Until 1955, it was agreed that human beings had twenty-four pairs of chromosomes.For thirty years, nobody disputed this 'fact'. One group of scientists abandoned their experiments on human liver cells because they could only find twenty-three pairs of chromosomes in each cell. Another researcher invented a method of separating the chromosomes, but still he thought he saw twenty-four pairs. It was not until 1955, when an Indonesian named Joe-Hin Tjio travelled from Spain to Sweden to work with Albert Levan, that the truth dawned. Tjio and Levan, using better techniques, plainly saw twenty-three pairs. They even went back and counted twenty-three pairs in photographs in books where the caption stated that there were twenty-four pairs. There are none so blind as do not wish to see. It is actually rather surprising that human beings do not have twenty-four pairs of chromosomes. Chimpanzees have twenty-four pairs of chromosomes; so do gorillas and orangutans. Among the apes we are the exception. Under the microscope, the most striking and obvious difference between ourselves and all the other great apes is that we have one pair less. The reason, it immediately becomes apparent, is not that a pair of ape chromosomes has gone missing in us, but that two ape chromosomes have fused together in us. Chromosome 2, the second biggest of the human chromosomes, is in fact formed from the fusion of two medium-sized ape chromosomes, as can be seen from the pattern of black bands on the respective chromosomes.
Natural selection is simply the process by which life-forms change to suit the myriad opportunities afforded by the physical environment and by other life-forms. The black-smoker bacterium, living in a sulphurous vent on the floor of the Atlantic ocean and descended from a stock of bacteria  that parted company with our ancestors soon after Luca's day, is arguably more highly evolved than a bank clerk, at least at the genetic level. Given that it has a shorter generation time, it has had more time to perfect its genes.
Human beings are of course unique. They have, perched between their ears, the most complicated biological machine on the planet. But complexity is not everything, and it is not the goal of evolution. Every species on the planet is unique.  
Human beings are an ecological success. They are probably the most abundant large animal on the whole planet.  
Moreover, the human species has shown a remarkable capacity for colonising different habitats, cold or hot, dry or wet, high or low, marine or desert. Ospreys, barn owls and roseate terns are the only other large species to thrive in every continent except Antarctica and they remain strictly confined to certain habitats.
Yet the remarkable truth is that we come from a long line of failures. We are apes, a group that almost went extinct fifteen million years ago in competition with the better-designed monkeys. We are primates, a group of mammals that almost went extinct forty-five million years ago in competition with the better-designed rodents. We are synapsid tetrapods, a group of reptiles that almost went extinct 200 million years ago in competition with the better-designed dinosaurs. We are descended from limbed fishes, which almost went extinct 360 million years ago in competition with the better-designed ray-finned fishes. We are chordates, a phylum that survived the Cambrian era 500 million years ago by the skin of its teeth in competition with the brilliantly successful arthropods. Our ecological success came against humbling odds. In the four billion years since Luca, the word grew adept at building what Richard Dawkins has called 'survival machines': large, fleshy entities known as bodies that were good at locally reversing entropy the better to replicate the genes within them. They had done this by a venerable and massive process of trial and error, known as natural selection.  
Three billion years during which trillions of trillions of single-celled creatures lived, each one reproducing and dying every few days or so, amounts to a big heap of trial and error. But it turned out that life was not finished. About a billion years ago, there came, quite suddenly, a new world order, with the invention of bigger, multicellular bodies, a sudden explosion of large creatures. Within the blink of a geological eye (the so-called Cambrian explosion may have lasted a mere ten or twenty million years), there were vast creatures of immense complexity: scuttling trilobites nearly a foot long; slimy worms even longer; waving algae half a yard across. Single-celled creatures still dominated, but these great unwieldy forms of giant survival machines were carving out a niche for themselves.
Apart from the fusion of chromosome 2, visible differences between chimp and human chromosomes are few and tiny. We are, to a ninety-eight per cent approximation, chimpanzees, and they are, with ninety-eight per cent confidence limits, human beings. If you took two Plasticene amoebae and turned one into a chimpanzee, the other into a human being, almost all the changes you would make would be the same. Both would need thirty-two teeth, five fingers, two eyes, four limbs and a liver.  There is no bone in the chimpanzee body that I do not share.
In a last, desperate defence of his species against the theory of descent from the apes, the Victorian anatomist Sir Richard Owen once claimed that the hippocampus minor was a brain lobe unique to human brains, so it must be the seat of the soul and the proof of divine creation. He could not find the hippocampus minor in the freshly pickled brains of gorillas brought back from the Congo by the adventurer Paul du Chaillu. Thomas Henry Huxley furiously responded that the hippocampus minor was there in ape brains. 'No, it wasn't', said Owen. Was, too', said Huxley. Huxley, by the way, was right. After all, it is less than 300,000 human generations since the common ancestor of both species lived in central Africa.
Five million years is a long time, but evolution works not in years but in generations. Bacteria can pack in that many generations in just twenty-five years.
Whatever the mechanism, we can guess that our ancestors were a small, isolated band, while those of the chimpanzees were the main race. We can guess this because we know from the genes that human beings went through a much tighter genetic bottleneck (i.e., a small population size) than chimpanzees ever did: there is much less random variability in the human genome than the chimp genome.

In his work at St Bartholomew's Hospital and Great Ormond Street in London, Garrod had come across a number of patients with a rare and not very serious disease, known as alkaptonuria. Among other more uncomfortable symptoms such as arthritis, their urine and the ear wax turned reddish or inky black on exposure to the air, depending on what they had been eating. In 1901, the parents of one of these patients, a little boy, had a fifth child who also had the affliction. That set Garrod to thinking about whether the problem ran in families. He noticed that the two children's parents were first cousins. So he went back and re-examined the other cases: three of the four families were first-cousin marriages, and of the seventeen alkaptonuria cases he saw, eight were second cousins of each other. But the affliction was not simply passed on from parent to child. Most sufferers had normal children, but the disease could reappear later in their descendants.

Garrod knew he was dealing with a Mendelian recessive - a character that could be carried by one generation but would only be expressed if inherited from both parents. 

Thus was born Garrod's bold hypothesis of the 'inborn errors of metabolism', with its far-reaching assumption that genes were there to produce chemical catalysts, one gene to each highly specialised catalyst. Perhaps that was what genes were: devices for making proteins. 'Inborn errors of metabolism', Garrod wrote, 'are due to the failure of a step in the metabolic sequence due to loss or malfunction of an enzyme.' Since enzymes are made of protein, they must be the 'seat of chemical individuality'. Garrod's book, published in 1909, was widely and positively reviewed, but his reviewers comprehensively missed the point. They thought he was talking about rare diseases, not something fundamental to all life.

We now know that the main purpose of genes is to store the recipe for making proteins. It is proteins that do almost every chemical, structural and regulatory thing that is done in the body: they generate energy, fight infection, digest food, form hair, carry oxygen and so on and on. Every single protein in the body is made from a gene by a translation of the genetic code.

Garrod's conjecture is basically correct: what we inherit from our parents is a gigantic list of recipes for making proteins and for making protein-making machines - and little more.

