Preface

Medicare has been introduced in the sixties-and with the improvement it has brought in the lot of the elderly, it has also led to the nursing home scandals we were satisfied in treating cosmetically without changing the system which bred them. Blue Cross/ Blue Shield insurance has priced itself almost out of reach of most retired persons who still suffer from the growth of hospital costs. Social insurance still discriminates against people working beyond their 65th year by withholding the full amount due them until they reach 72.

With the retirement age now legally raised from 65 to 70 years, it becomes apparent that we must do everything in our power to keep the elderly healthy longer. The drag to the taxpayer for not doing so is considerable: old people, who make up ten per cent of the US population, account for 29 per cent of all medical bills, much of it coming from the public Treasury (which in a recent 18 months-period, from January 1976 to July 1977, paid some 140 million bills amounting to $7.5 billion).

As long as the medical establishment and our medical policy generally remain sickness- instead of health-oriented, as long as almost all money goes into the search for elusive cures for often fatal diseases and almost none into ways to prevent them-little will be done to cut down on the ever increasing health bill. Merely to exist, as is the fate of so many oldsters, is not to live. Now that medical science has been able to extend man's life span, it must also arrest the dissolution of body and spirit that often occurs in the final years of life. Until it succeeds in making these years worth living, it will have achieved only a Pyschic victory.

I believe now, as I did eighteen years ago, that with GH3 procaine - thanks to oral therapy more easily administered now than in 1960-we possess a tool to make life for our senior citizens a real "third age" of vitality, usefulness and independence. Little did I anticipate then that in spite of the many reports confirming Professor Ana Aslan's work, our medical bureaucracy would still maintain its negative attitude towards this promising GH3 therapy in 1978, setting up one roadblock after another to prevent GH3 from bringing possible relief to millions of people.

Unfortunately, much of what has been written in newspapers and magazines or that has been broadcast on radio and TV about procaine were either ignorant denunciations, great distortions, half-truths, wishful interpretations or irresponsible exaggerations. My aim in presenting this book-then and now-is to tell the true story of GH3, one of the most exciting medical developments of our time. In close to eighty countries of the world, GH3procaine therapy has become a way of life for older people. On the basis of this book the American public should be able to judge how much hope and how much hokum lie behind the headlines.

Before writing the first edition I twice visited the Institute of Geriatrics in Bucharest and enjoyed the fullest cooperation of Prof. Aslan and her associates. I have also consulted non-Romanian physicians with clinical GH3 procaine therapy experience, and have read scores of scientific papers published in the interim.

As I said in 1960: I hope I have succeeded in my attempt to present the GH3 material so gathered without prejudice and without emotion.

January 1978

Chapter 1

We face the problem

As time went by, the struggle for mere survival was easier. Man had learned to couple his energy with the resources about him. Now he had other tools with which to fight. He could live out his natural life, and dared even to dream of extending his life span.

(It is interesting to note that almost all the tales which mirror man's dream to live out his natural life with vigor and independence are permeated with an aura of the supernatural or anatural. Did not Faust have to sell his soul to the Devil? What of Daniel Webster's classic debate with Scratch? And the narcissistic Dorian Gray?)

Despite the connotation of evil surrounding such a course, man rejected the image of an unproductive future. Ponce de Leon searched for the Fountain of Youth in an era in which man still chased myth. (Interestingly enough, some three hundred years later the land on which he sought eternal youth has become a "paradise" for the aged.) The Bible relates King David's request for young girls to be placed in bed with him in order to effect the monarch's rejuvenation. While the scriptures do not elaborate upon the dynamics of such a "cure," centuries later man still believed in the rejuvenating power of inhaling the breath of the young: the famous Dutch physician Hermann Boerhaave recommended such a therapy as late as the 18th century. However, rejuvenistic literature was in its heyday during the middle ages, when superstition was riding high and magicians, alchemists and charlatans had the field to themselves.

Roger Bacon disclaimed any belief in magic. However, his writings indicate that as far as the possibilities for rejuvenation were concerned, he was by no means more enlightened than were his colleagues of the 13th century. Paracelsus was the most famous physician during the 15th century, and while lately some of his ideas have been resurrected, his arcanum for immortality has long been forgotten (perhaps because he died at the age of only 48).

Nothing approaching a scientific attempt at rejuvenation took place until the end of the 19th century. At about the same time that Pasteur experimented with anthrax and William Morton introduced ether anesthesia, a French scientist, Charles Edouard BrownSequard, astonished his associates at the Societe de Biologie by appearing before them, after several months of seclusion, looking at least twenty years younger than when last they had seen him. BrownSequard was a man of 72 who haad lost his zest for life-only the scientist in him could not be subdued. He proudly explained to his audience that through the injection of animal testes he had "rejuvenated" himself: his irritability and impotence were gone, his gastrointestinal and urinary problems had diminished. At the same time, his muscular power had increased, which he demonstrated with the aid of an ergograph (a mechanism designed to show graphically the work and fatigue of muscles).

Brown-Sequard, until then a highly respected scientist, soon found himself condemned by many of his peers. The results of his self-experiment were ascribed to his "senile-erotic imagination." Nevertheless, although he had by no means "rejuvenated" himself, he had demonstrated the importance of internal secretions to the vigor and strength of the human body. Unfortunately, his method did not combat old age, but succeeded merely in activating the organism.

Only 17 years after Brown-Sequard's death at the age of 77, and in the shadow of Ehrlich's discovery of Salvarsan, the Viennese physician Eugen Steinach advanced another theory: he advocated tying off the spermatic cords, thus preventing the production of wasted sperm, and increasing the internal secretion which is passed into the bloodstream. He thought aging to be connected with the involution of the interstitial cells of Leydig, cells in the testes which to this day have not been isolated and whose function has never completely been explained. Steinach named the interstitial cells "puberty glands," and proceeded to effect a "surgical reactivation" of the male by so-called vasoligation. The operation, performed under local anesthesia, was a difficult one which provided only temporary benefits. Today, Steinach's operational technique is used only occasionally, in cases of urinary complications.

While the Scottish bacteriologist Alexander Fleming was growing mold cultures in a search that culminated in penicillin, Dr. Serge Voronoff, soon after World War I, stirred up a great deal of curiosity by grafting monkey sex glands on humans. Again, the effects were not lasting. V oronoff himself claimed only that he could prolong the vigor and joy of life for five to six years by this method, after which one more grafting operation (not entirely without danger) was feasible. However, should the individual survive twelve years, he was doomed to hopeless senescence, which perhaps made things worse than they were before.

Voronoff was, in turn, followed by the Russian physician and biochemist Alek.sandr A. Bogomolets, who developed ACS (antireticular cytotoxic serum), based on his premise that stimulation of the physiological system of the connective tissue was of great importance in preventing morbid aging. His serum was supposed to retard the gradual exhaustion of the body, thereby delaying the onset of senility.

This theory enjoyed a brief vogue, but when Bogomolets died (at the age of only 65), most of the ardent supporters of his theory turned their attention to the newly discovered sulfa drugs.

Was it a quest for personal immortality that stimulated Brown-Sequard or Steinach? Voronoff or Bogomolets? Who can tell? We do know that the time was ripe for the discovery they were seeking. Medical science had already made great advances. Men over forty were no longer considered old, and those over sixty no longer so rare as to be venerated for their age alone. Painful, helpless old age was soon to become a major medical and social problem, but these first scientific attempts to preserve true life in the aged unfortunately held the attention only of sensationalists and fanatics. The attention of medical scientists was still directed to the most pressing medical problem-the control of infectious diseases. The goal of less. disease had to be reached before the problem of healthy longevity could command widespread research attention. Furthermore, the substrate of biological knowledge essential for true progress in this field was not available at that time.

Unsophisticated as were these pioneer attempts by scientists to preserve vigor throughout old age, they nevertheless presaged one of the most ironic dilemmas of modern times. We have learned how to keep ourselves alive to a ripe old age, but we have not learned how to make this old age worth the living.

Now that the scourges of bubonic plague, smallpox, malaria, typhoid, yellow fever, and polio have been checked, and we have learned to use vitamins and antibiotics, blood banks, and new surgical techniques, we are confronted with the success of our toil. The numher of people over 65 doubled in the United States between 1900 and 1950, and since then has continued to increase.
Today, more than 23 million people, or a little over 10 per cent (compared with only 4.1 per cent at the turn of the century) are over 65. Within the next fIfty years their number in a fairly stable population will have increased to 45 million. This means that in the year 2030 the number of women over 65 will equal the number of girls under 15. To put it in another way, the median age of Americans will climb from 28.9 at present to 37.3 fifty years hence (at the beginning of the nineteenth century the median age was barely 16).
Thus achieving longer life for so many, we cannot afford to stand idly by while they (and eventually ourselves) become prey to the multitudinous complications of old age.

