Rejuvenation! The wish of many a tired old man, and not so old: to regain the physical and sexual vigour of youth.
During the early decades of this century it was widely though not universally believed that such a rejuvenation, a turning back of the clock, could be achieved. It was thought that the secret of youth lay in the primary sex organs, so transplantation of the testis from young to old was the method adopted. In the 1920s a dozen or more surgeons around the world were ministering to this fervent desire by grafting the testes of young animals into those patients who could afford the fee.
We now know that this operation was quite useless, yet the surgeons and their hundreds of patients were on the whole convinced that the latter were indeed made to feel younger and fitter. Since that time we have discovered what formidable barriers the body raises against the introduction into it of “non-self” tissues. Material even from close relatives is rejected, and only in very recent times have methods been found for breaching the body’s defences to allow the intrusion of carefully matched foreign organs. This type of operation still makes newspaper headlines. Grafting between different species, using the techniques of sixty or more years ago, is impossible; rejection, the complete killing of the graft, would have been very rapid.
We have here, then, a most powerful example of the placebo effect, so a closer look at these events would follow naturally on Bill Morris’s article on the subject in the previous issue (Skeptic 27).
To set the scene, the medical background to the activities of the gland grafters, we note that as the century began the science of endocrinology was just beginning. The powerfully acting secretions of the endocrine glands were slowly being discovered and studied. First, the effect of extracts of thyroid glands on cretinism and myxoedema, then in the early twenties the anti-diabetic action of the pancreas extract insulin.
Gland Extracts to Restore Virility
It seemed a natural extension that an extract of the testis gland should restore flagging virility, and some unsuccessful trials along these lines took place. (when a hormone was, many years later, isolated from testes, and named testosterone. it was found not to have the effect sought.)
Seeking a more successful way of using the sex gland, surgeons looked to grafting. It was known at that time that cornea and bone could be transplanted from one person to another; it was not then realised that these successful grafts were rare exceptions — rather they were taken to indicate that grafts between people of any organ were possible. This view was strengthened when the discovery of blood groups enabled doctors to avoid the disasters which attended many of the early attempts at blood transfusion. The fact that some skin grafts did not “take” was ascribed to less-than-perfect technique, and many apparent “takes” were only the growth of the recipient’s own skin, and not the graft at all.
So the grafters got to work, initially on animals, and then on human patients. The usual technique was to excise the testis from the donor animal, open the scrotum of the recipient, and to place either the whole donor testis, or a slice, close up against one of the recipient’s testes, and then to sew him up again. In most cases the implanted tissue appeared to persist over time, giving the impression that the graft had “taken”. From our present standpoint we view this effect as the result of the rapid invasion of the graft by host cells, so the apparent “extra” gland was merely inactive host tissue.
Some of the earliest transplants into humans (1919 on) were carried out on those well-known experimental subjects, the residents of US gaols. These were man-to-man transplants, the “death row” of the prison serving as a regular source of fresh donor material. Dr Leo Stanley, chief Medico at San Quentin Prison in California, was the leader in this work, and carried out many transplants into “volunteer” prisoners during the 1920s. He and his patients were generally pleased with the results, and he impressed his fellow physicians sufficiently that several of them underwent the operation themselves.
In spite of this, there is no doubt that the most famous of the testis grafters was Serge Voronoff, a Russian émigré doctor of great wealth and charisma, active in Paris from the 1880s until the Second World War. Already in his 50s, and with a successful and fashionable medical career behind him, he turned in 1919 to the work that made him famous, his rejuvenation treatment. Lacking access to human material, he chose as donor animal the chimpanzee.
Believing that human grafts were possible, he picked on man’s closest relative as being the most likely to provide a transplant acceptable to the recipient’s tissues. Despite the expense (the chimpanzees alone cost a small fortune, as they each had to be caught in Africa and brought safely to France), he had many patients.
Voronoff’s fame during the 1920s arose not only from the “success” of his grafts, but also from his copious output of books on the subject, which he continued to publish long after the operation had passed out of favour. He had had from the outset critics who doubted the efficacy of the testis grafts, but it is uncertain whether, judged by the knowledge of the time, they had more reason for their skepticism than Voronoff had for his optimism.