Christened Johann Mendel, he was born in the tiny village of Heinzendorf (now Hynoice) in Northern Moravia in 1822. His father, Anton, was a smallholder who paid his rent in work for his landlord; his health and livelihood were shattered by a falling tree when Johann was sixteen and doing well at the grammar school in Troppau. Anton sold the farm to his son-in-law so he could afford the fees for his son at school and then at university in Olmiitz. But it was a struggle and Johann needed a wealthier sponsor, so he became an Augustinian friar, taking the name Brother Gregor. He trundled through theological college in Brunn (now Brno) and emerged a priest. He did a stint as a parish priest, but it was not a success. He tried to become a science teacher after studying at Vienna University, but failed the examination. Back to Brunn he went, a thirty-one-year-old nonentity, fit only for monastic life. He was good at mathematics and chess playing, had a decent head for figures and possessed a cheerful disposition. He was also a passionate gardener, having learnt from his father how to graft and breed fruit trees. It is here, in the folk knowledge of the peasant culture, that the roots of his insight truly lay. The rudiments of particulate inheritance were dimly understood already by the breeders of cattle and apples, but nobody was being systematic.

So Father Mendel, aged thirty-four, started a series of experiments on peas in the monastery gardens that were to last eight years, involve the planting of over 30,000 different plants - 6,000 in 1860 alone - and eventually change the world forever. In the garden, Mendel had been hybridising: crossing different varieties of pea plant. But this was no amateur gardener playing at science; this was a massive, systematic and carefully thought-out experiment. Mendel chose seven pairs of varieties of peas to cross. He crossed round-seeded peas with wrinkled ones; yellow cotyledons with green ones; inflated seed pods with wrinkled seed pods; grey seed coats with white seed coats; green unripe pods with yellow unripe pods; axial flowers with terminal flowers; tall stems with dwarf stems. 

In every case, the resulting hybrids were always like just one parent. The other parent's essence seemed to have vanished. But it had not: Mendel allowed the hybrids to self-fertilise and the essence of the missing grandparent reappeared intact in roughly one-quarter of the cases. He counted and counted - 19,959 plants in the second generation, with the dominant characters outnumbering the recessives by 14,949 to 5,010, or 2.98 to 1.

Like a man possessed, Mendel turned from peas to fuschias, maize and other plants. He found the same results. He knew that he had discovered something profound about heredity: characteristics do not mix. There is something hard, indivisible, quantum and particulate at the heart of inheritance. There is no mingling of fluids, no blending of blood; there is instead a temporary joining together of lots of little marbles. In retrospect, this was obvious all along. How else could people account for the fact that a family might contain a child with blue eyes and a child with brown? Darwin, who none the less based his theory on blending inheritance, hinted at the problem several times. 'I have lately been inclined to speculate', he wrote to Huxley in 1857, 'very crudely and indistinctly, that propagation by true fertilisation will turn out to be a sort of mixture, and not true fusion, of two distinct individuals . . . 

Darwin was not a little nervous on the subject. He had recently come under attack from a fierce Scottish professor of engineering, strangely named Fleeming Jenkin, who had pointed out the simple and unassailable fact that natural selection and blending inheritance did not mix. If heredity consisted of blended fluids, then Darwin's theory probably would not work, because each new and advantageous change would be lost in the general dilution of descent. Jenkin illustrated his point with the story of a white man attempting to convert an island of black people to whiteness merely by breeding with them. His white blood would soon be diluted to insignificance. In his heart Darwin knew Jenkin was right, and even the usually ferocious Thomas Henry Huxley was silenced by Jenkin's argument, but Darwin also knew that his own theory was right. He could not square the two. If only he had read Mendel.

For four years, starting in 1866, Mendel sent his papers and his ideas to Karl-Wilhelm Nageli, professor of botany in Munich. With increasing boldness he tried to point out the significance of what he had found. For four years Nageli missed the point. He wrote back to the persistent monk polite but patronising letters, and told him to try breeding hawkweed. He could not have given more mischievous advice if he tried: hawkweed is apomictic, that is it needs pollen to breed but does not incorporate the genes of the pollinating partner, so cross-breeding experiments give strange results. After struggling with hawkweed Mendel gave up and turned
to bees. The results of his extensive experiments on the breeding of bees have never been found. Did he discover their strange 'haplodiploid' genetics?

Muller's great discovery, for which he was to win the Nobel prize, was that genes are artificially mutable.
By bombarding fruit flies with X-rays, Muller caused their genes to mutate so that their offspring sported new deformities.
Like atoms, Mendel's particles must have some internal structure, too. They could be changed by X-rays. They were still genes after mutation, but not the same genes.

Using Muller's X-rays, in 1940 two scientists named George Beadle and Edward Tatum created mutant versions of a bread mould called Neurospora. They then worked out that the mutants failed to make a certain chemical because they lacked the working version of a certain enzyme. They proposed a law of biology, which caught on and has proved to be more or less correct: one gene specifies one enzyme.

Muller, meanwhile, was out of the picture. In 1932 his fervent socialism and his equally fervent belief in the selective breeding of human beings, eugenics (he wanted to see children carefully bred with the character of Marx or Lenin, though in later editions of his book he judiciously altered this to Lincoln and Descartes), led him across the Atlantic to Europe. He arrived in Berlin just a few months before Hitler came to power. He watched, horrified, as the Nazis smashed the laboratories of his boss, Oscar Vogt, for not expelling the Jews under his charge. Muller went east once more, to Leningrad, arriving in the laboratory of Nikolay Vavilov just before the anti-Mendelist Trofim Lysenko caught the ear of Stalin and began his persecution of Mendelian geneticists in support of his own crackpot theories that wheat plants, like Russian souls, could be trained rather than bred to new regimes; and that those who believed otherwise should not be persuaded, but shot. Vavilov died in prison. Ever hopeful, Muller sent Stalin a copy of his latest eugenic book, but hearing it had not gone down well, found an excuse to get out of the country just in time. He went to the Spanish Civil War, where he worked in the blood bank of the International Brigade, and thence to Edinburgh,
arriving with his usual ill luck just in time for the outbreak of the Second World War. He found it hard to do science in a blacked-out Scottish winter wearing gloves in the laboratory and he tried desperately to return to America. But nobody wanted a belligerent, prickly socialist who lectured ineptly and had been living in Soviet Russia. Eventually Indiana University gave him a job. The following year he won the Nobel prize for his discovery of artificial mutation.

True, there was something else in chromosomes: that dull little nucleic acid called DNA. It had first been isolated, from the pus-soaked bandages of wounded soldiers, in the German town of Tubingen in 1869 by a Swiss doctor named Friedrich Miescher.

Drawn by the presence of Muller, there arrived in Bloomington, Indiana, a precocious and confident nineteen-year-old, already equipped with a bachelor's degree, named James Watson. He must have seemed an unlikely solution to the gene problem, but the solution he was. Trained at Indiana University by the Italian emigre Salvador Luria (predictably, Watson did not hit it off with Muller), Watson developed an obsessive conviction that genes were made of DNA, not protein. In search of vindication, he went to Denmark, then, dissatisfied with the colleagues he found there, to Cambridge in October 1951. Chance threw him together in the Cavendish laboratory with a mind of equal brilliance captivated by the same conviction about the importance of DNA, Francis Crick.

But he did not have the patience to stick to his own problems, or the humility to stick to small questions. His laugh, his confident intelligence and his knack of telling people the answers to their own scientific questions were getting on nerves at the Cavendish.