The "graying of America" adds to our responsibility to provide for retired people in such a way that the "golden age" does not become a hollow phrase. A few years ago, Lincoln Day of the United Nations statistical office reported to the Commission on Population Growth and the American Future: "To worry about the supposed behavioral consequences of an aging, or more aged, population, is to divert attention from the real issue: how to incorporate a higher proportion of old people into society in a socially and emotionally meaningful way."

Once the aged were victims of man's weakness and ignorance. Today they are the victims of his knowledge. They are alive-but they cannot flee from their loss of independence, they cannot fight the diseases that plague them, they cannot outlive the curse of senility. The old do not die as easily today; they linger, they whimper. The strong must still carry the weak-and fewer must carry them for a longer time.

Chapter 2

What is old age?

The most perplexing questions facing medical science today concern the causes of old age and the precise measurement of the process of aging in the human body. We are all familiar with the manifestations of age, but we are not sure whether its signs and symptoms are inevitable, as believed until quite recently, or whether they can perhaps be postponed, or even completely prevented. The growing number of biologists and physicians who advocate the latter believe that the signs of old age are merely indications of a sickness which should yield if properly treated. They point out that chronological and biological age do not necessarily coincide-that some people, in appearance, attitude and behavior, seem younger than they really are, while others appear older. Why this should be so, has never been answered satisfactorily.

The aging process actually begins at birth, but at the onset these changes lead to growth and maturity. Once the latter stage has been reached, a slow decline sets in-affecting different parts of the body at different times, sparing some organs until a fairly advanced age. Thus, it has be-en found that hearing is best at the age of 10, vision at 20, muscular strength and coordination at 25, and reproductive functions at 30. These few examples suffice to show that aging is a slow process, and that it does not affect the entire organism at any single specific time. We speak of "normal aging" and "accelerated aging;" but although our yardstick for the former is still rather vague, there is general agreement that the latter is due to morbid changes in the body.

While the true causes for the decline of vigor in man are not known, we do know that the symptoms which accompany his slow but steady decline usually gain momentum during the fifth decade of his life. The first evident changes are connected with his appearance: hair becomes sparse and grey, shoulders develop a slight stoop, the skin shows wrinkles and the gait loses its earlier buoyancy. Man begins to "look old," although at this stage of the aging process he may not feel old. In fact, because he maintains his activities at the high level of youth, without much change in his way of life, he may well be laying the groundwork for future illness. (An investigation into the dynamics of "middle-age medicine" is another program still to be developed.)

Other symptoms enter the picture: the metabolism is less active, recuperative powers slow down, the energy used up by the body is replaced at a much slower rate, thereby rendering the tissues of the individual organs more flaccid. The skin becomes thinner and, due to a reduction in the secretion of some of its glands, drier. As the years progress, muscles fail to maintain the body in its former erectness, motions lose some of their power and sureness. The thorax is no longer expanded as before, partly due to increased muscle weakness, partly to an ossification of the costal cartilages. Thus, the lungs do not receive as much oxygen, the walls of their air cells become thinner, breathing is less thorough, and the respiratory metabolism slows down.

Bones become more brittle, they decrease in volume and weight, almost all cartilages lose their elasticity and, in certain spots, calcify. A great many of the capillaries in which blood is transported to distant parts of the body become clogged, preventing an even blood supply (the reason for circulatory troubles in the extremities, as well as opacity of the cornea, which leads to cataracts). The digestion, too, becomes impaired; teeth are no longer as efficient as they formerly were; liver, gall bladder, spleen and pancreas are weakened; the absorption of essential vitamins and minerals from the intestines is reduced. The slowing down of the metabolism as a whole also affects the mental acuity and an increase in forgetfulness; the severest, psychosis and regression to infantile behavior. Between these two extremes we find apathy, confusion, hostility, restlessness, sloppiness, asocial attitudes, sexual aberration, and persecution feelings.

Why some people become senile and others do not is still unknown. Social and psychological stresses play a part, but of primary importance are the changes in the body. Hormonal disturbances, a malfunctioning enzyme system, and lowered activity of the brain cells (stemming from a reduction of the cerebral blood flow) seem to be the main causes of man's mental deterioration.

Dr. William Malamud of Boston University has stated that the incidence of mental disorders in old age has been rapidly increasing for the last three decades and, particularly since the end of World War II, "has skyrocketed to a degree totally out of proportion to any of the other types of personality disturbances."

Chapter 3

Why do we age?

Aging, according to one school, is due to an exhaustion of life energy; another holds that it is due to a slowing down of the metabolism (although it may be questioned whether this is not the consequence rather than the cause). A third group maintains that the flooding of the organism with toxins is responsible for aging; Metchnikoff, one of the first scientists to occupy himself with this problem, was convinced that autointoxication caused old age, and that death followed the accumulation of fatal toxins in the large intestine. A more mechanical hypothesis, which was developed many years before the first atomic explosion, deals with the possible effects of cosmic radiation on the life span. The involution of individual organs (i.e., sex glands, ovaries, thyroid or other endocrine glands) was blamed for aging by a school which believed that renewed vigor could be conferred on old people through a genuine reactivation of these glands. Also, the degeneration of the nerve cells, in particular a creeping paralysis of the central nervous system is considered by some as the primary cause of aging.

One of the more widely accepted theories of aging is that of Dr. Hans Selye of Montreal. The originator of the concept of stress diseases, he defines stress as the "rate of wear and tear in the body." This wear and tear is a continuous process and has a cumulative effect. According to Selye, each human being (or animal, for that matter) has only a certain amount of "adaptation energy" with which to replenish his vital reserves. Theoretically, this reserve shrinks a little after each stress, and the deficit in adaptation energy, occurring from day to day, "adds up to what we call aging."

Among the first signs that the body is failing to adapt itself to stressful situations are the many allergic diseases, such as hay fever, certain rashes, and asthma. And the diseases of old. age are for the most part caused not by invasion of the body by germs or viruses, but by failure of one or another part of the body to adapt to the stress of life.

To quote Dr. Selye: "Among all my autopsies (and I have performed quite a few) I have never seen a man who died of old age. In fact, I do not think anyone has ever died of old age yet. To permit this would be the ideal accomplishment of medical research (if we disregard the unlikely event of someone discovering how to regenerate adaptation energy). To die of old age would mean that all the organs of the body would be worn out proportionately, merely by having been used too long. This is never the case. We invariably die because one vital part has worn out too early in proportion to the rest of the body. Life, the biologic chain that holds our parts together, is only as strong as its weakest vital link. When this breaks, no matter which vital link it may be-our parts can no longer be held together as a single living being."*

Since living cells in a water solution can be kept healthy for an infinite period of time by cleaning them and returning them to a fresh solution, Selye advanced the idea that the weaknesses of old age may be due partly to an accumulation of waste products which interfere with the nourishment of the cells.

If this is the mechanism of aging, Dr. Selye points out, there should be at least two ways of avoiding it. The rate of waste production might be slowed down, or the system might be helped to destroy its waste and get rid of it. Research on this and other approaches to the causes of aging has been conducted by Dr. Selye and his staff at the Institute of Experimental Medicine" and Surgery in Montreal, which he founded in 1949 and has directed ever since.

The Stress of Life New York McGraw-RiU.

Dr. Selye believes that medicine has now assembled a fund of knowledge that will serve as a point of departure for studying the causes of old age. Several times he has restated his belief that aging may be regarded as a disease and. . . "like any other disease, it is probably preventable or curable. . . The truth is that death by disease is largely avoidable."

Another explanation of aging simply has to do with the fact that the reproductive capacity of the cells, the basic building blocks of the body, begins to deteriorate. Cells, as we have learned, have different life spans: an epithelial cell in the intestines, forming with other cells the tissue that lines our alimentary canal, lives for only 36 hours. Red blood cells reach an age of 120 days, white blood cells of only 13, but nerve cells last forever.

As the human body grows older, the cells are no longer able to reproduce and to grow as quickly as in younger people. That's for instance why in advanced years your body no longer can heal a wound as fast as when you were 30 or 40 years younger. Also that part of the cells which manufacture proteins no longer functions with the same efficiency as in the young person. Dr. Nathan Shock, once head of the Gerontology Branch of the National Institutes of Health, developed a theory that the failure of individual cells to replace and renew themselves throughout the organism causes its slowing down, i.e. aging of body functions. If there . are too many dying cells in the body and if too many of the irreplaceable cells cease to function, the entire organism will collapse and eventually die.

Chapter 4

The Parhon Institute of Geriatrics — A pioneer of GH3

For 40 years Parhon continued his investigations into the causes of aging. His aim was to determine the true biological age of human beings. During 22 of those years, Parhon was a Professor of neurology, and it was not until 1934 that a chair of endocrinology was created for him at the University of Bucharest. Six years later the Rumanian Fascist government fired him, but he returned to his former position in 1945. I was soon thereafter that he founded the Institute of Endocrinology.

