330 



NATURE 



[August 6, 1891 



the organs which ^sop describes in his fables actually occurs 

 between the cells in some vertebrate animals, and the schism 

 predicted by St. Paul as the result of such a fight actually takes 

 place. For in the tadpole, at one stage of its existence some of 

 the cells at the base of the tail begin to eat up others, with the 

 result that schism occurs and the tail falls off. 



Phagocytosis. — This struggle for existence between the cells 

 of an organism and microbes has been beautifully shown by 

 Metschnikoff in the Daphne or water flea, where the process 

 of the cells eating up the microbes or the microbes destroying 

 the cells can be actually observed under the microscope. 

 This process of phagocytosis is now regarded by many as only 

 a small part of the struggle between an organism and a 

 microbe, but it is impossible to see one part of a microbe half 

 digested by the cell in which it is embedded, while the 

 part outside remains unaltered, without believing that the 

 process is one of great importance. At the same time, it 

 seems that the process of phagocytosis, where the microbe 

 and the cells meet in close conflict, bears about the same re- 

 lationship to the total struggle that a bayonet charge bears to 

 a modern battle. The main part of the fight is really carried 

 on at some distance by deadly weapons — by bullets in the case 

 of the soldier, and by ferments, poisonous albumoses, and 

 alkaloids on the part of the cells and the microbes In some 

 of Metschnikoff"s observations we can almost see this process, 

 for he has figured leucocytes dead, and apparently burst by the 

 action of conidia, lying close to but yet outside them, as if these 

 conidia, 1 ke the dragons of fable, had spit out some venom 

 which had destroyed them. 



Venom of Microbes. — Within the last few years attention has 

 been gradually becoming directed less to microscopical ex- 

 amination of the microbes themselves and more to chemical 

 investigation of the ferments and poisons which they produce ; 

 yet, strangely enough, the very moment when chemistry is 

 becoming more important than ever has been chosen to mini- 

 mize the teaching of it in medical schools, and examination in 

 it by licensing bodies. It is now possible to separate the albu- 

 moses and poisons from the microbes which produce them either 

 by filtration, or by destroying the microbes by graduated heat ; 

 for, as a rule, they are destroyed by a lower temperature than 

 the albumose or poisons which they form. 



Microbes and Enzymes. — As the albumoses produced by 

 microbes are nearly allied, chemically and physiologically, to 

 those formed in the alimentary canal of the higher animals by 

 digestive ferments, it is natural to suppose that microbes, like 

 the higher animals, split up proteids, starches, and sugars by 

 enzymes, which they secrete, and which in both cases may be 

 obtained apart from the living organisms which produce them ; 

 that, in fact, we should be able to isolate from microbes bodies 

 which correspond to pepsin or trypsin, just as we can isolate 

 these from the stomach or pancreas of an animal. In some, 

 although not in all cases, this attempt has succeeded.^ 



Poisonous Albumoses. — The albumoses produced by microbes 

 resemble those formed during normal digestion in being poison- 

 ous when injected directly into the circulation, although they 

 may not be so greatly absorbed from the intestinal canal. One 

 of the most remarkable discoveries in regard to albuminous 

 bodies is the fact that some of them which are perfectly innocuous, 

 and, indeed, probably advantageous to the organism in their 

 own place, become most deadly poisons when they get out of 

 it. Thus, the thyroid and thymus glands, which are perfectly 

 harmless and probably useful, were found by Wooldridge, when 

 broken up in water, to yield a proteid which instantaneously 

 coagulated the blood if injected into a vein, so that the animal 

 died as if struck by lightning ; while Schmidt- Miihlheim, under 

 Ludwig's direction, found that peptones had an exactly opposite 

 effect, and prevented coagulation altogether. 



Neutralization of Poisonous Albumoses. — Perhaps the analogy 

 is too vague, but we seem to find here something very like 

 Pasteur's two kinds of tartaric acid, one rotating polarized light 

 to the right, the other to the left ; but, when united together, 

 having no action at all, for here we have two bodies, one of 

 which destroys coagulability entirely, the other increases it 

 enormously ; while many albuminous bodies have no action 

 upon coagulation whatever. This view would lead us to sup- 

 pose that one form of albumose may neutralize the action of 

 another, thus rendering them both completely innocuous, whilst 



— I Vide Brunton and Macfayden, Croonian Lectures on " Chemical Struc- 

 ture and Physiological Action," British Medical Journal, June 15, 1889, 

 p. 1336. 



