August 6, 1891] 



NA TURE 



329 



would make his fortune. Amongst others, Perkins tried to do 

 this, and, although he failed, yet in the attempt he discovered 

 the anilin dyes, whose staining powers have not only helped 

 us so much in ordinary histological research, but have made it 

 possible to distinguish disease germs which without them would 

 have been invisible. But the discovery of the anilin colours 

 was only one outcome of the attempt to make quinine syntheti- 

 cally, for the impulse which it gave to the study of aromatic 

 compounds has led to the production of salicylic acid and 

 acetanilide, antipyrin, phenacetin, and all the other antipyretic 

 remedies whose number is probably legion, and whose names 

 already have become so numerous as to be troublesome. Here 

 we see good has arisen out of evil ; for if the price of quinine 

 had not been so high, the researches which have proved so useful 

 might not have been begun even yet. 



Small and Great, Foolish and Wise. — In looking at another of 

 the greatest advances which medicine has made — namely, the 

 knowledge of infective disease — we can see how enormous re- 

 sults can arise out of very small beginnings, and the safety of 

 nations may be consequent upon a research which many men 

 would have termed useless or even frivolous. I can hardly 

 fancy any better illustration of St. Paul's observation about 

 the foolish things of this world confounding the wise than 

 Pasteur's researches on tartaric acid ; for what could seem 

 more foolish to the so-called practical man than the question, 

 "Why does a crystal of tartaric acid sometimes take one 

 shape and sometimes another ? " Yet from an attempt to 

 answer this question has arisen the whole of Pasteur's work 

 on fermentation in general, and on that of wine, beer, and 

 vinegar in particular, whereby he has been able to save millions 

 to his country by accelerating the production of vinegar and pre- 

 venting the souring of wine and beer. His observation that 

 tartaric acid sometimes turned the ray of polarization to the 

 right, sometimes to the left; that, indeed, there were two 

 crystals apparently alike, but really different ; and that these 

 could be combined so as to form a symmetrical crystal having 

 no power of rotation, led him to look to life and living beings 

 as the source of asymmetry. He tried to produce this asym- 

 metry in saJis of tartaric acid by fermentation, and found that 

 during the process an organism developed which eats up the 

 dextro-tartaric acid, and leaves the Isevo-tartaric acid behind. 

 This led him to investigate such minute organisms, and, by 

 simplifying the s^il in which they grew, and separating the 

 organisms one from another, he learned the conditions of their 

 growth, and showed that most processes of fermentation were 

 due to the presence of living organisms. It is true that while 

 Pasteur was still a lioy at school, Peyen and Persoz had shown 

 that the liquefacticm of starch and its conversion into sugar was 

 due to diastase, and that Dumas in a report on a paper by 

 Guerin-Varry had pointed out that, although unlike diastase, 

 the active principle of the gastric juice had not been isolated, it 

 was probably a ferment of a somewhat similar kind. Dumas 

 classed yeast as a ferment along with diastase, and the fact that 

 such a process as conversion of starch into sugar could be effected 

 without a living organism naturally repdered it all the more 

 difficult for Pasteur to prove his thesis that most fermentations 

 were due to living organisms. 



Chemical and Biological Views of Fermentation. — The two 

 views of the action of ferments — namely, the chemical and the 

 biological — may, I think, fitly be likened to Pasteur's two kinds 

 of tartaric acid, each by itself being lopsided and incomplete, 

 forming a symmetrical whole only when united. There can be 

 no doubt of the truth of the chemical view that diastase is not a 

 living organism, and yet converts starch into sugar. There can 

 be as little doubt of the biological view that yeast and other 

 organisms which cause fermentation are living bodies, and that 

 without the presence of these living bodies alcoholic, acetic, and 

 other forms of fermentation would not exist. 



Microbes and Enzymes. — But recently we have come to re- 

 cognize that these living organisms may produce their effect 

 by manufacturing chemical ferments, and that these ferments 

 may occasionally do the work, although the organisms which 

 form -them may be absent. It is quite true that it is difficult 

 — perhaps impossible — to get fermentation from the dead 

 yeast plant, but we may find a parallel for this in the fact 

 that the pancreas of the higher animals sometimes yields an 

 active ferment and sometimes not. Nor need we wonder that 

 the ferments produced by microbes have but a slight action com- 

 pared with those of the microbes themselves, if we remember 

 how very little power of digestion a dead pig's stomach has as 



NO. I 136, VOL. 44] 



compared with the amount which can be digested not by the live 

 animal itself only, but by the herds of swine consisting of its 

 " fathers and mothers, its brothers and sisters, its cousins and 

 its aunts," during all the term of their natural lives ; for in the 

 process of fermentation microbes are growing, fermenting, and 

 dying with great rapidity, and many generations occur in a 

 fermenting fluid in the space of a few hours, so that the total 

 effect they produce will be out of all proportion to any which 

 can be got from the microbes themselves at a single instant. 