So was born one of the great, amicably competitive and therefore productive collaborations in the history of science: the young, ambitious, suppleminded American who knew some biology and the effortlessly brilliant but unfocused older Briton who knew some physics. It was an exothermic reaction. Within a few short months, using other people's laboriously gathered but under-analysed facts, they had made possibly the greatest scientific discovery of all time, the structure of DNA. Not even Archimedes leaping from his bath had been granted greater reason to boast, as Francis Crick did in the Eagle pub on 28 February 1953, 'We've discovered the secret of life.' Watson was mortified; he still feared that they might have made a mistake. But they had not. All was suddenly clear: DNA contained a code written along the length of an elegant, intertwined staircase of a double helix, of potentially infinite length. That code copied itself by means of chemical affinities between its letters and spelt out the recipes for proteins by means of an as yet unknown phrasebook linking DNA to protein.

A month after the Watson-Crick structure was published, Britain crowned a new queen and a British expedition conquered Mount Everest on the same day. Apart from a small piece in the News Chronicle, the double helix did not make the newspapers. 

Finding the code had been, for Watson and Crick, almost easy — a mixture of guesswork, good physics and inspiration. Cracking the code required true brilliance.

Most of the best ideas that led to the answer came from Crick, including what he called the adaptor molecule - what we now call transfer RNA. Independendy of all evidence, Crick arrived at the conclusion that such a molecule must exist. It duly turned up. But Crick also had an idea that was so good it has been called the greatest wrong theory in history. Crick's 'comma-free' code is more elegant than the one Mother Nature uses. It works like this. Suppose that the code uses three letters in each word (if it uses two, that only gives sixteen combinations, which is too few). Suppose that it has no commas, and nogapsbetweenthewords. Now suppose that it excludes all words that can be misread if you start in the wrong place. So, to take an analogy used by Brian Hayes, imagine all three-letter English words that can be written with the four letters A, S, E and T: ass, ate, eat, sat, sea, see, set, tat, tea and tee. Now eliminate those that can be misread as another word if you start in the wrong place. For example, the phrase ateateat can be misread as 'a tea tea t' or as 'at eat eat' or as 'ate ate at'. Only one of these three words can survive in the code. Crick did the same with A, C, G and T. He eliminated AAA, CCC, GGG and TTT for a start. He then grouped the remaining sixty words into threes, each group containing the same three letters in the same rotating order. For example, ACT, CTA and TAC are in one group, because C follows A, T follows C, and A follows T in each; while ATC, TCA and CAT are in another group. Only one word in each group survived. Exactly twenty are left - and there are twenty amino acid letters in the protein alphabet! A fourletter code gives a twenty-letter alphabet.

But the time for theorising was past. In 1961, while everybody else was thinking, Marshall Nirenberg and Johann Matthaei decoded a 'word' of the code by the simple means of making a piece of RNA out of pure U (uracil - the equivalent of DNA' s T) and putting it in a solution of amino acids. The ribosomes made a protein by stitching together lots of phenylalanines. The first word of the code had been cracked: UUU means phenylalanine. The commafree code was wrong, after all. Its great beauty had been that it cannot have what are called reading-shift mutations, in which the loss of one letter makes nonsense of all that follows. Yet the version that Nature has instead chosen, though less elegant, is more tolerant of other kinds of errors. It contains much redundancy with many different three-letter words meaning the same thing.

Wolf-Hirschhorn syndrome is so rare and so serious - its gene is so vital — that its victims die young. A mutated version of the gene causes Huntington's chorea; a complete lack of the gene causes Wolf-Hirschhorn syndrome.
The gene contains a single 'word', repeated over and over again: CAG, CAG, CAG, CAG . . . The repetition continues sometimes just six times, sometimes thirty, sometimes more than a hundred times. Your destiny, your sanity and your life hang by the thread of this repetition. If the 'word' is repeated thirty-five times or fewer, you will be fine.
The age at which the madness will appear depends strictly and implacably on the number of repetitions of the 'word' CAG in one place in one gene.
The scale is this: if your chromosomes were long enough to stretch around the equator, the difference between health and insanity would be less than one extra inch. No horoscope matches this accuracy. No theory of human causality, Freudian, Marxist, Christian or animist, has ever been so precise. No prophet in the Old Testament, no entrail-gazing oracle in ancient Greece, no crystal-ball gipsy clairvoyant on the pier at Bognor Regis ever pretended to tell people exactly when their lives would fall apart, let alone got it right. We are dealing here with a prophecy of terrifying, cruel and inflexible truth. There are a billion three-letter 'words' in your genome. Yet the length of just this one little motif is all that stands between each of us and mental illness. Huntington's disease, which became notorious when it killed the folk singer Woody Guthrie in 1967, was first diagnosed by a doctor, George Huntington, in 1872 on the eastern tip of Long Island. He noticed that it seemed to run in families. Later work revealed that the Long Island cases were part of a much larger family tree originating
in New England. In twelve generations of this pedigree more than a thousand cases of the disease could be found. All were descended from two brothers who emigrated from Suffolk in 1630. Several of their descendants were burnt as witches in Salem in 1693, possibly because of the alarming nature of the disease. But because the mutation only makes itself manifest in middle age, when people have already had children, there is little selective pressure on it to
die out naturally. Indeed, in several studies, those with the mutations appear to breed more prolifically than their unaffected siblings. Huntington's was the first completely dominant human genetic disease to come to light. That means it is not like alkaptonuria in which you must have two copies of the mutant gene, one from each parent, to suffer the symptoms. Just one copy of the mutation will do. 
In the late 1970s, a determined woman set out to find the Huntington gene. Acting on the report of a Venezuelan doctor, Americo Negrette, in 1979 she flew to Venezuela to visit three rural villages called San Luis, Barranquitas and Laguneta on the shores of Lake Maracaibo. The area contained a vast, extended family with a high incidence of Huntington's disease. The story they told each other was that the affliction came from an eighteenth-century sailor, and Wexler was able to trace the family tree of the disease back to the early nineteenth century and a woman called, appropriately, Maria Conception. She lived in the Pueblos de Agua, villages of houses built on stilts over the water. A fecund ancestor, she had 11,000 descendants in eight generations, 9,000 of whom were still alive in 1981. No less than 371 of them had Huntington's disease when Wexler first visited and 3,600 carried a risk of at least a quarter that they would develop the disease, because at least one grandparent had the symptoms. Wexler's courage was extraordinary, given that she too might have the mutation. 'It is crushing to look at these exuberant children', she wrote,4 'full of hope and expectation, despite poverty, despite illiteracy, despite dangerous and exhausting work for the boys fishing in small boats in the turbulent lake, or for even the tiny girls tending house and caring for ill parents, despite a brutalising disease robbing them of parents, grandparents, aunts, uncles, and cousins - they are joyous and wild with life, until the disease attacks.'
The most unexpected feature of the stuttering repetition of the word CAG is that it is not confined to Huntington's disease. There are five other neurological diseases caused by so-called 'unstable CAG repeats' in entirely different genes
Moreover, there are other diseases of nerve degeneration caused by other stuttering repeats of 'words' and in every case the repeated 'word' begins with C and ends in G.