NO. II 36, VOL. 44] 



either one or other alone might be a deadly poison. The 

 albumoses formed by microbes appear frequently, if not always, 

 to have a double action, destructive and protective, on the higher 

 animals. Pasteur's treatment of hydrophobia is based on the 

 idea that the spinal cord of rabid animals contains a virus, and 

 its antidote — Koch's tuberculin — may be similar in this respect, 

 and may yet, by suitable alterations, fulfil the hopes of its able 

 and single-minded discoverer. 



Zymogens and Enzymes. — Perhaps a similar process of split- 

 ting up and recombination may explain the formation and 

 disappearance of the enzymes, such as pepsin and trypsin, 

 by which digestion is carried on. The pancreas of a fasting 

 animal will not digest albuminous bodies like fihrin, while 

 the pancreas of an animal killed during full digestion will do 

 so rapidly. Yet the fasting pancreas contains the zymogen, 

 or mother substance, which yields the digestive ferment, and, 

 as Kiihne has shown, by treating it first with acid and then 

 with alkali, it becomes active. Again, to recur to the analogy 

 of Pasteur's tartaric acid, we seem to find that the inactive, 

 and possibly symmetrical, albuminous substance of the fast- 

 ing pancreas is split up by this treatment after death or 

 during the process of digestion in life, and yields the lopsided 

 and active pancreatic ferment. But, if this be so, what be- 

 comes of the other half which has been split off? We do not 

 at present know, but curiously enough Lepme has lately 

 shown that while the pancreas is pouring into the digestive 

 canal a ferment which will form sugar, it is at the same time 

 pouring into the circulation another ferment which will 

 destroy sugar. 



Immunity. — We must be very careful in our speculations, 

 and test them by experiment, but such observations as these 

 may tend to throw some light upon the nature of immunity. 

 Immunity is probably a very complex condition, and is not 

 dependent altogether upon any single factor, but we can now 

 understand that if a microbe has gained an entrance into an 

 organism, and produces a proteid or an albumose poisonous 

 to the organism which it enters, it may grow, thrive, and 

 destroy that organism, while the injection of some other pro- 

 teid which would neutralize the poison might save the animal 

 while the microbe would perish. 



Cure of Anthrax. — Thus Hankin has found that, while a 

 mouse inoculated with anthrax will die within twenty-four 

 hours, a rat resists the poison altogether ; but if the mouse 

 after being inoculated whh the disease has a few drops of 

 rat's serum injected into it, instead of dying, as it would other- 

 wise certainly do, it survives just like the rat, and from the 

 spleen of the rat Hankin has isolated a proteid which has a 

 similar protective action to that of the serum. 



Cure for Tubercle. — Working on similar lines, Bernheim and 

 Lepine used the injection of goat's blood in phthisis so as to 

 stop, if possible, the progress of tubercle, and Richet has used 

 the serum of dog's blood, for the goat is quite immune, 

 and the dog is to a great extent, though not entirely, im- 

 mune from attacks of tuberculosis. The injection of goat's 

 blood in somewhat large quantities has been given up, while 

 dog's and goat's serum in small quantities of 15 to 20 minims 

 at intervals of several days is still under trial. 



Action of Blisters. — But if immunity can be insured by such 

 slight changes in the organism as a few drops of serum from 

 a rat will produce in the body of a mouse, it is natural to 

 suppose that a similar change might possibly be effected by 

 removing the albuminous substance from one part of the 

 body, and introducing it, perhaps after it has undergone slight 

 change, into another. As I have already mentioned, the 

 albumoses of ordinary digestion are poisonous when they are 

 injected into the circulation, and s 1 are the proteid sub- 

 stances obtained from the thyroid and thymus glands. Why, 

 then, may not the serum of one's own blood, withdrawn from 

 the vessels by a blister and reabsorbed again, not be as 

 good as the serum obtained from the blood of an animal ? . . . 



Bleeding. — It is quite possible, too, that the good effects of 

 bleeding may be due to a similar cause. . 



Speculation and Expcri7?ient. — The human body is a most 

 complex piece of mechanism. We learn its action bit by bit 

 very slowly indeed, and we are only too apt to regard the little 

 piece which attracts attention at the moment as all-important 

 and to leave the other parts out of sight. But this is not 

 true of our study of the body only, for the same tendency 

 manifests itself in the pursuit of knowledge of all kinds, yet 

 it is in medicine more especially that this tendency comes to 



