904 



NATURE 



[December 22, 1923 



Rejuvenescence and the Testicular Graft 

 By Dr. F. H. A. Marshall, F.R.S. 



IT has l)ccn known from very early times that 

 castration in both man and animals, besides 

 causing the suppression of the sexual instinct, produces 

 marked changes in the bodily conformation and the 

 secondary characters of sex, and that these effects are 

 far more definite if the operation l)e performed before 

 pul)erty. There are numerous references to the sub- 

 ject in the works of Aristotle, who remarks on the 

 immense modifications in the general configuration 

 iirought alx)ut by the mutilation of a comparatively 

 minute organ. The abnormal height of the eunuch, 

 his undeveloped larynx and soprano voice, and the 

 absence of hair on the face and other parts of the 

 body where it is usually present in men are among 

 the well-known effects of testicular deprivation. The 

 domestic animals also furnish striking examples of the 

 consequences of castration, and the same may be said 

 about birds. Thus the testes, besides being responsible 

 for the development of the sexual instinct, are an 

 essential factor in the formation of the l)odily characters 

 associated* with maleness. The manner in which this 

 influence is exerted, however, has only comparatively 

 recently been ascertained, and there are still many 

 gaps in our knowledge. 



According to Herman, the author of " The Glands 

 regulating Human Personality," the first to conceive 

 the idea that the gonads exert their effect through an 

 internal secretion poured into the blood was Bordeu, 

 who was Court Physician to Louis XV. in the eighteenth 

 century. Berthold, however, in 1849 was the earliest 

 to base the idea on experimental proof. This investiga- 

 tor removed the testes from cocks and transplanted 

 them into new positions in the body, and he noted that 

 the birds developed or retained their male character- 

 istics (voice, sexual and combative instincts, growth 

 of comb, wattle, etc.) just as though they were normal 

 males. These results were attributed by Berthold to 

 substances formed by the testes irrespective of their 

 position, and thus he was the first to put on a definite 

 experimental basis the idea of an organ elaborating a 

 hormone which, after being carried in the circulation, 

 acted upon other and distant parts of the body. Little 

 account was taken of Berthold 's work at the time, and 

 it was not until much later that the conception of 

 organs having an endocrine function was revived by 

 Claude Bernard, who applied it to the liver. In recent 

 times Berthold 's work on the testicular graft has been 

 confirmed for a large number of animals, and the fact 

 that the testis, in addition to producing the semen, 

 gives rise also to one or more chemical substances of 

 the nature of hormones has been established. 



The notion that the testis produces an internal 

 secretion which, besides being responsible for the male 

 characters, possesses also a rejuvenating influence, is 

 a somewhat different one. It was originally put for- 

 ward in 1889 by Brown-Sequard, who injected testicular 

 extract, first into animals and then into himself. He 

 was convinced that in both cases beneficial effects 

 accrued, and claimed that he himself underwent a 

 radical change and regained the force and vitality of 

 former years. The extracts were made from dogs' and 



NO. 2825, VOL. I 12] 



guinea-pigs' testes, and were injected subcutaneously. 

 At this time, Brown-.S^uard was seventy-two years old. 

 The supposed rejuvenating effects, however, did not 

 last, and although this form of treatment was extended 

 to some hundreds of patients suffering from various 

 diseases (rheumatism, sciatica, locomotor ataxia, tuber- 

 culosis, etc.) by Brown-Sequard and Brainard, who 

 claimed that good results often followed, the practi* » 

 of testicular injection was soon discontinued and becaii^ 

 generally discredited. 



In recent years, however, the idea of testicular 

 rejuvenation has been revived in connexion with graft- 

 ing experiments. In 1913, Lespinasse, an American 

 doctor, recorded a case of testicular transplantation in 

 a man, but gave no evidence of the persistence of the 

 graft beyond that afforded by sexual potency. About 

 the same time Lydston, of Chicago, is reported to have 

 done similar work with human grafts, and the medical 

 department of the California State Prison Is said to 

 have organised transplantation experiments in which 

 testicles obtained from executed criminals were grafted 

 on to senile individuals, but there is no satisfactory 

 evidence as to the results obtained. 



More recently (191 8) Stanley and Kelker have per- 

 formed the same operation, and in further experiments 

 the testes of animals were substituted for human ones. 

 It was believed, however, that in all cases the grafts 

 became necrotic and were either absorbed or else the 

 site of operation opened up and the necrotic material 

 was discharged. In a later paper, Stanley has de- 

 scribed a large number of experiments (more than 1000 

 had been carried out by 1922) in which men were in- 

 jected with partially macerated testis by a s>Tinge. 

 With this method the danger of sloughing was much 

 reduced, and the injected substance could be felt under 

 the skin for months, but it was eventually absorbed. 

 From these experiments Stanley concluded that animal 

 testicular substance injected into the human body 

 caused decided benefit for some time. Among those 

 treated were patients suffering from neurasthenia, 

 epilepsy, asthma, tuberculosis, diabetes, and many other 

 chronic diseases, as well as senile decay. Most of the 

 subjects reported increased sexual activity and resump>- 

 tion of virility where this had been lost. It is said, 

 further, that testicular substance often has a beneficial 

 effect in relieving pain of unknown origin and in 

 promoting bodily well-being, and that the power of 

 vision is sometimes greatly strengthened. The testicles 

 used were those of goats, rams, deer and boars. 



Three cases have been described by Lyons in which 

 rams' testicles were transplanted on to men sufferiiiLr 

 from debility and impotence, and in two of these 

 favourable results were claimed, but the fate of the graft s 

 was unknown. 



The above recorded experiments were all carried out 

 in America in the last decade. In the same peric] 

 numerous operations of a similar order have bt t :. 

 carried out in Europe. In 1915, Lichtenstem, of Vienn.; 

 operated on a soldier who had lost his testicles as .1 

 result of being wounded in the War. After a fc > 

 months, the patient showed all the usual signs 't 



