DR. HANS SELYE= AUGUST 15 1959
Aging is a disease that could be cured, says Montreal’s Dr. Selye, the world-famous pioneer in the study of stress. There’s no good reason why a limit should be placed on the human life span. Here’s his urgent plea for more research into the supreme medical riddle as told to Ken Lefolii
When a living cell is nourished, washed and sheltered in a test tube it neither decays nor dies; it divides and endures. It defeats death.
Biologists were familiar with this technical form of immortality when I was a medical student thirty years ago. Cell tissue from rats and chicks born at about that time is alive and healthy in laboratory test tubes today. On the human scale of life, this tissue would be nearly a thousand years old. No one knows how far man can prolong his life.
Since this ancient tissue began its life medical researchers have learned how to pull the sting of death from one disease after another.
Medicine has assembled a fund of knowledge that will now serve, I believe, as a point of departure for studying the causes of old age. If the causes of aging can be found, there is no good medical reason to believe that it will not be possible for science to find some practical way of slow-¡ng the process down or even bringing it to a standstill.
In the terms 1 am using here aging can be regarded as a disease. Like any other disease, it is probably preventable or curable. And since tissue is technically immortal, the “normal” life span of a human being may be described as any number of years the medical science of the moment is capable of making it—seventy years, a hundred, two hundred. or perhaps more. There is no theoretical limit, although by this I do not mean to suggest immortality for mankind. There will always be a practical limit set by imperfect medical skill and knowledge, and the risky but unavoidable adventure of living outside a test tube.
But 1 do mean to suggest that our world is governed by a false idea of mortality: the idea that mortality is a death sentence that falls inevitably on each of us in the weakness of old age, within a foregone number of years. In this view life is cheap. Although heart diseases are the killers in half Canada’s yearly toll of death, these killings are accepted as natural if unwelcome events. Each death by automobile accident, on the other hand, is decried as an avoidable tragedy.
The truth is that death by disease is largely avoidable. On the record, medicine has made a good deal more progress toward defeating death by disease than safety authorities have made in curbing the far smaller but growing number of deaths on the highways. Yet despite this and everything else 1 have said about the nature of life, most of the decisions made by nations and individuals are governed by the death-sentence view’ of mortality. The cheap view of life is the common view .
To most people, of course, the suggestion that they hold life cheaply will be surprising and quite possibly shocking:
they are convinced that their actions prove otherwise. But it seems doubtful to me whether most people have given close thought to what their actions really are in this ultimate issue of life and death.
To cite one action that is on public record: the people of Canada spend about a million dollars a year on underground vaults to inter a few’ of their dead, and about a quarter of a million dollars on research into the causes and cures of heart disease. (Exact figures on medical research expenditure are difficult to compile. The ones I am using here are taken from the most recent national report, made in 1957 by Dr. Basil Layton, principal medical officer for research of the federal Health and Welfare Department. Later figures are fragmentary.) Although disease is responsible for all but roughly six percent of our deaths, research into the causes and cures of diseases of all types in Canada commands an outlay of about ten million dollars a year. Funeral expenses of all kinds account for almost forty million dollars a year. We apparently value the dignity of death four times more highly than the hope of life.
In another of our joint actions, our elected representatives have set our defense budget for this year at one and a half billion dollars. It is not unreasonable to describe the money we spend on medical research as our defense budget against disease, and this amount, as I mentioned, is about ten million dollars a year. In other words, our defense budget against death by disease—a certain killer that will claim every one of us but the handful that die from accidents, suicide or murder—is three quarters of one percent of our budget against death by war, which may or may not come and may or may not kill as many as half of us if it does. War is not my study, and this is not a criticism of our de-fense preparations. It is merely a comparison of our public actions in the two fields.
To refine the view from the general to the particular, every year when the circus comes to Montreal a troupe of clowns and jugglers visits the Shrine Hospital for Crippled Children to play for the paralytics who are unable to leave their beds. For some of these children, the ones who are totally paralyzed, the nurses arrange systems of mirrors so that their patients can see the clowns without moving their heads. Few of the paralytic patients who watch the circus in this way are more than ten years old. If the research that culminated in the polio vaccines had been finished as little as five years sooner, it is fair to assume that some of the children lying beneath their arrangements of mirrors would have been downtown trying to sneak into the circus through a side door.
An important contradiction immediately suggests itself here. Is there any assurance that just by spending more money the polio vaccines could have been discovered sooner? Or insulin? Or penicillin, or cortisone, or the technique of open-heart surgery, or any of the other great medical discoveries of these years?
No. There is no such assurance. But to pose this as a serious reason for limiting financial support to medical research, an attitude that is constantly taken, is a mistake that can only be explained by complete unfamiliarity with the methods of science. To compress the essence of this method into a word, it is experimental. No count has ever been made, but it is quite certain that for every series of expert ments that ends in a “useful” result like insulin, some thousands of series are completed that are apparently useless.