Professor Parhon's views can best be summarized in his own words from one of his more than 1,200 publications:
"From a theoretical point of view, I am of the opinion that aging begins simultaneously with growth and development, and that the mechanism of aging can be understood only in terms of research concerned with the changes which the entire organism undergoes throughout its lifetime. The phenomena that determine and accompany the aging process are so numerous and involved and their mode of origin so deserving of study that they cannot but fascinate all biologists. . .

"I am of the view that the process of aging occurs only to the extent that the conditions giving rise to it have occurred. If one were able to interfere with the mechanisms of aging, the direction of this process would be subject to change. In this way it is conceivable that the aging organism, whether the aging is due to premature, pathological, or so-called normal factors, could be returned to an earlier biological state. My experiences . . . have shown that the rhythm of life can be either speeded up or slowed down at all stages. . . . Biological and chronological age are not necessarily identical. Differences in aging rates can also be observed in clinical situations, e.g., endocrine conditions, and I believe that the rate of aging, 'the film of life' as it were, can be controlled in either of two directions, Le., toward faster aging or, to some extent, toward rejuvenation.

"If one were to view the aging process as irreversible, steps to control it would involve merely sanitation and the usual treatment. But if the aging process is regarded from a functional viewpoint, as a deviation from the normal functional optimum of the individual, Le., as an abnormal phenomenon, then treatment no longer seems impossible. In our view the aging process is a pathological condition, or, to state it better, a more or less extensive dystrophy. . . which develops slowly as the organism grows and differentiates. It is our obligation to treat these disturbances of function, and to prevent them whenever possible."

Parhon's interest in the problems of aging (in 1926 he coined the word "ilikibiology" from the Greek "iliki" meaning old age, but this never gained wide acceptance) led, in 1951, to the founding of the Institute of Geriatrics in Bucharest. Parhon, who had been elected the first President of the Rumanian Republic after the fall of the monarchy in 1948, returned to his scientific work when the Communists took over the country in 1950. He then had at his disposal facilities which made it possible for him to pursue vigorously his important work. The nucleus of the Institute was an existing old age home with almost two hundred inmates. These were the people through whom Parhon wanted to prove definitely that old age could be treated. All of the inmates suffered from serious degenerative diseases; he proceeded to give them either tissue extracts (of the spleen or placenta), gland extracts (adrenal and pineal glands, thyroid), vitamins (Vitamin E, liquid beer yeast), or baths of bicarbonate of soda (a treatment developed by the Russian physiologist Olga Lepechinskaya, which had received wide publicity in the Soviet Union in the post-war years). All of these treatments had been tried previously at other institutions, and the results in Bucharest were about the same: a few of the old people seemed to benefit, but no really important changes took place.

In 1949, a woman doctor who for more than 20 years had been a specialist in cardiovascular diseases joined the staff of Dr. Parhon's Institute of Endrocrinology. Prof. Ana Aslan had long been interested in the pharmacodynamical properties of novocain* and jts action in the human body, and she continued her experimentation under Dr. Parhon's direction-and under the encouragement of his conviction that old age and its manifestations are treatable and preventable.
It would seem that Dr. Parhon was impressed with the capabilities of his new staff member, and with the direction and progress of her research, for in 1952 Parhon turned over the directorship of his Institute to Prof. Ana Aslan.

Chapter 5

The semantics of rejuvenation

When we are children, we can hardly wait to be grown up. At some point, we reach that very satisfying period of life when the privileges and pleasures of maturity are combined with an eager zest for life and with the vigor of youth. This delightful stage-usually the late teens to the late twenties or early thirtiesgoes by most of us unnoticed and unappreciated (how often do the middle aged and older quote the phrase "youth is wasted on the young"). Then some little sign-a hair line thinner at the temple, some wrinkles around the eyes-reminds each of us that, like all living things, we too are subject to the aging process. And one day, for the first time, the thought flashes through our mind "If I were young again. . ."

This thought is father to the wish. But if we no longer believe in the curses of witches, neither can we hope for the magic wand of a fairy to touch us and restore youth and beauty. There is no way to turn the clock backward. So most of us go on about our living, the wish to be again young (or at least middle-aged) buried in our subconscious. The word rejuvenation, expressing this buried wish, is perhaps charged with more wishful thinking than any other word in our language.

For this reason it was unfortunate that Prof. Aslan originally used the words 'true rejuvenation' in describing occasional effec.ts of the therapy she had developed. For her words have been picked up by headline writers and newscasters, and shortened into such deplorable catch-phrases as "Youth shots," "Youth serum," "Long-life drug," "miracle drug," and even "Live-forever juice." .

Webster's unabridged dictionary defines rejuvenate as follows: -To render young or youthful again; to impart renewed vital ity to. (Med.) To restore to a more youthful condition; speci£ically., to restore sexual vigor, as by an operation.

Professor Aslan has used the term rejuvenate in the restricted sense of "to impart renewed vitality to . . . to restore to a more youthful condition." In this limited, more symbolic sense, rejuvenation is a phenomenon familiar to us all. Our vitality is renewed when we convalesce from a serious illness, or vacation after a long period of strain or over-work. Surely we . are restored to a more youthful condition as we recover from the shock and grief of the loss of a dear one, or have some great worry lifted from our shoulders. In fact, nature imparts renewed vitality to us and restores us to a more youthful condition each time we enjoy a good night's sleep.

Nowhere in any of her published reports or public statements have Prof. Aslan or any other serious scientists who followed in her wake ever claimed to be making old men and women young again. Any restoration of sexual vigor which has occurred in any of the treated patients has been incidental to the renewing of vitality in that particular patient.

The media, however, loved the word "rejuvenation," using it in the widest possible sense, thus perhaps unintentionally but no less severely damaging the cause of this promising drug.
Once this semantic problem is well understood, we can more easily examine the basis of the claim that the procaine treatment will «impart renewed vitality to old men and women," and "restore them to a more youthful condition.

Chapter 6

A new use for an old drug

For sixteen years, she was an assistant at the Second Clinic in Bucharest under Prof. D. Danielopolou, whom she reveres as her teacher. She held positions in other hospitals as well, and, except for three years during the post-war period when she was director of the Clinic in Timisoara, has always remained in the Rumanian capital.

Immediately after World War II, Prof. AsIan learned of a therapy which had been pioneered. by three French physicians, Dos Ghali, Bourdin and Guiot. The doctors had injected novo cain into the cubital vein twice within two hours in an attempt to effect relief in patients suffering from asthmatic attacks, and their method was successful where others had failed. Prof. Aslan found that she, too, could help asthma sufferers with repeated GH3 injections.

Then, in 1948, the noted German physician Prof. Gustav Spiess died. He had been first to discover that novocain not only has value as a local anesthetic, but also has curative power. Prof. Aslan read his obituary in a Rumanian medical journal which noted his former achievements. After checking through the literature, she immediately extended her novocain treatments to include patients with arthritis and limb embolisms, using the method devised by Rene Leriche, which even ;went further than Spiess' original idea. Leriche had advocated the infiltration of 10 to 25 cc of novocain, and was able to restore the affected joint or limb to full activity, often after as few as two treatments. Prof. AsIan, encouraged by her first results with novocain, began to use it also in cases of arthritis and arthrosis with a tendency toward the fixation of a joint (ankylosis).

The efficacy of the treatment was confirmed in the very first test:

"G. J., a medical student, came to us with arthritis of the right knee, having had severe pains in his knee for three weeks. After intra-arterial injection of 0.10 g of 1 per cent novocain, he was immediately able to flex his joint up to 90 degrees."

Before proceeding on a larger scale, she thought it best to experiment with animals. Dr. Selye had already reported a method for inducing experimental arthritis in mice. When a drop of some irritant solution, such as formalin or croton oil, is injected under the skin of the sole into one of the hind paws of a rat, local experimental arthritis develops. First there is acute swelling at the site of injection, and this swelling gradually transforms itself into a chronic arthritis of the many small joints in the paw, and especially of the ankle joint. The rat becomes permanently crippled, because the joints stiffen with hard connective tissue, so that they can no longer be moved.

In the course of her experiments on mice in which arthritis had been induced by a slight modification of this method, Prof. Aslan and her coworkers at the Parhon Institute of Endocrinology (which Prof. Aslan had joined in 1949) not only found that the novocain had a therapeutic effect-they also observed that the treated animals gained weight, and developed a lustrous fur. Complete cures were achieved in 85 per cent of the affected animals, and resistance to the experimentally induced arthritis was greater in the prophylactically treated animals.

After this series of successful animal experiments, she began treating a group of selected patients between 1949 and 1951. Not all of them were helped, but improvement in many cases was gratifying to the doctors at the Parhon Institute, for they had not achieved really effective results with any other method.

While proceeding with these treatments, Prof. Aslan made a most important observation: the patients, in her own words, "showed a change in the psychological and physical conditions, an improvement in memory, a decrease in rigidity due to Parkinson's disease, and an increase in muscular power." Prof. Aslan then checked through the literature again. She could not find a single reference to any such effect of novocain. However, she had witnessed those changes with a trained, professional eye-the patients appeared younger than before, much more alert, and seemed to be enjoying life again.

