All this seems to matter less if you are black. Surveys of APOE genes have shown that ?4 is very common in sub-Saharan Africa. Nearly half of African pygmies carry at least one copy. Does this really mean that Alzheimer’s disease is rampant among the Efe? The short answer is that we don’t know. No studies on the epidemiology of Alzheimer’s seem to have been carried out on pygmies, and they would be hard to do since a high rate of death due to infection and accidents means that few pygmies survive to an age when Alzheimer’s might be seen. This, in itself, may explain why ?4 is so common among them, but a more likely explanation is that it is less dangerous to Africans than it is to Europeans. Several studies have sought, and failed, to find an increased risk of Alzheimer’s in Nigerians and African Americans who carry the ?4 variant. Why this should be so is something of a mystery.
In Europeans, at least, the genetics of Alzheimer’s provide a beautiful illustration of the evolutionary theory of ageing that is, if anything, even more persuasive than that of Huntington’s. Even among the clearly susceptible (white) French, ?4 is common for such a lethal variant, and its presence can only be explained by the fact that it has little net effect on the reproductive success of its carriers. The contrast with other genes that cause Alzheimer’s is instructive. Mutations in at least three other genes cause Alzheimer’s but do so at around age thirty. They kill their carriers in their prime and, exposed to the full force of natural selection, are accordingly – thankfully – rare.
These kinds of findings are only the beginning. Within a few years, dozens, if not hundreds, of polymorphisms will be found that add years to our lives or else take them away. Most of these polymorphisms will either hasten or else delay the features of ageing with which we are familiar: senile dementia, arteriosclerosis, kidney failure, prostate failure, menopause, cancer and the like. No single person’s genome will possess all the variants that might be desirable for long life. This much is already apparent from the sheer diversity of ways in which we die. But it will be possible to describe in actuarial terms the relative risk of possessing a given genome. Here is a taste of what is to come. All else being equal, a forty-year-old whose genome has the following variants:
SRY(–/–); APOE(ε2/ε2); ACE(D/D); MTHFR(Ala222/Ala222)
will have a lower risk of cardiovascular disease, and hence a lower yearly risk of death, than someone with the following:
SRYf(+/-); APOE(ε4/ε4); ACE(I/I); MTHFR(Val222/Val222).
The difference between these two lists is quite unmysterious. There are four genes – SRY, APOE, ACE and MTHFR – each of which has two variants known to be associated with a difference in the mortality rates of middle-aged or elderly people. These two lists are, then, a predictive theory of longevity, but one that is no more profound than the assertion than someone who neither smokes, drinks, drives or has sex will generally live longer than someone who does all those things. Only here the risk factors lie in the genome.
Possession of the second genome does not inevitably spell an early death. While it is not possible to diet your way out of Alzheimer’s, much can be done to prevent a heart attack. That these genes confer different risks of death at any given age seems certain, but it is not yet possible to translate those differences into years. To do so requires large population studies of a sort that have not yet been done, but that surely will. There is one exception to this. In the USA, SRY(-/-) individuals live, on average, five years longer than those who are SRY(+/-). This, of course, is rather hard on those of us who are SRY(+/-), but there’s not a lot that can be done about it except to give a Gallic shrug and mutter Vive la différence.
EVER UPWARDS
In 1994 a remarkable thing happened. Not a single eight-year-old Swedish girl died. Not one succumbed to the ‘flu; not one was hit by a bus. At the beginning of the year there were 112,521 of them. At the end of the year they were all still there.
It was, of course, a statistical fluke. In that same year some eight-year-old Swedish boys died, so did some seven- and nine-year-old girls, and a few eight-year-olds of both sexes died the following year. But the survival, in that year, of those Swedish girls may be taken as symbolic of the greatest accomplishment of industrial civilisation: the protection of children from death.
Childhood mortality rates in the most advanced economies have become vanishingly small, particularly when death due to accident or violence is excluded. It is this accomplishment, at least 250 years in the making, which has driven the long climb in human life expectancy. Before 1750, a newborn child could expect to live to twenty years of age; today in the wealthiest countries a newborn can expect to live to about seventy-five. Most of this increase can be credited to the elimination of infectious diseases that preferentially strike the young. The curious thing, however, is that even though the protection of the young is largely a completed project – in the wealthiest countries – life expectancy continues to rise.
The 1960s were, it is said, revolutionary. But far from the Sturm und Drang of the cultural and sexual revolutions, something far more important was happening. Mortality rates of the old began to decline. An American woman who turned eighty in 1970 had a 30 per cent chance of surviving another decade; had she turned eighty in 1997 her chance of doing so would have increased to 40 per cent. The same phenomenon can be seen in the progress of maximum longevity in Sweden. Between 1860 and 1960, the age at death of Sweden’s oldest person increased steadily, decade by decade, at rate of about 0.4 years. Between 1969 and 1999, the rate of increase climbed to about 1.1 years per decade. We have been living longer for some time, but since the 1960s we have been living longer ever faster.
These numbers tell us that not only can ageing be cured, but that cures have been coming thick and fast. If ageing is the age-dependent increase in the mortality rate, then anything that ameliorates the mortality rate is, by definition, its cure. The decline of mortality rates among the old is mainly due to a several-decades-long decline in cardiovascular disease and cancer. Cardiovascular disease has been the leading cause of death in the United States since the 1920s, but between 1950 and 1996 its contribution to the death rate declined by half. In Japan, cancer rates began to decline in the 1960s; in the rest of the industrialised world the decline began about twenty years later. Nothing spectacular, then, just the incremental advance of public health.
But incremental advance is all we can reasonably expect. Evolutionary theory and the increasing flow of information about the genetics of ageing, be it premature or postponed, tell us that ageing is many diseases that will have to be cured one by one. At the same time, there is no obvious impediment to that advance; nothing to make us think that human beings have a fixed lifespan. In 1994, 1674 eighty-year-old Swedish women died. It is impossible to predict what medical breakthroughs will be required to ensure that none will die in the future. But when that day comes, it will mark the completion of industrial civilisation’s second great project: the protection of the old from death.
X
ANTHROPOMETAMORPHOSIS
[AN EPILOGUE]
The authors of books about genetics – at least books written for the general reader – disagree about many things. What they agree on is the need either to predict the future course of humanity or to moralise about it, or, better yet, to do both. The predictions invariably concern the role that the ‘new genetic technologies’ – mass genetic screening, embryo selection, cloning, germ-line modification and the like – will have in the lives of individuals and societies. Some writers are sanguine, and assure us that these technologies are as nothing compared to the great demographic forces such as birth rates and migrations that shape the gene pool of our species; others contemplate, with surprising equanimity, the transformation of the human species into something resembling a highly intelligent plant. Some – media scientists usually – would like to clone themselves; others would like to restructure the tax system so that people with inherited disorders have a disincentive to reproduce. Others again – soi-disant ethicists, dialectical biologists and bishops – speak portentously of ‘human dignity’, rail against ‘genetic determinism’ or else mutter darkly about the ‘ethical dilemmas that face us all’ – though rarely condescend to explain exactly what these might be.