474 



NATURE 



[September i6, 1897 



regarded as a branch of pharmacology, because some of the 

 latest researches regarding the processes of life have been made 

 by pharmacological methods, using the products of animal life 

 instead of vegetable poisons. Amongst the pioneers in this 

 line I may mention my two masters, Kiihne and Ludwig ; the 

 former of whom by his chemical investigations has enabled us 

 to differentiate the various products of albuminous decomposi- 

 tion, whilst the latter, with his pupils Schmidt-Miihlheim and 

 Wooldridge, discovered the poisonous action of albumoses and 

 peptones, and of the juices of various tissues when injected 

 ■directly into the blood. 



Before the proteid constituents of our food can. be absorbed 

 they must be split up during digestion into albumoses and 

 peptones ; yet these researches show that the very substances 

 which are necessary to repair waste and are indispensable for 

 the continuance of life, prove fatal when introduced into the 

 body in a wrong way, or too great quantity. But the products 

 of the digestion of albumin do not normally enter the circulation 

 as albumoses and peptones. During absorption they undergo 

 changes of a synthetic nature in the walls of the intestine, and 

 probably to a certain extent also in the liver, so that they again 

 form harmless substances, and their poisonous properties are 

 destroyed before they enter the general blood stream. 



But how is it that the ferments which decompose albuminous 

 food and form poisons from it in the intestine do not pass into 

 the blood and kill the animal by digesting the tissues and form- 

 ing poisons from them ? Of course pepsin cannot do so as it only 

 acts in an acid medium, but there is no such hindrance to the 

 action of trypsin, and yet it does not destroy the tissues com- 

 posing the body itself. In all probability the reason why 

 digestive ferments do not digest the tissues is not that they are 

 destroyed in the digestive canal, nor yet that they are not 

 absorbed, but that they are altered from active enzymes into 

 inert zymogens which can be stored up without risk, and can 

 again liberate active enzymes when these are required to digest 

 a subsequent meal. In this respect they may be compared to the 

 knives used by wandering peoples to cut up their meat, and 

 which are not thrown away after each meal, but are simply put 

 into sheaths which cover their edges and deprive them for a time 

 of their cutting power. 



But it is not in the intestine only that enzymes are found, 

 they are also poured into the blood by the pancreas and prob- 

 ably by the thyroid and other glands. As our acquaintance 

 with the processes of cell life increases, it seems more and more 

 likely that the tissue change on which functional activity 

 •depends is effected by enzymes, and the truer do the specula- 

 tions of Van Helmont appear — that life is a process of fermen- 

 tation. 



There can be little doubt that if enzymes in a free state were 

 to circulate through the body they would do much harm, and 

 indeed we may regard this as well-nigh proved in regard to the 

 enzyme of tetanus. 



But their action is limited either by their conversion into 

 zymogens or their localisation to the cells or tissues where their 

 action is required. This is more readily seen in plants than in 

 animals, and one of the best examples of it is that in germinating 

 wheat. 



In the ordinary state of the grain the diastatic ferment is kept 

 apart from the starch by a small layer of cellulose, through 

 which the diastase cannot pass, but during germination 

 another ferment appears which has the power of dissolving 

 cellulose, and by breaking down this dividing membrane it 

 allows the diastatic ferment to act upon the starch, and renders 

 it available for the needs of the growing plant. 



Enzymes appear to differ amongst themselves nearly as much 

 as do albumin, albumoses and peptones. Some are easily 

 separated from the cells in which they exist, whilst others are 

 so closely united to the protoplasm that their separate existence 

 apart from it has been denied. The yeast plant, for example, 

 yields an invert enzyme which can be extracted with comparative 

 ■ease, but the enzyme which splits up sugar into alcohol and car- 

 bonic acid is so firmly attached to the protoplasm of the cell 

 that it is only within the last few months that it has been isolated 

 by Buchner by the application of enormous pressure. It is prob- 

 able that the enzymes contained in the cells of animal tissues 

 differ in like manner, and that by the use of similar methods we 

 may obtain a number of enzymes with which we are at present 

 unacquainted. 



