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TRANSLATION OF AN

AddressON

THE GERM THEORY.Delivered at the Meeting of the InternationalMedical Congress,

BY PROFESSOR PASTEUR.

GENTLEMEN,-I had no intention of addressing this:admirable Congress, which brings together the most eminentmedical men in the world, and the great success of which doesso much credit to its principal organiser, Mr. Mac Cormac.The goodwill of your esteemed President has decided other-wise. How could one, in fact, resist the sympathetic wordsof that eminent man whose goodness of heart is associatedin no small degree with great oratorical ability? Twomotives have brought me to London. The first was to

gain instruction, to profit by your learned discussions; andthe second was to ascertain the place now occupied inmedicine and surgery by the germ theory. Certainly Ishall return to Paris well satisfied. During the past weekI have learned much. I carry away with me the convictionthat the English people are a great people, and as forthe influence of the new doctrine, I have been not onlystruck by the progress it has made, but by its triumph.I should be guilty of ingratitude and of false modesty if Idid not accept the welcome I have received among youand in English society as a mark of homage paid to mylabours during the past five-and-twenty years upon thenature of ferments-their life and their nutrition, theirpreparation in a pure state by the introduction of organisms(ensemencement) under natural and artificial conditions-labours which have established the principles and the methods- of microbie (microbism), if the expression is allowable.Your cordial welcome has revived within me the lively feel-ing of satisfaction I experienced when your great surgeonLister declarel that my publication in 1857 on milk fermen-tation had inspired him with his first ideas on his valuablesurgical method. You have reawakened the pleasure I feltwhen our eminent physician Dr. Davaine declared that hislabours upon charbon (splenic fever or malignant pustule)had been suggested by my studies on butyric fermentationand the vibrion which is characteristic of it. Gentlemen, Iam happy to be able to thank you by bringing to yournotice a new advance in the study of microbie as applied tothe prevention of transmissible diseases-diseases which forthe most part are fraught with terrible consequences, bothfor man and domestic animals. The subject of my com-munication is vaccination in relation to chicken cholera andsplenic fever, and a statement of the method by which wehave arrived at these results-a method the fruitfulness ofwhich inspires me with boundless anticipations. Before- discussing the question of splenic fever vaccine, which is themost important, permit me to recall the results of my in-vestigations of chicken cholera. It is through this inquirythat new and highly important principles have been intro-duced into science concerning the virus or contagiousquality of transmissible diseases. More than once in whatI am about to say I shall employ the expression virus-culture,as formerly, in my investigations on fermentation, I used theexpressions, the culture of milk ferment, the culture of thebutyric vibrion, &c. Let us take, then, a fowl which is aboutto die of chicken cholera, and let us dip the end of a delicateglass rod in the blood of the fowl with the usual precautions,upon which I need not here dwell. Let us then touch withthis chaged point some bouillon de paule, very clear, but firstof all rendered sterile under a temperature of about 115°Centigrade, and under conditions in which neither the outerair nor the vases employed can introduce exterior germs-those germs which are in the air, or on the surface of allobjects. In a short time, if the little culture vase is placedin a temperature of 25° to 35°, you will see the liquidbecome turbid, and full of tiny microbes, shaped like thefigure 8, but often so small that under a high magnifyingpower they appear like points. Take from this vase a dropas small as you please, no more than can be carried on thepoint of a glass rod as sharp as a needle, and touch with

this point a fresh quantity of sterilised bouillon de poule,placed in a second vase, and the same phenomenon is pro-duced. You deal in the same way with a third culture vase,with a fourth, and so on to a hundred, or even a thousand,and invariably within a few hours the culture liquid be-comes turbid and filled with the same minute organisms.At the end of two or three days’ exposure to a temperatureof about 30° C. the thickness of the liquid disappears,and a sediment is formed at the bottom of the vase. Thissignifies that the development of the minute organism hasceased-in other words, all the little points which caused theturbid appearance of the liquid have fallen to the bottom ofthe vase, and things will remain in this condition for alonger or shorter time, for months even, without either theliquid or the deposit undergoing any visible modification, in-asmuch as we have taken care to exclude the germs of theatmosphere. A little stopper of cotton sifts the air whichenters or issues from the vase through changes of tempera-ture. Let us take one of our series of culture preparations-the hundredth or the thousandth, for instance-and com-pare it in respect to its virulence with the blood of a fowlwhich has died of cholera; in other words, let us inoculateunder the skin ten fowls, for instance, each separately witha tiny drop of infectious blood, and ten others with a similarquantity of the liquid in which the deposit has first beenshaken up. Strange to say, the latter ten fowls will die as

