by Steve Jones
Family studies show that much of the variation in resting blood pressure is due to inherited variation. To most of the students this proved the existence of a genetic difference in blood-pressure between dark and fair-haired people. Only when let into the simple secret of the differences in the experiences of each group was it obvious what is wrong in that claim. The students had made the same mistake as the educationists. High heritability combined with a difference between groups need not say anything about genes. The race and IQ story is, in the main, one of a dismal failure to understand basic biology.
A belief in heredity, rather like faith in predestination, is a good excuse for doing nothing. At least the environmentalist version can be used to try to improve matters. The genetkal view is often taken as a chance to blame the victim; to excuse injustice because it is determined by nature. In the last chapter of Daniel Deronda, biology wins. The hero returns to his ancestral roots and marries Mirah Mordecai, with the Cohen family in attendance. His admirer Gwendolen Harleth is left to console herself with the memory of her unlikeablc mate Henleigh Grand-court, drowned a few pages earlier. Determinism triumphs, which is convenient for the novelist. Fortunately, real life is more complicated than that. One of the most remarkable discoveries made by the new genetics has been to show how little we understand about the human condition that we did not know before.
Chapter Six BEHIND THE SCREEN
If, by chance, you are reading this book on a train, or in a library, or anywhere apart from in solitude, steal a glance at the person to your left and to your right. Then, comfort yourself with the knowledge that two of the three of you will die as a result of errors in (or side-effects of) the genes you carry. Should that idea be unwelcome, it is worth remembering that a century ago, in that train or library (and depending on the age of your companions) two of the three of you would be dead already.
Life, towards the end of the second millennium, underwent a great change. A British baby born today who lives through the difficult first six months has only about one chance in a hundred of failing to make it to adulthood. In Victorian times — and long before — the figure was, for most newborns, about one in two. In those days, death came from outside: from starvation, infection, or cold. The eugenicists were concerned about the inborn weaknesses of future generations, but in fact most of their fellow citizens died for reasons not directly connected with their genes. Now things are different: we have won the battle against the external world and face the enemy within; our innate failings, central as they are to ailments such as heart disease, diabetes or cancer. As a result, most of us nowadays die of a genetic disease (although not many notice). Genes impinge upon us more than they did in Galton's time and our new ability to read their message may alter lives and deaths in unexpected ways.
Both Galton's Laboratory for National Eugenics and Davenport's Eugenics Records Office (which changed its identity through a merger with the Cold Spring Harbor Laboratory) are now world centres for human genetics. They and the hundreds of research groups that descend from them have come up with the technology for searching out genetic imperfection thut (I.ilion and Davenport lacked. Many of the questions ih.it obsessed ilu- biologists of a century ago have been answered. What is the relationship between people and genes now that we may soon have the tools to identify the inadequate and to carry out some kind of eugenical programme if one was called for? Will we screen all babies at birth; or is that a step too far?
No serious scientist has any interest in a genetically planned society. But the explosion in genetics means that, like it or not, we must face ethical problems of the kind so comprehensively ignored by its founders. Can, or should, choices be made on the basis of DNA? What is the balance between the rights of individuals and of society in the light of the new biology; and is there any need to worry — as the eugenicists thought — about those of unborn generations? One intellectual hero, Sam Goldwyn, dismissed the issue by asking 'what did posterity ever do for me?', but his predecessor, Plato, saw a moral duty to the future in that 'mankind gains its hope of immortality by having children7. To interfere with the genes of the present has an effect on that future and to diagnose an error in one individual at once draws in his family; those alive and those yet to be. Where should the duties of science end?
Genetics has undergone a healthy shift in attitude. Most of its practitioners are not concerned with the quality of the distant future. They feel responsible to people rather than to populations; to today and not to tomorrow. Biologists are, indeed, more cautious about their work than is the public. In one poll three out of four Americans found the idea of inserting genes into human sperm or egg quite acceptable but almost no scientist would contemplate the idea.
In the nineteenth century the bacterial theory revolutionized medicine. Some hope that DNA will do the same in the twenty-first. Genetics might help to predict disease before symptoms appear, prevent it before damage is done or even cure it by molecular microsurgery. Whether or not it succeeds, it will reveal many secrets. DNA may have shattered Plato's notion of the perfect human, but reminds us of his notion that men may be classified by their very nature — not just into those of gold, silver, iron and brass; but into thousands of classes, each at risk of certain diseases, of certain environments, and each, perhaps, endowed with some unique and inborn talent. Are we ready to expose the skeletons hidden in every genetical cupboard? Mass screens for genetic defects are in the air (with the British government among the first to offer its population for the task). The eugenicists would have been happy with the idea and libertarians are alarmed; but now it seems that the job may be more difficult than anyone had hoped — or feared.
