Genome: The Autobiography of a Species in 23 Chapters. Matt Ridley
sorrow’, said Tiresias to Oedipus, ‘to be wise when wisdom profits not.’ Or as Wexler puts it, ‘Do you want to know when you are going to die, especially if you have no power to change the outcome?’ Many of those at risk from Huntington’s disease, who since 1986 can have themselves tested for the mutation, choose ignorance. Only about twenty per cent of them choose to take the test. Curiously, but perhaps understandably, men are three times as likely to choose ignorance as women. Men are more concerned with themselves rather than their progeny.12
Even if those at risk choose to know, the ethics are byzantine. If one member of a family takes the test, he or she is in effect testing the whole family. Many parents take the test reluctantly but for the sake of their children. And misconceptions abound, even in textbooks and medical leaflets. Half your children may suffer, says one, addressing parents with the mutation. Not so: each child has a fifty per cent chance, which is very different. How the result of the test is presented is also immensely sensitive. Psychologists have found that people feel better about being told they have a three-quarter chance of an unaffected baby than if they are told they have a one-quarter chance of an affected one. Yet they are the same thing.
Huntington’s disease is at the far end of a spectrum of genetics. It is pure fatalism, undiluted by environmental variability. Good living, good medicine, healthy food, loving families or great riches can do nothing about. Your fate is in your genes. Like a pure Augustinian, you go to heaven by God’s grace, not by good works. It reminds us that the genome, great book that it is, may give us the bleakest kind of self-knowledge: the knowledge of our destiny, not the kind of knowledge that you can do something about, but the curse of Tiresias.
Yet Nancy Wexler’s obsession with finding the gene was driven by her desire to mend it or cure it when she did find it. And she is undoubtedly closer to that goal now than ten years ago. ‘I am an optimist’, she writes,4 ‘Even though I feel this hiatus in which we will be able only to predict and not to prevent will be exceedingly difficult…I believe the knowledge will be worth the risks.’
What of Nancy Wexler herself? Several times in the late 1980s, she and her elder sister Alice sat down with their father Milton to discuss whether either of the women should take the test. The debates were tense, angry and inconclusive. Milton was against taking the test, stressing its uncertainties and the danger of a false diagnosis. Nancy had been determined that she wanted the test, but her determination gradually evaporated in the face of a real possibility. Alice chronicled the discussions in a diary that later became a soul-searching book called Mapping fate. The result was that neither woman took the test. Nancy is now the same age as her mother was when she was diagnosed.13
Errors, like straws, upon the surface flow; He who would search for pearls must dive below.
John Dryden, All for Love
It is time for a cold shower. Reader, the author of this book has been misleading you. He has repeatedly used the word ‘simple’ and burbled on about the surprising simplicity at the heart of genetics. A gene is just a sentence of prose written in a very simple language, he says, preening himself at the metaphor. Such a simple gene on chromosome 3 is the cause, when broken, of alkaptonuria. Another gene on chromosome 4 is the cause, when elongated, of Huntington’s chorea. You either have mutations, in which case you get these genetic diseases, or you don’t. No need for waffle, statistics or fudge. It is a digital world, this genetics stuff, all particulate inheritance. Your peas are either wrinkled or they are smooth.
You have been misled. The world is not like that. It is a world of greys, of nuances, of qualifiers, of ‘it depends’. Mendelian genetics is no more relevant to understanding heredity in the real world than Euclidean geometry is to understanding the shape of an oak tree. Unless you are unlucky enough to have a rare and serious genetic condition, and most of us do not, the impact of genes upon our lives is a gradual, partial, blended sort of thing. You are not tall or dwarf, like Mendel’s pea plants, you are somewhere in between. You are not wrinkled or smooth, but somewhere in between. This comes as no great surprise, because just as we know it is unhelpful to think of water as a lot of little billiard balls called atoms, so it is unhelpful to think of bodies as the products of single, discrete genes. We know in our folk wisdom that genes are messy. There is a hint of your father’s looks in your face, but it blends with a hint of your mother’s looks, too, and yet is not the same as your sister’s – there is something unique about your own looks.
Welcome to pleiotropy and pluralism. Your looks are affected not by a single ‘looks’ gene, but by lots of them, and by non-genetic factors as well, fashion and free will prominently among them. Chromosome 5 is a good place to start muddying the genetic waters by trying to build a picture that is a little more complicated, a little more subtle and a little more grey than I have painted so far. But I shall not stray too far into this territory yet. I must take things one step at a time, so I will still talk about a disease, though not a very clear-cut one and certainly not a ‘genetic’ one. Chromosome 5 is the home of several of the leading candidates for the title of the ‘asthma gene’. But everything about them screams out pleiotropy – a technical term for multiple effects of multiple genes. Asthma has proved impossible to pin down in the genes. It is maddeningly resistant to being simplified. It remains all things to all people. Almost everybody gets it or some other kind of allergy at some stage in their life. You can support almost any theory about how or why they do so. And there is plenty of room for allowing your political viewpoint to influence your scientific opinion. Those fighting pollution are keen to blame pollution for the increase in asthma. Those who think we have gone soft attribute asthma to central heating and fitted carpets. Those who mistrust compulsory education can lay the blame for asthma at the feet of playground colds. Those who don’t like washing their hands can blame excessive hygiene. Asthma, in other words, is much more like real life.
Asthma, moreover, is the tip of an iceberg of ‘atopy’. Most asthmatics are also allergic to something. Asthma, eczema, allergy and anaphylaxis are all part of the same syndrome, caused by the same ‘mast’ cells in the body, alerted and triggered by the same immunoglobulin-E molecules. One person in ten has some form of allergy, the consequences in different people ranging from the mild inconvenience of a bout of hay fever to the sudden and fatal collapse of the whole body caused by a bee sting or a peanut. Whatever factor is invoked to explain the increase in asthma must also be capable of explaining other outbreaks of atopy. In children with a serious allergy to peanuts, if the allergy fades in later life then they are less likely to have asthma.
Yet just about every statement you care to make about asthma can be challenged, including the assertion that it is getting worse. One study asserts that asthma incidence has grown by sixty per cent in the last ten years and that asthma mortality has trebled. Peanut allergy is up by seventy per cent in ten years. Another study, published just a few months later, asserts with equal confidence that the increase is illusory. People are more aware of asthma, more ready to go to the doctor with mild cases, more prepared to define as asthma something that would once have been called a cold. In the 1870s, Armand Trousseau included a chapter on asthma in his Clinique Médicale. He described two twin brothers whose asthma was bad in Marseilles and other places but who were cured as soon as they went to Toulon. Trousseau thought this very strange. His emphasis hardly suggests a rare disease. Still, the balance of probability is that asthma and allergy are getting worse and that the cause is, in a word, pollution.
But what kind of pollution? Most of us inhale far less smoke than our ancestors, with their wood fires and poor chimneys, would have done. So it seems unlikely that general smoke can have caused the recent increase. Some modern, synthetic chemicals can cause dramatic and dangerous attacks of asthma. Transported about the countryside in tankers, used in the manufacture of plastics and leaked into the air we breathe, chemicals such as isocyanates, trimellitic anhydride and phthalic anhydride are a new form of pollution and a possible cause of asthma. When one such tanker spilled its load of isocyanate in America it turned the policeman