Instinct is a word applied to animals: the salmon seeking the stream of its birth; the digger wasp repeating the behaviour of its long-dead parents; the swallow migrating south for the winter - these are instincts. Human beings do not have to rely on instinct; they learn instead; they are creative, cultural, conscious creatures. Everything they do is the product of free will, giant brains and brainwashing parents.
In one case, in Nicaragua, special schools for the deaf, established for the first time in the 1980s, led to the invention, de novo, of a whole new language. The schools taught lip-reading with little success, but in the playground the children brought together the various hand signs they used at home and established a crude pidgin language. Within a few years, as younger children learnt this pidgin, it was transformed into a true sign language with all the complexity, economy, efficiency and grammar of a spoken language. Once again, it was children who made the language, a fact that seems to suggest that the language instinct is one that is switched off as the child reaches adulthood. 
For example, if Gopnik shows somebody a cartoon of an imaginary creature and with it the words 'This is a Wug', then shows them a picture of two such creatures together with the words 'These are . . .', most people reply, quick as a flash, 'Wugs'. Those with SLI rarely do so, and if they do, it is after careful thought. The English plural rule, that you add an 's' to the end of most words, is one they seem not to know. This does not prevent those with SLI knowing the plural of most words, but they are stumped by novel words that they have not seen before, and they make the mistake of adding 's' to fictitious words that the rest of us would not, such as 'saess'. Gopnik hypothesises that they store English plurals in their minds as separate lexical entries, in the same way that we all store singulars. They do not store the grammatical rule.

Mother Nature concealed a dirty little secret in the genome. Each gene is far more complicated than it needs to be, it is broken up into many different 'paragraphs' (called exons) and in between lie long stretches (called introns) of random nonsense and repetitive bursts of wholly irrelevant sense, some of which contain real genes of a completely different (and sinister) kind. The reason for this textual confusion is that the genome is a book that wrote itself, continually adding, deleting and amending over four billion years. Documents that write themselves have unusual properties. In particular, they are prone to parasitism.
Actually, with the advent of email, the analogy is no longer as farfetched as it once was. Suppose I sent you an email that read: 'Beware, there is a nasty computer virus about; if you open a message with the word "marmalade" in the title, it will erase your hard disk! Please pass this warning on to everybody you can think of.' I made up the bit about the virus; there are, so far as I know, no emails called 'marmalade' doing the rounds. But I have very effectively hijacked your morning and caused you to send on my warning. My email was the virus.
Genes, remember, are stretches of DNA that comprise the recipe for proteins. But ninety-seven per cent of our genome does not consist of true genes at all. It consists of a menagerie of strange entities called pseudogenes, retropseudogenes, satellites, minisatellites, microsatellites, transposons and retrotransposons: all collectively known as 'junk DNA' , or sometimes, probably more accurately, as 'selfish DNA' . Some of these are genes of a special kind, but most are just chunks of DNA that are never transcribed into the language of protein.
Yet, ironically, junk DNA is the first part of the human genome that has found a real, practical, everyday use in the human world. It has led to DNA fingerprinting. Genes are protein recipes. But not all protein recipes are desirable. The commonest protein recipe in the entire human genome is the gene for a protein called reverse transcriptase. Reverse transcriptase is a gene that serves no purpose at all as far as the human body is concerned. If every copy of it were carefully and magically removed from the genome of a person at the moment of conception, the person's health, longevity and happiness would be more likely to be improved than damaged. Reverse transcriptase is vital for a certain kind of parasite. It is an extremely useful — nay essential - part of the genome of the AIDS virus: a crucial contributor to its ability to infect and kill its victims. For human beings, in contrast, the gene is a nuisance and a threat. Yet it is one of the commonest genes in the whole genome. There are several hundred copies of it, possibly thousands, spread about the human chromosomes. This is an astonishing fact, akin to discovering that the commonest use of cars is for getting away from crimes. Why is it there? A clue comes from what reverse transcriptase does. It takes an RNA copy of a gene, copies it back into DNA and stitches it back into the genome. It is a return ticket for a copy of a gene. By this means the AIDS virus can integrate a copy of its own genome into human DNA the better to conceal it, maintain it and get it efficiently copied. A good many of the copies of the reverse transcriptase gene in the human genome are there because recognisable 'retroviruses' put them there, long ago or even relatively recently. There are several thousand nearly complete viral genomes integrated into the human genome, most of them now inert or missing a crucial gene. These 'human endogenous retroviruses' or Hervs, account for 1.3% of the entire genome. That may not sound like much, but 'proper' genes account for only 3%.
A true genetic parasite. Such 'retrotransposons' are far commoner even than retroviruses. The commonest of all is a sequence of 'letters' known as a LINE-1. This is a 'paragraph' of DNA, between a thousand and six thousand 'letters' long, that includes a complete recipe for reverse transcriptase near the middle. LINE-1s are not only very common - there may be 100,000 copies of them in each copy of your genome — but they are also gregarious, so that the paragraph may be repeated several times in succession on the chromosome. They account for a staggering 14.6% of the entire genome, that is, they are nearly five times as common as 'proper' genes. The implications of this are terrifying. LINE-1s have their own return tickets. A single LINE-1 can get itself transcribed, make its own reverse transcriptase, use that reverse transcriptase to make a DNA copy of itself and insert that copy anywhere among the genes. This is presumably how there come to be so many copies of LINE- 1 in the first place. In other words, this repetitive 'paragraph' of 'text' is there because it is good at getting itself duplicated - no other reason.
Even commoner than LINE-1s are shorter 'paragraphs' called Alus. Each Alu contains between 180 and 280 'letters', and seems to be especially good at using other people's reverse transcriptase to get itself duplicated. The Alu text may be repeated a million times in the human genome - amounting to perhaps ten per cent of the entire 'book'.
We are full of digital chain letters and warnings about marmalade. Approximately thirtyfive per cent of human DNA consists of various forms of selfish DNA, which means that replicating our genes takes thirty-five per cent more energy than it need.
 There are worms in animals' guts, bacteria in their blood, viruses in their cells. Why not retrotransposons in their genes? Moreover, by the mid-1970s, it was dawning on many evolutionary biologists, especially those interested in behaviour, that evolution by natural selection was not much about competition between species, not much about competition between groups, not even mostly about competition between individuals, but was about competition between genes using individuals and occasionally societies as their temporary vehicles. For instance, given the choice between a safe, comfortable and long life for the individual or a risky, tiring and dangerous attempt to breed, virtually all animals (and indeed plants) choose the latter. They choose to shorten their odds of death in order to have offspring. Indeed, their bodies are designed with planned obsolescence called ageing that causes them to decay after they reach breeding age — or, in the case of squid or Pacific salmon, to die at once. None of this makes any sense unless you view the body as a vehicle for the genes, as a tool used by genes in their competition to perpetuate themselves. The body's survival is secondary to the goal of getting another generation started. 
To explain the fact that the genome contained huge gene-less regions, two pairs of scientists suggested in 1980 that these regions were replete with selfish sequences whose only function was survival within the genome.
Genes do indeed behave as if they have selfish goals, not consciously, but retrospectively: genes that behave in this way thrive and genes that don't don't.
In human beings, LINE-1s and Alus have caused mutations by landing in the middle of all sorts of genes. They have caused haemophilia, for instance, by landing in clotting-factor genes. But, for reasons that are not well understood, as a species we are less troubled by DNA parasites than some other species. Approximately 1 in every 700 human mutations is caused by 'jumping genes', whereas in mice nearly ten per cent of mutations are caused by jumping genes. The potential danger posed by jumping genes was dramatically illustrated by a sort of natural experiment in the 1950s in the tiny fruit fly, Drosophila. The fruit fly is the favourite experimental animal for geneticists. The species they study, called Drosophila melanogaster, has been transported all over the world to be bred in laboratories. It has frequently escaped and has met other, native species of fruit fly. One of these species, called Drosophila willistoni, carries a jumping gene called a P element. Somehow in about 1950, somewhere in South America, perhaps via a blood-sucking mite, Drosophila willistoni's jumping gene entered the Drosophila melanogaster species. (One of the great concerns attached to so-called 'xeno-transplants' of organs from pigs or baboons is that they might unleash a new form of jumping gene upon our species, like the P element of fruit flies.) The P element has since spread like wildfire, so that most fruit flies have the P element, though not those collected from the wild before 1950 and kept in isolation since. The P element is a piece of selfish DNA that shows its presence by disrupting the genes into which it jumps. Gradually, the rest of the genes in the fruit fly's genome have fought back, inventing ways of suppressing the P element's jumping habit. The P elements are settling down as passengers.
Human beings possess nothing so sinister as a P element, at least not at the moment. 
What we see in the human genome is not some rapidly advancing parasitic infection, but the dormant cysts of many past parasites, each of which spread rapidly until the genome found a way of suppressing them, but not excising them. In this respect (as in others) we seem to be more fortunate than fruit flies. We appear to have a general mechanism for suppressing selfish DNA, at least if you believe a controversial new theory. The suppression mechanism goes by the name of cytosine methylation.
The new theory holds that during the early development of the embryo, all genes are briefly stripped of any methylation and switched on. This is then followed by a close inspection of the whole genome by molecules whose job is to spot repetitive sequences and close them down with methylation. In cancer tumours, one of the first things to happen is demethylation of the genes. As a result, the selfish DNA is released from its handcuffs and richly expressed in tumours. 
LINE-1 is generally about 1,400 'letters' long. Alu is generally at least 180 'letters' long. There are, however, sequences even shorter than Alu that also accumulate in vast, repetitive stutters.
It is one of these short sequences that has a practical use in forensic and other sciences. Meet the 'hypervariable minisatellite'. This neat little sequence is found on all the chromosomes; it crops up at more than one thousand locations in the genome. In every case the sequence consists of a single 'phrase', usually about twenty 'letters' long, repeated over and over again many times. 
Following instructions, the cell starts swapping the phrases with the equivalent series on the other copy of the same chromosome. But in doing so it makes fairly frequent mistakes, adding or subtracting to the number of repeats. In this way each series of repeats gradually changes length, fast enough so that it is different in every individual, but slowly enough so that people mostly have the same repeat lengths as their parents. Since there are thousands of series, the result is a unique set of numbers for each individual.

