Kitabı oku: «The Language of the Genes», sayfa 2

Another political leader had similar views. ‘The unnatural and increasingly rapid growth of the feeble-minded and insane classes, coupled as it is with steady restriction among all the thrifty, energetic and superior stocks constitutes a national and race danger which it is impossible to exaggerate. I feel that the source from which the stream of madness is fed should be cut off and sealed off before another year has passed.’ Such were the words of Winston Churchill when Home Secretary in 1910. His beliefs were seen as so inflammatory by later British governments that they were not made public until 1992.

One of Galton’s followers was the German embryologist Ernst Haeckel. Haeckel was a keen supporter of evolution. He came up with the idea (which later influenced Freud) that every animal re-lived its evolutionary past during its embryonic development. His interest in Galton and Darwin and his belief in inheritance as fate led him to found the Monist League, which had thousands of members before the First World War. It argued for the application of biological rules to society and for the survival of some races – those with the finest heritage – at the expense of others. Haeckel claimed social rules were the natural laws of heredity and adaptation. The evolutionary destiny of the Germans was to overcome inferior peoples: ‘The Germans have deviated furthest from the common form of ape-like men … The lower races are psychologically nearer to the animals than to civilized Europeans. We must, therefore, assign a totally different value to their lives.’

In 1900 the arms manufacturer Krupp offered a large prize for the best essay on ‘What can the Theory of Evolution tell us about Domestic Political Development and the Legislation of the State?’ There were sixty entries. In spite of the interests of capital, the first German eugenic sterilisation was carried out by a socialist doctor (albeit one who claimed that trade union leaders were more likely to be blond than were their followers).

While imprisoned after the Beer Hall Putsch, Hitler read the standard German text on human genetics, The Principles of Human Heredity and Race Hygiene, by Eugene Fischer. Fischer was the director of the Berlin Institute for Anthropology, Human Heredity and Eugenics. One of his assistants, Joseph Mengele, later achieved a certain notoriety for his attempts to put Galtonian ideas into practice. Fischer’s book contained a chilling phrase: ‘The question of the quality of our hereditary endowment’ – it said – ‘is a hundred times more important than the dispute over capitalism or socialism.’

His thoughts were echoed in Mein Kampf: ‘Whoever is not bodily and spiritually healthy and worthy shall not have the right to pass on his suffering in the body of his children’. Hitler took this to its dreadful conclusion with the murder of those he saw as less favoured in order to breed from the best. The task was taken seriously, with four hundred thousand sterilisations of those deemed unworthy to pass on their genes, sometimes by the secret use of X-rays as the victims filled in forms. Those in charge of the programme in Hamburg estimated that one fifth of its people deserved to be treated in this way.

By 1936 the German Society for Race Hygiene had more than sixty branches and doctorates in racial science were offered at several German universities. Certain peoples were, they claimed, inferior because of inheritance. Half of those at the Wannsee Conference (which decided on the final solution of the Jewish problem) had doctorates and many justified their crimes on scientific grounds. The eugenics movement in Germany was opposed to abortion (except of the unfit) and imposed stiff penalties – up to ten years in prison – on any doctor rash enough to carry it out. The number of children born to women of approved stock went up by a fifth. The Hitlerian conjunction of extreme right wing views, an obsession with racial purity and a hatred of abortion has its echoes today.

Concern for the purity of German blood reached absurd lengths. One unfortunate member of the National Socialist Party received a transfusion from a Jew after he had been in a road accident. He was brought before a disciplinary court to see if he should he excluded from the Party. Fortunately, the donor had fought in the First World War, so that his Jewish red cells were – just about – acceptable.

The disaster of the Nazi experiment ended the eugenics movement, at least in its primitive form. Its blemished past means that human genetics is marked by the fingerprints of its own history. It sometimes seems to find them hard to wipe off. They should not be forgotten now that the subject is, for the first time, in a position to control the biological future.

Galton and his followers felt free to invent a science which accorded with their own prejudices. They believed that the duty to genes outweighs that to those who bear them. They were filled with extraordinary self-assurance and great weight was placed on their views although in retrospect it is obvious that they knew almost nothing.

