The birth of rejuvenation: gland grafting and the dawn of endocrinology

Here is light relief after the last post about fertility preservation for boys. This is an abridged chapter from my book Cheating Time—Science, Sex & Aging (1996) about the history of famous scientists and doctors and several quacks at the dawn of endocrinology who offered radical remedies for aging in men (gerontology from Greek means the study of old men!). If we bask with pride in knowing we can never be so gullible, remember that hope of conquering the final enemy springs eternal. A book reviewer at the Economist wrote in 2022 about modern enterprises for pushing the human lifespan beyond its natural limit: “The idea of living forever … is now pursued by a motley crew of fringe scientists, cultish groups and tech billionaires, united by a conviction that a way to make humans immortal will eventually be found.” I asked a friend at the summit of gerontology and Alzheimer’s research if he shared that optimism. “Phooey,” was his reply, although I moderated his word choice.

Gland Grafters is a history split to manage its length for publishing alternately with contemporary topics. Best read at the end of the day, curled in an armchair with a glass of wine, and laughing along with the author.

New Glands for Old.

At the start of the 20th century, the prospects for organ transplantation were brighter than ever before. Striking improvements in aseptic surgery enabled more patients to survive abdominal operations. In 1912, the Nobel Committee signaled its blessing to the promising new field by awarding the prize for physiology and medicine to Alexis Carrel at the Rockefeller Institute of New York. Together with the Chicago physiologist Charles Guthrie, they perfected a method for joining the blood vessels of organ grafts to those of the host. In a brilliant series of experiments, they showed that the heart, kidneys, and ovaries could be removed and returned to the same animal afterward. But Carrel doubted whether it would ever be possible to graft organs from one individual to another, so he turned attention to growing cells outside the body or in vitro. Despite his warning, “rejuvenators” pressed forward with sex gland grafts, encouraged by celebrated results from the past.

The Scottish surgeon John Hunter had grafted testes from cocks into hens, and ovaries into cocks, back in the 1780s. His reason for bizarre experiments was the impression that females become masculinized as they get older, noting this “obtains to a certain degree in every class of animals. We find something similar taking place even in the human species.” He was also aware of the possibility of sex changing in the opposite direction, including the case of the famous cock pheasant in the 15th century Basel solemnly tried for witchcraft after laying an egg. After the luckless creature had been burnt at the stake, three more “cock’s eggs” were discovered among the roasted remains.

After one of his experiments, Hunter recorded in his notebook, “I have formerly transplanted the testicle of a cock into the abdomen of a hen, and they had taken root there, but not frequently, and then had never come to perfection.” Some of his successful grafts pickled in alcohol are preserved at the Royal College of Surgeons in London. The mixed success with grafting puzzled him, given that it works well with trees and shrubs, but the reasons for rejection were not discovered until much later.

The Göttingen biologist A.A. Berthold in 1849 was not deterred by historic failures. He made a crucial difference by grafting cockerel testes back to their original owners. Blood vessels soon sprouted and nourished the organ as if welcoming back an old friend. The size and appearance of both comb and wattle were well maintained compared with those of capons, and the birds showed “the customary attention to the hens.” Since any testicular nerves would have been severed during the operation, Berthold rightly inferred that the male organ must have exerted its effects on body shape and behavior by releasing something into the bloodstream. The significance was out of proportion for a paper of only four pages, for it hinted at the existence of testosterone. But, like the contemporary geneticist Gregor Mendel, Berthold did not live to enjoy recognition for a momentous discovery.

At the turn of the 20th century, grafting was playing a major role in the infant science of endocrinology. Scientists discovered that, unlike most other organs, hormone-secreting glands can sometimes be simply implanted without hooking up blood vessels. They even worked in unnatural sites if they attracted a blood supply to bring oxygen and nutrients and distribute hormones to distant parts.

Professor Eugen Steinach of Vienna was a pioneer. Early in the century, he discovered the glandular cells in the testis later shown to produce testosterone and called Leydig cells. He followed John Hunter by testing testes and ovaries grafted to castrated rats of the same or opposite sex and made inferences typical for his time. Animals appeared to be male or female depending on the sex of the grafted organ rather than the original gonad, from which he reached a mistaken conclusion about human homosexuality.

He switched to grafting sex organs for rejuvenating animals on the assumption that, if gender is so easily altered, so can the signs and symptoms of aging. Steinach used his elevated post in an Austrian laboratory to inspire belief in rejuvenation science as a natural sister of endocrinology, and just as respectable. After proving that Brown-Séquard’s elixirs are inactive [described in the book], he grafted testes from young to old rats expecting a longer-lasting effect. The results vindicated his hunch when formerly decrepit animals easily defeated rivals and recovered interest in females. They lived 25 percent longer than normal.

