The Language of the Genes

by Steve Jones

  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 tel! many of us how and when we may die. Alie.uly, ir is possible to diagnose at birth genes which will kill in childhood, youth or middle age. More will soon be louml. Will people want to know that they are at risk of;i disease which cannot be treated? Many genes show their etleus 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 whet her to have children? Attitudes to inborn disease arc 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. AH 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.ire of two kinds, X or Y. At fertilisation, both XY males and XX females are produced in equal number. Sex is as much;i 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 a*-Hs 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 he 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.ur implanted into the mother. This technique has led to the birth of hundreds of babies.

  Pregnancy termination is a loss 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 fcm.ilr 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 'I'very 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 rilled with milk.' The rulers' many wives were said to have produced no grown-up daughter^ ror more than a century. The government nowadays pays a bonus for girl babies, but some states now have four female.'** 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 tivl that to terminate a pregnancy jusl because it is the wroiij.; m-x w;is also wrong. They might worry less about tin* choice ot 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 foeral tissues al
so involves a certain hazard. This has become smaller.is 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 lhat 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 192.6 the American Eugenics Society had a board that counted up the Si00 per second supposed to be spent on people with 'bad heredity'. Sixty yens 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, gcm-iics 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 arc, 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, vaj;m* statements of inherited importance were not enough. They needed-and awarded themselves-concrete symbols ol wen It h.ind 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 i 177. 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 Wicrr-Effroy near Calais in the fifteenth century. Even today pilgrims pray in the village church of Sainte Godeleinc, 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 l',r: inilp.imiis, 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 depend
s first on whether any pigment is present. If none is made the eye is pale blue. Other lints 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.