by Steve Jones
Humans have interfered with their biological heritage since they appeared on earth. Stone tools, agriculture and private property all had an effect on society and in turn on genes. Many people are concerned that the next phase of history will be one in which genetics makes plans for the future. That asks too much of science. Inadvertent change-evolution by mistake-will be far more important than is any conscious attempt to engineer our own biology.
Even the most determined efforts of doctors, genetic counsellors or gene therapists will have only a small effect on the future. Part of that lies in the healing power of lust: in the desire of people to have children for reasons that have nothing to do with science. More is a matter of arithmetic. For recessive conditions, far more genes are hidden in normal people than in those with disease — a hundred times as many for cystic fibrosis, thousands of times for rarer diseases. Whatever happens to those who receive two copies — death in infancy or by pregnancy termination, orcure by gene therapy — is more or less irrelevant to the future. Social pressure against the genetically unfortunate has decreased. In the 1950s a small minority of achondro-plastic dwarves found a spouse, but now more than eighty per cent are married, often to someone else in the same circumstances. They often have children but, even so, the great majority of newborns with the condition appear — as they always have — because of new mutation.
Many inherited diseases appear anew each generation for the same reason. Is, as many dystopians claim, the evolutionary future in danger because of an increase in the mutation rate? H J Muller, who won the Nobel Prize for his discovery that radiation causes mutations, himself wrote a dark novel of the future, Out of the Night, in which life has been blighted by the accumulation of genetic damage. Perhaps modern civilization — with its dubious benefits of nuclear radiation and poisonous chemicals — will damage our genetic heritage. Certainly, such things do alter DNA, but the obvious threats such as man-made radiation and industrial by-products, have a smaller effect than do natural sources such as the radon gas that leaks from granite and the poisonous chemicals found in mouldy food. The Sellafield nuclear power station in the North of England is one of the dirtiest in the western world (and the North Sea its most radioactive body of water). The name of the station has itself mutated from Calder Hall to Windscale to Sellafield in a feeble attempt to calm public suspicion. Compared to other sources of radiation, its effects arc minor. Avid consumers of shellfish collected near the discharge pipe (and there are not many of those) receive about as much excess radiation as those who fly from London to Los Angeles and back four times a year and are exposed to cosmic radiation as a result.
A more subtle transformation has had a dramatic effect on the mutation rate. In the western world at least, a change in the age at which people have children means chat amounts of DNA damage will drop. The rate of mutation goes up with age and the effect accelerates as the years go on. Most mutations (apart from chromosome mutations, most of which are so damaging that they do not pass to the next generation) take place among males. Fathers of thirty-five do not have a rate much greater than those of eighteen, but after that mid-life moment the incidence of damage shoots up (to a rate twenty times higher in pensioners compared to schoolboys). The more old fathers, the more the genetic damage.
People now live for far longer than in earlier times, allowing mutation to take its toll on a higher proportion of the population. The cancer epidemic in the modern world is confined to older people. Cells that give rise to sperm or egg are also exposed to the destructive effects of age, which is why older parents are more likely to have damaged children. Any change in the age of reproduction will hence have an effect on the mutation rate. If the number of elderly parents goes up, there will be more inherited changes; if it decreases, fewer. Social progress has led to just such a shift. The general picture — which applies to much of the third world as well as to developed countries — is subtle and unexpected.
Before the recent improvements in public health most children died young. Parents started having children when they were themselves youthful and continued until death or the menopause. Throughout history the average number of children per couple has been two, or a little more; as, on the average, it still approximately is. The figure is now reached in a new way: not with perhaps a dozen births accompanied by ten deaths in infancy, but with around two planned and healthy offspring.
A drop in infant mortality means less pressure to have children as an insurance against old age. Contraception allows parents to delay their first child (in Britain now until the late twenties, on average) but then to complete their families quickly. Most people stop soon after they have started. As a result, and although the age at which parents have their first offspring has increased, the number of elderly mothers and fathers has gone down. As recently as the 1920s the average Englishwoman began her final pregnancy at over forty; a figure that has dropped by almost ten years. The occasional births to much older women with the help of technology (and the oldest is in her mid sixties) are so rare as to be insignificant.
Males over thirty-five are the crucial group; but the data for men are harder to gather than are those for their partners. Husbands and wives tend to share, if nothing else, about the same date of birth so that, in spite of a few aged (and anonymous) Lotharios, the figures for women contain most of the information for men. Aristotle advised that girls marry at eighteen, and men at thirty-seven. Although the age difference between the sexes is less than that husbands do tend to be three to five years older than their wives.
