But an appeal to chance is never satisfying; we would prefer a deterministic theory. In 1957, an American evolutionary biologist, George Williams, proposed one. He argued that the mutations that cause ageing spread not by chance but because they confer some benefit, albeit only to the young. Imagine, once again, a mutation that causes impotence at age ninety, but that also confers unusual virility at age twenty. The carrier of such a mutation might well sire more children than other men, and so the gene would spread. In the calculus of natural selection, small benefits reaped early often outweigh severe costs paid later on. Old age, in this view, is the price we pay for the lavish beauty and exuberant excess of youth.
Some geneticists have used this logic to explain why Huntington disease is so common. They argue that women with the disorder are, in the first stages of their disease, unusually promiscuous, or feckless, or at least unusually fecund. One study has shown that women with Huntington disease have more illegitimate children than their unaffected siblings. Perhaps, the argument goes, the disorder causes unusually high levels of gonadotropin, a hormone that influences sexual behaviour. There is little evidence to support any of this.
More generally, so little is known about the genes that cause human ageing that it is difficult to know whether Medawar’s or Williams’s view is the more accurate. In a way, the difference between the two theories does not matter; they may both be right, for they are similar in their causes and their consequences. Both propose that ageing is not for anything, but is, instead, just an epiphenomenon of evolution. It is ultimately due to the inability of natural selection to act against the mutations that cause disease in the old. Neither theory says much about the mechanical or molecular causes of ageing. They do not point to any one molecular device that we can fix and so ensure our immortality. Rather, both suggest that no such device will be found, and imply that ageing is the collective consequence of many different mutations that gradually wear down and then destroy our bodies.
Perhaps this is why, despite much effort, the mechanistic causes of ageing remain so elusive. The root of ageing’s evil has been claimed, at one time or another, to lie in any one of a dozen aspects of human biology. Some have claimed that it is caused by the fermentation of bacteria in our guts; others by a slow-down in the rate at which the body’s cells divide; yet others have pointed to the exhausting effects of bearing and raising children. Others again have proposed that ageing is caused by the exhaustion of some vital substance, or else that chemicals produced by our own cells gradually poison us. Many of these ideas are probably absurd, but some probably contain at least an element of truth. What follows is a survey of some of the most plausible ones: a brief history of decay.
GERONTOCRATS
In his declining years, flush with cash and fame from having invented the telephone, Alexander Graham Bell turned his attention to genetics. His first efforts were modest. He bred a variety of sheep with four nipples instead of the usual two. Then, combining his interests in sound and heredity, he studied the genetics of deafness. But his passion was the genetics of human longevity. He began with the family of one of America’s Pilgrim Fathers, a William Hyde (settled Norwich, Connecticut, in 1660), whose descendants, all 8797 of them, had been traced by genealogists. Analysing their records, Bell concluded that longevity was mostly inherited. Neither his data nor his statistics justified this conclusion. But he wasn’t far wrong – modern estimates put the heritability of European longevity between 20 and 50 per cent. In the event, it was enough to set him off on far grander plans.
Like many early-twentieth-century scientific men, Bell was an enthusiast of eugenics. Not ‘negative’ eugenics – the state-enforced sterilisation of the mentally disabled and the antisocial – that were vogueish in the 1920s, for this he found repugnant. Bell was a humane man; it is not for nothing that America’s premier organisation for the deaf bears his name. His view of eugenics was more ‘positive’, liberal, indeed entrepreneuriaclass="underline" he saw it as an instrument in the marketplace of human affections. Bell proposed, and then began, the compilation of vast numbers of longevity records from Washington, DC, area schools. His idea was to ask children how old their parents and grandparents were, and then publish the results along with their names and addresses in a volume that he called, without equivocation, a ‘human stud-book’. People, he thought, would be sure to consult his stud-book; the descendants of long-lived individuals would search each other out, fall in love, and breed. What of the descendants of short-lived people? Perhaps they would simply remain unmarried. Or perhaps long-lived and short-lived people would separate into distinct races; there would be true gerontocracy. Genetic progress, like economic progress, requires efficient markets, and efficient markets need information; it was all very clear.
Alexander Graham Bell’s scheme was visionary and only slightly mad. (Who among us would choose the object of our desires on the basis of mean grandparental longevity?) Unsurprisingly, it foundered with his death in 1922. Yet had the scheme become universal, and had people behaved as Bell hoped they would, the results would surely have been spectacular. There is no doubt that the careful breeding of long-lived families would, with time, have resulted in a strain of long-lived people. Perhaps not patriarchially long-lived, but a good deal longer than the seventy-something years that is all we can reasonably hope for. We can guess this, because experimental schemes, not too different from Bell’s, work in other creatures.
In the 1980s the evolutionary account of ageing given by Williams and Medawar inspired researchers to attempt the creation of a breed of long-lived fruit flies. If the ultimate cause of ageing lay in the absence of natural selection late in life, they reasoned, perhaps long-lived flies could be produced by forcing natural selection upon old flies. A fruit fly can breed at two weeks of age, almost as soon as it emerges from its pupa, but by ten weeks it is quite old, perhaps as old as an octogenarian human. Male fruit flies never survive to this age, and the few females that do, the hardy survivors, have depleted metabolic reserves, tattered wings and feeble legs.
They can, however, lay at least a few eggs. And so populations of fruit flies were bred, generation after generation, only from the eggs of the oldest flies. The effect of this was to favour genetic polymorphisms that promoted survival and fertility at old age. As these increased in frequency, the flies evolved ever-longer lifespans. The speed at which this happened was remarkable. Ten generations of selective breeding were enough to increase the average longevity by 30 per cent – in human terms the equivalent of raising life expectancy from seventy-eight to just over a hundred. Fifty generations of selection, and life expectancy doubled.
Closer examination of these long-lived fruit flies showed that they were amazingly hardy. Deprived of food or water or subjected to noxious chemicals, they survived where shorter-lived flies expired. But glory in old age exacted a cost. As the flies’ longevity evolved ever upwards, fertility in early life declined. Females laid fewer eggs, males were less inclined to mate. Eschewing profligacy, long-lived fruit flies hoarded their resources and established reserves of fats and sugars instead. They became sluggards, moving, breathing and metabolising slower than normal flies.
This result was just as predicted by George Williams’s theory. If ageing is the genetic price of early-life reproductive success, then, conversely, increased longevity must be bought at the cost of a vigorous and fertile youth. This implies a simple economic relationship between fertility and longevity. A fly has only so many resources; it may use them to live to an old age or it may expend them on its progeny, but it cannot do both. It’s a line of argument that goes back to Aristotle. In his account of animal physiology he supposed that animals need ‘moisture’ to live, and that they had a limited amount of it: life is warm and wet, and death is cold and dry. ‘This is why,’ he writes, ‘animals that copulate frequently and those abounding in seed age quickly; the seed is a residue, and further, by being lost, it produces dryness.’