The first and best known of the blood group systems is the ABO system. 

People with type A blood could safely donate to those with A or AB; those with B could donate to those with B and AB; those with AB could donate only to those with AB; and those with O blood could donate to anybody - O is therefore known as the universal donor. Nor was there any obvious geographic or racial reason underlying the different types. Roughly forty per cent of Europeans have type O blood, forty per cent have type A blood, fifteen per cent have type B blood and five per cent have type AB blood. The proportions are similar in other continents, with the marked exception of the Americas, where the native American population was almost exclusively type O, save for some Canadian tribes, who were very often type A, and Eskimos, who were sometimes type AB or B.

The difference between the A gene and the B gene is seven letters out of 1,062, of which three are synonymous or silent: that is, they make no difference to the amino acid chosen in the protein chain. The four that matter are letters 523, 700, 793 and 800. In people with type A blood these letters read C, G, C, G. In people with type B blood they read G, A, A, C. 

The O group has just a single spelling change compared with A, but instead of a substitution of one letter for another, it is a deletion. In people with type O blood, the 258th letter, which should read 'G', is missing altogether. The effect of this is far-reaching, because it causes what is known as a reading-shift or frame-shift mutation, which is far more consequential. (Recall that if Francis Crick's ingenious comma-free code of 1957 had been correct, reading-shift mutations would not have existed.) The genetic code is read in three-letter words and has no punctuation. An English sentence written in three-letter words might read something like: the fat cat sat top mat and big dog ran bit cat. Not exactly poetry, I admit, but it will do. Change one letter and it still makes fairly good sense: the fat xat sat top mat and big dog ran bit cat. But delete the same letter instead, and read the remaining letters in groups of three, and you render the whole sentence meaningless: the fat ats att opm ata ndb igd ogr anb itc at. This is what has happened to the ABO gene in people with the O blood group. Because they lack just one letter fairly early in the message, the whole subsequent message says something completely different. A different protein is made with different properties. The chemical reaction is not catalysed.

Indeed, the remarkable thing about blood groups, the thing that has made them so useful and so politically neutral, is that they seem to be completely invisible; they correlate with nothing.

At first glance the blood groups seem to be an example of the neutral theory of evolution, promulgated by Motoo Kimura in 1968: the notion that most genetic diversity is there because it makes no difference, not because it has been picked by natural selection for a purpose.

Remember that we each have two copies of each chromosome, so A people are actually AAs, that is they have an A gene on each of their ninth chromosomes, and B people are actually BBs. Now imagine a population with just these three kinds of blood groups: AA, BB and AB. The A gene is better for cholera resistance than the B gene. AA people are therefore likely to have more surviving children than BB people. Therefore the B gene is likely to die out - that's natural selection. But it doesn't happen like that, because AB people survive best of all. So the healthiest children will be the offspring of AAs and BBs. All their children will be AB, the most cholera-resistant type. But even if an AB mates with another AB, only half their children will be AB; the rest will be AA and BB, the latter being the most susceptible type. It is a world of strangely fluctuating fortunes.

 The sickle-cell mutation, which causes blood cells to collapse in the absence of oxygen, is frequently fatal to those with two copies of it, but only mildly harmful to those with just one copy. But those with one copy are largely resistant to malaria.

Sickle-cell disease is a high price paid today for malaria resistance in the past.
​
Approximately one in five people are genetically unable to release the water-soluble form of the ABO blood group proteins into their saliva and other body fluids. These 'non-secretors' are more likely to suffer from various forms of disease, including meningitis, yeast infection and recurrent urinary tract infection. But they are less likely to suffer from influenza or respiratory syncitial virus. Wherever you look, the reasons behind genetic variability seem to have something to do with infectious disease. We have barely scratched the surface of this subject. As they scourged our ancestors, the great epidemic diseases of the past - plague, measles, smallpox, typhus, influenza, syphilis, typhoid, chicken pox, and others - left behind their imprint on our genes. Mutations which granted resistance thrived, but that resistance often came at a price, the price varying from severe (sickle-cell anaemia) to theoretical (the inability to receive transfusions of the wrong type of blood).

There is a gene on chromosome 10 called CYP17. It makes an enzyme, which enables the body to convert cholesterol into Cortisol, testosterone and oestradiol.
Cortisol is used in virtually every system in the body, a hormone that literally integrates the body and the mind by altering the configuration of the brain. Cortisol interferes with the immune system, changes the sensitivity of the ears, nose and eyes, and alters various bodily functions. When you have a lot of Cortisol coursing through your veins, you are - by definition — under stress.