But it is not merely the products formed in the digestive canal, 

 or in the organs of animals during life, nor even the alkaloids 



NO. 1455, VOL. 56] 



that are formed by the higher plants, that act as poisons. The 

 processes of life are much the same in the lowest microbes as in 

 animals, or in the higher plants, and these microbes, by 

 forming ferments and poisons, give rise to disturbance of function 

 or death in animals. When grown in suitable media outside the 

 body they produce enzymes and poisons, albumoses and alkaloids, 

 and many of them continue to do so after their introduction into 

 the body. 



One of the most curious points, both in the chemistry of the 

 higher plants and of microbes, is that they tend to form at the 

 same time a poison and its antidote. In Calabar bean, for ex- 

 ample, we find there are two poisons — physostigmine and cala- 

 barine, the former tending to paralyse the spinal cord and the 

 latter to stimulate it, so that each poison to a certain extent 

 antagonises the other. The same condition is found even more 

 markedly in jaborandi, of which the two alkaloids pilocarpine 

 and jaborine antagonise one another's action so that, although 

 pilocarpine generally greatly predominates, it might be possible 

 to get a specimen of the leaf having no action at all although it 

 contained a quantity of alkaloids. 



When injected into animals the toxins formed by microbes 

 and the venins of serpents cause the production of anti-toxins 

 and anti-venins which neutralise their action apparently by 

 chemical combination in somewhat the same way as an acid and 

 alkali, each poisonous by itself, combine to form a comparatively 

 inert salt. But the two components here, like an organic acid 

 and a mineral base, are unequally affected by destructive 

 agencies, and the anti-venin may be destroyed, so that the venin 

 again regains its activity. 



The conversion of zymogens into enzymes may be compared 

 to the freeing of venins from their compounds, while the con- 

 version of active venins into inert bodies by combination with 

 anti-venins suggest that a similar process may occur in the case 

 of active enzymes, by which they may be converted into inactive 

 zymogens. 



Perhaps the hypothesis I mentioned eight years ago to my 

 pupil and friend, Mr. Hankin, that the germicidal power of 

 organisms is proportional to their power to produce enzymes 

 may not be altogether unfounded, and possibly we may discover 

 also that immunity, natural or acquired, is nothing more than 

 an extension to the cells of the tissues generally of a power 

 which is constantly exercised during digestion by those of the 

 intestine and liver. 



This problem is one which pertains to all three sciences, and 

 has a most important bearing on practical medicine. 



Practical medicine, except when empirical, depends for its 

 advance on physiology, pharmacology, and pathology. A know- 

 ledge of the physiology of digestion has led to the satisfactory 

 treatment of dyspepsia by the administration of digestive 

 enzymes, and pharmacological research has enabled us to treat 

 diseases of the circulation with a success previously undreamt of, 

 by teaching us not only how to use aright old remedies, such as 

 digitalis, but also how to apply new ones, such as strophanthus 

 and amyl nitrite, and even to manufacture others, such as nitro- 

 erythrol, which possess the special actions we desire, but are 

 lacking in the drugs we already have. Indeed new remedies, 

 which shall alter tissue change, lower temperature, relieve pain, 

 and procure sleep, are now being made in such numbers that it 

 is hard to keep count of them. 



But amongst all the new gains of practical medicine none are 

 so remarkable as those which we owe to pathology. Tinie 

 would fail me to speak of the prevention and cure of zymotic 

 diseases, but no less astonishing is the discovery that myxoedema 

 depends on inactivity or absence of the thyroid gland, and can 

 be cured by the administration of its extract, which seems to act 

 as an enzyme on living tissues, so that the heavy, shapeless 

 features of the patient resume their natural expression, and the 

 sluggish mental processes become quickened. An exhaustive 

 I study of enzymes and their products appears to be the most 

 i promising way of advancing our knowledge both of the nature 

 and treatment of disease. Probably more is to be hoped for 

 i from an investigation into the nature and properties of those 

 enzymes which are intimately associated with the protoplasm 

 of the cells in the various tissues and organs than even of those 

 which are poured into the blood by glands having an internal 

 secretion, such as the thyroid. For all organs, even those which 

 like muscles and nerves are not glandular, have an action on 

 the blood comparable to that of the yeast plant, which modifies 

 the fluid in which it lives by the substances which it removes 

 from or adds to it. It is to a knowledge of the processes which 