It seemed to him that Brown-Séquard had been on the right track all along in the 19th century, even if his methods were flawed. Sex organs were the powerhouses of the body, and hormone deficiency was the root of aging. Any means of boosting hormone levels should therefore reinvigorate the whole body and preserve vital functions. Carrel had recognized the potential ability of grafts to overcome the failure of specific organs, but Steinach grasped the enormous significance of transplanting sex glands as a tonic for everyone.

But grafting was far from reliable and raised skeptical brows. Would it last long enough to rejuvenate patients? Would they have to be given repeatedly, and, if so, would there be enough material to go around? Steinach responded to criticism with reassuring news that young organs can reinvigorate failing testes and ovaries in old animals. He claimed the benefit remained even after the grafts failed or were removed; they only needed to last long enough to rekindle native organs. These results encouraged the gung-ho efforts of an enterprising breed of surgeons I call “the rejuvenators.”

In 1916 Chicago, Dr. Frank Lydston dumbfounded a colleague by taking him aside to show a lump of tissue in his scrotum. He had stitched a slice of testis from another man beside his pair. At age 54 and the peak of his career, he felt less energetic until the self-experiment and claimed, “I feel strengthened in my … impressions of the value of sex gland implantation, notably in the matter of increasing physical efficiency and especially physiosexual efficiency.”

Within months, he offered the operation to patients whose organs had failed or been injured. The first had been castrated twelve years earlier for a crush injury from football. An organ procured from an autopsy of a teenage boy so improved the situation that the patient was said to need an ice pack to control spontaneous erections! Even if the graft had been a success, we now realize that testosterone is not required for penile tumescence, as erections in infancy testify. Still, the result was taken as a positive omen.

A wave of success can carry a tide of new obstacles. Where would suitable young donors come from to meet demands? The supply from accident victims and executed prisoners was unpredictable and seedy. If a rare specimen arrived on a weekend, it was stored in the refrigerator until Monday. Few glandular cells stand up to abusive storage, and testes deteriorate quickly, but Lydston claimed remarkable cures.

Publicity encouraged other surgeons. Robert Lichtenstein, one of Steinach’s colleagues, operated on a young soldier wounded in 1915 by a gunshot that blasted off his testes. A “spare” organ was procured from another soldier undergoing surgery for undescended testes. After stitching a slice to the abdominal muscle, the man’s beard regrew and his sex life improved, though he obviously couldn’t father a child.

Dr. Stanley, the physician in charge of California’s San Quentin Prison, was another enthusiastic gland grafter. Prisoners are often willing to be guinea pigs in clinical trials for trivial inducements and distraction from the tedium of prison routine. In the antediluvian era of medical ethics, he could persuade other doctors and even women to be subjects for implanting testicular tissue from prisoners or substituting if the supply ran out with organs from goats, rams, boars, or deer. The tissues were ground to a pulp and injected through a wide-bore needle into the belly muscle. He argued that hormone secretion was equally effective there as in the scrotum, and homogenization encouraged blood vessels to sprout faster. He recorded striking recoveries from asthma, acne, rheumatism, and senility and, more dramatically, subjects performed well running circuits on prison sports days.

Gland grafting seemed on a safe path to respectability in the 1920s and was only hindered by the struggle for organ donors.

Steinach’s Operation

Steinach hoped to avoid grafting by boosting hormones from intact organs. His experiments had revealed seminiferous tubules degenerated after vasectomy (sic) while neighboring Leydig cells hypertrophied, implying a boost to testosterone production. He thought that back pressure from ligaturing the vas deferens killed developing sperm cells, which created space for glandular cells to multiply. Could the simple and safe procedure of vasectomy achieve the same ends as gland grafting?

He confirmed his hunch when old rats looked younger and sleeker after vasectomy. They had more vitality and virility, like grafted animals. The operation called “vasoligation” soon became known as “Steinach’s operation.”

He persuaded Lichtenstein to test it on patients. Tying only one tube left the opposite member as a backup for another operation and additional fee, obviously sacrificing fatherhood in future. Word got around that the operation cured “male menopause.” Claims circulated for lasting improvements in blood pressure, tremor, vertigo, and rheumatic pain, sight, and hearing, even regrowth of dark hair on bald pates. Some doctors praised its sexual benefits after noticing testicular enlargement and sexual potency in undersexed men. The power of suggestion is enormous in the realms of human sexual physiology and behavior but then not sufficiently credited.