Short-term stressors cause an immediate increase in epinephrine and norepinephrine, the hormones that make the heart beat faster, the feet go cold.
Stressors that last for longer activate a different pathway that results in a much slower, but more persistent increase in Cortisol. One of Cortisol's most surprising effects is that it suppresses the working of the immune system.
Those who lived near Three Mile Island nuclear plant at the time of its accident had more cancers than expected three years later, not because they were exposed to radiation (they weren't), but because their Cortisol levels had risen, reducing the responsiveness of their immune system to cancer cells.
People with most psychological stress in their past get more colds than people who have led happy lives.
You can trigger activity in the 'happiness centres' of the brain with a deliberate smile, as surely as you trigger a smile with happy thoughts. It really does make you feel better to smile.
By consistently choosing which males to mate with over many generations, female animals can alter the shape, colour, size or song of males of their species. Indeed, as I described in the chapter on chromosomes X and Y, Darwin suggested that this is exactly what has happened in the case of peacocks. It was not until a century later, in the 1970s and 1980s, that a series of theoretical and experimental studies demonstrated that Darwin was right, and that the tails, plumes, antlers, songs and size of male animals are bred into them by consistent trends of passive or active female choice, generation after generation.

Dopamine is perhaps the brain's motivation chemical. Too little and the person lacks initiative and motivation. Too much and the person is easily bored and frequently seeks new adventures.

  The gene for blue eyes is common in people who are bad at using chopsticks, but nobody would dream of suggesting that chopstick skill is genetically determined by the gene for eye colour. It just happens that both blue eyes and chopstick incompetence correlate with non-oriental origin for a blindingly obvious non-genetic reason called culture. 

People with 'long' D4DR genes have low responsiveness to dopamine, so they need to take a more adventurous approach to life to get the same dopamine 'buzz' that short-gened people get from simple things. 

Marriage counsellors, too, report good results from encouraging their clients to accept that they cannot change their partners' irritating habits - because they are probably innate - but must find ways to live with them.

Shy adolescents were more likely to be blue-eyed (all the subjects were of European descent), susceptible to allergies, tall and thin, narrow-faced, to have more heat-generating activity under the right forehead and a faster heartbeat, than the less shy individuals. All of these features are under the control of a particular set of cells in the embryo called the neural crest, from which a particular part of the brain, the amygdala, derives. They also all use the same neurotransmitter, called norepinephrine, a substance very like dopamine. All these features are also characteristic of northern Europeans, Nordic types for the most part. Kagan's argument goes that the Ice Age selected those better able to withstand cold in these parts: people with high metabolic rates. But a high metabolic rate is produced by an active norepinephrine system in the amygdala, and brings with it lots of different baggage - a phlegmatic and shy personality being one aspect and a pale appearance being another. 

  If you have unusually high levels of serotonin in your brain you will probably be a compulsive person, given to tidiness and caution, even to the point of being neurotic about it. People with the pathological condition known as obsessive—compulsive disorder can usually alleviate their symptoms by lowering their serotonin levels. At the other end of the spectrum, people with unusually low serotonin levels in their brains tend to be impulsive.  
​
Increased serotonin alleviates anxiety and depression and can turn even fairly ordinary people into optimists

Indeed, even drugs and diets designed to lower blood cholesterol can influence serotonin. It is a curious fact that nearly all studies of cholesterol-lowering drugs and diets in ordinary people show an increase in violent death compared with control samples that usually matches the decrease in deaths from heart disease. In all studies put together, cholesterol treatment cut heart attacks by fourteen per cent, but raised violent deaths by an even more significant seventy-eight per cent. Because violent deaths are rarer than heart attacks, the numerical effect roughly cancels out, but violent deaths can sometimes involve innocent bystanders. So treating high cholesterol levels has its dangers. It has been known for twenty years that impulsive, antisocial and depressed people - including prisoners, violent offenders and failed suicides - have generally lower cholesterol levels than the population at large.

In the so-called MrFit trial, in which 351,000 people from seven countries were followed for seven years, people with very low cholesterol and people with very high cholesterol proved twice as likely to die at a given age as people with medium cholesterol. The extra deaths among low-cholesterol people are mainly due to accident, suicide or murder.

The link between low cholesterol and violence almost certainly involves serotonin. Monkeys fed on low-cholesterol diets become more aggressive and bad-tempered (even if they are not losing weight), and the cause seems to be a drop in serotonin levels.

Low serotonin is an accurate predictor of aggressiveness in monkeys, just as it is an accurate predictor of impulsive murder, suicide, fighting or arson in human beings.

Serotonin levels are not innate and inflexible. They are themselves the product of social status. The higher your selfesteem and social rank relative to those around you, the higher your serotonin level is. Experiments with monkeys reveals that it is the social behaviour that comes first. Serotonin is richly present in dominant monkeys and much more dilute in the brains of subordinates. Cause or effect? Almost everybody assumed the chemical was at least partly the cause: it just stands to reason that the dominant behaviour results from the chemical, not vice versa. It turns out to be the reverse: serotonin levels respond to the monkey's perception of its own position in the hierarchy, not vice versa. Contrary to what most people think, high rank means low aggressiveness, even in vervet monkeys. The high-ranking individuals are not especially large, fierce or violent. They are good at things like reconciliation and recruiting allies. They are notable for their calm demeanour. They are less impulsive, less likely to misinterpret playfighting as aggression. 

There is little doubt that the monkey's mood is set by its high serotonin levels. If you artificially reverse the pecking order so that the monkey is now a subordinate, not only does its serotonin drop, but its behaviour changes, too. Moreover, much the same seems to happen in human beings. In university fraternities, the leading figures are blessed with rich serotonin concentrations which fall if they are deposed. Telling people they have low or high serotonin levels could become a self-fulfilling prophecy.

There is a Dutch family in which the men have been criminals for three generations, and the cause is undoubtedly a gene. The criminal men have an unusual version of a gene on the X chromosome called the monoamine oxidase A gene. Monoamine oxidase is responsible for breaking down serotonin among other chemicals.

In 1786 Sir William Jones, a British judge in Calcutta, announced to a meeting of the Royal Asiatic Society that his studies of the archaic Indian language Sanskrit had led him to conclude that it was a cousin of Latin and Greek. Being a learned fellow he also thought he saw similarities between these three languages and Celtic, Gothic and Persian. They had all, he suggested, 'sprung from some common source'. His reasoning was exactly the same as the reasoning which led modern geneticists to propose the existence of the Roundish Flat Worm of 530 million years ago: similarities of vocabulary. For instance, the word for three is 'tres' in Latin, 'treis' in Greek and 'tryas' in Sanskrit. Of course, the great difference between spoken languages and genetic languages is that there is much more horizontal borrowing of words in spoken language. Perhaps the word for three had somehow been inserted into Sanskrit from a western tongue. But subsequent research has confirmed that Jones was absolutely right and that there was once a single people, speaking a single language in a single place and that descendants of those people brought that language to lands as far apart as Ireland and India, where it gradually diverged into modern tongues.
Where invading men have imposed their language upon a land but married the local women, there should be a distinct set of Y-chromosome genes but a less distinct set of other genes. This is the case in Finland. The Finns are genetically no different from the other western Europeans who surround them, except in one notable respect: they have a distinct Y chromosome, which looks much more like the Y chromosome of northern Asian people.
Iceland is the perfect genetic laboratory because it was settled by such a small group of Norwegians around AD 900, and has seen so little immigration since. Virtually all of the 270,000 Icelanders trace their descent in all lines from those few thousand Vikings who reached Iceland before the little ice age. Eleven hundred years of chilly solitude and a devastating fourteenth-century plague have rendered the island so inbred that it is a happy genetic hunting ground.
A different mutation in the same gene, the deletion of the 6,174th 'letter', is common in people of Ashkenazi Jewish descent. Approximately eight per cent of Jewish breast-cancer cases under the age of forty-two are attributable to this one mutation.
Jewish people retained their genetic integrity by adding few converts to the faith and losing many people who married outsiders. As a result, the Ashkenazim in particular are a favourite people for genetic studies. In the United States the Committee for the Prevention of Jewish Genetic Disease organises the testing of schoolchildren's blood. When matchmakers are later considering a marriage between two young people, they can call a hotline and quote the two anonymous numbers they were each assigned at the testing. If they are both carriers of the same mutation, for Tay-Sachs disease or cystic fibrosis, the committee advises against the marriage. The practical results of this voluntary policy — which was criticised in 1993 by the New York Times as eugenic — are already impressive. Cystic fibrosis has been virtually eliminated from the Jewish population in the United States.
A similar story is taught by a gene on chromosome 1, the gene for lactase. This enzyme is necessary for the digestion of lactose, a sugar abundant in milk. We are all born with this gene switched on in our digestive system, but in most mammals - and therefore in most people — it switches off during infancy. This makes sense: milk is something you drink in infancy and it is a waste of energy making the enzyme after that.
Occasionally, however, the control gene which switches off the lactase gene must suffer a mutation and the lactase production fails to cease at the end of infancy. This mutation allows its carrier to drink and digest milk all through life. Fortunately for the makers of Corn Flakes and Weetabix, most western people have acquired the mutation. More than seventy per cent of western Europeans by descent can drink milk as adults, compared with less than thirty per cent of people from parts of Africa, eastern and south-eastern Asia and Oceania.
The Tutsi of central Africa, the Fulani of western Africa, the Bedouin, Tuareg and Beja of the desert, the Irish, Czech and Spanish people — this list of people has almost nothing in common except that all have a history of herding sheep, goats or cattle. They are the champion milk digesters of the human race. The evidence suggests that such people took up a pastoral way of life first, and developed milk-digesting ability later in response to it.

