We have investigated the proposition that a freshly dead body can be frozen, stored for a long time at low temperature, and thawed again without excessive damage. But after this has been done, it is still just a freshly dead body (although it may be hundreds of years old) and much more is required. We need assurance that we can be revived, and not only that; if we die sick, we want to be made well; if we die broken, we want to be made whole; and if we die old, we want to be made young.
(Indeed, we want yet more. We hope to be made not only good as new, but eventually much better than new. This part of the discussion, however, will be mostly reserved for later chapters.)
Absolute, rigorous proof of the future capabilities of science cannot, of course, be offered. For example, no engineer today could prove that it will ever be possible to manufacture a cheap, safe, reliable family helicopter. He cannot prove it can be done, because he does not know exactly how to do it. Nevertheless many engineers, and probably most, would make such a prediction with confidence; there are favorable hints in current research, and the whole march of history is obviously in this direction
That future technicians will be able to repair and rejuvenate us cannot be proven, but it can be made convincing all the same. Let us review briefly, and with no strenuous effort to be
orderly, some of the striking accomplishments and prospects of modern medicine and biology, especially those relevant to repair and rejuvenation
Revival after Clinical Death
It is well known that hundreds of people have been revived after being clinically dead for many minutes, i.e. after heart-beat and breathing stopped. Most of these died of such things as heart trouble, shock, asphyxiation, and drowning. They were revived by rather simple measures including artificial respiration, blood transfusions, heart massage, and stimulation by drugs or electricity. (97
A remarkable example of what can be done even in these primitive times is offered by the case of Professor Lev Landau, a famous Russian physicist who suffered an auto accident in 1962. He is reported to have sustained a fractured skull, brain contusions, severe shock, nine broken ribs, a punctured chest, a fractured pelvis, a ruptured bladder, paralysis of the left arm, partial paralysis of the right arm and both legs, and failing respiration and circulation. During the next fourteen months he died four times, and was four times resuscitated. In the spring of 1963 he was still alive and apparently improving. (180
The people in the freezers-you and I-will have died mostly of disease or old age. The immediate cause of death will usually be the failure of some vital organ. The future medicos, then, will perhaps proceed somewhat as follows: first, either restore or provide respiration and circulation; next, repair or replace the defective organ that was the proximate cause of death; then cure any acute disease and make any other urgent repairs; lastly, and at leisure, make a general overhaul and rejuvenation.
The first stage, the restoration and support of life while
biological repairs are being made, will demand the use of mechanical devices, some of which are already well known.
Mechanical Aids and Prostheses
There exists right now a rather imposing list of inventions to perform biological functions. To assist breathing, we have respirators of various kinds, oxygen masks, pressure chambers, and iron lungs." To help a faulty heart keep proper time we have electronic "pacemakers," some of which can be implanted in the body. There are pumps which can be connected to the circulatory system and do the work of the heart. There are even ma- chines which can take the place of both heart and lungs, aerating the blood as well as pumping it. These are all matters of common knowledge.
Slightly less familiar is the use of a machine to perform the function of a missing or diseased kidney. Dr. B. H. Scribner of the University of Washington, for example, has been reported treating patients once or twice a week by running their blood (out an artery and back into a vein) through the device, which removes the wastes ordinarily handled by the kidney. Just a very few years ago these patients would have been doomed, unless they were lucky enough to get a successful kidney transplant, but now they can apparently live indefinitely without kidneys. (21)
Pacemakers or electronic stimulators have been used not only for the heart, but also in cases (as after abdominal surgery) when the intestine is paralyzed, and in the case of dogs when the bladder is paralyzed. (82)
The future outlook for prosthetics is even more impressive. Dr. Lee B. Lusted (professor of biochemical engineering, University of Rochester) thinks that within fifty years it will be possible to replace nearly all of the body organs by compact artificial organs
with built-in electronic control systems-including, for example, the heart, kidneys, stomach, and even the liver. (64) (Imagine an artificial stomach, which would tolerate unlimited insult in the way of greasy and spicy foods, and never dream of growing an ulcer! Imagine a gin-resistant liver! Like most blessings, these would no doubt be mixed.)
