One of them was Denham Harman, born in 1916 and still at work when Aubrey entered the field of gerontology toward the end of the century. (Harman is still going strong as I write, in the fall of 2009, at the age of ninety-three.) For decades, Harman had been trying to persuade more scientists to explore the causes of aging. In 1970 he founded a new association, the American Aging Association, which goes by the acronym AGE. It is a society of scientists who focus on the study of aging and its cure, and publish the peer-reviewed journal Age. Aubrey felt stirred and inspired when he listened to Harman, or to Richard Miller, another leader of the field, who opened one international gerontological conference with the simple words, “Aging is bad for you.” Optimists like Harman and Miller surveyed the spectacle of the body’s almost endless self-consumption and renewal and felt hopeful. Aubrey read Harman’s studies of the potential of antioxidants: natural or artificial compounds that can soak up the free radicals in the body and prevent their doing so much damage. He read Miller’s studies of calorie restriction. Somehow the two were clearly connected. If we eat less we burn less; the metabolic fires slow down and there are fewer free radicals shooting around in the cells like sparks.
After all, we are looking at a body that is constantly and creatively and minutely maintaining itself as long as the body is alive. Even our skeletons are alive. Every one of our 206 bones is constantly being torn down, restored and remodeled like every other part of our living machinery. Cells called osteoclasts carve away the old bone, and cells called osteoblasts build up the new. As at most construction sites, the demolition goes faster than the rebuilding. Three weeks per site for demolition; three months for reconstruction. Even in our bones, a careful balance of creation and destruction, day and night. Too much destruction and we develop diseases like periodontitis, rheumatoid arthritis, osteoporosis. Too much creation and we suffer, too, as in the rare condition osteopetrosis, literally bones of stone, in which the osteoclasts fail to do their jobs and the osteoblasts make the skeleton increasingly dense, heavy, and brittle; or another rare condition, fibrodysplasia ossificans progressiva, in which even muscles, tendons, and ligaments turn to bone.
Our very skeletons are full of youth, and fight all the way down to the dust. Like the Phoenix, we destroy ourselves and restore ourselves—burn ourselves down and build ourselves up—not every thousand years but daily and hourly—all the way down to the bone. Life seen this close up looks like a kind of bonfire, like the flames of the Phoenix when it self-immolates in its nest. But the Phoenix of legend is immortal and we are not. Why did life evolve this way, so that the miracle of the resurrection succeeds brilliantly in our youth and then fails? Why not perfect renewal of the body forever?
Life is a kind of sacrifice, a sacrifice we have made from the beginning, and make every day of our lives. Each mortal body is a story of sacrifice and renewal that slowly fails. It is a very old story for which we all, at least at one time or other, would love to change the ending.
PART II
THE HYDRA
They are ill discoverers that think there is no
land, when they can see nothing but sea.
—FRANCIS BACON,
THE ADVANCEMENT OF LEARNING
Chapter 5
THE EVOLUTION OF AGING
Not long ago I was talking about the problem of mortality with a physicist and he told me, with a smile, that it’s in the nature of everything to fall apart. That is what the law of entropy tells us about inanimate objects like planes, trains, and automobiles. That’s also what common sense tells us about animate objects like our own warm, breathing bodies. But we don’t fall apart between the years of, say, six and twelve. We grow bigger and stronger in those years. If we can do that much when we are growing, then why can’t we at least hold steady, hold our ground, from the ages of twenty to a hundred and twenty? We don’t, but that doesn’t mean our failure to do so is mandated by the laws of physics. If that’s breaking the laws of physics and common sense, then we’ve already broken them. Every human body breaks those laws in the womb from the moment sperm meets egg. Those two microscopic cells meet in the dark and nine months later, after a miraculous construction project, a baby is born with a body made of trillions upon trillions of cells, from the brain cells inside the still-soft skull to the skin cells in the ten fingers and ten toes. And the history of the development of life on Earth is at least as spectacular as the development of each life in the womb. Life on Earth, from small beginnings, has attained extraordinary profusion. Three billion years ago, life was all microscopic single cells. And now there are millions of species of living things, from shrimp to whales, from mites to elephants. The development of life on Earth is like the development of a life in the womb: it defies common sense, and the intuitions of physicists, like a ball that rolls uphill.
