Why We Get Sick (18 page)

Is there even such a thing as a normal human genome? Certainly no one string of DNA code is ideal, with all deviations to be stigmatized as abnormal. While we humans have much in common, our genes are diverse. There is no one ideal type but only the many varied phenotypes that express the diversity of human genes, all competing in varying environments to get copies of themselves into the next generation.

T
here are widespread but totally unjustified fears and pessimism about genetic influences on human disease and behavior. There is an associated pervasive distrust of scientists who recognize and study these influences. To some extent these anti-gene sentiments reflect a more general antagonism to biological and especially evolutionary explanations among social scientists, the general public, and even some medical professionals. Many people suppose that human behavior and any aspects of human disease that arise from human nature are matters to be dealt with entirely by religion or sociopolitical action, not by seeking biological causes and remedies. When they get cancer or heart disease, however, most people become less concerned about such abstractions.

Is it pointless to try to alter biologically inherited conditions? For some reason, this seems to be a widespread assumption. A recent discussion of myopia contrasted a “use-abuse theory,” said to imply that the condition was preventable, with a “genetically determined” theory, said to imply the impossibility of prevention. Fortunately, the subsequent discussion supported the idea expressed in this chapter that myopia is indeed genetically determined and also undoubtedly preventable. In fact, the finding that a medical condition is inherited should generally be considered good news. Genetically programmed development is very much a material process and susceptible to material manipulation. It was the study of the genetic cause of PKU that led to the discovery that its effects could be prevented by a diet free of phenylalanine. Studies of the actions of genes, and of their occasional failure to act, are already preventing and curing many diseases. As Melvin Konner observed in 1983, “The discovery of a genetic determination for a disorder may provide the best hope for an environmental treatment of it.” Many others have since made the same point.

Studies of the genetic bases of disease deserve every encouragement, and clinical medicine makes good use of information provided by such studies. When a gene acts against the interests of the patient, the physician should act against the gene. As Oxford biologist Richard Dawkins puts it, we should “rebel against the tyranny of the selfish replicators.”

T
he plane sat on the Minneapolis runway in the hot June sun of 1970, the air inside stuffy to the point of apprehension. A white-haired woman, about seventy, turned to the young man in the seat to her left.

“Are you a student?” she asked.

“Well, I just graduated from college. Now I’m about to start med school.”

“How wonderful, to have the opportunity to save lives, you must look forward to it.”

“Well, uh, yes.”

The plane lifted off, fresh air blew from the nozzles above, and a typical airplane conversation ensued—hometowns, common acquaintances, the weather. Then the woman paused, turned to the young man, and spoke plaintively.

“Do you know that there is one disease that we really, really need a cure for, one disease worse than all others, one we all get? Do you know what it is?”

“Uh, no. What?”

“What we really need, what I hope you will look for, is a cure for the worst disease, for old age. It
is so
terrible,
it
makes me feel so helpless, and no one has found a cure. Please, please, try to find a cure.” Then, she turned away, silent, to gaze out the window.

O
f the many burdens of consciousness, the fact of death is the heaviest. The possibility of untimely death is frightening, but the inevitability of aging and dying casts the longest shadow on human life. Even apart from religious doctrine, humankind’s efforts to overcome aging have been impressively persistent. From Ponce de León searching the wilds of Florida for the fountain of youth to
Life
magazine reporters searching out native Georgians in the former Soviet Union who claim to be 150 years old, human hope lives forever. We, however, do not. By age 80, half of us will die; by age 100, 99 percent; and by about age 115, every one of us will be dead, medical breakthroughs and hopeful news stories notwithstanding.

During the past few hundred years, the
average
length of life (life expectancy) in modern societies has steadily increased, but the
maximum
duration of life (life span) has not. Centuries ago a few people may have lived to 115; today this maximum remains about the same. All the wonders of medicine, all the advances in public health have not demonstrably increased the maximum duration of life. If aging is a disease, it seems to be incurable.

Technically, we are not really talking about aging, the process of growing older from birth onward, but
senescence
, the process of bodily deterioration that occurs at older ages. Senescence is not a single process but is manifested in an increased susceptibility to many diseases and a decreasing ability to repair damage. Death rates in the United States are very low at age 10 to 12, about 0.2 per 1000 children per year. The death rate increases slowly to 1.35 per 1000 at age 30,
then increases exponentially, doubling every 8 years. As
Figure 8-1
shows, by age 90, the death rate is 169 per 1000. A person age 100 has only a one-in-three chance of living another year. Every year the mortality curve becomes steeper, until eventually we all are gone.