Artificial limbs are less important than vital organs, but tremendously advanced arms and legs will be available from the shop if needed. Russians at the Central Scientific Research Institute for Prosthetics in Moscow already claim they have an artificial hand device operated by thought control! A metal bracket strapped to the arm is supposed to pick up biopotentials (electrical nerve impulses) generated by an effort of will; in other words, they claim the nerves of the body are used to control metal instead of muscle. Furthermore, they say they are working on a way to produce artificial hands with a sense of touch! (11)
Since there have been many sensational announcements from Russia which turned out to be exaggerated or premature, a healthy skepticism is proper in this instance. Nevertheless, the principle is sound, and sooner or later the hardware will be ready. Mechanical limbs and their controls are so far crude, bulky, and inefficient, but steady strides are being made toward miniaturization of both controls and motors, with only power sources still lagging behind from the point of view of compactness. To get a n idea of how compact computing machinery used for controls may become, we need only note what Dr. Fernandez-Moran has said: "At the present time . . . advanced techniques of ultraminiaturization . . . are bringing us ever closer to practical realization of information storage and integrated electronic circuits at the mc secular level ...(31) A computing machine which functioned at the molecular level might rival the human brain for compactness! And to get an idea of how small machinery may be,
we may note that in 1961 a young engineer collected a $1,000 prize by constructing an electric motor .oo6 inch in diameter. (126)
Artificial organs and limbs will be used if natural repairs or replacements cannot be had; and they will probably be used again in the more distant future when they become so efficient that they are to be preferred over the biological. But our ability to repair or replace natural organs and limbs is growing rapidly, and probably for a long time this will be the dominant theme.
The routine transplanting or grafting of any organ of the body (obtained for example from a fresh corpse or from a cold-storage bank) is not yet possible, because the "immune reaction causes the body of the host to reject the "foreign matter." But leading biologists such as Dr. Jean Rostand are confident this barrier will be overcome. (119) In fact, it has been partly overcome already, and very impressive advances have also been made in the surgical techniques needed for these operations.
One of the very difficult but very active fields is that of lung transplants. Apparently the first successful reimplantation (into the same animal) of a lung taken from a dog occurred in 195 I. In 1963 Dr. S. L. Nigro and coworkers reported this technique so far perfected that dogs are surviving after 11/2 years on the replanted lung alone. (83) Dr. J. D. Hardy of the University of Mississippi, a leading worker in the field, in 1963 reported temporarily successful transplants of lungs from one dog to another; in some cases be kept the lungs in cold storage for two to six hours before using them. The immune reaction, however, was not sufficiently suppressed, and the transplanted lungs eventually died. (38)
Dr. Hardy was also reported in 1963 to have performed the
first human lung transplant. A fifty-six-year old man, a heavy cigarette smoker, had cancer of the left lung as well as impairment of the right lung. The donor lung was taken from a man of about the same age immediately following death. After the operation, the patient was reported as doing well. (24) It is not clear from this report, however, whether new methods were used to suppress the immune reaction or whether only temporary success is expected.
Another major organ, the kidney, has often been successfully transplanted. In earlier years there was usually very limited success unless the donor was a twin of the host; in this case, since they share the same genetic heritage, the new kidney knows the password, so to speak, and is not shot down as an intruder. Recently, however, the use of certain drugs and of X-ray treatment to suppress the immune reaction has led to more success with transplants from more distant relatives or strangers.