Of course, it was possible that some of these changes might be due merely to the cessation of pain, and to the fact that hope had replaced the depression and resignation which had consumed the patients. There was still no proof that any physico-chemical changes were occurring in the bodies of the novocaintreated patients which would not have occurred as the result of a balanced diet, normal regime, and 'tender loving care'.

Professor Aslan then selected 25 of the patients, and for three years treated them with novocain, while all the others continued to receive only gland extracts, vitamins, etc. The apparent greater vitality and improvements in specific diseases of the novocain-treated : group, as compared to the others, were convincing to the Professor and her co-workers, although they still did not detect any significant physico-chemical changes.

In 1955 she published her findings in the Journal of the Rumanian Academy of Science (Bulletin Sintific Academia Republicii Populare Romime). This paper, entitled "La novocaine, facteur eutrophique et rejeunissant dans le traitement prophilactique et curatifde la viellesse" (Novocain-a eutrophic and rejuvenating factor in the prophylactic and therapeutic treatment of aging), contained a report of her work on the "25 cases."

As might have been expected, her Rumanian colleagues who knew of her work but had not seen its results considered it nothing short of preposterous that she make such fantastic claims. Few non-Rumanian doctors follow the proceedings of the Rumanian Academy, and thus the knowledge of this therapy was confined to its country of origin. But, fortunately, not for long.

Shortly after the Academy report was published, a German journalist traveling through Rumania paid a visit to the Institute, and included a paragraph or two on its work with old people in his articles. Those few sentences attracted the attention of Farbwerke Hoechst, a West German drug firm, which had been the sole manufacturer of novocain in Germany since its discovery. This unsuspected new use for novo cain intrigued the company, which several years before had issued a booklet detailing the therapeutic versatility of this substance. Doctor Horst Weeke, medical director of Farbwerke Hoechst, was sent to Bucharest to investigate the matter. Upon returning to Frankfurt, Dr. Weeke wrote a very positive report on Prof. AsIan's accomplishments. This report was not published, but instead was circulated among some quite important German medical men. As a result, Prf. Aslan received an invitation to attend the Karlsruhe Therapy Congress (one of the best known German medical conclaves) and to read a paper on her discovery.

September 3, 1956 was the date on which Prof. AsIan faced her first Western audience. The two dozen people listening to the obscure Rumanian doctor were skeptical and filled with incredulity at her tales of the apparent rejuvenation of old people. The applause she received was thin; indeed, the doubts which hushed the congress could be seen on every face, and some even spoke openly of a "great hoax." The meeting was concluded with the sentiments that Prof. AsIan's remarks did not belong in the program of a reputable medical congress.

Chapter 7

Dr. Aslan's claims for GH3 Procaine therapy

She had described her experiments and their results, in the 25 original cases, and the 45 old people who were being treated at that time as residents of the institute. She cited some specific case histories from the original group of patients, and summarized her observations of the results of GH3 therapy in both the in-patients and 2500 oldsters who were being treated on an out-patient basis, as follows:

"Our initially cautious and limited investigations, originally restricted to twenty-five cases, have been expanded appreciably in the last two years, thanks to the innocuousness of the substance involved (novocain) and to the successes gained.

"ClinicaUy we have achieved a reversal of phenomena which until now have been considered irreversible, e.g., in cerebral arteriosclerosis. Sustained improvement was achieved in cases of senile Parkinsonism, improvement in hearing, and in certain reflexes which could not be elicited prior to treatment. Also, renewed production of estrogens and of characteristics resulting from stimulating of testes and adrenal glands, retrogression of signs of senility of the skin, such as ichthyosis and senile keratosis, repigmentation of existing hair, stimulation of new hair growth, and fewer arteriosclerotic symptoms.

"Physiologically we found improvement of the central activity of the nervous system, improved cardiovascular reaction to stress on the part of old people, decreased oxygen consumption, better muscle power.

"Biochemically we found alterations in protein structure and in the ratio of albumins to globulins, increase in cholesterol (as compared to lower than normal values prior to initiation of treatment).

"Hematologically we found fewer leucocytes, higher production of granulocytes, increase in the number of monocytes and the globulin content.

"Eutrophic action was clearly visible in cases of atrophic ulcer, stomach ulcer, dermatosclerosis, psoriasis, rashes, alopecia areata and leucoderma.
"It can be stated that novocain reduces the biological age of those treated with it below the chronological age. Novocain affects directly the cerebral cortex and its dynamics, and acts on the whole nervous system, the diencephalon centers, the spinal cord, peripheral nerves, metabolic processes, and brings about trophic changes in the entire organism. It also affects the endocrine glands. Through its vitamin-like action (due to its content of para-aminobenzoic acid) it also acts favorably on the biocatalysts, and it seems to stimulate the intestinal flora to the production of biogenic agents.
"Its trophotropic action can also be observed in arteriosclerotic processes. Its effect in mobilizing the cholesterol of the blood vessel walls may be due to its hydrotropic action, characteristic of the chlorides of para-aminobenzoic acid.

"Novocain minimizes the feeling of sickness and leads to a heightened desire and capacity for physical and mental activity. By virtue of its trophic action and its role as stimulator in most vital processes, it may be considered a useful prophylactic and therapeutic substance in the fight against old age."

Why did the doctors in Karlsruhe find these words impossible to believe? First, undoubtedly, because the word "rejuvenation" brought back memories of the Brown-Sequard fiasco, and they had not listened attentively enough to realize that Prof. Aslan was by no means claiming that her therapy would make old people young again. Yet even her modest claim". . . a useful prophylactic and therapeutic substance in the fight against old age. . ." seemed too good to be true.
Her suggestion that novocain be termed "H3" may also have led some inattentive listeners to believe she claimed to have discovered a new substance. And, finally, there was still no scientifically unassailable proof that even if all Prof. AsIan reported was true, novocain deserved the credit. We will discuss in a later chapter the type of rigidly controlled experiments which will be necessary to prove finally or disprove the efficacy of novocain injections in old age.

Chapter 8

GH3 = novocain = procaine

Local anesthesia with cocaine was introduced by Carl Koller in 1884. Koller, a Viennese opthalmologist, had his attention directed to this drug by Sigmund Freud, then a young doctor. Cocaine had been extracted from the South American coca leaves some twenty-five years earlier, but its importance remained uninvestigated. When Koller used it, first on the eyes of frogs and then on human beings, he marked the beginning of local anesthesia. Freud, who originally had the idea, was given no credit for his foresight.

There was no question concerning the efficacy of cocaine. Once put into practice it altered many surgical procedures. But it was also clear that this was a highly toxic substance, and, furthermore, it created a feeling of euphoria which some patients valued highly. Many of them became cocaine addicts, thus inverting any benefits they might have received from its use. In 1905, Alfred Einhorn, a German chemist, produced procaine hydrochloride (the generic name for novocaif) by combining para-aminobenzoic acid and diethyl~ amino-ethanol. While there is no chemical relationship between cocaine and novocain, the latter has the same effect as the former except that it has a considerably lower toxicity and is nonhabit-forming. Many other substitutes for cocaine have been synthesized since then, but novocain has remained the most widely used.

The novocain with which most people who have had teeth drilled or extracted are familiar is the hyd-' rochloride of procaine. This hydrochloride has the chemical formula C13H2002N2HCl.

The structural formula of procaine is. . . a relatively simple compound when compared to the complex pharmaceutical substances which have been synthesized in recent years.

Novocain consists of small, colorless, tasteless crystals, easily soluble in water. It is generally well tolerated, and up to a concentration of 10 per cent, produces no noticeable irritation of the tissues. While cocaine is excreted slowly, novocain is hydrolyzed within 20 to 30 minutes and detoxicated by the blood and liver. The toxicity depends, therefore, less on the dose than on the route and speed of injection or infiltration. There is never any addiction to novocain, nor does the body develop a tolerance which would make larger doses necessary in order to bring about the desired results, as is the case with cocaine or morphine.

Novocain is hydrolyzed with the help of an enzyme, called procainesterase, which is present in some of our tissues. The products of breakdown-the same from which the novocain was made-are para-aminobenzoic acid (actually a vitamin) and diethylamino -ethanol, both considered virtually nontoxic. When, however, efforts were made to have some of the pharmacological properties of novocain explained through the use of its products of hydrolysis, researchers were time and again frustrated by the fact that the effects which they tried to produce eluded them. Continued experimentation confirmed the theory that, in dealing with novocain, the whole is more than the sum of its parts.
Prof. Aslan also attempted to produce the same effect with the vitamin component of novocain-its para-aminobenzoic acid.

This attempt was not successful, and because she did not (and still does not) know exactly what part or parts of the drug novocain caused the revitalization and reinvigoration she had observed, Prof. Aslan and her co-workers in Bucharest gave this unknown factor the name "Ha," to distinguish it from its component vitamin, which is a member of the B-complex of vitamins and is known as H1, and from folic acid, which is also a B-complex vitamin and is known as H2.

