Monkey business: Voronoff’s promises and the fall of the rejuvenators

Monkey-gland business

The French surgeon Serge Voronoff had the (false) impression that eunuchs in a Cairo Ottoman court don’t live as long as other men. It set him thinking about the causes of aging. A few years later, the military doctor and future Nobelist Alexis Carrel encouraged him to specialize in transplant surgery when he was demobilized after the Great War. The enormous casualties meant fewer able-bodied partners for young women in France, so many married disabled veterans and an older generation. Voronoff vowed to help rejuvenate their physical and sexual vigor using transplantation surgery.

He honed his skills with sheep testes, not intending to graft them into men as John Brinkley had with goat organs in rural Kansas. He wanted donors with greater genetic affinity, from humans if possible or primate animals if necessary. The first experiments won acclaim. Young grafts stimulated longer, stouter horns and a thicker fleece in worn-out and castrated rams. The results so impressed a medical congress in Paris that he applied for a government grant to boost wool production in sheep.

A follow-up study confirmed that old rams became more bellicose and eager to mate. He supposed the grafts made more male sex hormone, the molecule we call testosterone but unknown and unnamed then. The rams returned to their former feeble state after removing the grafts, which seemed conclusive proof of benefit. They lived strikingly longer lives, at least 25% more than the normal span of 12 to 14 years. He now dared to have grandiose hopes of prolonging human life, at least for men.

The government sent Voronoff to Algeria to improve sheep and cattle stock in the French colony. On his first visit in 1924, he treated a 17-year-old prize bull called Jacky put out to pasture as a useless stud, although still a spirited beast. Voronoff wrote: “I grafted into him the testes of a native three-year-old bull (under local anesthesia) in front of a great number of breeders … Although the animal was made to lie upon its side and was kept in this position by some ten Arabs, it gave frequent signs of impatience which resulted in the frequent upsetting of all the surgeons.”

An Algerian correspondent sent an update to Paris three months later. “The bull we operated upon is keeping very fit; its hair has become glossy, its eyes sparkling and …(it) now seems full of ardor. During the last few days, he was put with a cow that was on heat, and he covered this animal four times in a morning, which number is quite a record.” In another letter he recorded Jacky “scarcely ever ceased to exercise his reproductive functions.” The bull produced six calves in 1925 alone, although needing another graft to reverse his dwindling energy three years later.

This outstanding case attracted attention. His critics might have thought the claims a load of bull, but the publicity eased him into a prestigious professorship at the Collège de France. He now had the confidence to apply his skills to old men, inspired by Frank Lydston’s example, the Chicago doctor who self-experimented with a human donor testis. However, the procurement of donor organs proved to be an obstacle. Families grieving for accident victims were slow to consent, as were the authorities when he sought approval for taking biopsies from guillotined prisoners. Young men demanded exorbitant compensation for parting with one of their organs so that left animals as a last resort.

He preferred chimpanzees as our closest relatives whose large testes characterize promiscuous species that could be divided between several men. He made a long incision in the scrotal sac of anesthetized patients to stitch a donor’s slice beside a resident testis. Imagine the scene of an animal lying on a table in the O.R. close to a sleeping patient, but unlike an altruistic human donor, the apes who donated never gave consent! When the supply of chimps ran out, he switched to monkeys. Too small to divide, he grafted them whole after burning holes in the capsule (“lanternization”) to encourage blood vessels from the spermatic cord.

You might expect other doctors would condemn the operations, but the hurdles of xenotransplantation were poorly known, or public protests would have halted them. But sensibilities about animal rights were muted and Jane Goodall was then only a babe in arms. But there was plenty of gossipy news and sensational headlines touting the “Monkey-gland Campaign,” so-called because it was deemed vulgar to print the word “testicle” in the American press. Bars served a cocktail drink containing absinthe, called Monkey Gland, said to extend longevity. You can be sure when there is a rumor of a new cure for aging, there are pecuniary interests fanning adverts.