For much of the time genetics deals with healthy people, either carriers of single copies of recessive genes, or those with damaged DNA that might affect their future health. By so doing, it draws more and more under the aegis of medicine. Genetics was once a science of the exceptions. Dreadful as inherited disease might be for the families involved, it did not seem to impose upon most people. Genes are responsible for severe inborn defects, but most are impossible to treat (so that those affected die young) and each is rare. With an overall incidence of one or two in a hundred live births, genetic problems seem a minor part of the history of death; crucial to a few, but irrelevant to the many. For such rare diseases rests do pay, to use that term in its crudest sense, because of the effectiveness of pre-natal diagnosis and pregnancy termination. In Holland the national counselling service costs about thirty million pounds a year. It prevents the birth of from eight hundred to twice that number of severely handicapped children. Even in that small and efficient system, the expense of their lifetime healthcare would be between about.1 tjuarrer and three-quarters of a billion pounds. For Untjiii, with a population four times as great, the figures must be multiplied in proportion. In the United States, for fragile X syndrome (a common cause of inborn mental defect) the cost of prevention of a single birth is $12, 000 compared to the million-dollar cost of support.
Such calculations sound offensive, or even brutal, but equations like these are commonplace in medicine. To balance cash against quality and length of life is unavoidable; and the sums may be stark. Even so, given that so many single-gene conditions cannot be treated and that many of the others demand permanent care, they are relatively simple to cost. At first sight, and forgetting any moral dimension, the equations seem clear, both for pre-natal diagnosis and for the care of those born with an inherited illness. For genetics, though, costs and benefits have ambiguities of their own. Now that DNA has entered the domain of common diseases it will allow early diagnosis of conditions, treatable and not, that come on in later years. As it does so it may produce a whole new social class, the healthy ill, who — hale and hearty as they are until the fate coded into their genes makes its presence felt — turn to doctors for help that they cannot give.
The biggest difficulty may prove to be diagnosis by proxy, the inadvertent discovery that a third party, a relative, is at risk
. Should doctors inform other family members, even those outside their own care, of their situ- ation? Already physicians have been sued for not telling relatives of a death from inherited colon cancer because the information might have allowed them to protect themselves. In the USA some states see doctors as responsible for informing the wife of a psychopath of her own risk and insist that physicians must tell the rest of the family about inherited disease. Others feel that to inform the patient is enough and leave it to him what he does (the practice recommended by a British Select Committee). Most people, when asked, agree that relatives should be told about inborn conditions and this may become common practice — which changes the normal taws of confidentiality. And how long must a hospital keep in contact with a patient? As more accurate tests emerge, as they will, those who once scored negative on a DNA checkup might then not do so.
Genetics hence calls for decisions about what information should be gathered, by whom, and to whom it should be available. It shifts the boundary between private and public responsibility. To what extent do duties extend within a family? Where do medical decisions end and the values of society take over? Fortunately, perhaps, the more we learn, the more unlikely the notion of a universal screen for imperfection appears.
Without doubt, genetic tests may be helpful. To terminate a pregnancy can be a great relief to a woman found to be carrying a damaged foetus. On a more positive note, any parent with a child with phenylketonuria or inherited colon cancer (each of which can be treated) knows how important genetic checks can be. Perhaps screens of whole populations will find many of tomorrow's patients. They could identify those at particular risk, be they for smoking, stress, chemicals, or certain foods. The new insight into how DNA interacts with the world outside may at least change attitudes to risk. Most people know that to smoke causes cancer and that a fatty diet may lead to heart disease. Certain genes predispose their carriers to the harmful effects of tobacco or rat and some individuals may be able to drink, smoke or eat lard with impunity. Propaganda about smoking and lung cancer has not been very effective. Those exposed to it have an impressive capacity to assume that if one smoker in ten contracts rhe disease, then that will be someone else. If it is possible to identify exactly who will get cancer if they smoke, individual terror may prove a better deterrent than collective risk. One form of the gene for a protein called alpha-i anrrypsin much increases the risk of emphysema among smokers. The incidence of those with two copies is around one in five thousand; and half of all smokers unlucky enough to fall into that group die younger than forty, whereas the lifespan for gene carriers who do not smoke is extended by twenty years. To discover one's individual danger concentrates the mind: and in Sweden one in ten teenagers with the high-risk genotype smokes, compares to a fifth of others.
To assess future health is not new. All doctors check their patients for high blood pressure and healthy women are examined for signs of breast cancer. As technology advances, signs of other cancers (such as prostate cancer, which generates antigens in the urine) can be checked long before symptoms appear. DNA will make diagnosis easier, with tests for a wide variety of diseases, either inherited or the result of mutations in body cells themselves. Once a patient or someone worried about a family problem turns up, DNA is just another weapon in the doctor's armoury. Medicine has already opened up, with home blood-pressure and cholesterol kits. Home pregnancy tests are in some senses already genetic screens, for many positive results end in termination, whatever the genes of the foetus. In the United States, over-the-counter tests are available for cystic fibrosis carrier status and for genes that predispose to breast cancer.