Microbes and Disease. — From organisms as a cause of fer- 

 mentation and of the diseases of wine and beer, Pasteur went 

 on to investigate their action as causes of disease in living beings 

 —first in the silkworm, next in the lower animals, and, lastly, 

 in man. He established the dependence of the silkworm disease 

 and of anthrax upon the presence of specific microbes which 

 could be transmitted and communicate the disease, and by 

 destroying the infected eggs of the silkworm he eradicated the 

 disease and restored the silk industry to France. 



Weakening of Disease Germs. — V,\iX while this investigation is 

 interesting to us as illustrating the probable cause of the dis- 

 appearance of typhus fever, to which I have already alluded, 

 Pasteur's researches on anthrax are still more important as 

 bearing upon the question of protective inoculation ; for he 

 found that the disease germ could be cultivated outside the living 

 body and grown in flasks under varying conditions, some of 

 which were favourable and others unfavourable to its growth. 

 High temperature enfeebled the virus, so that it no longer killed 

 an animal with the same certainty, and by inoculating first with 

 a weak virus and then with one successively stronger and stronger, 

 he found that animals could be completely protected either from 

 inoculation by the strongest virus or by infection from other 

 animals suffering from the actual disease. 



Jficrease in Virulence of Disease Germs. — Another extra- 

 ordinary fact which he made out was that the virus thus weak- 

 ened, so that it will not kill a guinea-pig a year old, and still less 

 a sheep or ox, may again be rendered most potent by inoculating 

 a feeble animal, such as a guinea-pig a day or two old, from 

 this older and stronger guinea-pig's, the strength of the disease 

 germs increasing with every inoculation, until finally sheep and 

 cows may be killed by it. We can thus see how an epidemic of 

 disease beginning sporadically, and attacking weak individuals, 

 may gradually acquire such strength as to attack and carry ofi 

 the strongest. 



Pure Cultures. — Pasteur's plan of growing disease germs out- 

 side the body in broth, although of the utmost value, did not 

 allow a convenient separation of different germs ; but this can 

 now readily be done by Koch's plan of sowing them, not in a 

 liquid medium, but on solid gelatine spread on glass plates, so 

 that the growth of the germs can be daily watched under the 

 microscope, and inoculations made from single colonies on other 

 plates until pure cultures have been obtained. By thus isolating 

 the different microbes, we learn their life-history, the mode in 

 which their growth is influenced by differences of soil, of tem- 

 perature, of moisture, by the addition of various substances 

 which either favour or retard their growth, and, last but not 

 least, the effect which one microbe has upon another when they 

 are grown together at the same time. 



Struggle for Existence amongst Microbes.— Yox even amongst 

 these minute organisms the struggle for existence and the 

 survival of the fittest exists, like that which Darwin pointed out 

 so clearly in the case of higher plants and animals. • • • 



Struggle for Existence between Microbes and the Organism. — 

 But it is not merely between different species of microbes 

 or different cells in' an organism that this struggle occurs. 

 It takes place also between the disease germs and the cells 

 of the organism which they invade, and the result of the 

 struggle may be determined, not by some powerful agency 

 which weakens or destroys either the organism or the mi- 

 crobe, but by some little thing which simply inclines the 

 scale in favour of one or the other. Thus, in the potato 

 disease, the victory of the invading miciobe and the destruc- 

 tion of the potato, or the death of the microbe and the health 

 of the tuber, may depend upon some condition of moisture or 

 possibly of electrical change in the atmosphere which aids the 

 growth of the microbe disproportionately to that of the potato. 

 These atmospheric conditions need not necessarily be antagonistic 

 to the potato, they may even in themselves be advantageous to 

 it ; but if they help the microbe more than the plant, the microbe 

 will gain the victory and the plant be destroyed. 



Fii;ht bei-iveen Cells in Higher Organisms.— The fight between 