If life can do so much in the first half, why does it fail in the second? Why can’t it keep the ball rolling? Bacon makes this point in the first pages of his History of Life and Death. He chastises the physicians and philosophers of his time for missing it. Conventional wisdom in Bacon’s day held that there is something in the body that can’t be repaired, some “radical moisture” that can never be replenished. Our bodies lose that moisture and dry out and that’s why we get old. But that idea is “both ignorant and vain,” Bacon writes; “for all things in living creatures are in their youth repaired entirely; nay, they are for a time increased in quantity, bettered in quality.” So much so that “the matter of reparation might be eternal, if the manner of reparation did not fail.”
We grow up, and then we seem to hold steady for years. A woman between the end of puberty and the onset of menopause balances the building up and the tearing down of her bones so perfectly that they grow neither too heavy nor too light. Her whole body—flesh, blood, bone, and sinew—is a kind of fountain in which the new continually replaces the old and the form stands as if it would stand forever. Then, after menopause, the balance fails, and bone mass declines, and osteoporosis sets in. But why does the balance have to fail? Why did this failure evolve? Which is to ask the most fundamental question of the science of mortality: How did old age and death come into the world?
The answer that has now emerged in the science of mortality gives hope to the field’s optimists.
Darwin himself does not seem to have thought about this question. Apparently, like most of us, he took aging for granted. But one of Darwin’s first great supporters, the German biologist August Weismann, did think about it. His own conclusion was dark—so dark that it may have contributed to the doldrums that gripped the field for much of the twentieth century.
Weismann laid out his argument about the evolution of aging in one of his first lectures as prorector of the University of Freiburg in the spring of 1883. He published the lecture that summer as an essay, “Upon the Eternal Duration of Life.” “In my opinion,” Weismann said, “life became limited in its duration, not because it was contrary to its very nature to be unlimited, but because an unlimited persistence of the individual would be a luxury without a purpose.” In other words, he believed that life on Earth had been immortal, once upon a time. Immortality was just as natural a state for living creatures as mortality. “Among unicellular organisms natural death was impossible,” Weismann wrote. An amoeba and the paramecium never die only because they can’t—because they are too simple to die. But as soon as multicellular life evolved on this earth, aging did become possible for them, and they began to grow old and die.
In the beginning, in Weismann’s view, death did not exist; and then life invented it. In fact, if human beings ever did find a way to make ourselves immortal, said Weismann, then our descendants would just evolve mortality all over again. “Let us imagine that one of the higher animals became immortal,” Weismann writes; “it then becomes perfectly obvious that it would cease to be of value to the species to which it belonged.” Think of it this way, he says. Even if a tree or an elephant or a mouse never got killed by some accident, even if it l
ived for eternity—which is, of course, impossible—it would be bound to get damaged and then crippled by this and that affliction, somewhere along the line; “and thus the longer the individual lived, the more defective and crippled it would become, and the less perfectly would it fulfill the purpose of its species.” The species would have to keep producing new and healthy specimens to take the place of its sick, hobbled, and infirm; “and this necessity would remain even if the individuals possessed the power of living eternally.”
So death is a sacrifice that each generation has to make for the sake of the next. We reproduce, and then we have to die. “Worn-out individuals are not only valueless to the species, but they are even harmful,” he says, “for they take the place of those which are sound. Hence by the operation of natural selection, the life of our hypothetically immortal individual would be shorted by the amount which was useless to the species.” Life’s invention of death proved to be so successful and necessary, death made species that possessed it so vital, that once death arose it became universal; so that “the higher organisms, as they are now constructed, contain within themselves the germs of death.”