Today’s new knowledge is as controversial as was the old ignorance. Even so, disputes among modern biologists are not about the vague general issues that obsessed their predecessors. Instead they concern themselves with the fate of individuals rather than of all humanity. Genetics has become a science and, as such, has narrowed its horizons.

Nevertheless, it raises ethical issues which will not go away. The newspapers are filled with debates about the morals of gene therapy or of human cloning, neither of which show any sign of becoming a reality. However, the diagnosis of defective genes before birth has already shifted the balance between birth and abortion to reduce the number of damaged children. This raises passions, from those who feel – in spite of the high natural wastage of fertilised eggs – that all foetuses are sacred, to others who consider that to pass on a faulty gene is equivalent to child abuse. Genetics presents a more universal difficulty – the problem of knowledge. Soon, it will tell many of us how and when we may die. Already, it is possible to diagnose at birth genes which will kill in childhood, youth or middle age. More will soon be found. Will people want to know that they are at risk of a disease which cannot be treated? Many genes show their effects in those who inherit damaged DNA from each parent. As everyone is likely to pass on a single copy of at least one such gene, will this help to choose a partner or to decide whether to have children?

Attitudes to inborn disease are flexible. In Ghana, babies are sometimes born with an extra finger or toe. Some tribal groups take no notice, others rejoice as it means that the new member of the family will become rich; but others, just a few miles away, regard such children with horror and they are drowned at birth. Even Christianity has seen the genetically unfortunate as less than human. Martin Luther himself declared that Siamese twins were monsters without a soul. Attitudes to genetics will always be influenced by those to abortion, which vary with time and place. St Augustine saw a foetus as part of its mother and not worthy of protection and in spite of its present views the Catholic Church did not condemn abortion until the thirteenth century. Ireland has a constitutional clause that establishes the right to life of the unborn child; while across the Irish Sea abortion until the third month is available almost on demand. Embryo research (which is becoming important with the discovery that embryonic cells can be used to treat adult disease) is forbidden in Germany but lightly controlled in Britain. All this shows how hard it is to set ethical limits to the new biology.

The problem can be illustrated with some old-fashioned biological discrimination. There has always been prejudice against certain genes, those carried on the chromosomes that determine sex. Women have two ‘X’ chromosomes, men a single X chromosome and a much smaller ‘Y’. All eggs have an X but that of sperm are of two kinds, X or Y. At fertilisation, both XY males and XX females are produced in equal number. Sex is as much a product of genes as are blood groups.

How the value of these genes is judged shows how biological choice can depend on circumstances. Sometimes, Y chromosomes seem to be worth less than Xs. When it comes to wars, murders and executions, males have always been more acceptable victims than females. But the balance can shift. Many parents express a preference for sons, especially as a first-born. Some even try to achieve them. The recipes vary from the heroic to the hopeful. In ancient Greece, to tie off the left testicle was said to do the job, while mediaeval husbands drank wine and lion’s blood before copulating under a full moon. Less drastic methods included sex in a north wind and hanging one’s underpants on the right side of the bed.

To sell gender is an easy way to make money. It has, after all, a guaranteed fifty per cent success rate. Today’s methods vary from the use of baking soda or vinegar at the appropriate moment (to take advantage of a supposed difference in the resistance of X and Y-bearing sperm to acids and alkalis) to sex at particular times of the female cycle. A diet high or low in salt is also said to help. Such recipes are useless and some of those who sell them have been prosecuted for fraud.

Now, fraud is out of date. Sex can be chosen in many ways. One is to separate X and Y sperm and to fertilise a woman with the appropriate type. The methods are not absolute, but shift the ratios by about two to one for males and four to one for females. Since Louise Brown in 1978, thousands of children have been born by in-vitro fertilisation, with sperm added to egg in a test-tube. A single cell can be taken from the embryo and its sex determined (and, indeed, as young male embryos grow faster, simply to choose the largest embryo biases the ratio of males). Only those of the desired gender are implanted into the mother. This technique has led to the birth of hundreds of babies.