Dunce is a mutant fruit fly incapable of learning that a certain smell is always followed by an electric shock. Discovered in the 1970s, it was the first of a string of 'learning mutants' to be discovered by giving irradiated flies simple tasks to learn and breeding from those that could not manage the tasks.

​By removing the gene for the CREB protein, he created a fly that could learn, but not remember that it had learnt - the lesson soon faded from its memory.
By systematically searching for other mutant flies incapable of learning or memory, Ronald Davis, Michael Grotewiel and their colleagues in Houston came up with a different kind of mutant fly, which they called volado. ('Volado', they helpfully explain, is a Chilean colloquialism meaning something akin to 'absent-minded' or 'forgetful', and generally applied to professors.)

They took some flies in which the volado gene had been knocked out, and inserted a fresh copy linked with a 'heat-shock' gene - a gene that becomes switched on when suddenly heated up. They had carefully arranged the two so that the volado gene only worked when the heat-shock gene was on. At cool temperatures, the flies could not learn. Three hours after a heat shock, however, they suddenly became good learners. A few hours after that, as the heat shock faded into the past, they again lost the ability to learn. This means that volado is needed at the exact moment of learning; it is not just a gene required to build the structures that do the learning. The fact that the volado gene's job is to make a protein that binds cells together raises the intriguing hint that memory may consist, quite literally, of the tightening of the connections between neurons.
When you learn something, you alter the physical network of your brain so as to create new, tight connections where there were none or weaker ones before. 

​A pyramidal neuron is difficult to 'fire', but if two separate inputs arrive at once, their combined effect will fire it. Once fired, it is much easier to fire but only by one of the two inputs that originally fired it, and not by another input. Thus, the sight of a pyramid and the sound of the word 'Egypt' can combine to fire a pyramidal cell, creating an associative memory between the two, but the thought of a sea-horse, although perhaps connected to the same pyramidal cell, is not 'potentiated' in the same way because it did not coincide in time.
That is an example of long-term potentiation. If you think, too simplistically, of the pyramidal cell as the memory of Egypt, then it can now be fired by the word or the picture, but not by a sea-horse.

Prodded by genes like ced-9, the unneeded cells commit mass suicide (other ced genes cause suicide in other body tissues). The dying cells obediently follow a precise protocol. In microscopic nematode worms, the growing embryo eventually contains 1,090 cells, but precisely 131 of these kill themselves during development, leaving 959 cells in an adult worm. It is as if they sacrifice themselves for the greater good of the body. 'Dulce et decorum est pro corpore mori'' they cry and fade heroically away, like soldiers going over the top at Verdun, or worker bees suicidally stinging an intruder. The analogy is far from specious. The relationship between body cells is indeed very much like that between bees in a hive. The ancestors of your cells were once individual entities and their evolutionary 'decision' to co-operate, some 600 million years ago, is almost exactly equivalent to the same decision, taken perhaps fifty million years ago by the social insects, to co-operate on the level of the body: close genetic relatives discovered they could reproduce more effectively if they did so vicariously, delegating the task to germ cells in the cells' case, or to a queen in the case of bees. The analogy is so good that evolutionary biologists have begun to realise that the co-operative spirit goes only so far. Just as soldiers at Verdun were occasionally driven to mutiny against the greater good, so worker bees are capable of reproducing on their own if they get the chance; only the vigilance of other workers prevents them. The queen buys the loyalty of those other workers to herself rather than to their sister workers by mating with several males to ensure that most workers are only half-sisters of each other and therefore share little genetic common interest. And so it is with cells in the body. Mutiny is a perpetual problem. Cells are continually forgetting their patriotic duty, which is to serve the germ cells, and
setting out to reproduce themselves. After all, each cell is descended from a long line of reproducing cells; it goes against the grain to cease dividing for a whole generation. And so, in every tissue every day, there is a cell that breaks ranks and starts to divide again, as if unable to resist the age-old call of the genes to reproduce themselves. If the cell cannot be stopped, we call the result cancer. But usually, it can be stopped. The problem of cancerous mutiny is so old that in all large bodied animals the cells are equipped with an elaborate series of switches designed to induce the cell to commit suicide if it should find itself turning cancerous. The most famous and important of these switches, in fact possibly the most talked about of all human genes since its discovery in 1979, is TP53, which lies on the short arm of chromosome 17. This chapter tells the remarkable story of cancer, through the eyes of a gene whose principal job is to prevent it.

The longer we live, the more mistakes we accumulate in our genes, and the greater the chance that an oncogene may be jammed on and three tumour-suppressor genes jammed off in the same cell.

Mainly by switching on other genes, p53 tells the cell to do one of two things: either to halt proliferation, stop replicating its DNA and pause until repaired; or to kill itself.

TP53 seems to encode the greater good, like a suicide pill in the mouth of a soldier that dissolves only when it detects evidence that he is about to mutiny. The suicide of cells in this way is known as apoptosis, from the Greek for the fall of autumn leaves. It is the most important of the body's weapons against cancer, the last line of defence.

These treatments do indeed cause a little DNA damage, he says, but not enough to kill the cells. Instead, the DNA damage is just sufficient to alert p53, which tells the cells to commit suicide. So chemotherapy and radiation therapy are actually, like vaccination, treatments that work by helping the body to help itself.

 If a cell detects that it has been infected with a virus, it can kill itself for the good of the body as a whole (ants and bees may do this as well, for the good of their colonies). There is good evidence that some cells do indeed do exactly this. There is also, inevitably, evidence that some viruses have evolved a way of preventing this from happening. Epstein¬ Barr virus, the cause of glandular fever or mononucleosis, contains a latent membrane protein whose job seems to be to head off any tendency the infected cell shows to commit suicide. Human papilloma virus, cause of cervical cancer, has two genes aboard whose job is to switch off TP53 and another tumour-suppressor gene.