His first two patients came for treatment after castration for tuberculosis of the scrotum. The results disappointed them, merely casting a slight shadow instead of a mustache and beard. However, a third man aged 59 with memory loss and depression felt much better. And a 61-year-old man of letters with early signs of senility claimed to be sufficiently vigorous he returned to work. A formerly haggard English patient aged 74 presented at a medical congress appeared stronger and more agile than in pre-operative photographs, leaning on a walking cane. He credited treatment with turning back his biological clock by 20 years.

In other (apparently) convincing cases, mental health improved, flabby abdominal fat absorbed, scalp hair sprouted, sexual appetite restored, and intellectual power returned. Voronoff attributed these benefits to the physiological refreshment of the whole body by the sex hormone from grafts. No doubt some of them felt better from the wonderful effects of autosuggestion.

Voronoff avoided alienating the prudish public by emphasizing the benefits of a long and healthy life and downplayed a boost of libido. In an interview with the Scientific American, he said: “If we consider one year of a ram’s life equivalent to six years of a man’s life, then we may estimate that by grafting we can add 30 or 40 years to a human life . . . When a man will have lived to be 125, we will at last have found a path towards the abolition of old age.” We don’t know if he took his own medicine, but he missed that goal, living to age 85 whereas his contemporary, Mme. Jeanne Calment, died at 122, still the world record.

In his heyday and the frothy 1920s, Voronoff was in constant demand for lectures and chased by the paparazzi for scoops about his latest cases. A master of self-publicity, he was more courteous than Professor Steinach and more sophisticated than “Doc” Brinkley previously featured in this series. A man of tall stature and grave deportment, he impressed patients and doctors, some hailing a great man.

His American counterpart, Max Thorek, a chief surgeon in Chicago, carried out 97 monkey and human gland transplants between 1919 and 1923 of which 59 cases showed improvement. Although courteous to the Frenchman, he disagreed with claims to prolong life and over the source of the male sex hormone. Thorek agreed with Steinach that Leydig cells are responsible for hormone production, and as the better microscopists, they were correct.

Salacious newspapers on both sides of the Atlantic milked the monkey-gland story. They published tall tales about thieves waylaying taxi drivers to snatch their glands for black-market sales to senile millionaires. Newspapers speculated if revitalized men might father human-monkey hybrids for gullible readers poorly informed about genetics. Monkey glands made fertile entertainment for cartoonists and writers. Bertram Gaymer’s play, The Gland Stealers, was a popular spoof. George Bernard Shaw quipped that “man will remain what he is despite all Dr. Voronoff’s efforts to make a good ape of him.”

Victorian morality and strict attitudes to matrimony and privacy faded after the war. Patients felt more at ease talking to their doctor about sexual problems. Middle-aged men wrote to Marie Stopes, the British pioneer of contraception, seeking advice about physical appearance, libido, and erectile dysfunction. Gland grafting didn’t seem so objectionable after the medical establishment eased its hostility, even inviting a certain Dr. Walker to give the Hunterian Lecture on the subject in 1924. He declared it “distinctly promising.” The BMJ printed a favorable review of Voronoff’s latest book: “Dr. Voronoff has been the victim of a certain amount of misrepresentation and prejudice, largely owing to the premature interest which the lay press has taken in his work . . . No doubt the use of monkey tissue for the rejuvenation of men – a return, as it were, to our ancestry for refreshment – has certain elements of humour which have not passed unrecognized… The testicular graft is something worthy of serious consideration.”

A dash more respectability at last!

Nemesis

The fortunes of rejuvenators were stifled in the gloomy years of the Great Depression with a looming European war. The battle against aging was pushed aside by struggles to preserve living standards and international peace. Controversy over rejuvenation science that started late in the previous decade, would travel like a spark in a fuse toward a bombshell in the 1930s.