Imagine a world in which all causes of premature death have been eliminated, so that all deaths result from the effects of aging. We would live hearty, healthy lives, until, in a sharp peak of a few years centered at age 85, we would nearly all die. Conversely, imagine a world in which senescence is eliminated, so that death rates do not increase with age but remain throughout life at the level for eighteen-year-olds, that is, about one per thousand per year. Some people would still die at all ages, but half the population would live to age 693, and more than 13 percent would live to age 2000! (See
Figure 8-2
.) Even if death rates were much higher, say the 10 per 1000 estimates for young adults in India in 1900, eliminating the effects of senescence would still give a substantial advantage, with some people living to age 300. From an evolutionist’s point of view, an individual who did not senesce would have, to put it mildly, a substantial reproductive advantage.

This brings us to the mystery. If senescence so devastates our fitness, why hasn’t natural selection eliminated it? This possibility seems preposterous only because senescence is such an inescapable part of our experience. Consider, however, the miracle of development: from a single cell with forty-six strands of nucleic acid, a body gradually forms, with each often trillion cells in the right place, making tissues and organs that function together for the good of the whole. Certainly it should be easier to maintain this body than to form it!

Furthermore, our bodies have remarkable maintenance capacities. Skin and blood cells are replaced every few weeks. Our teeth get replaced once—but why not six times, like those of elephants? Damaged liver tissue can be rapidly replaced. Most wounds heal quickly. Broken bones grow back together. We can replace missing bits of skin and bone and liver, but some tissues, like heart and brain, do not regenerate. There are revealing differences between species in this regard. In some species of lizards, when the tail is cut off, a new one immediately starts growing. Our bodies do have some capacity to repair damage and replace worn-out parts; it is just that this capacity is limited. The body can’t maintain itself indefinitely. Why not?

F
IGURE
8-1.
The number of deaths per year per 1000 individuals entering each age is shown at each age for the United States in the years 1910 and 1970.

F
or most of us, there is a moment in the mid-forties when we suddenly realize that we can no longer read a book except at arm’s length. Yes, some of our hair has fallen out or turned white, and our faces sport some wrinkles, but these changes can be denied far more easily than the weight of a book held on outstretched arms. Fiftieth-birthday parties usually are sickly affairs, where new devotees of mineral water tell nervous jokes about memory loss, hot flashes, and impotence. We know all too well what is to come, but few realize that aging has had a long running start. Senescence starts not at forty or fifty but with far more subtle changes shortly after puberty.

In sports, you don’t have to be very old to be past your prime. Look at
Figure 8-3
, which shows the best times for each age group in running a marathon. The curve looks remarkably like the mortality curves in
Figure 8-1
. Performance is best in early adult life and thereafter worsens with increasing rapidity. These declines are a sign of senescence. Yes, many people can still run fast at forty, but not as fast as they could at thirty. They would be at a bit of a disadvantage whether chasing an impala or escaping a tiger, and it is the
relative
disadvantage that counts. There is a joke about two men who are running away from a tiger. One stops to put on a pair of running shoes.

“What are you doing that for?” the other asks. “Even with running shoes you can’t outrun a tiger.”

“No,” he says, “but I can outrun you.”

T
he “one-hoss shay” in the poem by Oliver Wendell Holmes is the classic metaphor for the remarkable apparent coordination of the effects of senescence. That one-horse carriage …

F
IGURE
8-2.
Reproductive advantage, if there were no senescence.

Our organ systems also all seem to wear out at about the same rate, on average. Researchers Strehler and Mildvan have measured the reserve capacity of heart, lungs, kidneys, neurons, and other body systems at different ages and found that these diverse bodily systems deteriorate at remarkably similar rates. By the time a person reaches age 100, every system has lost almost all its capacity for meeting increased demands, so that even the tiniest challenge to any system causes a fatal failure. Senescence itself is not a disease but the result of every bodily capacity steadily declining so that we grow steadily more vulnerable to a myriad of diseases, not only cancer and stroke but also infections, autoimmune diseases, and even accidents.

S
enescence is a first-class evolutionary mystery. Any explanation must account for the phenomena we’ve just described. Some clues come from other species. One warm summer evening one of us walked with a group of friends to a picnic on the western shore of Beaver Island in the northern reaches of Lake Michigan. As we mounted the dune overlooking the lake, the last
rays of golden sun broke through fiery clouds. We stopped short, breathless at the sight of millions of iridescent wings, flashing in the dying sun. The mayflies formed a golden cloud hovering over the breaking surf, waiting for a chance to mate, lay eggs, and then die on the same day they matured. It seems so wasteful. Yet other species share the mayflies’ fate. In the fall, salmon rush up nearby streams, lay their eggs, and die, their rotting bodies washing back to the big lake. This is senescence with a vengeance. How can we understand it?