral animal. Pantheon, New York.

8. Silver, B. (1998). The ascent of science. Oxford University Press, Oxford.

9. Ayer, A. J. (1954). Philosophical essays. Macmillan, London.

10. Lyndon Eaves, quoted in Wright, L. (1997). Twins: genes, environment and mystery of identity. Weidenfeld and Nicolson, London.

I N D E X

ADA, 249 Asquith, Herbert, 294

Affymetrix, 267 asthma, 66-75

ageing, 196—205 Austad, Steven, 201—2

AIDS, 124-5, 265, 267—9 Avery, Oswald, 14-15

Alkaptonuria, 39, 52, 71 Avery, Roy, 14

Allison, Anthony, 141 Ayer, A. J., 313

Altman, Sidney, 18

Alzheimer's disease: baboon, 154-60

A P O - E 4 association with, 261-8 Bailey, Michael, 118

inheritance of, 54, 59, 273, 309 Bakewell, Robert, 272

American Lung Association, 68, 73 Baldwin, James Mark, 220-22, 230

Ames, Bruce, 233-4 Balfour, Arthur, 293

Amnion's horn, 227-8 Bateson, William, 39, 4 5 - 6 , 174

Amos, William, 111, 112 BCG, 69

Anderson, French, 248-9 Beadle, George, 47

Anderson, Gerry, 293 Beckwith-Wiedemann syndrome, 210

Angelman, Harry, 207-8 Bede, Venerable, 35

Angelman syndrome, 212-4 bell curve, The (R. J. Herrnstein, C.

apoptosis, 238-42 Murray), 86

Apple, 181 Belloc, Hilaire, 293

Applied Biosystems, 245 Bell Telephone Company, 155

Ardipithecus skeleton, 30 Berg, Paul, 244, 261

Aristode, 13, 16, 174, 184 Bickerton, Derek, 94-5

Ashkenazi Jews, 191-2 Binet, Alfred, 78, 88

Ashworth, Dawn, 132-3 Biogen, 245

338 G E N O M E

Blackburn, Elizabeth, 197 Cech, Thomas, 18

Blaese, Michael, 248—9 Cecil, Lord Robert, 295

Blanchard, Ray, 119 Celera, 246

Blanchflower, Danny, 266 cerebellar ataxia, 59

blood groups, 156—47 Cetus, 245

Blunt, Wilfred Scawen, 294 Chagas' disease, 157

BMP4, 179 Chaplin, Charlie, 136

Boas, Franz, 92 Chesterton, G. K., 293

Boer War (1899-1902), 288 chimpanzee, 24, 27-37, 127

Borna disease, 143 Chomsky, Noam, 9 2 - 3 , 103

Bouchard, Thomas, 82 chronic fatigue syndrome see ME

Bowman Gray Medical School, North Churchill, Winston, 294

Carolina, 170 Cline, Martin, 247

Brave new world (Aldous Huxley), 303 Clinique Medicale (Armand Trousseau), breast cancer see cancer 67

Brittan, Sam, 308 cloning, 212-3, 255-7

Broca's aphasia, 96, 101 Cold Spring Harbour Laboratory, 224, Brock report (1934), 296-7 238, 289

Brock, Sir Laurence, 296 Collins, John, 308

BSE (bovine spongiform encephalopathy), Colossus (computer), 15

59, 281—5 Columbia University, 46

Buck v Bell (1927), 290 'comma-free code', 50

Buck, Carrie, 290 Committee for the Prevention of Jewish Buck, Doris, 290 Genetic Disease, 191, 299

Buck, Emma, 290 Concepcion, Maria, 57

Buck, Vivian, 290 Consilience (Edward Wilson), 310

Buckland, Richard, 132-3 Cookson, William, 72-3

Burt, Cyril, 88 Coppens, Yves, 31

Butler, Samuel, 17 Correns, Carl, 44

Cortisol, 149-56

Caldicott, Dame Fiona, 265 Cosmides, Leda, 102-3

California Institute of Technology, 312 CREB, 224-6, 229, 302

California Supreme Court, 136 Creutzfeldt, Hans, 274

Calment, Jeanne, 203 Creutzfeldt-Jakob disease (CJD), 274—6, Calvin, John, 54, 56 278-80, 284-5