Pregnancy termination is a less kind, but equally effective, way of choosing the sex of a child. Aristotle himself felt that a male foetus should be protected from abortion after forty days, but a female only after ninety. A recent survey of geneticists themselves showed that, in Holland, none would accept pregnancy termination just to choose the sex of a child, in Britain one in six, and in Russia nine out of ten. The Indian government was forced to shut down clinics which chose the sex of a baby with a test of the chromosomes of the foetus and aborted those with two Xs. More than two thousand pregnancies a year were ended for this reason in Bombay alone. The main reason was the need for large dowries when daughters were married off. The advertisements said ‘Spend six hundred rupees now, save fifty thousand later.’ The preference is an old one. A nineteenth-century visitor to Benares recorded that ‘Every female infant in the Rajah’s family born of a lawful wife, or Rani, was drowned as soon as it was born in a hole in the earth filled with milk.’ The rulers’ many wives were said to have produced no grown-up daughters for more than a century. The government nowadays pays a bonus for girl babies, but some states now have four females to five males and the country as a whole has a deficit of girls and women equivalent to the entire British female population.

All these methods interfere with genes. Their acceptability varies from the reasonably uncontentious choice of sperm to a crime where the murder of girl children is concerned. Where to draw the line depends on one’s own social, political or religious background; on how acceptable the notion might be that fate should depend on biological merit. All readers of this book would, I imagine, abhor infanticide, and most might feel that to terminate a pregnancy just because it is the wrong sex was also wrong. They might worry less about the choice of X or Y sperm.

The choice of a child’s sex can, however, involve more than parental self-indulgence. Sometimes it is a matter of life and death. Many inherited diseases are carried on the X chromosome. In most girls, an abnormal X is masked by a normal copy. Boys do not have this option, as they have but a single X. For this reason, sex-linked abnormalities, as they are known, are much more common in boys than in girls. They can be distressing. Duchenne muscular dystrophy is a wasting disease of the muscles. Symptoms can appear even in three year-olds and affected children have to wear leg braces by the age of seven, are often in a wheelchair by eleven and may die before the age of twenty-five. Parents who have seen one of their sons die of muscular dystrophy are in the agonising position of knowing that any later son has a one in two chance of having inherited it. A couple who have had a son with the illness can scarcely be blamed for a desire to ensure that no later child is affected. They hope to control the quality of their offspring and few will criticise them for doing so. Genetics has changed their ethical balance.

If a couple has a son with muscular dystrophy they know at once that the mother carries the gene. The chance of a second son with the disease is hence far greater than before. It is still just one in two, so that to terminate all male pregnancies means a real possibility of losing a normal boy. Even those who dislike the idea of choice of a child’s sex with X-bearing sperm might change their minds in these circumstances. Others would go further and accept the option of an externally fertilised embryo or the termination of all pregnancies which would produce a son.

Now, such choices have become more precise. The gene for muscular dystrophy has been found and changes in the DNA can show whether a foetus bears it. Hundreds of centres use the test. But the method is far from perfect. The gene can go wrong in many ways and not all of them show up. A foetus that appears normal may hence, in a proportion of cases, carry the gene. This complicates the parents’ decision as to whether to continue with a pregnancy. To sample foetal tissues also involves a certain hazard. This has become smaller as technology improves, with a check of foetal cells in the mother’s blood, but the risks of the test must themselves be weighed in the moral scales.

As more is found about the genes that cause death not at birth, or in the teens, but in middle or old age the dilemmas increase. Given the opportunity, some might avoid the birth of a baby doomed to dementia through Alzheimer’s disease in its forties. Others would argue that forty years of life are not to be dismissed; and that, in four decades of science, the cure may be found.

Decisions about the future of an unborn child will, as a result, more and more be influenced by estimates of risk and of quality: by whether the rights of a foetus depend on its genes. Such judgements are not just scientific decisions, but depend on the society and the people who make them. The debacle of the eugenics movement led to an understandable reluctance even to consider the idea of choices about rights based on inherited merit, but the new knowledge means that they are unavoidable.