The changes in sexual pattern are most obvious in postwar Europe. In Britain, Poland and Switzerland the proportion of mothers over thirty-five — and hence of fathers over about forty, the group most at risk of mutation — dropped from around twenty per cent in 1950 to less than five per cent in 1985. In that year, just one mother in fifty in what was then East Germany was more than thirty-five years old, a figure probably smaller than any time in history. In Ireland the influence of the Church, and the many young men who spent a period working overseas, meant that until a few years ago the only means of birth control was self-denial. Most Irish people did not marry until their late twenties, or later, and until not long ago almost a third of all mothers {and a higher fraction of fathers) were over the crucial age; more than twice the proportion anywhere else in Europe. The number is now much lower (albeit still above the average). There has been some reversal of the trend over the past two decades, with the numbers of mothers over thirty-five increasing from its low point of around one in twenty.
The general picture remains clear: old mothers (and fathers) are rarer than they have been for much of the past. This is bound to have an effect on the mutation rate. Down's syndrome (ten times more frequent among mothers over forty-five than in teenagers) is three times more common in Pakistan (which has almost no family planning) than in Britain, because Pakistani mothers are older than their British equivalents. From the male point of view, in Britain the mutation rate in men is about one and a half times that expected if all fathers were less than thirty, but in Pakistan it is three times this low figure. At the moment, at least, it looks as if the human mutation rate is on the way down. Whether this will continue is not certain, but it puts fears about a new race of mutated monsters into context.
Mutation is the fuel of evolution but, as far as can be seen, evolution rarely runs out of steam. Natural selection, though, is its engine and, like most engines, often speeds up and slows down to face changing circumstances.
Selection is an elusive process and it is more difficult to forecast what its future might be. Nature is always liable to come up — as it has so often before — with a nasty shock. The emergence of the AIDS virus shows the risk of this happening again. Even so, in the western world at least, some of the greatest challenges have gone, because of the control of infectious disease. Once such a disease has disappeared the future of the genes that combat it will change. Cypriots carry the inherited anaemia beta-thalassaemia because it def
ended their ancestors against malaria. That illness has now disappeared from the island — as, in time, will thalassaemia, with the incidence of carriers dropping by as much as one per cent per generation. In time, and given success in public health, the same will happen to the many other genes that resist the infection elsewhere in the world. Soon, they will remain only as mute and waning witnesses to an ancient past.
Life has also got better for babies. They are important; changes in the survival of adults — essential to individuals as they may be — are of not much relevance to selection because they kill those who have already passed on their genes. What counts for evolution is death before reproduction. What happens to the rest of us is, more or less, beside the point. The history of one inherited character, the weight of newborns, shows just how effective improved conditions at an early age can be in reducing the action of natural selection.
At birth, it pays to be average. Underweight babies, needless to say, survive less well than do others. However, babies heavier than normal are also more likely to die in the first few weeks. In the 1930s about half the babies who died in their first year did so because they were above or below the ideal weight. A difference of just one pound had a large effect. Since some of the variation in this character is genetic, natural selection was at work against genes for extreme birth weight as it had been, no doubt, since our species began.
Now, such selection has almost gone. Improved care means that only very underweight babies, or those much larger than average, are at risk. The intensity of selection has gone down by more than two thirds since the 1950s. Nowadays there is little risk in being a baby of even a kilogram above or below the mean weight. What was once a powerful agent of evolution is on the way out.
Improved child-care has also changed the ratio of the sexes at the age when people begin to choose a mate. At birth, there are slightly more boys than girls. Boys once had less chance of surviving the hazards of childhood, which led to an almost exact balance of the sexes in the late teens. Now, boys survive almost as well as girls do, so that in future there will be a slight but noticeable excess of young men looking for a mate. If (and many dispute the idea) the differences between men and women in size, or in appearance, are driven by sexual selection, perhaps in years to come that aspect of our evolution will (unlike most of it) advance, to give a generation of taller, hairier and more libidinous males.
There are better ways of looking at the future of selection than just to multiply examples of how it works. Natural selection acts only on differences. If everyone lived to adulthood, found a partner and had the same number of children (whether that number was one, two, or ten) it could not operate. We do not need to know what genes are involved to estimate how important selection might be. Simple changes in the pattern of birth and death reveal its actions in the past, the present and, perhaps, in the future.
In affluent countries, the differences between families in how many people survive have much decreased. This much reduces the power of the evolutionary engine. Ten thousand — even two hundred — years ago, the struggle for existence meant a lot. Skeletons from cave cemeteries show that few lived to be more than twenty. If ancient fertility was like that of modern tribal groups each female had about eight children, most of whom died young. For nine tenths of human evolution, society was like a village school, with lots of infants, plenty of teenagers and a few — probably harassed — adult survivors. Almost every death was potential raw material for selection as it involved someone young enough still to have a hope of passing on their genes. Now, ninety-eight our of every hundred new-born British babies live to the age of eighteen, so that selection acting through the deaths of the young once its main mode of operation has almost disappeared.
