August 23, 1894J 



NATURE 



405 



by Brown-Sequard that when these bodies are totally removed 

 in any animal the removal is speedily followed by a fatal result. 

 These experiments of Brown-Suquard's were made in 1858, and 

 at the time attracted some attention. They were repeated by 

 other experimenters with similar effects. But some of those 

 who removed the supra-renal capsules obtained contrary results, 

 and for many years the matter remained in an undecided con- 

 dition. It was even supposed that the fatal results which were 

 got by Brown-Sequard might be due to the shock of the 

 operation or to the fact that the removal necessarily in- 

 volves certain parts of the sympathetic nervous system, 

 and were not necessarily due to the removal of the 

 supra-renals. Recently, however, attention has been again 

 directed to the subject, and the experiment of Brown-Sequard 

 has been repeated by Tizzoni (1S89) and by Abelous and Lang- 

 lois (1891 to 1894) '" various animals, viz. frogs, guinea-pigs, 

 rabbits, and dogs. I have myself performed two confirmatory 

 experiments in monkeys. The result of all these recent ob- 

 servations is to show that the complete removal of the supra- 

 renal capsules is not compatible with prolonged existence of 

 life, and Abelous and Langlois have shown that it is accom- 

 panied by an alteration in the blood, which renders that fluid 

 poisonous to other animals. The contrary results which have 

 been obtained by some investigators are apparently due to the 

 fact that in certain cases there are, as with the thyroid body, 

 small isolated portions of supra-renal substance (" accessory 

 capsules," as they are sometimes called) which have not been 

 noticed and removed at the time of the operation, and that 

 these small portions of supra-renal substance have served to 

 maintain that proper relation between the blood and the gland 

 which is sufficient to prevent the supervention of the symptoms 

 in question. 



Now the weight of both supra- renal capsules taken together 

 is not more than three drachms, and their weight, as compared 

 with that of the whole body, is only as I to 6000 or less. The 

 accessory supra-renal capsules which may be left after the 

 removal of the main bodies probably do not originally weigh 

 more than one-twentieth of the whole structure, and yet this 

 minute proportion of material (a material, so far as we know, 

 unique in the organism) is nevertheless sufficient to maintain the 

 composition of the blood and the nutritive equilibrium of the 

 body, and thus to prevent the necessarily fatal result of complete 

 removal. 



Now it has been found in the case of the thyroid gland that 

 patients in which this structure has been so diseased that its 

 function is seriously interfered with, and animals in which it has 

 lieen removed entirely, may be greatly benefited, if not 

 indeed cured, by the inception, either subcutaneously or 

 with food, of the thyroid glands of animals, or of the 

 juice of such glands. Even where no affection of the 

 thyroid can actually be detected, the exhibition of thyroid 

 juice is frequently beneficial in certain conditions of the system, 

 and it was noticed by Dr. Oliver, of Harrogate, that this 

 is especially the case where there is a too marked constriction 

 of the blood-vessels, the juice of this body tending in such 

 cases to reduce the extreme tone of the vascular walls, which is 

 the cause of this condition. Encouraged by this result, Dr. 

 Oliver was led to examine the effects of other animal extracts, 

 and among them that of extract of supra-renal capsule. The 

 effect of this was precisely the reverse of that which he had got 

 with the thyroid body, for he obtained evidence tending to 

 show that in certain cases in man extract of suprarenal capsule 

 can produce an incvt'ase of vascular tone and a diminution in 

 the size of the arteries. Beyond this point, however. Dr. 

 Oliver was unable to proceed by clinical experiment, and be 

 accordingly came to my laboratory with the object of determin- 

 ing the precise physiological effect of the active substance of the 

 capsules. The results which were obtained show that there is 

 present in both alcoholic and watery extracts of the gland a most 

 potent physiological substance which when injected into the 

 body of an animal produces, even in minute doses, a remarkable 

 effect upon certain parts of the nervous system, upon the muscular 

 system, upon the heart, and upon the blood-vessels. If only as 

 much as a grain by weight of supra-renal capsule be ex- 

 tracted with alcohol, and if this alcoliolic extract be allowed to 

 dry, and then be redissolved in a little water or salt solution and 

 injected into the blood of a dog, the results which are obtained, 

 considering the minute amount of substance added to the blood, 

 are certainly most extraordinary. The nervous centre which 

 regulates the action of the heart is powerfully affected, so that 



NO. 1295, VOL. 50I 



the heart either beats very slowly and weakly, or the auricles 

 may even for a time stop beating altogether. If, however, these 

 inhibitory influences be cut off by division of the vagi nerves, 

 the effect of the poison upon the heart is of an opposite character. 