Galton himself would have been delighted by the idea of preventing the birth of the damaged. The new eugenics can be overt. The Chinese People’s Daily is frank in its views. It reported a scheme to ban the marriage of those with mental disease unless they were sterilised with a robust simplification of Mendelism: ‘Idiots give birth to idiots!’ the eugenical message is often justified on financial grounds. At the Sesquicentennial Exhibition in Philadelphia in 1926 the American Eugenics Society had a board that counted up the $100 per second supposed to be spent on people with ‘bad heredity’. Sixty years later, one proponent of the plan to sequence the human genome claimed that the project would pay for itself by ‘curing’ schizophrenia – by which he meant the termination of pregnancies carrying the as yet hypothetical and undiscovered gene for the disease. The 1930s were a period of financial squeeze for health care. Seventy years on, the state is still anxious to limit the amount spent on medicine in the face of an inexorable rise in costs, with inborn diseases among the most expensive. There is a fresh danger that genetics will be used as an excuse to discriminate against the handicapped in order to save money.

Genetics – science as a whole – owes its success to the fact that it is reductionist: that to understand a problem, it helps to break it down into its component parts. The human genome project marks the extreme application of such a view. The approach works well in biology as far as it goes, but it only goes so far. Its limits are seen in a phrase once notorious in British politics, the late Prime Minister Mrs Thatcher’s statement that ‘There is no such thing as society, there are only individuals.’ The failures of her philosophy are all around us. To say, with Galton and his successors, ‘There are no people, there are only genes’ is to fall into the same trap.

In spite of the lessons of the past, there has been a resurgence of the dangerous and antique myth that biology can explain everything. Some have again begun to claim that we are controlled by our inheritance. They promote a kind of biological fatalism. Humanity, they say, is driven by its inheritance. The predicament of those who fail comes from their own weakness and has little to do with the rest of us. Such nouvelle Galtonism suggests that human existence is programmed and that, apart from a little selective pregnancy termination, there is no point in any attempt to change it – which is convenient for those who like things the way they are.

After the Second World War, genetics had – it seemed – at last begun to accept its own limits and to escape its confines as the haunt of the obsessed. Most of those in the field today are cautious about claims that the essence of humanity lies in DNA. Although it can say extraordinary things about ourselves, genetics is one of the few sciences that has reduced its expectations.

In mediaeval Japan, the science of dactylomancy – the interpretation of personality from fingerprints – had it that people with complex patterns were good craftsmen, those with many loops lacked perseverance, while those whose fingers carried an arched pattern were crude characters without mercy. Human genetics has escaped from its dactylomantic origins. The more we learn about inheritance the more it seems that there is to know. The shadow of eugenics has not yet disappeared but is fainter than it was. Now that genetics has matured as a subject it is beginning to reveal an extraordinary portrait of who we are, what we were, and what we may become. This book is about what that picture contains.

Chapter One A MESSAGE FROM OUR ANCESTORS

The rich were the first geneticists. For them, vague statements of inherited importance were not enough. They needed – and awarded themselves – concrete symbols of wealth and consequence that could persist when those who invented them were long dead. The Lion of the Hebrew Tribe of Judah was, until a few years ago, the symbol of the Emperor of Ethiopia, while those of England descend from the lions awarded to Geoffroy Plantagenet in 1177. The fetish for ancestry means that royal families are important in genetics (Prince Charles, for example, has 262,142 ancestors recorded on his pedigree). The obsession persists against all attempts to deny it. Heraldry was cut off by the American Revolution, but George Washington himself attempted to make a connection with the Washingtons of Northamptonshire and used, illegally, their five-pointed stars as a book plate.

Heraldic symbols were invented because only when the past is preserved does it make sense. For much of history wealth was dissipated on funerary ornaments to remind the unborn from whence they sprang. University College London contains an eccentric object; the stuffed body of the philosopher Jeremy Bentham (who was associated with the College at its foundation). Bentham hoped to start a fashion for such ‘auto-icons’ in the hope of reducing the cost of monuments to the deceased. It did not catch on, although the popularity of his corpse with visitors suggests that it ought to have done.