Many other examples could be cited. A recent one, rather interesting if not tremendously important, concerns tooth transplants reportedly made by Dr. Miklos Cserepfalvi of Washington, D.C. Of 146 tooth transplants made since 1956, 140 resulted in permanent, live teeth; by contrast, earlier attempts had usually resulted in rejection of the new tooth as foreign matter within a year or so. The teeth had been extracted from children eight to twelve during orthodontic work; they had not yet erupted through the gum, and the tooth was removed complete with the sac surrounding it. Dr. Cserepfalvi is quoted as saying, "There is no reason for anyone in this country today to have a false or missing tooth in his head." (15)
The general outlook is entirely favorable. In 1963 Dr. Robert Brittain (University of Colorado) and Dr. Richard Lillehei (University of Minnesota) are reported to have said at a convention of the American College of Physicians that within only
five years it will be possible successfully to transplant all human organs, except those of the central nervous system! (40)
But even the central nervous system is not inaccessible to these techniques, although mastery will take longer, and of course we are only interested in repair of the brain, and not its replacement. A Yugoslav researcher, Dr. Mira Pavlovic, has successfully grafted a large part of the brain of one embryo chick to that of another; some of these subjects hatched and lived as long as two months. (119)
As already suggested, the organs for transplant will often be obtained from cold storage banks. Dr. Lillehei, together with Drs. Bloch and Longerbeam, expect surgical deep freezes of the near future to store kidneys, spleens, and lungs, as well as other organs. They have already quick frozen organs, kept them up to two weeks at dry ice temperature, then thawed them rapidly by microwave diathermy, treated them with a substance called LMD (low molecular weight dextran) and replanted them. (102)
But now a question arises: if everybody is frozen, there will be no cadavers to scavenge; where will the spare parts come from? Fortunately, answers are in sight.
In the relatively near future, and for a certain period in history, we may use organs from lower animals. There has been some success in suppressing the "immune reaction" even in the case of "heterografts," or transplants between different species.
On December 22, 1963, many newspapers throughout the country featured the remarkable story of Jefferson Davis, a New Orleans dock worker, whose diseased kidneys were replaced by those of a ninety-pound chimpanzee. The historic operation was reported performed by a team of Tulane University surgeons headed by Dr. Keith Reemtsma. A few days after the operation, the grafted kidneys seemed to be functioning satisfactorily, although the prognosis, of course, was uncertain.
It seems unlikely that this pioneering effort will be completely successful. The measures now used to induce the host body to tolerate the foreign tissue are usually inadequate, unless applied in such massive doses that the side effects become critical. Radiation and/or presently known drugs have poisonous effects themselves; furthermore, along with suppressing the immune reaction, they depress the body's ability to fight off infections, opening the way to complications. But the research is being vigorously pressed, and it may not be many years before lower animals can supply us with replacements for such organs as the lungs, kidneys, heart, liver, spleen, stomach, or pancreas.
Organ Culture and Regeneration
To the question of where the spare parts will come from in the more distant future, there is a beautifully simple answer: they will come from ourselves!
We know that germ cells-sperm or egg-produced by our re- productive organs contain chromosomes carrying our genetic in- formation or blueprints, and that these germ cells, after combining with one from the opposite sex, are capable of developing into complete human beings. It is less widely known among laymen that either the sperm or the egg alone is considered capable of developing into a person, although so far this has seldom if ever happened. (119) Still less is it realized that ordinary body or somatic cells, which also carry the chromosomes, may retain potential "totipotence"; even though they are differentiated and specialized, it may be possible to reverse and then generalize their development, and in fact such cases have actually occurred, where an ordinary body cell (in certain lower forms of life) has taken the place of a germ cell and led to growth of a complete individual. (79)
The possibilities, then, are obvious. As soon as enough is
known about guiding growth and development, a germ cell or an ordinary somatic cell, perhaps even from the skin, can be taken from the resuscitee's body, and from this will be grown, not a complete individual, but just the organ or organs needed for repair. It will not even be necessary to suppress the immune reaction when making the implant, because it will be his own tissue; it will be an autograft and not a homograft. You may get a new heart, for example-your very own, exactly like the original, but young and strong and ready for another three-score-ten of faithful pumping service.
Can we really be sure this will come about? Is not the guidance of growth and development an exceedingly intricate and difficult business? The answer, as usual, is that the problem is indeed complex, but there is ample optimism among the experts and there are already successful beginnings.
Tissue culture, the growth of cells in a test tube or other artificial environment, is of course old hat. The famous Dr. Carrel "maintained a strain of chick embryonic cells in this way for more than thirty years (much longer than the lifetime of the hen which would have grown from the embryo). . . . For obvious reasons this strain of cells was called Carrel's 'immortal' strain. It died (of neglect) during the Second World War... (87) Complete organs have also been maintained outside the body of the animal for varying lengths of time, and test-tube grown organs require no great stretch of the imagination.