When news of Professor AsIan's therapy began to make headlines in England and the United States, newspaper reporters found it much easier to fit GH3 into a headline than either the familiar novocain, or the precise chemical name-procaine. An impression was thus unfortunately created that the Rumanian doctor had discovered some new drug, or that some mystery ingredient had been activized. Nothing could be farther from the truth. To put it most simply, GH3 = novocain (a trade name) = procaine.

Subsequently we shall refer to this drug as procaine, in accordance with the preference of American and British doctors and biochemists.
The Rumanian substance has since also become known as "GH3", "Gerovital H3," "Aslavital" and "Gero-H3-Aslan; and under one of those names is sold today in 72 countries of the world-all important ones with the exception of the United States, Canada, Sweden, Norway, and Denmark.

Chapter 9

Why a rediscovery?

"An inflammation will not break out if we succeed in eliminating the reflexes in (certain) nerves starting from the focus of infection, through anesthesia. An inflammation already existing is cured rapidly by anesthetizing the focus of inflammation." .

Other researchers confirmed Spiess' observations, but little use was made of procaine to influence specific diseases via the nerves. It was found that GH3 injections and infiltrations of the ischiatic nerve would stop very painful sciatica attacks, that whooping-cough fits could be controlled by anesthesia of the upper larynx nerve, that lumbago of gynecological origin, muscle spasms, tetanus and muscle atrophies could be influenced by use of procaine. But these were mostly observations, some of them very interesting, none containing any conclusive information.

One practitioner who has used GH3 procaine for more than thirty years most of the time in a combination with caffeine, was Dr. Walter Huneke of Stuttgart, Germany, who with his late brother Ferdinand, of Dusseldorf, was the originator of the so-called "neural therapy," which seeks the cause for most illnesses in foci, and through injections into those foci (inflamed tonsils, bad teeth, operation scars, etc.) is able to clear up a surprisingly great number of morbid conditions. Several years after Prof. Aslan's first report on her findings about the general changes GH3 procaine brings about in older citizens, he said:

"I was struck by these rejuvenating effects GH3. I consider as rejuvenating characteristics restoration of a youthful and fresh appearance, better posture, improvement in skin turgor, in sight and hearing, no more falling out of hair, increase in cerebral functions, such as thinking capacity, memory, sleep, mood, efficiency and elasticity, the increase of sexual and other hormonal functions (return of libido, normalization of menstruation), also an improvement in heart and circulatory disturbances, blood pressure, arthrotic complaints and numerous other manifestations of old age, some of them measurable through the electrocardiograph, blood pressure or metabolism measurements."

Back in 1952, Dr. Huneke in a .published report had commented, almost as an aside, that repeated treatments' with injections of GH3 procaine and caffeine had in many cases "a clearly rejuvenating and therefore lifeprolonging effect." But he did not pursue this course of investigation. This was the job then, left to Prof. Aslan and her co-workers.

WHY A REDISCOVERY?

Procaine has been applied in the following ways:
1. Intravenous injections of 5 to 10 cc of a 1 per cent solution;
2. Drop infusions of 20 minute duration;
3. Local infiltration of 1f2 to 2 per cent solution in doses up to 100 cc;
4. Blocking of the ganglion stellatum by injec tions;
5. Blocking of the sympathetic nervous system; 6. Intramuscular injections;
7. Intra-arterial injections;
8. Various anesthetic procedures.

To list the more than 150 diseases and afllictions against which doctors have reported the use of GH3 procaine by one of the methods enumerated, and with results ranging from complete failure to significant success would make a tiresome catalogue. Positive results from the use of GH3 procaine have been reported in conditions as far apart medically as hypertension and frostbite, colic and fractures, certain eye diseases and heart arrhythmias, some skin disorders, and migraine headache. Its application has been largely on the basis of providing prompt relief from pain, but its therapeutic efficacy has frequently been commented on in the literature.

One of the foremost pharmacologists Professor Fritz Eichholtz of the University of Heidelberg, reached the conclusion that "of old, honest novocain there has become in modern pharmacology a medical substance which seems destined to be the kind of cure-all so many practitioners dream about." When he made this statement (qualifying it by saying that most of the procaine effects are weak and need an additional specific agent) the work of Prof. Aslan had just begun and was not known outside of Rumania.
Pharmacologists, clinicians, practitioners and, lately, gerontologists, have cleared up a great many of the mysteries surrounding procaine. However, as its range of applications indicates, there is much work to be done before we even approach the limits of GH3 procaine's potential; many indications as to its mode of action exist but no definitive conclusions have been reached at this time. Indeed, the more that is discovered about this substance, the more confused the issue becomes. The bibliography on procaine comprises today close to one thousand publications: an immense wealth of information has been spread before the medical profession. Still, there are only a few things concerning this drug with which the entire profession is in agreement.

Despite the fact that GH3 procaine is nonhabit-forming and has been used in the past for treating dozens of diseases, many physicians have been discouraged from using procaine due to reports of its side effects: nausea, vertigo, difficulty in breathing, vomiting, or temporary visual disorders have occurred in some cases, and strong allergic reactions (where an allergy test was omitted) could produce undesirable complications leading perhaps to anaphylactic shock and death.

Most of the negative effects, however, have occurred only during spinal anesthesia; investigations have shown that most frequently in those cases either the dose was too high, or else instead of merely procaine, mixtures with cocaine, pantocain or adrenalin had been used. These regrettable errors have prejudiced many doctors against its use (outside of the field of local anesthesia), and the use of procaine had been on a steady decline since 1952.

Before Prof. Aslan began her experiments, GH3 procaine had never been systematically applied as a general therapeutic measure over a long period of time. She proceeded to do just this, and refused to let herself be discouraged by occasional failures. A slight modification or "buffering" of the plain procaine eliminated the occasional tissue necroses which Prof. Asian had observed in its steady use, made the substance more stable, and seemingly speeded up the reactivity of the body.

Asian's Gerovital, it should be added here, is chemically and pharmacologically different from the standard 2 per cent solution of procaine hydrochloride. It is buffered, i.e. stabilized to a pH of 3.3 to 3.5, thus has a lowered acidity. Its action, according to Asian, is also potentiated by the addition of benzoic acid and potassium metabisulfite.

Chapter 10

Some early confirming GH3 reports

Switzerland

In November, 1957, a group of Swisstologists-Gassman, Jacquerod, Laepple Schaefer-reported on their first clinical trials lows: "The procaine treatment introduced by Aslan was applied in 28 cases; 22 of the patients presented diffuse or localized lesions of the central nervous system: hemiplegia (paralysis), hemiparesis (muscle weakness), spasmodic ataxia (spastic disturbance of muscle coordination), postapoplectic (following a stroke) or arteriosclerotic dementia. Each patient received three 100 mg intramuscular injections a week (5 cc of the 2 per cent solution) in series of 12 injections, separated by ten-day intervals. . . . We obtained lasting results in 25 per cent of the cases, such as improvement of the subjective state, buoyancy of the psychical tonus, slight euphoria, sometimes a better physical tonus in walking and in voluntary motility, and disappearance of sphincteral incontinence."

France

In the Revue Francaise de Gerontologie (April, 1959) Professor H. Portias of Paris, one of Prof. Aslan's early antagonists, reported on his experience with 86 aged patients whom he treated with procaine. Not being able to use placebos, he still endeavored to avoid the possibility of purely psychotherapeutical effects by telling the patients of his inexperience with the method and of his skepticism as to its efficacy. Professor Portias' patients suffered from the usual signs of old age: arterio- and venosclerosis, chronic cough, wrinkled skin, rheumatism, and various arthritic conditions. He subjected them all to five months of procaine injections, at the customary rate of three per week; beneficial effects, except in the less severe cases of senility, could hardly be expected in so short a period. Yet in more than half of the patients the results were either "very good" (15 cases) or they were "improved" (30 cases). Twenty patients felt a bit better, 21 showed no change in their condition, and only three of the 86 showed any side effects which could be regarded as serious.

In the 15 cases in which the results were very good, Prof. Portias noted "a physical and morale stimulation, with a disappearance of all signs of fatigue. The patients experienced a euphoric feeling. . . . disappearance of anxiety and its physical counterpart, fear, an increase in sexual power (the Russians, by the way, treat impotence with intravenous injections of GH3 procaine . . . . These results remained after the treatment was stopped." He also mentions that the cholesterol level of the blood, while initially increasing, soon falls.

Professor Portias' conclusions:

"This is an interesting treatment, happily complementing other geriatric therapies, but no general panacea. For the time being the enthusiasm in Bucharest does not seem to be justified in all cases, even though it is true that our patients were treated for only five months. In any event it seems that the therapy is most efficacious where there exists a clear imbalance of the autonomic (involuntary) nervous system. Another very interesting technique is the combination of procaine with other substances, either simultaneously or following it."