Such pride in family would now be greeted, mainly, with derision. Harold Wilson, the British Prime Minister of the 1960s, did as much when he mocked his predecessor, Lord Home, for being the Seventeenth Earl of that name. Lord Home deflected the jest when he pointed out that his critic must be the seventeenth Mr Wilson. He made a valid claim: that while only a few preserve their heritage in an ostentatious way, every family, aristocratic or not, retains the record of their ancestors. Everyone, however deficient in history, can decipher their past in the narrative of the DNA.

Some can use inherited abnormalities. A form of juvenile blindness called hereditary glaucoma is found in France. Parish records show that most cases descend from a couple who lived in the village of Wierr-Effroy near Calais in the fifteenth century. Even today pilgrims pray in the village church of Sainte Godeleine, which contains a cistern whose waters are believed to cure blindness. Thirty thousand descendants have been traced and for many the diagnosis of the disease was their first clue about where their ancestors came from and who their relatives might be. The gene went with French emigrants to the New World.

Human genetics was, until recently, restricted to studying pedigrees that stood out because they contained an inborn disease. Its ability to trace descent was limited to those few kindreds who appear to deviate from some perfect form. Biology has now shown that perfection is a mirage and that, instead, variation rules. Thousands of characters – normal diversity, not diseases – distinguish each nation, each family and each person. Everyone alive today is different from everyone who ever has lived or ever will live. Such variation can be used to look at shared ancestry in any lineage, healthy or ill, aristocratic or plebeian. Every modern gene brings clues from parents and grandparents, from the earliest humans a hundred thousand years and more ago and from the origin of life four thousand million years before that.

Most of genetics is no more than a search for diversity. Some differences can be seen with the naked eye. Others need the most sophisticated methods of molecular biology. As a sample of how different each individual is we can glance beneath the way we look to ask about variation in how we sense the world and how the world perceives us.

Obviously, people do not much resemble each other. The inheritance of appearance is not simple. Eye colour depends first on whether any pigment is present. If none is made the eye is pale blue. Other tints vary in the amounts of the pigment made by several distinct genes, so that colour is not a dependable way of working out who fathered a particular child. The inheritance of hair type is also rather complex. Apart from very blonde or very red hair, the genetics of the rest of the range is confused and is further complicated by the effects of age and exposure to the sun.

Even a trivial test shows that individuals differ in other ways. Stick your tongue out. Can you roll it into a tube? About half those of European descent can and half cannot. Clasp your hands together. Which thumb is on top? Again, about half the population folds the left thumb above the right and about half do it the other way. These attributes run in families but their inheritance, like that of physical appearance, is uncertain.

People vary not just in the way the world sees them, but how they see it. A few are colour-blind. They lack a receptor for red, green or blue light. All three are needed to perceive the full range of colour. The absence of (or damage to) one (usually that for green, less often for red, almost never for blue) gives rise to a mild disability that may have made a difference when gathering food in ancient times. The three genes involved have now been tracked down. Those for red and green are similar and diverged not long ago, while the blue receptor has an identity of its own. John Dalton, best known for his atomic theory, was himself so colour-blind as to match red sealing-wax with a leaf (which must have made things difficult for a chemist). He believed that his own eyes were tinted with a blue filter and asked that they be examined after his death. They were, and no filter was found, but, a century and a half later, a check of the DNA in his pickled eyeballs showed him to have lacked the green-sensitive pigment.

Colour-blindness marks the extreme of a system of normal variation in perception. When asked to mix red and green light until they match a standard orange colour, people divide into two groups that differ in the hue of the red light chosen. There are two distinct receptors for red, differing in a single change in the DNA. About sixty per cent of Europeans have one form, forty per cent the other. Both groups are normal (in the sense that they are aware of no handicap) but one sees the world through rather more rose-tinted spectacles than the other. The contrast is small but noticeable. If two men with different red receptors were to choose jacket and trousers for Father Christmas there would be a perceptible clash between upper and lower halves.