In November of 1927, a delegation of senior scientists set sail for Algeria to meet Voronoff. He gave them a lecture and research portfolio with details of the famous bull Jacky. They traveled to his research station in the arid southern territories to inspect “super sheep” hailed as the heaviest and healthiest in the flock after grafting.

A friendly Arab herdsman whispered to one of the visitors, “We ensure the doctor has the best animals.” Well-meaning intentions backfired. If animals are selected for high quality, the results are biased and worthless. Voronoff may have been under the illusion that his scientific methods were kosher.

The visitors went home to write reports. The British team criticized record-keeping and the selection of prize animals. It is a rare bull that survives to 17, a sign of singular vitality. Voronoff accused the stuffy Brits of being out of step with other experts, but they dug in their heels.

More serious clouds gathered. Voronoff et al. complacently assumed grafts had survived if they could feel hard lumps in the scrotum after several weeks. They whistled in the dark. Careful observers took biopsies for microscopy and couldn’t find a single living cell. Only scars.

The gland grafters went out of business, pursued by patients and their lawyers. Persisting scrotal sores and abscesses were irritating reminders of being duped. Grafts didn’t even give temporary relief from symptoms; couldn’t because testosterone production stopped abruptly, and cells don’t store steroid hormones. Worse still, vulnerable patients may have been harmed by transferring disease, and public health threatened by zoonoses from viruses leaping between species.

We feel self-righteous excoriating the gland grafters’ goals, vanity, and motives as false merchants of longevity. But they aren’t the only medical practitioners or scientists who deceived themselves and hurt people they wanted to help. The history of medicine records many reversals and apologies. Consider prefrontal lobotomy, thalidomide and diethylstilbestrol prescribed in pregnancy, infants exposed to heavy metals, etc. In Voronoff’s era, my father had scalp X-irradiation as a young child for ringworm, which gave us cause to wonder about a condition later in his life.

The rejuvenators presumed aging is a systemic phenomenon triggered by hormone deficiencies, and therefore reversible with youthful glands. But the root cause lies inside cells and still defies deep understanding. However, a modern brood of rejuvenators liberally funded by some tech titans believe they can repair what millions of years of evolution ordained. We shall see! I am loath to give Voronoff and company credit for anything, yet admit they unknowingly foreshadowed the triumph of chemical endocrinology and the effective treatment of deficiency with pure and synthesized hormones.

Before we scoff at their blunders with grafts between species, remember even the existence of histocompatibility antigens and B- and T-lymphocytes was unknown. When grafts are not closely matched, they are soon rejected, even faster at the second attempt. Only a few avascular tissues, like corneas and cartilage, escape surveillance, but gonadal tissues don’t have that immune privilege.

Monkey-gland surgery collapsed under the weight of science, but testicular tissue can survive transplantation in genetically matched cases provided with a blood supply. I wrote earlier about an application for preserving fertility in children with frozen grafts. Fifty years earlier than our studies, an American worker had his tissue grafted back after retrieving it from factory machinery that castrated him. But simple grafts like those pale beside the technical virtuosity of vascular microsurgery and vasovasostomy. My friend, Sherman Silber of Saint Louis, reported the first successful whole testis transplant in 1977 between genetically identical twins with gonadal discordancy. The fertile sibling’s organ quickly raised his brother’s testosterone and generated sperm for four children, all conceived naturally.

Peter Medawar settled the tenets of transplantation in the 1950s and 1960s. The arrival of immunosuppressive drugs flung open the door to organ donation with less than perfectly matched transplants of kidney, heart, uterus, etc. And now pig heart transplants are lending credibility to xenografting it never deserved in Voronoff’s hands. Wise people say history is circular. That may be true – sometimes – but I don’t expect old men will ever seek monkey glands again to reverse the arrow of time.

Image #1: DALL-E (OIA)

Image #2: Voronoff’s English patient before and after a “rejuvenating” graft

Image #3: The 1927 delegation reviewing Serge Voronoff’s experiments in Algeria (S.V. in the foreground, hand across his jacket)