Steve Jones - The Language of the Genes

The most notable aspect of non-insulin dependent diabetes is the power of the environment. A change in diet is to blame. Native Americans' or Pacific Islanders' genes are less able to cope with large amounts of fat and starch than are those of Europeans, and the illness follows. DNA is a less effective predictor than is diet. A change in habits would benefit the whole population, whether or not they are at specific risk of the illness.

For diabetes, what seemed to be a single disease is in fact two, or several, or many, each of which might demand different treatments. Some therapies are successful, some less so; and some involve not drugs but a change in habits. Certain patients may be detected before symptoms appear by virtue of the genes they carry, but others will be missed by any screening programme. A few people will develop diabetes whatever their diet, while others may, in spite of an inherited susceptibility, avoid it because of how they live. The genetics of the illness — like that of many others — involves a minority of individuals with a single gene that predisposes to disease, and a larger number who have drawn an unlucky hand of several low-value genetic cards, which can come in many ways. Together they increase the danger but any one is of little use in prediction. For the adult-onset form, to identify those at high risk may concentrate their minds but in the end the genes have little relevance: to ban cheeseburgers would do more ih;m anything medicine can do.

Many (and perhaps most) diseases are rather like this. Susceptibility will be difficult to test for. Variation in otic gene that makes a protein important in controlling Kit levels in the blood influences the chances of heart disease (although, of course, diet is also important). It also has a great effect on the chances of pre-senile dementia, Alzheimer's disease. For those with two copies of one form of the gene, the disease usually begins before the age of seventy, fifteen years earlier than those inheriting two copies of a more favourable allele. Most patients have no overt predisposition at all; many of those at high risk die for other reasons before the symptoms appear, and footballers, whatever their genes, are in danger of a similar illness because they head the ball. Heart disease is just as complicated. Some families inherit a tendency towards high levels of blood cholesterol, bur almost two hundred different combinations of genes can generate the effect. Risk of the disease is affected by how fat a person is (which may itself have a genetic element), blood pressure and insulin levels as well as the genes more directly implicated. As a result, such families are easier to identify with a simple blood-cholesterol test than with the most complicated DNA technology.

All this means that the study of the inheritance of common illnesses is plagued with results that cannot be replicated. Many claims that particular genes are associated with mental diseases such as schizophrenia or depression have not been sustained on further study. In spite of plans for huge (and expensive) sweeps through the genetic undergrowth, with thousands of sick people scanned to sec if their DNA is special, the chances of success in the search for the genes involved are small. As a result genetics will have less of a role in the diagnosis and treatment of common disease than is often claimed. What it may do first is to show that what once appeared to be single illnesses — from schizophrenia to obesity — are in fact many, each of which might need a separate treatment. As a result, the prospect of screening whole populations for those at risk is far away.

Even so, the science can bring unwelcome news to some. Many inherited diseases cannot be treated even if they are diagnosed, which at once raises the question as to who would want a test. Half of those who have a parent with Huntington's disease may contract it. Because of the delay in symptoms appearing, those at risk were once left in uncertainty about their fate. The first signs often appear in a patient's thirties or forties as a general restlessness and depression, followed by involuntary movements and ending in paralysis and death, usually within twenty years of diagnosis. As symptoms may not appear until middle age, those in danger are left in an ambiguous position. In Britain a mere one in ten choose to be tested. For them, doubt is preferable to certainty (even if, among those who do test positive, the fear that many would commit suicide has not been realised). In contrast, half those at risk of inherited breast cancer (where drugs may help although their efficacy has not been proved) take up the offer, and eight-tenths accept a test for familial colon cancer, which can in effect be cured by surgery. For those at risk of a genetic illness whether a condition is treatable is central. For a disease about which nothing can be done, most people see little point in a test.

All this is a tribute to common sense. Some decisions are less rational. One in ten of those offered the chance of testing to see if they carry a single copy of a cystic fibrosis gene by post agrees and one in four when an appointment is made; but almost everyone given the chance of an immediate check accepts. All the great killers in the developed world are influenced by genes; and, in principle at least, genetics might be able to tell many people the probable date of their death long before it happens. Why, one might ask, would anyone want to know?

As the blind seer Tiresias put it in Oedipus Rex, ll low terrible it is to have wisdom when it does not benefit those who have it!'. Genetics — science in general — produces knowledge; wisdom, how that knowledge is to be used, demands much more and may come only after long and painful experience. Tiresias himself was struck blind for revealing the secrets of the gods. Those of the genes are still in part concealed: and the two of every three people that they will kill can, for the time being, be grateful for that.

Biologists have an adolescent fascination with sex. Like teenagers, they are embarrassed by the subject because of their ignorance. What sex is, why it evolved and how it works were once the biggest unsolved problems in biology. The pastime must be important as it is so expensive. If some creatures can manage with just females, so that every individual produces copies of herself, why do so many bother with males? A female who gave them up might be able to produce twice as many daughters as before and they would carry every one of her genes. Instead, a sexual female wastes time, first in the search for a mate and then in the birth of sons who carry but half of her inheritance. It is still not certain why males exist; and why, if they are unavoidable, nature needs so many. Surely, one or two would be enough to impregnate all the females but, with few exceptions, the ratio of one to the other remains stub bornly equal throughout the living world.

An obsession with sex goes back a long way. The Venus of Galgenberg, an elegant serpentine statuette without the exaggerated breasts and buttocks of later variations on the theme, is thirty thousand years old. Aesthetic interest in the female form goes back even further. A small pebble from an excavation in Israel has been grooved to resemble a woman's body. At eight hundred thousand years old, it is the oldest known work of art.

Curiosity about the meaning of sex is not new. Plato, in the Symposium, suggested that there were once three sexes; males, females and androgynes or hermaphrodites. The third sex was split apart by an angry Zeus and doomed to spend eternity forever seeking its partner: 'Zeus moved their privates to the front and made them propagate upon themselves. If, in all these claspings, a man should chance upon a woman, conception would take place and the race would be continued; whereas if man should conjugate with man, he might at least obtain such satisfaction as would allow him to turn his energies to the everyday affairs of life'. This provided Plato with an explanation tor the origin of sex and the sex ratio and a neat explanation of the variety of sexual attractions common from ancient Greece to the present day. Two thousand years later the English wit Sydney Smith had the same idea, although his three sexes were men, women and clergymen.