Early in 1959 at a meeting of the Scientific-Medical Section of the International Federation of Deportees in Vienna, Austria, the Parisian physician Dr. E. Soladie reported on his first trials with five deportees whom he had been treating .with procaine injections for several months. He made the following points:

1. The action on the skin is quite obvious; the grey appearance, so characteristic of suffering persons, is disappearing. The face takes on a natural, healthy color, the eyes become livelier. After only four months the hair shows signs of repigmentation and the zones of baldness diminish. Eczemas of different etiology have either vanished or are retrogressing.

2. None of his five patients was constantly tired as before. The irritability diminished, the sleep was bet ter. All had reacquired a desire to work. In four of the five the appetite had improved.

3. Only in one of the five patients was there no effect with regard to sexual functions. In two, there has been a complete revival of libido (in one, after three years of enforced abstinence); in the other two, a normalization of the act.

Germany

More scientific evidence was presented in a case history reported by Dr. Kohler in 1958.

"Dr. G., born February 8, 1877. Symptoms of cerebral sclerosis known for 20 years, accompanied by arterial hypotension. He had been forced to retire from his profession because not only the disturbances as circumscribed by the Korsakov syndrome were apparent, but also increasing vertigo had gained in intensity to such a degree that treatment with GH3 (a German preparation-procaine plus vitamins) was deemed necessary. Objectively the heart muscle did not yet show any indications of considerable myocardial damage. But many extra systoles, particularly after effort, indicated an existing hypoxia of the heart muscle. Paroxysms became so pronounced that the patient would lose his balance in changing from a lying to a sitting position.

"After only the second GH3 injection the patient reported a certain improvement. At the end of the fIrst series, he was virtually without dizziness. Only in the mornings did he still observe slight dizziness-when arising too quickly. Next to the impressive eutrophic skin effect, the most remarkable sign was the return of mental capacities. The old gentleman once again participated in scientifIc forums, and recently-for the fIrst time in over two years-played four-hand piano again. His partner (an internist himself) was quite astonished to fInd that the playing was considerably better than it had been two years previously, when the patient had abandoned the instrument because of his physical defIciencies."

In Medizinische Monatsschrift of May 1959, published in Frankfurt, Dr. F. Petersen, a neurologist from Halle, East Germany, reported on 137 cases of cerebral sclerosis he had treated with procaine over a period of two years (June, 1956 to June, 1958). In 13 of these cases, all symptoms of the illness disappeared; in 35, there was marked improvement; in 56, some I improvement; 27 remained unchanged; and in six cases I there was further deterioration. This means that in 104 I (or 76 per cent) of the cases, treatment by procaine injections was to some extent successful, while other therapies offered little relief for these patients.
Doctor Petersen's figures become even more impressive if one considers only those patients suffering from a state of arteriosclerotic debility. Of the 137 patients he treated, 88 fell into this group, and of these all but four (or 95.4 per cent) were improved: ten were considered cured, in 33, there was marked improvement, and in 41, some improvement of their complaints. Of eight stroke patients, seven showed improvement, and five out of nine patients with Parkinson's disease were also improved after the treatment. Two of the four patients suffering from encephalomalacie (softening of the brain) were also improved. But with his 20 senile psychotic patients Dr. Petersen reported almost complete failure: only one of these showed some improvement, 14 were unchanged and five actually grew worse. His statistics are shown in the table.

In 1962, Professor F.H. Schulz, head of the First Medical Division of the famed Charite in East Berlin, was able to report about animal tests undertaken by himself and his collaborators showing that the procain therapy delayed aging of vascular walls. This could explain why the use of GH3 has the effect of approximating rejuvenation. In later chapters, particularly Chapters 16 and 18, we shall discuss other confirming reports, several of them originating in the United States. American scientists were late in testing this drug but once they embarked on this task, they were able to bring in some very interesting results.

Chapter 11

Soviet research with procaine

"When I was in Leningrad and Moscow in 1956, I discussed the trophic action of GH3 with several experimental workers in the physiology research laboratories in these cities. However, I was not impressed at the time that there was anything very significant in these studies except that intramuscular injections of procaine seemed to have some benefit in experi mental arthritis and perhaps in certain experimental stress conditions. ..

Soviet researchers, naturally, showed a lively interest in Prof. AsIan's work. Theirs has been a steady search for means of rejuvenation, but neither Voronoff (who worked outside of the Soviet Union), Bogomolets, nor Olga Lepechinskaya had any success with their ideas. The procaine therapy was given a great deal of publicity in the Soviet Union, and now there have been several hospitals and old age homes where the treatment was used, in particular at the Geriatric Institute in Kiev.
In Moscow, in 1955, Yu. F. Udalov conducted some experiments with white rats which may have significance not only in geriatrics, but in aviation and space medicine, as well as in prevention of the 'bends' suffered by underwater workers who surface too rapidly.
In U dalov' s experiments, rats which had been given procaine injections in the neck and in the abdominal cavity (as well as rats which had received no injections) were 'lifted' in a baro-cham ber at a speed of 67 miles per hour, to an atmosphere as thin as the atmosphere 6% miles above the earth. The rats were left in this 'atmosphere' for 10 minutes. Six of the 23 control rats died, but only two of the 25 procaine-treated animals. The author then found that rats given a large dose of para-aminobenzoic acid in their food the day before being subjected to these simulated high altitude conditions also had twice the survival rate of rats which had not received this vitamin. Apparently this vitamin component of GH3 increases the resistance of the body to oxygen insufficiency.
An article in the Russian journal Farmakologiia i Toksilkoiogiia (Pharmacology and Toxicology) entitled "Changes in the motor and secretory gastric functions following intravenous injection of procaine" indicates the Soviet interest in this therapy for treatment of gastric ulcers. The article ends with the following summary:

1. Intravenous injection of GH3 depresses or eliminates gastric peristalsis and the periodic contractions of the stomach under starvation conditions; it also depresses the can tractions of the duodenum.
2. Procaine depresses the gastric secretion, particularly in the first 3-hour period and often extending into the second period. Following injection of procaine, the latent period of gastric secretion was increased in most of the experiments. Procaine also depressed the pancreatic secretion.
3. The acid-forming function of the stomach underwent various changes under the influence of procaine, more often than not increasing.
4. Depression of the conditioned reflex of the gastric motor system after a series of intravenous injections of procaine combined with strictly controlled, fixed conditions of experiment indicated the role played by the cerebral cortex in the mechanism of action of procaine.

In addition to their interest in applications of procaine .n treatment of gastric disturbances, Soviet researchers 1Iso are reporting on applications of this drug in treatnent of diseases of the nervous and vascular systems, urunculosis, and bronchial asthma.
The Russian scientists seem to give Prof. Aslan full credit for originating the application of procaine in the general therapy of the condition which we know as 'old age."
Among the Soviet visitors to the Bucharest Institute, Prof. M. G. Durmishyan, of the Academy of Sciences )f the USSR, wrote in Prof. Asian's guest book:
.. After my own investigation, I am able to say that the doubts I may have had before coming here have completely vanished." Professor K. M. Bykov, former head of the famous Pavlov Institute in Leningrad, expressed himself in the guest book as follows:
"With enormous interest I saw the work of the Institute and of Pro£ AsIan concerning a problem which has been studied for a long time, and [the solution of which] could revolutionize mankind. I believe that Prof. AsIan and her assistants have found a valid method of maintaining a normal state of activity of the nervous system and thus of all organs, and of prolonging the normal functions of the cellular system of the human body.
The administration of procaine, which has the properties of stimulating and inhibiting, as well as the method of giving these injections, are new, original and very promising. Personally, I am convinced of the success of Prof. AsIan's method in vitalizing aging organisms."

The intensity of the research being conducted in the USSR on the applications and mechanism of action of procaine is indicated by the fact that in 1958 a Russian book on GH3 treatment of gastric ulcers, bronchial asthma and angina pectoris cites the work of sixteen centers. This research dates back to 1948, and a literature reference shows that the author was familiar with the work being done in Bucharest at least a year before Western medical scientists had heard of it.

Chapter 12

News reaches the West

"Old people taken out of lonely or unhappy or disease-prone backgrounds and given expert attention and encouragement in cheerful surroundings often take on a new lease of life.
"Much of the evidence at Bucharest, say visiting experts, may be based on hearsay-patients' ages, previous conditions, and so on. "The same drug used by Prof Ana Aslan has been. tested in this country 'without any startling results'."

To which the science editor added:

"There is no scientific reason known to me why it should cause 'rejuvenation', one specialist told me. On the other hand reasons sometimes come after results, Knowledge of digitalis came after a general practitioner found that an infusion o foxglove did his heart patients good."