The technology to sell many more has arrived. Gene chips, is they are known, set out an array of probes for thousands of different genes at once. The idea began in the 1970s. A particular sequence of DNA is held in a stable in.mix, and possible matches, each one labelled with a r.ulio;icrivc probe or a fluorescent dye, floated past until one binds to it, in a sort of fishing for genes. Now, ten thousand bait sequences can be put on a single glass slide using methods developed by the computer industry. In principle one chip could test for all the common generic conditions at once; and, although no doubt they will be expensive, such devices may soon be on the market. The companies involved, some say, exaggerate risks and play on fears to increase sales. A test for a hereditary breast cancer gene costs $2500, far more than it costs to produce. Even so, their use will be hard to control, and in surveys most people think that they should be available. The interval between the discovery of a gene and the sale of a test is short and doctors will have to deal more and more with those who have, rightly or wrongly, diagnosed themselves or their children as at risk.
Medicine might gain from such information as it allows treatment to be targeted more accurately. To tailor pill to patient may become common. The ability to deal with anti-cancer drugs varies fifty-fold and a dose helpful to one individual may be fatal to another. For a certain drug used against leukaemia one child in ten has a low tolerance, so that the screen is essential. On the other hand, drugs not much used now because of their toxicity may turn out to be safe for some. The new approach might also change people's jobs. Nobody wants to be a passenger in an aeroplane with a colour-blind pilot and those with the gene do not get the job, for their own safety and that of others. That logic could extend a long way. People who inherit certain forms of the alpha-i antitrypsin enzyme find it hard to deal with dust or pollution. In the same way, some individuals with particular forms of the proteins used to make poisons safe are more susceptible to industrial carcinogens. Genetic screens might become part of employment and the tests become a company's duties. However, genes might also be used as an excuse not to improve the environment. The journal Chemical Week once wrote that '… it makes no economic sense to spend millions of dollars to tighten up a process which is dangerous only for a tiny fraction of employees… if the susceptible individuals can identified and isolated from it.'
In the United States and elsewhere, employers pay tor their employee's health insurance. Insurance, of any kind, is a mechanism for diffusing risk. The cost of an accident is diluted by sharing it with those who never make a claim. Those who enjoy driving drunk or keeping gold bars under the bed pay more and do not complain (much) that their lifestyle forces them to do so. But what about health insurance? In the USA (and more and more in Britain), access to medical care is limited by the ability to pay. Twenty million Americans must buy their own cover and tens of millions have no health insurance at all. Anyone buying a policy is asked to disclose any medical problems of which they are aware. Many applications are denied, and for the remainder all 'pre-existing conditions' — reported or not — are excluded.
Genetics raises interesting questions. Should an insurer have the right to demand the results of a test to help them decide the price or whether to offer cover at all? Is a damaged gene a "pre-existing condition"? After all, everyone must die; and DNA does no more than tell some (and, in years to come, perhaps most) people when that might happen. But, as insurance depends on spreading risk, genetics may be a terminal blow. It erodes our ignorance of the future. No-one will play with a gambler who knows his opponent's cards and no-one will pay for cover when they are certain that they will live to a ripe old age (and will not need it). The same may be true when the insurers know thar an expensive illness is programmed into the genes. Insurance already suffers because people at high risk.ire more likely to buy a policy. Genetics might spark off a war of cost escalation that ends with only the risk-prone paying for medical insurance.
Already, the companies refuse to cover those doomed to Huntington's Disease and other ailments. Denying cover is no empty threat. A woman in charge of a fragile X screening programme in the United States was refused insurance because her children had symptoms although she had none. In another case, the insurer agreed to pay for a foetus to be tested for cystic fibrosis — but only if the parents agreed to have an abortion if the test was positive.
A commercial health market sees good and bad buys and an employer who pays the bill faces pressure not to hire someone who may be in jeopardy. All this is an argument for a national service which diffuses risk among the whole population. Then health care will revert to the role of a policeman rather than a security-guard, with an acceptance that all must pay, even if some are in more danger than others.
Public health, like insurance, also involves a balance between individual rights and social obligations. Why, after all, is it no longer acceptable to spit in the street; and why do smokers regard themselves as a persecuted minority? Perhaps to screen a new-born child, or an adult, for its inborn weaknesses will come to be seen as a duty both to the person involved and to the social order rather than a mere commercial transaction. Already, every infant, with or without the knowledge of its parents, is checked for whether it carries a range of genetic diseases, PKU being only one.
There are plenty of cases in which this could be useful. Hemochromatosis is a recessive condition that leads to a failure to cope with iron in the food. Untreated, it may be fatal, with damage to heart and liver. About one European in four hundred is born with the disease, and it is even commoner among those of African ancestry. Hundreds of thousands of Britons are in danger (with men at five times the risk of women). The gene has been found and most patients carry one of two mutations. Treatment is cheap and simple. A vessel is opened to lose blood and to prevent the build-up of iron; medical wits have it that patients should grow roses as blood is such a good fertiliser. A simple scan early in life could save many lives and save much expense involved in the treatment of those to whom the damage has already been done.