Cambrian explosion, 26, 180-1 Crick, Francis, 13, 14, 4 9 - 5 1 , 61, 138, cancer: 276, 280

breast, 190—1, 236 Culver, Kenneth, 250

D C C suppresses, 244 cyclic AMP, 223-4, 226

TP53 prevents, 233-42 cystic fibrosis, 142 see also Tay-Sachs Capecchi, Mario, 254-5 disease

Carnegie, Andrew, 289

Carter, Rita, 311 Daily Telegraph, 116

Cavalli-Sforza, Luigi Luca, 188-90 Dalton, John, 43

I N D E X 339

Darwin, Charles, 12, 43, 44—6, 93, 103—4, embryological development, 173-84

157—8, 287, 294, 310 embryonic stem cells, 254-7

Darwin, Erasmus, 12, 22 eugenics, 286—300

Darwin, Leonard, 294 Eugenics Education Society, 292-4

Davenport, Charles, 289 European Union, 151, 284

Davies, Michael, 160 Evolution: the four-billion year war (M.

Davis, Ronald, 226 Majerus, W. Amos, G. Hurst), 109

Dawkins, Richard, 26, 50, 104, 128

DAX, 110 Fabian Society, 292-3

de LaPlace, Pierre-Simon, 311 First World War (1914-18), 38, 79

Delbruck, Max, 13 Fisher, Sir Ronald, 42, 46, 291-2

de Miranda, Juan Carreno, 206 Fleming, Alexander, 2 5 8

Department of Health, 296 Flynn, James, 89-90

de Robertas, Eddie, 177 Focke, W. O., 44

Descartes, Rene, 47, 153 Forensic Science Service, 134

Descent of Man, The (Charles Darwin), 158 Forterre, Patrick, 20

de Silva, Ashanthi, 249 Frankenstein, 219, 251, 252

de Vries, Hugo, 44 Franklin, Rosalind, 13, 14

Diamond, Milton, 218 Freeman, Derek, 92

D N A : free will, 75, 301-13

ageing process and, 203 Freud, Sigmund, 92, 119, 218, 305—6

chimpanzee, 28 Friends of the Earth, 252

discovery of, 12-17 fruit fly, 129, 175—84

fingerprinting, 132-6 Furi, Sandra, 144-5

function of, 7 - 9

libraries, 246 Gajdusek, Carleton, 273-4, 277

'recombinant', 244, 248 Galton, Francis, 78, 85, 89, 90, 287-9, scrapie agent, 276 291, 298

'selfish', 124, 127-31, 212, 246 Gardner, Howard, 80

structure of, 49-53 Garrod, Archibald, 38-41, 46, 47, 52

Dolgopolsky, Aharon, 187 Garrod, Sir Alfred Baring, 38

Dolly, 208, 213, 255 Gehring, Walter, 177, 178

dopamine, 162-7 Genentech, 245

D o w n syndrome, 287-8, 298 genetically modified organisms, 251-7

du Chaiilu, Paul, 29 genetic engineering, 244-50

Dulbecco, Renato, 240 genetic imprinting, 210-18

Dunnet, George, 201 genetic screening, 261-9

Geron Corporation, 199, 20;

'East Side Story', 31 Gerstmann-Straussler-Scheinker disease, Eaves, Lyndon, 313 278

Ebstein, Richard, 163 Gibbs, Joe, 274

Eli Lilly, 168 Gladstone, Herbert, 293

Ellis, Havelock, 292 Goddard, H. H., 78, 79, 289

Epstein-Barr virus, 241 Gopnik, Myrna, 98-100

3 4 0 G E N O M E

Gould, Stephen Jay, 88, 306 Human Genome Project, 5, 145, 246

Great Ormond Street Hospital, 39 Hume, David, 309

Greenberg, Joseph, 187 Hume's fork, 301, 309

Greenpeace, 252 Huntington's chorea, 55-66, 75, 241, 264, Greider, Carol, 197 280

