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 who directed traffic around the wreck into an acute and desperate asthmatic for the remainder of his life. Yet there is a difference between acute, concentrated exposure and the normal levels encountered in everyday life. So far there is no link between low-level exposure to such chemicals and asthma. Indeed, asthma appears in communities that never encounter them. Occupational asthma can be triggered in people who work in much more low-tech, old-fashioned professions, such as grooms, coffee roasters, hairdressers or metal grinders. There are more than 250 defined causes of occupational asthma. By far the commonest asthma trigger – which accounts for about half of all cases – is the droppings of the humble dust mite, a creature that likes our fondness for central-heated indoor winter stuffiness and makes its home inside our carpets and bedding.
The list of asthma triggers given by the American Lung Association covers all walks of life: pollen, feathers, moulds, foods, colds, emotional stress, vigorous exercise, cold air, plastics, metal vapours, wood, car exhaust, cigarette smoke, paint, sprays, aspirin, heart drugs – even, in one kind of asthma, sleep. There is material here for anybody to grind any axe they wish. For instance, asthma is largely an urban problem, as proved by its sudden appearance in places becoming urban for the first time. Jimma, in south-west Ethiopia, is a small city that has sprung up in the last ten years. Its local asthma epidemic is ten years old. Yet the meaning of this fact is uncertain. Urban centres are generally more polluted with car exhaust and ozone, true, but they are also somewhat sanitised.
One theory holds that people who wash themselves as children, or encounter less mud in everyday life, are more likely to become asthmatics: that hygiene, not lack of it, is the problem. Children with elder siblings are less likely to get asthma, perhaps because their siblings bring dirt into the house. In a study of 14,000 children near Bristol, it emerged that those who washed their hands five times a day or more and bathed twice a day, stood a twenty-five per cent chance of having asthma, while those who washed less than three times a day and bathed every other day had slightly over half that risk of asthma. The theory goes that dirt contains bacteria, especially mycobacteria, which stimulate one part of the immune system, whereas routine vaccination stimulates a different part of the immune system. Since these two parts of the immune system (the Th1 cells and the Th2 cells respectively) normally inhibit each other, the modern, sanitised, disinfected and vaccinated child is bequeathed a hyperactive Th2 system, and the Th2 system is specially designed to flush parasites from the wall of the gut with a massive release of histamine. Hence hay fever, asthma and eczema. Our immune systems are set up in such a way that they ‘expect’ to be educated by soil mycobacteria early in childhood; when they are not, the result is an unbalanced system prone to allergy. In support of this theory, asthmatic attacks can be staved off in mice that have been made allergic to egg-white proteins by the simple remedy of forcing them to inhale mycobacteria. Among Japanese schoolchildren, all of whom receive the BCG inoculation against tuberculosis but only sixty per cent of whom become immune as a result, the immune ones are much less likely to develop allergies and asthma than the non-immune ones. This may imply that giving the Th1 cells some stimulation with a mycobacterial inoculation enables them to suppress the asthmatic effects of their Th2 colleagues. Throw away that bottle steriliser and seek out mycobacteria.1