In fact, though, these unsuccessful experiments are as necessary and very nearly as useful as the successful ones. They reduce the number of possible solutions; every time an experimental series turns out to be “wrong,” medicine is a step closer to discovering a series that will turn out to be right. If Banting and the other investigators of his time had been provided with the necessary facilities to experiment more widely and rapidly, there is no assurance but every probability that the search for a diabetes remedy would have narrowed more quickly to the obscure pancreas, its secretion, insulin, and salvation for incalculable numbers of diabetics. Precisely the same considerations apply to the discovery of the polio vaccines and to the still-undiscovered means of dealing with diseases like cancer and cardiac accident.
My own work, as it happens, bears on this point with particular pertinence. For well over twenty-five years now I have been trying to learn just what happens to the body under the stresses of life. This has involved more “useless” experiments than l could conveniently calculate, but not long ago my associates and I were able to prove that under one set of conditions, at least, stress causes heart failure. We found that every time laboratory animals are given certain salts and hormones and then exposed to stress, they die of a cardiac accident. A short while later we showed that other salts will forestall heart failure and save their lives.
At a number of hospitals in several parts of the world clinicians are now beginning to test the ability of these substances to protect human lives against death by cardiac accident in the same way they protect our laboratory animals. Many years of intense study remain before it will be known whether this treatment is effective; you do not expose a man to lethal stress in order to test an experimental safeguard. At the end of a decade of work by many specialists, nothing more may have been shown than that there are unknown differences between human systems and animal systems, and substances that protect animals against heart failure are of no value in man.
There is no particular reason to expect this to happen but if it does, the work still will not have been useless. It will become part of the knowledge of later researchers. By rejecting this approach they will be able to follow one of the remaining lines of inquiry among which the solution must lie. Eventually the search will narrow down to a successful treatment.
It must be clear that the speed at which medicine approaches this solution depends to a very large extent on how many capable researchers are financially able to follow up promising lines of inquiry. Until the end of the search is reached, five hundred thousand people or more will die every year on this continent from heart and blood-vessel diseases.
But even after heart disease has been curbed or defeated, a larger problem remains. At the present stage of knowledge, elderly people saved from heart disease will soon succumb to one of the other illnesses that attack the weaknesses of old age.’ Defenses can be found against these diseases too, of course, but it seems to me that a more rewarding approach may be to look into the nature of the weaknesses and, if possible, remove them. My associates and I are now experimenting along this line, and we have had some curious and unexpected results that make us believe in its promise more firmly than before.
As I mentioned at the outset, biochemists long ago discovered a method of keeping tissue alive and healthy for indefinite periods. The tissue is bottled in a watery solution of nourishing substances. As long as the living cells are removed regularly, cleansed, and returned to a fresh solution, they show no sign of deterioration. Uncleansed, they die.
The value of guesswork
This indicates that the guess most often offered at the moment to explain the weaknesses of old age may be worth looking into. According to this guess, during life the system of cells that makes up an animal produces waste substances a little faster than the system can get rid of them. In the course of life the residue of waste that builds up interferes with the nourishment of the cells, and the deterioration of old age sets in.
If this is the mechanism of aging, there should be at least two ways of avoiding it: either by slowing down the rate of waste production or by helping the system to destroy its waste and get rid of it. These are the possibilities we are looking into now. They are guesswork, of course, but as far as our work is concerned it doesn’t matter much whether these particular guesses happen to be accurate or not. To a scientist any hypothesis is expendable; you might call it a launching platform for testing ideas.
In testing these ideas about age we discovered a new form of life with some odd and suggestive characteristics. It came about in this way:
We began by trying to find out what happens when you form an air sac inside an animal’s body, sealed beneath the skin. During these experiments we planted a small tube, open at both ends, in the body of a rat. We now know that every time you plant a tube beneath an animal’s skin in this way, several unusual changes take place. First, a fluid similar to blood plasma but richer in protein begins to fill the empty tube. Then membranes of living tissue grow across both open ends of the tube and seal the fluid in. The membranes, which I call basal plates, and the fluid both contain fibrin, the clotting agent in blood. The fibrin filaments in the basal plates soon begin to be pulled toward the centre of the plates by the process doctors call wound shrinkage, a process you see taking place every time you cut your finger.
Meanwhile the fibrin suspended in the fluid between the plates gathers together and shrinks into a thin cord. Then the cord floating in the fluid catches the fibrin gathered at the centre of the basal plates. Now the two membranes are connected by a cord of dead fibrin.
At this point living cells begin to descend the cord from the membrane plates at each end. like a spark sputtering down a fuse. When they meet in the middle, the cord is alive. It quickly organizes iteslf as a living organ, essentially like
"Even after heart disease has been curbed or defeated, old age will still take its toll"
a tendon but in many respects unlike any organ that ever before existed, with a blood-supply system, connective tissues, and the other necessary characteristics of organic life.