Grotewiel, Michael, 226 Huntington, George, 56

Gusella, Jim, 58 Huxley, Aldous, 303-4

Guthrie, Woody, 56, 57 Huxley, Julian, 292

Guy's Hospital, 60 Huxley, Thomas Henry, 29, 43

H-Y antigens, 119-21

Hadlow, Bill, 273-4

Haeckel, Ernst, 182, 288-9 ICE (interlocus contest evolution), 109, Haig, David, 3, 114, 209-11 116

Haldane, J. B. S., 146, 201, 292, 297 Identigene, 134

Hall, Peter, 235 IGF2R, 77, 87, 210

Hamer, Dean, 116, 117-8, 163-5, 168 Illich-Svitych, Vladislav, 187

Hamilton, W. D., 120, 146 Immigration Restriction Act 1924

Harley, Cal, 199 (American), 79, 289-90

Harris, Henry, 235 infectious disease, 272—85

Harris, Judith Rich, 305-7 Ingram, Tony, 311

Harwood, John, 112 Institute of Child Health, 98, 216

Hayes, Brian, 51 intelligence:

heart disease: ape, 29-30, 33

effects of A P O E activity on causes of, contested relationship with IGF2R, 77, 259-61 87

MrFit trial, 169-70 effects of SLI on, 100-01

relation of cholesterol levels with, inheritance of, 76-77, 84-90

148-50, 155 testing, 77-90

relation of Cortisol levels with, 154—6 International Brigade, 48

relation of testosterone levels with, International Eugenics Conference 159-60 (London, 1912), 293

Heisenberg, Werner Karl, 311 Iwasa, Yoh, 215—6

Hill, Adrian, 142

Hiroshima bombing, 233, 280 Jakob, Alfons, 275

Hitler, Adolf, 47 James, Henry, 93

H I V (human immunodeficiency virus), James, William, 93, 102, 10; 265 Janacek, Leos, 42

Holland, Brett, 114-6 Jansky's nomenclature, 137

Holmes, Justice Oliver Wendell, 290 Jayakar, Suresh, 146

homeobox, 177 Jefferson, Thomas, 134

H o m e Office forensic laboratory, 133 Jeffreys, Alec, 132-3

Hox genes, 177—81, 183, 184 Jenkin, Fleeming, 43

'human endogenous retroviruses' (Hervs), Jenner, Edward, 258

125 Johanson, Donald, 33

I N D E X 341

John-Paul II, Pope, 24 Luca (Last Universal Common Ancestor), Jones, Sir William, 186 19-22, 25, 26, 198

'jumping genes', 129—30 Luria, Salvador, 48

Lysenko, Trofim, 47

Kagan, Jerome, 166

Kamin, Leon, 307 'mad cow disease' see BSE

Kandel, Eric, 223-4 Maddox, John, 178, 266

Kaplan, Jay, 170 Maimonides, 71

Kelly, Ian, 133 Man and superman (George Bernard Shaw), Keynes, J. M., 292 292

K family, 9 8 - 9 Mangiarini, Laura, 60

Kimura, Motoo, 139 Mann, Lynda, 132-3

Kingsley, Charles, 29 Mao, Xin, 300

Kitcher, Philip, 298 Mappingfate (A. Wexler), 64

Klitzman, Robert, 274 Marsh, David, 73

Kuntz, Maurice, 248 Martin, Paul, 159-60

Marx, Karl, 47, 92

Labour Party (British), 292, 294, 297 Maternal and Infant Health Care Law Lacks, Henrietta, 204 (Chinese), 299

lactase, 192—4 Matthaei, Johann, 51

Laetoli footprints, 32 May, Robert, 146

Lake Maracaibo study, 57-8, 62 McClintock, Barbara, 128

'La Monstrua desnuda' (Juan Carreno de McGuire, Michael, 171

Miranda), 206 McKenna, Reginald, 294, 295

'La Monstrua vestida' (Juan Carreno de M E , 152

Miranda), 206 Mead, Margaret, 92, 297, 306

Lander, Eric, 264 Medawar, Peter, 201

Landsteiner, Karl, 137 memory:

Lane, David, 23; effects of CREB activity on, 224-6

language: long-term potentiation as key to,

as an instinct, 9 2 - 7 , 102-6 227-30

common ancestry of, 185—90 Mendel, Anton, 41

specific language impairment (SLI), Mendel, Gregor, 39-44, 4 7 - 8 , 52-3, 97—101, 106 65—6, 207, 289, 291—2