Speaking in a somewhat different but nevertheless appropriate sense, Dr. Philip Siekevitz (Rockefeller Institute of Medical Research) has said, "I shall not be surprised if in our lifetime we know in general, often in specific, terms how the body regulates its growth. And to know is to influence." (105)
We can wait in our timeless freezers for many lifetimes, if need be, but a sufficient degree of control may come fairly early. It need not be based on complete theoretical understanding, but
can be to a considerable extent empirical. Experiments based on clever guesses have shown, for example, that embryonic skin treated at a certain stage with vitamin A will develop into the kind of epithelial tissue which lines the intestines, whereas in the absence of vitamin A it forms a normal-appearing skin. (8 7) Another fascinating news item, bearing on the way in which simple environmental changes can affect reproduction and development, concerns chinchilla breeding. Those bred under ordinary incandescent light produce all-male offspring; under a bluish daylight incandescent light, nearly all progeny are female; in natural daylight, there are equal numbers of each! (99) This particular item invites skepticism, but who knows?
So far we have been talking about growing an organ in the laboratory, starting with a scrap of tissue or a single cell, and then grafting it into the body; but this is not the only possibility. Some parts of the body might be re-grown in situ.
In lower animals, promising beginnings in organ regeneration have been made. Professor Marcus Singer at Cornell University, by manipulating nerve tissue, has caused adult frogs to re-grow amputated limbs, although normally they cannot. As Dr. Singer says, "Obviously, there is some practical interest in the possibility that human beings might some day be able to re-grow tissues and organs which they presently cannot."(98)
Adult humans can regenerate many tissues (although virtually no organs). Skin is one; another, surprisingly and hopefully, is nervous tissue, at least of certain kinds. In the famous case of the boy whose right arm was severed below the shoulder in a freight train accident in 1961 and sewed back on by Dr. Ronald Malt and co-workers at Massachusetts General Hospital, nerve cells grew back in the arm. In the spring of 1963 healing was not complete, but the cells showed growth at the rate of about one inch per month. (81)
Other pioneering experiments include those at New York Uni-
versity in repairing gaps in human nerves. Frozen nerve grafts from dead donors were used; these were also irradiated to minimize the immune reaction. The grafts themselves are said to work for as long as three years, allowing restoration of muscle function and sensation; eventually the grafts die, but meanwhile there is regeneration of new nerve fibers, which gradually replace the graft. (22)
With such sparkling beginnings, with the quickening pace of research, and with the optimistic outlook of experts, it seems not too much to expect that the brain itself will eventually prove amenable to repair, although enough of the original must remain to preserve memory and personality.
What will no doubt happen, then, is that the more urgent repairs will be made while the resuscitee is still unconscious, with new organs or tissues either grown in the lab and implanted or else gradually regenerated in the body. After this has been done he will be alive, and in much better health than just before he died-but he will still be old.
Curing Old Age
In the discussion heretofore, we have been extrapolating from a solid basis of known achievement. But when we claim that old age will be curable, that senile debility in its varied manifestations will be reversible, we might seem to be on shakier ground. After all, there seem to have been no successes whatever so far in extending human life, except statistical successes based on reduction of infant mortality and conquest of disease.
Nevertheless, theory and expert opinion again provide ample reason for optimism. By way of analogy, one might compare the prediction of a family helicopter with the prediction of an interstellar space ship. The helicopter prediction is conservative; helicopters already exist, and not much daring is required to
prophesy that they will eventually become safer, cheaper, and more reliable. On the other hand, no star ship has ever been built or even planned. Even so, interstellar travel is in the cards; if necessary, it can be achieved with chemical fuels and known technology, if we have endless patience and a bottomless purse, but in practice we know we can count on new discoveries as well as the polishing of the old. Interstellar travel is entirely possible in principle, and the practical difficulties will without doubt be overcome; just so with biological immortality.