In Weismann’s view, then, aging and death are accomplishments that we complicated creatures should be proud of. Amoebae and other single-celled organisms are forced to remain immortal because they do nothing but divide and divide. But the immortality of protozoa is primitive compared with the mortality of metazoa like ourselves.
There’s a certain fascination in this idea, dark as it is. In Weismann’s view of life, aging is an adaptation. Death itself is an adaptation. Death is more important to us than eyes, ears, teeth, and hands; or flukes, gills, and flippers; or roots, branches, and green leaves. Just as a beetle never grows as large as a horse, because there are natural limits to its growth, so a beetle never lives as long as a horse, and a horse never lives as long as a man, because there are natural limits to their longevity.
Besides the protozoa, Weismann did recognize one other form of biological immortality on this earth. Our bodies are divided into two kinds of seeds, two kinds of cells, the mortal and the immortal. The seeds in our eggs and sperm have been passed down to us from generation to generation. Weismann called these seeds the germ cells, and the rest of our bodies the soma. The soma is doomed, but our germ cells are potentially immortal.
That part of his argument is still regarded as well established. But his basic premise is not, even though most of us still assume that it is true, because it makes intuitive sense. If asked why we grow old and die, most people today would answer, just as Weismann did, that we have to wear out and die to make room for the next generation.
And most biologists in Weismann’s generation and for several generations afterward did think his point made sense. Weismann’s argument helped inspire Sigmund Freud’s famous theory of the death instinct. “What lives,” Freud wrote in Beyond the Pleasure Principle, “wants to die again. Originating in dust, it wants to be dust again.”
The biologist who spotted the flaw in Weismann’s argument was Peter Medawar, who won a Nobel Prize for work in immunology during World War Two, when he developed new methods for skin grafts. A few years after the war, Medawar published two celebrated essays on the problem of aging, “Old Age and Natural Death” and “An Unsolved Problem of Biology.” There he both posed and solved the problem of aging, in the view of most gerontologists today; he explained why evolution brought old age and natural death into the world. At the time I visited Maria Rudzinska, back in 1984, Medawar was by far the greatest living scientist in their still-small field, even though the problem of aging was only one of a vast number of his interests. That year, he gave a public lecture in New York—at the Explorers Club, I think—and I went to hear him. He was a handsome, elegant, and sophisticated old man, crippled by a stroke. He lectured from a wheelchair, with his equally elegant wife standing at his side.
Medawar had studied Weismann’s argument about old age and decided that Weismann was completely wrong. In his essay “Old Age and Natural Death,” Medawar quotes those wise-sounding lines of Weismann’s about worn-out bodies, which are useless to the species, and even harmful, because they get in the way—so harmful that even if their ancestors had once been immortal, natural selection would have shortened their life spans and made them mortal.
“In this short passage,” says Medawar, “Weismann canters twice around the perimeter of a vicious circle. By assuming that the elders of his race are decrepit and worn out, he assumes all but a fraction of what he has set himself to prove.” Why are they worn out? That’s the whole question, says Medawar. That’s Weismann’s first canter around the vicious circle. And if bodies are worn out, then natural selection will weed them out. Bodies don’t have to invent or evolve an elaborate adaptation like Death by Old Age to take themselves off the stage. Give mortal bodies enough time on this earth, and sooner or later a cold winter or a hot summer, a drought or a flood, a famine, a pestilence, the wolf at the door, a chicken in the snow, or any one of nature’s myriad dangers will come and find them. Plain bad luck will take them out.
Mother Nature is infinitely inventive when it comes to fatal accidents. Because we have managed so successfully at insulating ourselves from most of them, we forget how tough it is out there, even for creatures that are young and healthy. Darwin makes this point in the most famous chapter in the Origin of Species, “Struggle for Existence,” which begins, “Nothing is easier than to admit in words the truth of the universal struggle for life, or more difficult—at least I have found it so—than constantly to bear this conclusion in mind.”