Not until the past few years have humans lived as long as they are able. For the first time in history, most people die old, perhaps as old as biology allows. Life expectancy has risen from forty-seven to seventy-six years in the past century. Progress has now stopped, for some social classes at least. In the USA in 1979 a white woman of sixty-five could expect to five for another eighteen and a half years. In 1999, the figure was almost the same. In Britain, even if all infectious diseases and all accidental deaths were to be eliminated by government decree, average life expectancy would go up by only a little more than a year. There is still room for progress because of class differences in health. A baby born to an unskilled worker in Britain can expect to live for eight years less than one born to a professional person, a difference which, to our national shame, was until recently increasing. In spite of the effects of class, the prospects for any dramatic improvement in longevity are dim. George Bernard Shaw was wrong. We will not go back to Methuselah.
This is important for the evolutionary future. The increase in the number of old people means that more people die for genetical reasons than in earlier times (in the main because fewer are killed by violence or by infection) but, paradoxically, it also means that selection is weaker. The genes that kill are those for cancer or heart disease, which act late in life. Those who die have already passed on their inheritance. Natural selection is much less powerful on genes such as these than on those that kill the young.
Other changes in the balance of birth and death also reduce its opportunities. Few modern peoples are as fertile as they once were. The Hutterites in North America wish for the largest possible family for religious reasons but even they, living in a healthy society as they do, do not often have more than ten children. For most of history — when families of that size were common — people had as many offspring as possible. Only recently has that number begun to decrease.
The new pattern of existence (with fewer children than ever before but most people lasting until the biological clock runs down) emerged about twenty generations ago, compared to the six thousand or so since we first appeared on earth. As a result, evolution has changed the way it works. Selection nowadays acts more on fertility than on survival.
Differences in fertility among families shot up as birth control became popular. The upper classes adopted the idea well before the lower orders. The French aristocracy caught on and reduced the number of children per marriage from six to two in just a hundred years. The Victorians differed in how fertile they were. Victoria herself did well, and Mr Quiverful, in Trollope's Barchester novels, had a dozen children at a time when other clergymen were discreetly limiting their own families to two or three. Now that birth control is widespread, the difference between families has dropped again, but selection through variation in the number of children born is, for the first time in history greater than that working on the number that survive. As a result, the evolutionary fate of our genes depends more on how many children we choose to have than on the chances of their staying alive.
All the best-understood forces of selection — disease, cold or starvation — act on survival rather than on fertility. The shift in the balance of the two may bring in new and unpredictable evolutionary forces. Perhaps inherited variations in the age of reproduction will become important,
399 as those who mature young squeeze in more generations than those who delay their first birth. There has been a drop in the age at which girls become mature {although, in opposition to this trend, western women now marry five years later than they did half a century ago). What this will do to them is hard to say. A good general rule in biology is that nobody gets a free lunch: success in one walk of life must be paid for by failure in another. Fruit-fly experiments suggest that a shift from high survival towards high fertility involves a trade-off in which those that produce lots of eggs die young. The same may happen to humans.
All this is speculation about details. It is clear than natural selection has ebbed away. Modern India is a microcosm of how evolution has lost its chance to mould the human condition. The continent contains a wide range of cultures, from almost tribal hill-peoples to affluent urbanites. It embodies the history of social change in birth and death over the past several thousand years. Differences
among individuals in the various groups in the chances of survival and in their numbers of children show that natural selection has lost eighty per cent of its potential in middle class town-dwellers compared to their fellow-citizens who still follow a tribal way of life.
Weakened — perhaps temporarily — as it may be, there is no reason to think that natural selection will change its tactics. Rather than making a new start by designing an ideal solution for a particular problem it will, as always, build on our imperfections. History gives little reason to hope that evolution will act as the agent of human perfectibility. It will never make humanity superhuman.
The raw material of evolution and the power of its prime mover are both running out and, as a result, the rate of change is slowing down. Another shift in modern society is bound to influence our prospects. It has to do with the geography of mating. For most of history, almost everyone had to marry the girl (or the boy) next door, because they had no choice. Society was based on small bands or isolated villages and marriages were within the group. In many places, populations were stable for many years and, as a result, became quite inbred. Almost nobody moved. The DNA in the brains of American Indians, drowned in a peat bog in Florida, show that people who died a thousand years apart had almost the same genes. There was little migration and the Indians had no option but to marry their relatives.
This pattern persisted in much of the West until a few years ago and still holds in many parts of the world. In most places it is changing. An increase in mating outside the group is the most dramatic shift in the developed world's demographic history. The effect has become stronger and stronger and will have more effect on geneti-cal health than anything medicine is able to do. It will also slow the rate of evolutionary advance.