Apoptosis is a decentralised business. There is no central planning, no bodily Politburo deciding who should die and who should live. That is the beauty of it. Like the development of the embryo, it harnesses the self-knowledge of each cell. There is only one conceptual difficulty: how apoptosis could have evolved. In passing the test of killing itself if infected, cancerous or genetically mischievous, a cell by definition dies. It cannot therefore pass on its goodness to its daughters. Known as 'the kamikaze conundrum', this problem is solved by a form of group selection: whole bodies in which apoptosis works well do better than whole bodies in which it fails to work; the former therefore pass on the right traits to the cells of their offspring. But it does mean that the apoptotic system cannot improve during a person's lifetime, because it cannot evolve by
natural selection within the body. We are stuck with the cell-suicide mechanism that we inherited.

 'What's the rush?' asked Anderson at one session. 'A patient dies of cancer every minute in this country. Since we began this discussion 146 minutes ago, 146 patients have died of cancer.'

At their birth, new technologies often seem hopelessly uncompetitive. The first railways were far more expensive than the existing canals and far less reliable. Only gradually and with time does the new invention bring down its own costs or raise its efficacy to the point where it can match the old.

In 1992 Kenneth Culver tried an audacious experiment that involved the first direct injection of gene-equipped retroviruses into the human body (as opposed to infection of cultured cells outside the body and transfusion of those cells back in). He injected retroviruses directly into brain tumours of twenty people. Injecting anything into the brain sounds horrifying enough, let alone a retrovirus. But wait till you hear what was in the retrovirus. Each one was equipped with a gene taken from a herpes virus. The tumour cells took up the retrovirus and expressed the herpes gene. But by then the cunning Dr Culver was treating the patient with drugs for herpes; the drugs attacked the tumours. It seemed to work on the first patient, but on four of the next five it failed.

Transgenic mice are scientific gold dust. They enable scientists to find out what genes are for and why. The inserted gene need not be derived from a mouse, but could be from a person: unlike in computers, virtually all biological bodies can run any kind of software.

Sheep have already been given the gene for a human clotting factor in the hope that it can be harvested from their milk and used to treat haemophiliacs. (Almost incidentally, the scientists who performed this procedure cloned the sheep Dolly and displayed her to an amazed world in early 1997.) A company in Quebec has taken the gene that enables spiders to make silk webs and inserted it into goats, hoping to extract raw silk protein from the goats' milk and spin it into silk.

You may be wondering why E4 exists at all, let alone at such high frequencies. If it exacerbates both heart disease and Alzheimer's, it should surely have been driven extinct by the more benign E3 and E2 long ago. I'm tempted to answer the question by saying that high-fat diets were until recently so rare that the coronary side-effects were of little importance, while Alzheimer's disease is all but irrelevant to natural selection, since it not only happens to people who have long ago reared their own children to independence, but strikes at an age when most Stone-Age folk were long dead anyway.
The difference between E4 and the commoner E3 is that the 334th 'letter' in the gene is G instead of A. The difference between E3 and E2 is that the 472nd 'letter' is a G instead of an A. The effect is to give E2's protein two extra cysteines and E4's two extra arginines compared with each other, E3 being intermediate. These tiny changes in a gene that is 897 'letters' long are sufficient to alter the way APOE's protein does its job.
If genetic testing were to become routine for lots of genes, the entire concept of pooled risk, on which insurance is based, would be undermined. Once my exact fate is known, I would be quoted a premium that covered the exact cost of my life. 

C H R O M O S O M E  20
Politics    

The story starts with sheep. In eighteenth-century Britain, agricul- ture was revolutionised by a group of pioneering entrepreneurs, among them Robert Bakewell of Leicestershire. It was Bakewell's discovery that sheep and cattle could be rapidly improved by select- ively breeding the best specimens with their own offspring to concentrate desirable features. Applied to sheep this inbreeding pro- duced fast-growing, fat lambs with long wool. But it had an unexpec- ted side-effect. Sheep of the Suffolk breed, in particular, began to exhibit symptoms of lunacy in later life. They scratched, stumbled, trotted with a peculiar gait, became anxious and seemed antisocial. They soon died. This incurable disease, called scrapie, became a large problem, often killing one ewe in ten. The scrapie followed Suffolk sheep, and to a lesser extent other breeds, to other parts of the world. Its cause remained mysterious. The disease did not seem to be inherited, but it could not be traced to another origin. 
About this time an American scientist, Bill Hadlow saw pictures of the damaged brains of scrapie-riddled sheep in an exhibit in the Wellcome Museum of Medicine in London. He was struck by their similarity to pictures he had seen from a very different place. Scrapie was about to get a lot more relevant to people. The place was Papua New Guinea, where a terrible debilitating disease of the brain, known as kuru, had been striking down large numbers of people, especially women, in one tribe known as the Fore. First, their legs began to wobble, then their whole bodies started to shake, their speech became slurred and they burst into unexpected laughter. Within a year, as the brain progressively dissolved from within, the victim would be dead. By the late 1950s, kuru was the leading cause of death among Fore women, and it had killed so many that men outnumbered women by three to one. Children also caught the disease, but comparatively few adult men. 
This proved a crucial clue. In 1957 Vincent Zigas and Carleton Gajdusek, two western doctors working in the area, soon realised what had been happening. When somebody died, the body was ceremonially dismembered by the women of the tribe as part of the funeral ritual and, according to anecdote, eaten. Funereal cannibalism was well on the way to being stamped out by the government, and it had acquired sufficient stigma that few people were prepared to talk openly about it. This has led some to question whether it ever happened. But Gajdusek and others gathered sufficient eye-witness accounts to leave little doubt that the Fore were not lying they described pre-1960 funeral rituals in Pidgin as 'katim na kukim na kaikai' - or cut up, cook and eat. Generally, the women and children ate the organs and brains; the men ate the muscle. This immediately suggested an explanation for kuru's pattern of appear- ance. It was commonest among women and children; it appeared among relatives of victims - but among married relations as well as blood relatives; and after cannibalism became illegal, the age of its victims steadily increased. In particular, Robert Klitzman, a student of Gajdusek's, identified three clusters of deaths, each of which included only those who attended certain funerals of kuru victims in the 1940s and 1950s. For instance, at the funeral of a woman called Neno in 1954, twelve of fifteen relatives who attended later died of kuru. The three who did not comprised somebody who died young of another cause, somebody who was forbidden by tradition to take part in the eating because she was married to the same man as the dead woman, and somebody who later claimed to have eaten only a hand. 

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.

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.

​If anything, CJD 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. 
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Perhaps because it is the smallest chromosome, with probably the fewest genes, chromosome 21 is the only chromo- some that can be present in three copies rather than two in a healthy human body. 
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 have Down syndrome. 

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 restrict immigration for more traditional, racist reasons. The Immigration Restriction Act of 1924 was a direct result of eugenic campaigning. 

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. 
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'.

Wedgwood probably thought he had failed. The forcible commit- tal 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. 
What is wrong with eugenics is not the science, but the coercion.

 

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 environ- ment 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 

​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. 
Stephen Mobley was convicted of the murder of a pizza-shop man- ager, 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. 
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