It is conceivable, although far-fetched, that extended life or even permanent life might result from some kind of "youth serum" such as crops up in the news from time to time. In 1963 a Swiss, Dr. Paul Niehans, is reported treating wealthy old patients with a serum made from the cells of stillborn lambs at $13,000 a shot. (20)
There have been many other reports of possible "youth serums," some of which are still being investigated. For example, in 1963 the National Medical Association heard about extraordinary results in reinvigoration of old people by thyroxine, a hormone of the thyroid gland. Every system of the body is said to be favorably affected, including the circulatory system, nervous system, and digestive system. This research seems to be carried on mainly by Dr. Charles A. Brusch, of Cambridge, Massachusetts, and Dr. Murray Israel of the Vascular Research Foundation, New York, who have treated many patients. They insist that there are no harmful side effects, even with relatively massive doses, and that the metabolism needs this extra spark in old age even when the usual tests ("basal metabolism" and "protein-bound iodine") show normal thyroid function. (See, for example, The Detroit Free Press, August 20, 1963.)
Another sensational report is that attributed in September of 1963 to Dr. Robert A. Wilson, gynecologist of the Methodist Hospital of Brooklyn, New York. He is said to claim, after treat
ing hundreds of patients, that two female sex hormones (estrogen and progesterone), when properly augmented and supplemented with special diets, vitamins, minerals, and exercises, can benefit older women immensely. The secondary effects of menopause are eliminated; heart disease and atherosclerosis are reduced; cancer of the breast or genitals becomes unlikely; the skin improves in texture and color; the bones do not tend nearly as much to become porous and brittle.
There is said to be a specific "juvenile hormone" in certain insects, injection of which will keep them young indefinitely. Although nothing of the kind has been found in mammals, conceivably it might be.
Vastly more likely, progress will come slowly on a mixed theoretical and empirical basis. The theory is just beginning tentatively to be laid, since it is based on obscure, small-scale phenomena which have heretofore been almost inaccessible both theoretically and experimentally.
The electron microscope, the digital computer, the formulas of quantum chemistry, and other experimental and theoretical tools now allow studies on the subcellular level, investigations of the inner workings of the life processes. Biochemistry and biophysics are making violent thrusts in all directions (including, I suppose, backwards).
Drs. B. L. Vallee and E. C. Wacker recently wrote, "Molecular biology, suddenly exploding on cellular biology-as did nuclear physics on atomic physics a generation ago has brought far- reaching challenges and hopes for the solution of questions of normal and diseased life processes thought to be experimentally inaccessible a decade ago." (123)
To get an idea of the ultrafine work being done, we may quote a fragment from a fairly recent paper by Fernandez-Moran: the electron microscope can now be used as a powerful tool both for the controlled production and the direct observation of
radiation damage in preselected macromolecular regions of hydrated biological systems. . . . Enhanced contrast and high resolution of the order of 6 to 8 A have been achieved in direct studies of the macromolecular organization of virus particles, ribosomes, and of isolated cell constituents." (32) An Angstrom unit, abbreviated A, is a hundred millionth of a centimeter, and there are 1.54 centimeters to the inch! Using such techniques, and others, Dr. Fernandez-Moran has found an "elementary particle," only 80 to 100 A in diameter, which he regards as the ultimate unit of the function of the mitochondria, which are tiny granules or rods located in the cytoplasm or outer portion of cells. (31)
Concerning the specific problem of aging, there have been many suggestive studies. Enough has been learned to encourage Dr. F. M. Sinex, chairman of the biochemistry department of the Boston University School of Medicine, to say, "The present development of biochemistry and biology suggests the question, 'Why do we get old?' may be answered in the foreseeable future. [Certain hypotheses about aging suggest that] preventative therapy . . . is a possibility." (108)
After prevention, the next step is cure. We may also note that even the prevention of further aging in an old brain might be good enough; most of us die with our strictly mental (as opposed to muscular and glandular) faculties still in reasonably good condition. But in all likelihood the aging process in brain and body will prove reversible.
There are many ideas regarding the cause or causes of biological aging, and a few of these will now be briefly reviewed, with no attempt to be systematic, let alone exhaustive.