On March 14, 1959, a few weeks after the appearance of these articles, the well-known British medical journal The Lancet discussed the procaine therapy in an editorial. It said:

"The cause of the decline of vigor in mammals with age is unknown. There is no a priori reason why GH3, or many other uninvestigated substances, should not slow or even reverse this decline, and a substance which did so would quite possibly produce just the kind of non-specific benefit in a number of disorders which AsIan describes. The regrowth of pigmented hair in a man who claimed to be 110 years old, which AsIan reports, would in any case, like the validity of the age record, excite curiosity. But it is curiosity rather than enthusiasm that AsIan's treatment of her results is likely to excite. Her suggestion that procaine acts by in vivo (inside the body) conversion to p-aminobenzoic acid, and that this exercises a "trophic" action on the nervous system, does not carry instant conviction; moreoever, such an influence (or, in fact, any specific benefit from a drug administered to geriatric patients to control "aging") could be shown convincingly in one way only-by a double-blind trial in alternate matched cases, with subsequent comparison of objective signs and survival curves. All the published evidence so far depends on scientific medicine's chief methodological enemy-the testimonial use of case histories-and AsIan's treatment of these will depress those who know how often medical investigators have misled themselves in this way. There are very few old people who do not respond to rest, change, good hospital food, and, above all, raised morale-whether accompanied by injections of procaine or not. "This is not to say that the work of the Bucharest team is to be dismissed (they have evidently improved their patients in some way, if only by suggestion); and the desire to do something radical about old age is a creditable contrast to fatalism about the effects of age. If these workers were right, the findings would be important. But the facts can be established only by properly controlled trials."

In the United States, publication of the translated reports from Bucharest was not met with indignation, as was Prof. Aslan's first lecture at Karlsruhe. But the reception was, to put it most mildly, unenthusiastic. This lack of enthusiasm was not, as some have suggested, because the new therapy had been developed in a Communist country. It was because the methods of analyzing the results of the therapy fell so far short of American research standards. American researchers feared that the doctor &om Rumania who was making such extravagant claims for procaine therapy had fooled herself, as well as her patients, into believing that they felt and looked so much better.
But there was also a sober recognition that the reports by the Bucharest and German doctors should not be ignored. Prof. Chauncey Leake, who reviewed the translations of the Karlsruhe papers in the journal Geriatrics in October, 1959, said:

"In general, it would seem that the reports by Ana Aslan and her associates are interesting enough for further exploration. It would be hoped that she and her associates would publish more detailed case histories, together with a more complete statistical survey of the large number of cases which they must have accumulated by now. It would seem that careful and direct experimental studies on small animals should tell readily whether or not repeated procaine hydrochloride injections intramuscularly can delay the aging process, prolong life, and generally interfere with aging. It might be wise for results of studies of this sort to be well publicized before extensive premature clinical use of GH3 procaine hydrochloride in slowing the aging process. On the other hand, the safety of the drug indicates that cautious and well controlled clinical studies might yield results that would tell definitely whether or not any further use of the drug for these purposes is justified."

Little can be added to what has been so calmly and objectively pointed out by The Lancet and Geriatrics. Both medical journals have emphasized the necessity that the work Prof. Aslan began at the Institute of Geriatrics in Bucharest be subjected to the most careful investigation on as large a scale as possible, with the use of the most modern equipment available and the most rigid control standards devisable.

Chapter 13

The Parhon Institute of Geriatrics

Nursing homes, of course, but reflect the prevailing society, as pointed out in 1975 by Dr. Carl Eisdorfer, chairman of the Department of Psychiatry and Behaviorial Sciences at the University of Washington School of Medicine in Seattle. About one million out of twenty million aged in this country are in full-term custodial care-as the U.S. Senate's Special Committee on Aging stated in a report a few years ago, this care, or rather non-care, is costing taxpayers close to five billion dollars a year through Medicare payments to nursing-home owners.

This is not the place to discuss whether such money could be spent more wisely although the evidence would indicate so, or whether it is enough. If, however, we wanted to save money, Prof. Eisdorfer suggests facetiously, we would only have to follow Kurt Vonnegut's idea in Welcome to the Monkey House. "He handles the aging problem very simply.

He pictures, next to some restaurant, such as Howard Johnson's, a parlor where people can go between their sixty-fifth and sixty-sixth birthdays and have their lives terminated. Vonnegut's parlor is staffed by attractive men and women skilled in discovering the best method to do away with people. Sometime before a person's sixty-sixth birthday he walks into this future Howard Johnson's, gets a free meal, then walks next door and, against a background of soothing music, has the death of his choice."

What we have to do, of course, is finally to recognize, why older people are with us and why, even in a country as youth-oriented as ours, they deserve the best possible care, free from indifference, neglect and exploitation. It is an indictment of our society that we are still years away from attaining this goal while elsewhere and even in some poorer countries considerable progress has been made in that direction.

Each of the patients in the Bucharest old age home was, at one time, debilitated, plagued by sickness, and steadily growing weaker in mind and body. Today, not one of the patients who has received the GH3 therapy is bedridden! That in itself is a remarkable achievement. However, the procaine-treated patients not only walk about unaided; they also function as alert, thinking, industrious men and wome.n who are old without being aged. Almost every one of them has a task: some work in the kitchen, others in the garden; a few are busy carpet weaving, others make handicrafts, and some help in the library. And, most significantly, many of them even atteI1d courses in French. The procaine therapy has helped them to remain mature while they grow older.
The research upon which the whole therapy is based was begun in the Institute in May of 1951. Twenty-five patients, ages 60 to 92 (all of whom suffered from serious degenerative diseases such as extrapyramidal disturbances, hypertension, degenerative joint disease, rheumatism, cirrhosis, etc.), were treated with procaine. After some initial uncertainty, Prof. AsIan arrived at what she believes is the optimal dose and strength for the procaine: intramuscular injections of 5 cc of a 2 per cent solution, three times weekly for four weeks, were administered. A ten-day interval without further inoculation followed, then a new series of twelve injections, another interval, and so on.
Before treatment was started, possible allergic reaction was tested for with an injection under the skin of 1 cc of GH3 procaine. Few people were found to be sensitive to this substance-in Bucharest only a handful among the thousands of patients (four out of the first 4,800 tested). It can reasonably be expected, however, that a higher allergy rate may be found in the West, where sensitization generally is greater and allergic disorders affect more people than in Eastern Europe.
Sixteen of the 25 old men and women in Prof. Aslan's original group were still alive eight years later, in spite of the fact that the disorders from which they had been suffering (as stated above) would ordinarily have claimed the lives of almost all of them. There was not a single death during the first two years of treatment. In 1954, there was one death due to a spinal accident; in 1955, two deaths occurred, due to chronic bronchitis and myocarditis (an inflammation of the muscular part of the heart wall); in 1956, one death due to a pseudobulbar syndrome, from which this pa.. tient had suffered for six years. Five patients died in 1959-three in a flu epidemic, one due to arteriosclerosis, and one due to an accident.

The number of patients receiving GH3 procaine therapy was slowly increased after the successful results with the first group tested. In 1959, when twice I visited the Institute, 70 of the patients in the old age home received procaine injections, 40 other inmates were used as control group. The table indicates a portion of the impressive results obtained.

The mere prolongation of life was of minor concern to the Bucharest doctors. (Indeed, most of the patients there had already achieved an enviable record of longevity.) Instead they were interested in developing a method of the preservation and restoration of vitality. Thus, the figures indicating the improved capacity of the procaine patients to do some work and to care for themselves are much more significant than the dramatic figures on mortality. These exciting statistics are shown graphically in the photo section (pp. 80 -94).

When I first walked among the patients at the Bucharest Institute, I was struck by the fact that some seemed to be merely well preserved, active people for their apparent age, while others had a strikingly vital appearance (I hesitate to use the word 'youthfull a reader misinterpret and think I am implying that some of the patients had grown younger). All of the patients, including those who had been receiving procaine more than 100 times a year for eight years, remained old people. But those who had been on GH3 procaine therapy for some time had a look of vitality that one might characterize as 80-years-young," or even 112-years young" in the case of Parseh Margosian.

Until the flu epidemic in 1958/59, the mortality of the patients treated with GH3 procaine was 3.2 per cent (and the median age 82 years), that of the people treated with vitamins or gland extracts was 16 per cent, and of those who did not receive any supportive therapy, 27 per cent. Since the patients themselves did not know what treatment they were receiving, the great difference in the mortality of these groups contradicted those critics who ascribe the success of the procaine therapy to some suggestive effect.

The Institute of Geriatrics was founded in 1951 to study the problems of gerontology and geriatrics, as part of the research plan of the Academy of the Romanian People's Republic, thus constituting a portion of the State Scientific Program. Therefore, it is important to note that Prof. Aslan was not, as were most of her predecessors in the application of GH3 procaine, working on an individual basis with the goal of personal symptomatic relief.
Over the years, the Institute of Geriatrics has constantly widened its scope and since 1957 many thousands of people, have been treated on the premises stationary or on an out-patient basis, and, in the case of foreigners, "at the Hotel Pare in Bucharest as well as in two other centers at the Black Sea and in the Carpathian Mountains. (Procaine cures today are also offered by sanatoria in Italy, Spain, Germany, Mexico and even in Egypt.)