The rest of the cord’s story cannot yet be explained. The structure has become a living part of the host animal, and you would expect the cord to follow the same life cycle as the host. Instead, within a month or two after it becomes full-grown the cord begins to break down. Ten or fifteen days later the cord is dead, apparently of old age, even though the host animal remains young and healthy. There is one way to save the cord: if you remove the fluid surrounding it every few days and allow fresh fluid to form, the cord remains healthy indefinitely. It neither ages nor dies.
To all appearances this peculiar cord is what I would cali a model of old age. The overwhelming difficulty in studying this subject has always been time; if a researcher studies the processes of aging in a man, his own lifetime is barely long enough to complete one experiment. Even when he studies aging in rats, a single experiment takes at least as long as the usual life cycle of a rat, three years from birth to death. By investigating the life processes of these cords, what seems to be old age can be studied from start to finish in a few weeks.
Who can say it’s fantastic?
The cord I’ve described may turn out to be an indispensable tool in deciphering the processes of life. It may turn out to be a medical curiosity with no larger significance at all. It may find its place in medicine somewhere between: doubtless there is some usefulness in looking into its possible applications for plastic surgery, where the problem of filling cavities with new tissue is acute.
For the time being, the cord is no more than an interesting discovery that will serve as the starting point for a great deal of future study. This is the first time I have discussed its implications in writing. But for that very reason the cord is a vivid illustration of a characteristic common to all basic research projects. They appear to begin a long way from the point they want to reach and at first they always seem unlikely to succeed. It is as far-fetched to look for the explanation of old age in a glass tube beneath the skin of a rat as it was for Banting to look for insulin in an obscure organ like the pancreas.
This element of apparent fantasy may be part of the reason why basic medical research is financed at one quarter the amount spent on burial in this country.
It is hard to imagine a group of busy men, a board of directors or a cabinet, finding much patience for a man who intends to spend their money, if he can get some of it, on activities like watching blue mold grow on a plate. Later, when the man—in this case Alexander Fleming—enriches the world with a new lance to use against disease—in this case penicillin—the busy men’s view of the affair presumably changes.
It appears to change, however, only momentarily. Since the beginning of this century life expectancy on this continent has lengthened from fifty to seventy years. Some of the twenty additional years, of course, are due to improved hospital methods and techniques of treatment. But most of them are due to discoveries of basic researchers, like the ones I have mentioned here. They have given every individual born on this continent the right to expect at least a decade more of life than his father. When
research has mastered heart disease there will be a dramatic leap in these extra years, and when we begin to master old age their number will leap again. There is, as I said, no theoretical limit.
Yet the people of Canada in 1959 decided to underwrite research against disease in the amount of roughly sixtythree cents each, the national average of our total research budget. I persist in doubting that most people would knowingly place a bargain-basement price of sixty-three cents a year on the hope of prolonging their own lives for ten days, much less for ten years or more, but the fact is impossible to evade. It contrasts curiously and, remembering the paralyzed children watching the clowns in their mirrors, perhaps even criminally with some of the other uses we make of our wealth. We have, for one, just finished spending about twenty-five dollars each for an airplane that never flew, the four-hundred-million-dollar Arrow. This is more money than Canada has spent on disease research in its entire history.
I am convinced there can be only one reason for the disastrous values implicit in these figures. This is the mistake I have been referring to as the cheap view of life—the false belief that disease, senility and death are inevitable.
Disease, senility and death, I repeat, can be combatted and largely defeated. Until they are overcome, all life is in the balance. Moreover, to overcome them at a much faster rate than our present one does not call for astronomical outlays. By doubling our yearly sixtythree cents for medical research we might double our rate of progress. By quadrupling it to something like three dollars a year, still an insignificant amount beside the hundred dollars a year we each spend for military defense, we would probably come close to making full use of all the capable brains and available facilities in the country.
This is a limited and realistic objective. Given full knowledge of the facts as I have gone over them here, there cannot be many people who would quarrel with either the amount or the purpose. Still, it seems clear from all I have said that this reasonable objective is beyond the competence of our present methods of financing medical research.
There is dispute between private voluntary bodies about their right to monopolize appeals for the various diseases. There is disagreement among federal, provincial and municipal governments about where responsibility lies for underwriting various projects the private groups cannot cope with. And while these no doubt weighty disputes are debated, efforts to overcome disease are given less financial priority than the niceties of burying its victims.
The lives in the balance, it should perhaps be pointed out, are not in a few private hands. They are the lives of the entire public. When the public itself adopts a clear view of death, the cheap viewof life will no longer be able to dictate public decisions. I think it is fair to say that to delay this change of mind is a form of murder—our own. ir