One of the major primary or secondary causes of death usually associated with old age is atherosclerosis, often thought of as "hardening of the arteries" and roughly analogous to scaling or rusting of pipes in plumbing. In recent years, much attention
has been given to the suspicion that its development is related to intake in the diet of saturated fats leading to the presence of cholesterol in the blood. However, this view does not seem to be held any longer by a majority of scientists. (113)
In fact, it is amusing to note that the unsaturated fats may be the dangerous ones. According to Dr. Bernard L. Strehler of the National Heart Institute, ". . . the unsaturated fats are particularly liable to cross-reaction and linkage, a fact that makes them extremely useful in the paint and varnish industry but which may be highly detrimental to biological systems over the long run. .. The gradual accumulation of a layer of varnish over various intracellular structures is an unpleasant prospect. The observation that the rate of accumulation of cardiac lipofuscin [fatty pigment] is higher in the Japanese, who incidentally consume a diet richer in unsaturated fats, is suggestive (113)
Another relatively ancient theory is that aging may be the result of somatic mutations brought on by radiation or other cause. That is, changes in the genetic structure of the body cells may occur haphazardly, from time to time, caused by cosmic rays or other natural radiation (or by fallout from nuclear bombs); since the mutations or changes are almost always for the worse, the percentage of defective cells mounts. This theory has some attractions, not the least of which is the fact that animals subjected to heavy doses of radiation exhibit symptoms resembling those of accelerated aging. Nevertheless, this theory has been fairly well demolished by Muller (79) and others.
One of the currently respectable theories seems to be that of Dr. Sinex, who thinks aging may be related to changes or breakdowns in irreplaceable molecules of protein in collagen, which is the main organic constituent of connective tissue. Contrary to a popularly held notion, it is not true that all of the material of our bodies is continually replaced and renewed; it is not true of cells and it is not true of molecules. The same brain cells last
us throughout life, and in collagen, at least in rats, the same molecules persist throughout life, or enjoy only limited replacement. If these are damaged by chemical, mechanical, or thermal accidents, the road is downhill.(107)
Another idea is that an "autoimmune reaction" occurs with age; roughly, that is, we can't stand ourselves any more. Still another is that the various subsystems of the body from time to time are taxed beyond their ability fully to recuperate, so that each such part is like a ball which on successive bounces doesn't reach quite as high, and eventually doesn't bounce at all. And so on.
The point is that much has been learned, many promising lines of inquiry are being followed, and as Dr. Joseph W. Still has said, "Medical experience has taught us that when we fully understand a chemical event, we are able to manipulate and alter or modify it. For this reason, we can be skeptical about the assumption that 'we can't live forever!" (111)
Dr. Strehler, a gerontology specialist, although pessimistic about the practical possibility of abolishing aging (in the comparatively near future, presumably), affirms that: "It appears to me that there is no inherent contradiction, no inherent property of cells or of Metazoa [many celled animals, including man] which precludes their organization into perpetually functioning and self-replenishing individuals." (113)
If nothing better were known, brute-force methods of rejuvenation could be employed. That is, brain cells could be grown in the lab, the appropriate information "read in" to them, and then used surgically to replace the senescent cells. Of course, this would have to be done gradually, over a period of time, and even then some tricky philosophical questions might arise; but these questions will be reserved for a later chapter, since they deserve extended treatment.
But again, in all probability brute-force methods will not be
required; more elegant methods are nearly certain to be discovered - provided we do not dawdle too much along the way.
In a recent article in the New England Journal of Medicine was the following remark, intended to be humorous: "If age alone were publicized as an eventually mortal cause of degeneration, associations would undoubtedly be organized to seek its abolishment, under huge federal grants." (47) Many a true word is spoken in jest, and precisely this is going to happen, although one cannot be sure whether the funds will be mainly public or private. Dr. Strehler has already made a plea for sponsorship of a long-term program of research into the biological problems of aging, with something like a National Institute of Gerontology at the helm. (113)
There can be no serious question about the trend of events. You and I, as resuscitees, may awaken still old, but before long we will gamble with the spring lambs-not to mention the young chicks, our wives.
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