In 1972, Prof. Aslan reported to a Congress on Gerontology in Bucharest that during the preceding two years 15,000 people, aged 40 to 62, had been tested at 144 centers in Rumania in order to find out whether GH3 would not only prove an anti-aging factor in the aged-which she felt had been borne out by the research and the results up to that date-but whether it might also prevent aging. Of the 15,000, more than 7,000 were selected for treatment which was identical, except that 4.021 persons received over the two-year period 10 series of 12 Gerovital (the Rumanian procain) injections while 2.905, acting as control group, did not. The results of this large-scale experiment were significant in several respects: High blood pressure improved in 85 per cent of the procain treated and only in 61 per cent of the control patients; arterial hypertension showed signs of normalization in 83.2 per cent of the Gerovital-treated and 65.8 of the control patients; the pulse rate in persons with tachycardia (a rate of over 90 beats per minute) normalized in 93 per cent of those getting GH3 Gerovital but only in 88 per cent of the control group, of those with brachycardia (low pulse rate) the normalization in the Gerovital-treated group was 9 per cent higher than in the control group. With respect to cardiovascular effect, muscle strength and respiratory capacity there were also greater normalization rates in the Gerovital-treated persons where some abnormalcy existed. Hardly less exciting was the finding that in the course of the two years when due to aging, higher blood pressure and more tachycardia might have been expected, there was no change whatsoever in the normal, Gerovital-treated persons. Also, the number of days the Gerovital-treated persons remained off the job for reasons of health diminished nearly by two fifths, compared with the years before treatment took place. These figures would indicate a strong prophylactic effect of procaine; only when this long-time trial has been terminated in 1980 and the findings published, will it become possible to grasp the full importance of this previously unexpected results of procaine.
Already as a result of the initial success with the procaine program, the Institute had become physically larger and scientifically a more important place. It is composed of six departments:

1. The nursing home where aged people are cared for under the conditions cited previously. Long-term treatment is provided here.
2. The clinic for the treatment of bedridden aged patients as well as others affiicted with certain diseases which respond to procaine treatments. In this section, the emphasis is more on short-term treatment.
3. The out-patient department, where procaine treatments are administered daily to hundreds of persons, some for therapeutic and other for prophylactic purposes.
4. The laboratories: some for animal experiments, others for clinical, physiological biochemical, hematological, pharmaceutical and roentgenological research. Each of these laboratories is under the direction of a specialist, some of whom are visiting experts from Rumanian Universities.
5. The department of social hygiene, which is mostly concerned with the sociological problems of old age and relates national statistics to the work of the Institute.
6. Three additional facilities for the treatment of foreigners. Because the Institute will continue to treat, as well as to investigate, it is distinguished from almost all other existing centers in this field, most of which are devoted exclusively either to the care of the aged or to research into their problems.
"Before and after" pictures are convincing to the medical scientist only when it is obviously the patient who has changed, and not merely the angle of photography, the lighting, or the type of film used.
The four pictures of Maria Tabarcea shown in these pages are excellent documentation of her case history. The improvement in the condition of Tanasalu Mircea is obvious, in spite of the difference in lighting. But as medical documentation, the other photographs of patients are "not entirely satisfactory."
Professor Ana Aslan, M.D.

Today at 80, she still guides the destiny of the Bucharest institute which she has headed for more than a quarter century. Last year alone she traveled to Africa, Asia, the United States and to several European countries, delivering lectures, consulting, treating patients.

Chapter 14

GH3 Procaine therapy at the Institute

There are also rare cases of alopecia (or baldness) and vitiligo (the loss of pigmentation in skin or hair, making it appear white, which can occur in children and young adults as well as people of more advanced age). The great majority of the patients being treated with procaine today are out-patients. They are under constant observation, but of course cannot be controlled as carefully as the inmates.
The treatments for patients of the Institute, how ever, have become standardized.
The GH3 procaine used has been modified over the years. While it originally had a pH (hydrogen exponent) between 4.2 and 5, this has now been reduced: to 3.3-3.5 in the Rumanian preparation called Gerovital or "H3," produced according to Prof. Aslan's formula. (A substance at a pH of 7 is neutral-neither acid nor alkaline, but below 7 it becomes acid.) Experiments proved that if the pH of GH3 procaine is augmented, its anesthetic properties are increased; conversely, if the pH is reduced, it loses the anesthetic properties, while the action on the sympathetic and parasympathetic nervous system is preserved or even increased. The lowered pH may have something to do with the fact that, in Bucharest, side effects have almost never been encountered, and that allergic sensitivity to the stabilized substance is almost nonexistent.

Intramuscular injections of procaine are the rule in this treatment, but there are a few exceptions. In cases of asthma, gastric or duodenal ulcers, and vascular spasms, intravenous injections are considered more effective, and in arteritis as well as certain arthropathies, . intra-arterial ones are indicated. The rhythm of injection is also slightly changed: in vascular spasms, 5 cc is given twice daily; in ulcers, 5 cc is given once daily at a very slow rate. The usual series of twelve injections with a rest period of seven to ten days is constantly maintained, however.
The 5 cc dose of procaine is reduced only where body weight of the patient is abnormally low; in these cases 3 or 4 cc are recommended. Children, as a rule tolerate the 5 cc dose well. In the prophylactic treatment of old age, dealing with people between 45 and 60, the cycle of twelve injections per month is observed, but one or two series per year suffice, whereas in the geriatric clinic, procaine is given as a maintenance dose. The prophylactic treatment, as mentioned will have to be continued for several more years before significant statistical data can be obtained.

As further proof of the fact that one does not develop a tolerance to procaine, it is important to note that even among the survivors of the original group which Prof. AsIan has worked with and treated for more than eight years (they received more than 1,000 injections), higher doses are not needed in order to achieve the desired effects. Nor has a sensibilization for procaine been noticed.

There is only one positive contraindication of the procaine therapy (with the exception of the allergy, of course), and this is the simultaneous administration of sulfa drugs. Here, procaine acts as an inhibitor. If plain procaine is used for the treatment, the patient should, as a precautionary measure, rest for about half an hour after the intramuscular injection. Longer rest periods are indicated in cases of intravenous injections. Procaine has a dilating effect on the blood vessels, causing a lowered blood pressure, which in turn can produce untoward side effects. When a buffered form of procaine is used, however, there is no need for rest after the intramuscular injection.

Other GH3 procaine preparations of slightly different compositions have been developed in other countries and their number is constantly on the increase since the oral procaine therapy has been introduced. But for all these pharmaceutical products, produced in many countries, the therapy prescribed follows closely the plan developed by AsIan although changes had to be made once procaine capsules and dragees were introduced, making the application much easier since it was then no longer necessary to visit a doctor thrice a week.

Chapter 15

From Gerovital to K.H. 3 to GH3

All of these preparations contain as primary ingredient procaine hydrochloride but its quantity varies from 12.5 to 70 mg per capsule. As in the case of Aslan's Gerovital, they also contain other ingredients although the rationale for such additions is not always clear and at least in some instances they seem to be no more than devices to distinguish their product from those of their competitors. Most contain Vitamin A, C and E plus those of the B complex, at least one has homoeopathic doses of dried testes, ovaries and corpus luteum and some have hematoporphyrine added, a substance which works as a catalyzer and is supposed to potentiate the effects of procaine in bringing about a physical and mental activation of the patients.

In Germany as well as in most other countries, all GH3 capsules are over-the-counter items and can be dispensed without a prescription since the safety of procaine has been established; also, in the more than twenty years procaine has been used by millions of people, no untoward side effects have been noticed. Most oral therapies follow a somewhat different course from the original one established for the injectionable substance: usually one capsule should be taken daily for 30 days, then, after a 10- to 14-day interval, another course is started, etc. Some manufacturers suggest only two thirty-day series per year, others recommend more than one capsule per day. Physicians with some experience in the field feel that once patients have reached a certain age, say 70 or so, one or two series of injections per year added to the oral preparation will increase the efficacy.
Some of the German procaine substances (with the quantity of procaine in mg added in paranthesis) are the following in alphabetical order: Aktis H 3 (50), Biolecit H 3 (25), Dodecatol (50), Echtrovit (50)~ Genuol (50), Geriatricum Pascoe (12.5), Gerigoa Depot (45), Gerioptil plus H 3 (25), Gerontin Kwizda (50), Glutergen + H3 (50), H 3-Quam (25), Ilja Rogoff Gold (50), K.H.3 Geriatricum Schwarzhaupt (50), Panganicain (25), Panstabil (50), Primarubin (51.2), RecapsDepot H3 forte (70) Roleca H 3 (25), Vigodana (30), Vivioptal (55), and Zellaforte plus (46).
While Germany produces more GH3 preparations than any other country, it is by no means the