 There is great acceleration of the rate of the beat and a great 

 increase of force. This is accompanied by a strongly marked 

 influence upon the blood-vessels, and especially upon the arteri- 

 oles. The walls of these are chiefly muscular, and the drug exerts 

 so powerful an action upon this muscular tissue as to cause the 

 calibre of the vessels to be almost obliterated. The heart being 

 thus increased in force and accelerated, and the calibre of the 

 vessels almost obliterated, the result is to raise the pressure of 

 the blood within the arterial system to an enormous extent, so 

 that from a blood-pressure which would be sufficient to balance 

 a column of some four inches of mercury the pressure may rise 

 so high as to be equal to a column of mercury of twelve or 

 more inches. 



This result is obtained, as we have seen, by a very 

 minute dose. We have to do here with a substance which 

 is as potent, although in a different direction, as strychnia. 

 Whether it is a useful substance formed by the supra-renals 

 from materials furnished by the blood, and sub-equently 

 gradually used in the economy for the virtue of its 

 action upon the circulatory system, or whether it is 

 to be regarded as a poison, formed by the tissues 

 during their activity and carried by the blood to the supra- 

 renals, there to be rendered innocuous, we do not as yel 

 certainly know. These are important points which must form 

 the subject of further investigation. But, however this may be, 

 it is clear that in this gland also we again meet with an instance 

 of the physiological importance of what Sir Frederick Bramwell 

 called the " next to nothing." 



I will give one more instance, taken this time from a gland 

 which is provided with a duct. Until quite recently it might 

 have been thought that there was nothing very obscure regard- 

 ing the functions of the pancreas. The pancreas is a digestive 

 gland which lies below and behind the stomach : it has a duct 

 which carries its secretion into the beginning of the intestine, and 

 that secretion acts powerfully upon all constituents of the food, 

 digesting starch, meat, and fat. It was not supposed that the 

 pancreas had any other function to perform. Animals can live 

 without this secretion, and to a large extent can continue to 

 digest and absorb their food much as before ; for it has been 

 possible to divert the secretion from the intestine and to 

 collect it at the surface of the body ; and it is found 

 under these circumstances that, although the food is not 

 quite so readily digested, nevertheless the animal does 

 not materially suffer from the lack of the secretion. It was 

 discovered, however, a few years ago (by v. Mering and 

 Minkowski) that if, instead of merely diverting its secretion, 

 the pancreas is bodily removed, the metabolic processes of the 

 organism, and especially the metabolism of carbohydrates, are 

 entirely deranged, the result being the production of permanent 

 diabetes. But if even a very small part of the gland is left 

 within the body, the carbohydrate metabolism remains un- 

 altered, and there is no diabetes. The small portion of the 

 organ which has been allowed to remain (and which need not 

 even be left in its proper place, but may be transplanted under the 

 skin or elsewhere) is sufficient, by the exchanges which go on 

 between it and the blood generally, to prevent those serious 

 consequences to the composition of the blood, and the general 

 constitution of the body which result from the complete re- 

 moval of this organ. Now, some years ago it was noticed by 

 Kuhne and Sheridan Lea th.it, besides its proper secreting 

 structure composed of tubular alveoli, lined by granule con- 

 taining cells, there are highly vascular patches of peculiar 

 epithelium-like cells scattered here and there in the sub- 

 stance of the pancreas, which are wholly unconnected 

 with the ducts and, so far as one can judge, with the 

 secretion of the gland. We do not know anything what- 

 ever about the function of these patches, although 

 from their vascularity it is extremely probable that they are not 

 without importance physiologically, and it is tempting to con- 

 jecture that it is these cells which are specially concerned in 

 effecting that influence upon the metabolism of carbohydrates 

 which experiment has shown to be peculiar to the pancreas. 



The lesson to be drawn from these results is clear. There is 

 no organ of the body, however small, however seemingly un- 

 important, which we can presume to neglect ; for it may be, as 

 with the supra-renal capsules.the thyroid gland, and thepancreas,. 