Steinach’s reputation grew as news of the revolutionary operation spread. His name became a byword for scientific wonder. People said even a cabbage could be Steinached (whatever that meant). The press portrayed him as a gentle genius whose labors benefited society. Like other rejuvenators, he published popular books extolling his theories and methods. He adapted Sir William Ostler’s felicitous dictum that “a man is only as old as his arteries” to “we are as old as our glands.” He also predicted, and not entirely in jest, “I think the day will come when vasoligature or some other process having a like effect, will be undertaken by the state for every man of fifty, just as every child is vaccinated for the prevention of smallpox today.” The long queues of patients at clinics seemed to confirm an immense breakthrough in medical care.

Patients were delighted with the well-being they hadn’t felt through many years of conventional treatment and quack remedies. Their enthusiasm contrasts with a common modern attitude to vasectomy, too often regarded by men as sacrificial and never health-promoting. No one is now heard to say that he feels reinvigorated and, if anything, expresses anxiety that tampering with nature harms (despite lack of evidence).

Women were not entirely forgotten in this quest for longevity (gerontology means from the Greek the study of old men). With eyes on business, the rejuvenators considered how to help the increasing population of older women. Would it help to tie off fallopian tubes by analogy with the vas deferens in males? Disappointing results turned them back to focus on males.

Although beyond the fringes of orthodox medicine, the desperation of patients willing to try anything encouraged unregulated rejuvenation surgery in all its varieties for every circumstance. There was diathermy for those who didn’t relish the operation. They put faith in sparks from electrodes across the testes to kick-start their ailing glands. Mild doses of X-rays or radium substituted for Steinach’s operation by destroying spermatogenic cells. The still mysterious properties of radiation added to the aura. An American company distributed apparatus by mail order containing radium for wearing in bed at night. A home rejuvenation kit took matters too far. Public safety was at risk besides putting professional reputations and private fortunes at stake.

The rejuvenators claimed a few deft scalpel strokes could achieve a complete overhaul of physiology, whereas a cosmetic surgeon’s handiwork is only skin deep. Celebrities signing up added gloss to a clinic’s reputation. For performers past their prime and written off by their fans, the possibility of rejuvenation was irresistible; even gossip column rumors of treatment were beneficial. Artists and writers suspected doubts about science at the prospect of reversing Old Man Time. The Irish poet W. B. Yeats, aged 69 in 1934, had stopped writing poetry after losing his companion, Lady Gregory. He opted for a Steinach operation by the Harley Street sexologist Norman Haire and allegedly regained former strength and creativity.

Follow-up was hard when patients returned home to distant places. Doctors needed a captive population for careful long-term studies. Thus, a medical officer at an Indiana penitentiary testing the Steinach operation on inmates could report: “I have 465 cases that have afforded splendid opportunity for postoperative observation, and I have never seen any unfavorable symptom. There is no atrophy of the testicle, there is no cystic degeneration following but, on the contrary, the patient becomes of a more sunny disposition, brighter of intellect, ceases excess masturbation, and advises his fellows to submit to the operation for their own good.” He meant their moral good.

Failures were harder to conceal for public figures. Albert Wilson was so euphoric about his operation – and sufficiently wealthy – that he hired the Royal Albert Hall in London to give an advertised lecture: “How I was Made Twenty Years Younger.” On the day before this engagement, he celebrated with a heavy drinking bout with his friends. As Haire recalled later: “He was a man over seventy, who had been most successfully operated on by Steinach before; but too confident in his renewed vigor, he overtaxed his powers and died (the day before his lecture) from an attack of angina pectoris, a disease from which he had suffered for many years before the operation. He had been warned not to be prodigal of his new-found strength but forgot that he was in his seventies and tried to live like a young man in his twenties. The result, of course, was disaster.”

So alarmed by exaggerated claims, critics condemned the entire enterprise. The editor of the prestigious JAMA, Morris Fishbein, thundered that all such attempts were worthless and likely dangerous. To encourage public revulsion, he pointed to the hidden goal of sexual rejuvenation. His reproach stung the rejuvenators. They scoffed at his lack of professional experience in endocrinology (true enough) and accused him of sanctimonious attacks on Steinach and Freud. Steinach’s reputation survived skirmishes and the subsequent critical gaze of history since he is remembered more as a pioneer of endocrinology than a dubious dabbler in gerontology.

Example of advertisement for animal gland extracts to treat the ailments of aging men. A fad lasting decades gained auspicious authority after Prof. Brown-Sequard’s self-experiment in Paris.