In the 1930s, a manufacturer of ice trays was surprised to receive complaints that his trays made ice taste bitter. This baffled the entrepreneur as the ice tasted just like ice to him, but was a hint of inherited differences in the ability to taste. To some, a trace of a substance used in the manufacturing process is intolerable, while to others a concentration a thousand times greater has no taste at all. Much of the difference depends on just one gene which exists in two forms. That observation, the ability or otherwise to perceive a substance, now called PROP, was the key to a new universe of taste. Genetic ‘supertasters’ are very sensitive to the hops in beer, to pungent vegetables like broccoli, to sugar and to spices, while non-tasters scarcely notice them. Half the population of India cannot taste the chemical at all, but just one African in thirty is unable to perceive it. Students of my day thought it witty to make tea containing PROP to see the bafflement of those who could drink it and those who could not. Today’s undergraduates have more sense.

As truffle-hunters know, scent and taste are related. There is genetic variation in the ability to smell, among other things, sweat, musk, hydrogen cyanide and the odour of freesias. Many animals communicate with each other through the nose. Female mice can smell not only who a male is, but how close a relative he might be. Humans also have an odorous identity, as police dogs find it more difficult to separate the trails of identical twins (who have all their genes in common) than those of unrelated people. Man has more scent glands than does any other primate, perhaps as a remnant of some uniqueness in smell which has lost its importance in a world full of sight. The tie between sex and scent in ourselves is made by a rare inborn disease that both prevents the growth of the sex organs and abolishes the sense of smell, suggesting that the two systems share a common pathway of development in the early embryo.

Variation in the way we look, see, smell and taste is but a tiny part of the universe of difference. The genes that enable mice to recognise each other by scent are part of a larger system of identifying outsiders. The threat of infection means that every creature is always in conflict with the external world. The immune system determines what should be kept out. It differentiates ‘self’ from ‘not-self’ and makes protective antibodies that interact with antigens (chemical clues on a native or foreign molecule) to define whether any substance is acceptable. The millions of antibodies each recognises a single antigen. Cells bear antigens of their own that, with great precision, separate each individual from his fellows. Antigens are a hint of the mass of uniqueness beneath the bland surface of the human race.

When blood from two people is mixed, it may turn into a sticky mess. The process is controlled by a system of antigens called the blood groups. Only certain combinations can mix successfully. Some groups, ABO and Rhesus for example, are familiar, while others, such as Duffy and Kell, are less so. Because of their importance in transfusion, millions of people have been tested. A dozen systems are screened on a routine basis and each comes in a number of forms. This small sample of genes generates plenty of diversity. The chances of two Englishmen having the same combination of all twelve blood groups is only about one in three thousand. Of an Englishman and a Welshman it is even less and of an English person and an African less again.

Since the discovery of the blood groups and other cues on the surfaces of cells, there has been a technical revolution. Like the stone age revolution a thousand centuries ago, it depends on simple tools that can be used in many ways. The DNA of different people can now be compared letter by letter, to test how unique we are. The Human Genome Diversity Project is a spin-off from the main mapping effort which has tested thousands of people. On the average, and depending on what piece of the DNA is tested, two people differ in about one or two DNA letters per thousand; that is, in about three to six million places in the whole inherited message. Some of the differences involve changes in single bases (single nucleotide polymorphisms, or ‘snips’ as they are called), some in the number of short repeats of particular sequences (‘microsatellites’ and ‘minisatellites’) and some turn on the presence or absence of bits of mobile DNA that leapt into a particular place in the genome long ago. Blood groups show how improbable it is that two will be the same when a mere twelve variable systems are used. The chance that they both have the same sequence of letters in the whole genetic alphabet is one in hundreds of billions. Genetics has made individuals of us all. It disproves Plato’s myth of the absolute, that there exists one ideal form of human being, with rare flaws that lead to inborn disease.