Laski, Harold, 292 Mengele, Josef, 14, 134

Leakey, Richard, 33 Mental Deficiency Bill (1912), 294

Lenin, Vladimir Ilyich, 47, 92 Mercer, Joe, 266

Levan, Albert, 24 Mest gene, 215

LeVay, Simon, 116 'Methuselah' flies, 204

Levi, Primo, 4 MHC, 144-5

Lewinsky, Monica, 134 microsatellites, 124

Lewontin, Richard, 164, 306, 307 Microsoft, 181, 244

Lorentz (encoding machine), 15 Miescher, Friedrich, 48

Lowe, Scott, 238, 239 Mingzhang, Chen, 299

342 G E N O M E

minisatellites: Pavlov, Ivan Petrovich, 223, 304

Alu, 126—7, 129—31 Pearson, Karl, 288—9, 291, 293,297,300

definition of, 124 P E G - A D A , 249-50

discovery of, 131-4 P element, 129—30

L I N E - 1 , 125-27, 129-31 personality:

Mobley, Stephen, 308 effects of dopamine levels on, 161-6

Money, John, 218 effects of serotonin levels on, 167-72

Monsanto, 2 5 2 Philosophical Transactions of the Royal Society, Morgan, Thomas Hunt, 4 5 - 6 108

Moss's nomenclature, 137 Philpott, Mark, 82

Muller, Hermann Joe, 4 6 - 8 , 49, 119, 176 Pinker, Steven, 94, 102-3, 310

Pioneer, 253—4

Nageli, Karl-Wilhelm, 44 Pitchfork, Colin, 133-4

Nariokotome skeleton, 33 pleiotropy, 66-75

National Geographic, 113 Plomin, Robert, 77, 87—8, 163

Nature, 178 Pontifical Academy of Sciences, 24

Nazi party, 291, 297 Prader-Willi syndrome:

Negrette, Americo, 57 causes of, 213—4

Neisser, Ulric, 90 identification of, 206-8

neurodegenerative disease, 54-65 Prado Museum, 206

New York Times, 191 prion genes, 278-81, 284-5

News Chronicle, 50 pronuclei, 208

Newton, Sir Issac, 16, 311 Prozac, 92, 168

Niemann-Pick disease, 54 PRP, 272, 277-8

Nietzsche, Friedrich, 289 Prusiner, Stanley, 276—9

Nirenberg, Marshall, 51 pseudogenes, 126—35

Nixon, Richard, 233 Punch, 29

Nobel prize, 13, 46, 48, 128, 234, 240,

271, 277 Radnor, Earl of, 293

Nuffield Council on Bioethics, 264-5 Reagan, Ronald, 264

Nusslein-Volhard, Jani, 176 Recombinant D N A Advisory Committee, 248

Occam's razor, 21 Rice, William, 113-6

origin of life, n - 2 6 Rift Valley, 30, 32

Osier, William, 38 RNA:

otx genes, 180 discovery of, 18—19

Owen, Sir Richard, 29 function of, 7—9, 16

relationship with D N A , 17-18

Painter, Theophilus, 23 transfer, 50

Paisley, Bill, 266 Robinson, W. J., 290

Paley, William, 104 Roman Catholic Church, 291, 297

Parkinson's disease, 162, 266 Roosevelt, Theodore, 289

Parry, James, 273 Rose, Michael, 203-4

Pauling, Linus, 47 Rose, Steven, 307

I N D E X 343

Rosenberg, Steven, 248 Sternberg, Robert, 80

Roundish Flat Worm (RFW), 181, 186 Stewart, Gershom, 294

Roundup, 252—3 stress:

Rous, Peyton, 234 as a cause of heart disease, 147—57

Royal Asiatic Society, 186 causes fall in levels of high-density Royal Commission on the care and lipoprotein, 154

control of the feeble-minded (1908), causes rise in levels of Cortisol, 149-52

293 relationship with testosterone levels,

Ruminant Feed Ban (1988), 282 157-60

Rutherford, Ernest, 46 Sulston, J o h n , 246

Supreme Court (American), 290

Sadiman volcano (Tanzania), 32 Sutton, Walter, 45

Salk Institute, 116 Syntactic structures (Noam Chomsky), 92

salmonella, 142 Szilard, Leo, 280

Sanger Centre, 246, 301

Sapir, Edward, 92 Tatum, Edward, 47

Schrodinger, Erwin, 12, 14 Tay-Sachs disease, 191

Science, 111 Three Mile Island, 153

SCID (severe combined immune Tjio, Joe-Hin, 24

deficiency), 249-50 Tooby, John, 102

scrapie, 272-4, 276—7, 279-82 Tredgold, Alfred, 294

Second World War (1939-45), 48, 79, 291 Trivers, Robert, 117-8, 215, 310

sexually antagonistic genes, 107-21 Trousseau, Armand, 67

sexual selection, 4 2 - 7 , 5 2 - 3 , 158-60 Tully, Tim, 224-5

Shannon, Claude, 15, 16 Turing, Alan, 15, 16

Shaw, George Bernard, 292 Turner's syndrome, 216-7

Shelley, Percy Bysshe, 171

Shimojo, Shin, 312 uracil, 51

sickening mind, The (Paul Martin), 159 'ur-gene', 18, 196

sickle-cell anaemia, 141

Sigmundson, Keith, 218 Vallejo, Eugenia Martinez, 206

Skinner, B. F., 92 van Helmont, Jan Baptist, 15

Skuse, David, 216-7 Vavilov, Nikolay, 4 7 - 8

SLI (specific language impairment), Venter, Craig, 246

9 7 - 1 0 1 , 106 Verdun, Battle of (1916), 232

Sociobiology (E. O. Wilson), 306 Vogt, Oscar, 47

Southwood committee (1988), 282 von Tschermak, Erich, 44

Spanish Civil War (1936-9), 48

Spearman, Charles, 80 Walker, Alan, 33

Specified Bovine Offals Ban (1989), 282 water babies, The (Charles Kingsley), 29

Spencer, Herbert, 287-8 Watson, James, 13, 14, 48-50, 61, 196, SRY, 110-12 299, 305-6, 308

St Bartholomew's Hospital, 39 Webb, Beatrice, 292

St Hilaire, Etienne Geoffroy, 180 Webb, Sidney, 292

344 GENOME

Wederkind, Claus, 144-5 Wilson, E. O., 306, 310

Wedgwood, Josiah, 294-5, 297 Wilson, Vicky, 132

Weinberg, Robert, 237 Woese, Carl, 20

Wellcome Museum of Medicine, 273 Wohler, Friedrich, 15

Wellcome Trust 246 Wolf-Hirschhorn syndrome, 54-5

Wells, H. G., 292 Wood report (1929), 296

Werner's syndrome, 203

Wernicke's area, 97, 101 'xeno-transplants', 129

Wexler, Alice, 64 X-rays, 47, 176, 233, 294

Wexler, Milton, 57-8, 64 Xq28, 117, 118

Wexler, Nancy, 6 2 - 3 , 64, 264

Whorf, Benjamin, 92 Yerkes, Robert, 79

Wieschaus, Eric, 176 Young, J. Z., 27

Wilkins, Maurice, 13, 14 Young, Lady, 116

Williams, George, 201

William's syndrome, 97 Zigas, Vincent, 273

Document Outline

Front

Contents

Acknowledgements

Preface

Chromosome 1: Life

Chromosome 2: Species

Chromosome 3: History

Chromosome 4: Fate

Chromosome 5: Environment

Chromosome 6: Intelligence

Chromosome 7: Instinct

Chromosomes X and Y: Conflict

Chromosome 8: Self-interest

Chromosome 9: Disease

Chromosome 10: Stress

Chromosome 11: Personality

Chromosome 12: Self-assembly

Chromosome 13: Pre-history

Chromosome 14: Immortality

Chromosome 15: Sex

Chromosome 16: Memory

Chromosome 17: Death

Chromosome 18: Cures

Chromosome 19: Prevention

Chromosome 20: Politics

Chromosome 21: Eugenics

Chromosome 22: Free will

Bibliography and notes

Index