As Darwin goes on to say in “Struggle for Existence,” most animals die young. Take wild mice. Nine out of ten wild mice die before they have lived a year. Some of them get pounced on by a cat or an owl. More of them die of the cold, at night, hungry and shivering. They die because they don’t have enough fuel in their bodies to keep warm. If you think of the life span of a mouse as having Seven Ages, like a man, then most wild mice don’t survive beyond the young lover in As You Like It, composing a sonnet to his mistress’s eyebrow. They don’t die of old age; they die huddling together for warmth in the long hours of the night. Virtually no wild mouse is ever so lucky as to survive to extreme old age, or about three years, which is the age when a well-fed mouse in a safe warm cage finally totters to its end, “sans teeth, sans everything.”
It’s the same with gray squirrels. They can climb trees to get away from cats and dogs and kids with slingshots. But even so, only about thirty in a hundred survive longer than one year. Only six or seven in a hundred survive more than four years. And yet when gray squirrels are kept in zoos they can sometimes live twenty years.
From the fact of the struggle for existence, Darwin drew a conclusion that seems simple in retrospect. Darwin’s process works by selecting slight variations—those that make a difference in the survival of an individual. There are times when the slightest variation will determine who lives and who dies; who gets to reproduce and who dies without passing on the genes.
And from this same hard fact of life, Medawar drew a second conclusion. In the wild, life is so hard that variations are weighed in the balance, with the best selected and the rest rejected, when the individual is young. It is only among the young that variations will be weeded out. Those that appear later in the creature’s life span won’t be culled, because the creature will almost never live that long anyhow. Again, as a general rule, life in the wild is so dangerous that no matter how fit they are, most creatures don’t live long enough to grow up, let alone grow old. Most don’t live long enough to pass on their genes. “We behold the fact of nature bright with gladness, we often see superabundance of food,” Darwin writes in “Struggle for Existence” “we do not see, or we forget, that the birds which are idly singing round us mostly live on insects or seeds, and are thus constantly destroying life.” They are cutting short the lives of many of those bugs and plants before they make more bugs or plants. And if the birds themse
lves run out of bugs and seeds, they die young, too.
You can convince yourself that most wild things die young by doing a simple thought experiment. Suppose, says Darwin, an oak produced only two seeds a year—“and there is no plant so unproductive as this.” If each of those two seedlings grew up the next year and produced just two more, and each of those produced two, and so on, and if each of the seeds germinated, then in twenty years that first oak would have produced a forest of one million oaks. Or take elephants, which are the slowest-breeding animals on the planet. Elephants start breeding at the age of thirty. If one pair began breeding when they were thirty and produced only six baby elephants by the time they were ninety, and if all of those babies grew up and bred, then, well before a thousand years had passed, that matriarch and patriarch would have produced a herd of almost nineteen million elephants. If oaks and elephants went on like that the whole planet would soon be oaks and elephants. What this arithmetic suggests is the brevity of life throughout all its kingdoms. Most animals don’t live long enough to become parents. Most seeds don’t live long enough to set seed themselves. One spring, Darwin tested that point with an experiment in his garden. He marked out a plot of ground three feet long and two feet wide. He dug and cleared it and counted all the weeds as they came up. Out of 357 weed seedlings, he says, 295 were destroyed, most of them chewed and swallowed by slugs and bugs. Those seedlings never passed on their genes. Even weeds die young—which is why they don’t completely take over the planet either.
Since oaks and elephants and dandelions never take over and engulf the earth, Darwin concludes, we may be sure “that this geometrical tendency to increase must be checked by destruction at some period of life.” And that period, Medawar adds, is youth. Death hovers everywhere and prevents the conquest of the planet by oaks or elephants or anything else alive. Everywhere in the living world a lucky few survive while the rest die young.
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