The two British doctors’ journals took differing views: the Lancet was consistently critical of Voronoff’s medical claims and reviewed his books unfavourably, while the British Medical Journal was generally more approving.
Perhaps surprisingly, Voronoff’s undoing came not from a medical but a veterinary quarter. Emboldened by his success with human patients, he returned to his earlier interest in animals, and put his talents at the service of French agriculture. In 1924 he secured the use of a flock of sheep at an agricultural station deep in the French colony of Algeria. Some of the young rams of this flock received a testis graft, others were left unoperated. On reaching maturity, the operated rams were found to be heavier, and yielded more wool, than the unoperated controls. Not only this, but the progeny of the grafted rams also gave more wool.
Success?
Conclusive proof! Surely this evidence would silence those who had doubted. The animal results could be assessed objectively, unlike the confidential and subjective observations on the human patients. So groups of veterinarians and agriculturalists were invited to inspect the “super sheep.” All but one of the international visiting parties were quite convinced; only the British put their fingers on the fatal flaw in Voronoff’s case.
Translated into present-day statisticians’ jargon, he had failed to randomise his young rams at the start of the trial. It is as if we judged the winner of a race by noting who first crosses the finish line, without ensuring that all competitors started from the same place at the same time.
Knowing now that these grafts must have been rejected, we can only conclude that Voronoff had, perhaps unconsciously, selected the better quality rams for the transplant group, and that this superiority had carried on into the animals’ maturity, and to their offspring.
Voronoff’s claims for the superiority of the offspring of his grafted rams implied “inheritance of acquired characteristics;” thus, all unwittingly, he had strayed onto the battlefield between the Lamarckians and the Darwinians. So, by his sheep experiments, he widened the area of interest in his work beyond the medical, attracting the attention of veterinarians, agriculturalists and finally general biologists.
By 1930 medical opinion was already turning against him; the scrutiny of the non-medical scientists hastened this process. By their nature, his human operations were very private, confidential affairs, the results of which were quite inaccessible for objective assessment by others.
When the fad for this operation died down, and its uselessness was realised, the practitioners were widely ridiculed, and reviled as quacks and charlatans. This was incorrect and sadly ungenerous; with few exceptions these surgeons were sincere men who wholeheartedly believed in what they were doing. Voronoff himself defended his work until his death in 1951.
A Change of Glands
That is not quite the end of the story of the gland-grafters. At the same time as testis transplants were going out of fashion, as described above, endocrinology was discovering more and more hormones produced by the body’s many glands, and these were available for “treating” a wide range of disorders.
The pituitary gland, in particular, was found to have a special role in controlling the activity of other glands (it was at one time called “the conductor of the hormonic orchestra”). Injection of cells of the pituitary, then, could be used by unscrupulous doctors to treat whatever glandular deficiency the patient could be persuaded he had.
The leading practitioner, Dr Niehans, a Swiss, was active until the 1950s, and counted Top People (from Hollywood to the Vatican) among his patients. None of his injections could have been of any use.
What lessons ought we to learn from this story, this false turning in medical science? Firstly, we see that misguided enthusiasts can be as dangerous as unscrupulous quacks. Furthermore, we should all subject our enthusiasms to rigorous self-scrutiny.
If Voronoff had kept better records of his operations, and taken a more objective view of the results, he might eventually have seen his error. Had he invited a histologist to examine his early sheep grafts he might have been convinced that they had indeed been rejected by the host. From the patient’s viewpoint, a person unhappy with his present state of health, having undergone a very expensive and uncomfortable operation, carried out by a charming, confident and persuasive surgeon, can almost be guaranteed to confirm whatever outcome of the operation the surgeon suggests to him.
A last thought: in a period which delivered to women the suffrage, protective labour laws and power-driven domestic appliances, the “rejuvenation” movement was almost entirely male-oriented. No-one seems to have considered whether anything could be done to help the post-menopausal woman who longed to be twenty again.
I am indebted for the information in this article to The Monkey Gland Affair by David Hamilton, London: Chatto & Windus, 1986.