quickly and with the same symptoms as the former ten; theblood of all will be found to contain after death the sameminute infectious organisms. This equality, so to speak, inthe virulence both of the culture preparation and of theblood is due to an apparently futile circumstance. I havemade a hundred culture preparations-at least, I haveunderstood that this was done-without leaving any con-siderable interval between the impregnations. Well, herewe have the cause of the equality in the virulence. Let usnow repeat exactly our successive cultures with this singledifference, that we pass from one culture, to that whichfollows it-from the hundredth to, say, the hundred andfirst, at intervals of a fortnight, a month, two months, threemonths, or ten months. If, now, we compare the virulenceof the successive cultures, a great change will be observed.It will be readily seen from an inoculation of a series of tenfowls that the virulence of one culture differs from that ofthe blood and from that of a preceding culture when asufficiently long interval elapses between the impregnationof one culture with the microbe of the preceding. Morethan that, we may recognise by this mode of observationthat it is possible to prepare cultures of varying degrees ofvirulence. One preparation will kill eight fowls out of ten,another five out of ten, another one out of ten, another noneat all, although the microbe may still be cultivated. Infact, what is no less strange, if you take each of thesecultures of attenuated virulence as a point of departure inthe preparation of successive cultures and without appre-ciable interval in the impregnation, the whole series of thesecultures will reproduce the attenuated virulence of thatwhich has served as the starting point. Similarly, wherethe virulence is null it produces no effect. How, then, itmay be asked, are the effects of these attenuating virulencesrevealed in the fowls ? They are revealed by a local dis-order, by a morbid modification more or less profound in amuscle, if it is a muscle which has been inoculated with thevirus. The muscle is filled with microbes which are easilyrecognised because the attenuated microbes have almost thebulk, the form, and the appearance of the most virulentmicrobes. But why is not the local disorder followed bydeath? For the moment let us answer by a statement offacts. They are these : the local disorder ceases of itselfmore or less speedily, the microbe is absorbed and digested,if one may say so, and little by little the muscle regains itsnormal condition. Then the disease has disappeared. Whenwe inoculate with the microbe the virulence of which is nullthere is not even local disorder, the naturae meclicatrixcarries it off at once, and here, indeed, we see the influenceof the resistance of life, since this microbe, the virulence ofwhich is null, multiplies itself. A little further, and wetouch the principle of vaccination. When the fowls havebeen rendered sufficiently ill by the attenuated virus whichthe vital resistance has arrested in its development, theywill, when inoculated with virulent virus, suffer no evileffects, or only effects of a passing character. In fact, theyno longer die from the mortal virus, and for a time suflicientlylong, which in some cases may exceed a year, chickencholera cannot touch them, especially under the ordinary

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conditions of contagion which exist in fowl-houses. At thiscritical point of our manipulation-that is to say, in thisinterval of time which we have placed between two cultures,and which causes the attenuation-what occurs? I shallshow you that in this interval the agent which intervenes isthe oxygen of the air. Nothing more easily admits of proof.Let us produce a culture in a tube containing very little air,and close this tube with an enameller’s lamp. The microbe indeveloping itself will speedily take all the oxygen of the tubeand of the liquid, after which it will be quite free from contactwith oxygen. In this case it does not appear that themicrobe becomes appreciably attenuated, even after a greatlapse of time. The oxygen of the air, then, would seem tobe a possible modifying agent of the virulence of the microbeof chicken cholera-that is to say, it may modify more orless the facility of its development in the body of animals.May we not be here in presence of a general law applicableto all kinds of virus? What benefits may not be the result?We may hope to discover in this way the vaccine of allvirulent diseases; and what is more natural than to beginour investigation of the vaccine of what we in French callcharbon, what you in England call splenic fever, and whatin Russia is known as the Siberian pest, and in Germany asthe Milzbrand. In this new investigation I have had theassistance of two devoted young savants—MM. Chamberlandand Roux. At the outset we were met by a difficulty.Among the inferior organisms, all do not resolve themselvesinto those corpuscle germs which I was the first to pointout as one of the forms of their possible development.Many infectious microbes do not resolve themselves in theircultures into corpuscle germs. Such is equally the casewith beer yeast, which we do not see develop itselfusually in breweries, for instance, except by a sortof scissiparity. One cell makes two or more, whichform themselves in wreaths ; the cells become detached,and the process recommences. In these cells real

germs are not usually seen. The microbe of chicken choleraand many others behave in this way, so much so that thecultures of this microbe, although they may last for monthswithout losing their power of fresh cultivation, perishfinally like beer yeast which has exhausted all its aliments.The anthracoid microbe in artificial cultures behaves verydifferently. In the blood of animals, as in cultures, it isfound in translucid filaments more or less segmented. Thisblood or these cultures freely exposed to air, instead of con-tinuing according to the first mode of generation, show atthe end of forty-eight hours corpuscle germs distributed inseries more or less regular along the filaments. All aroundthese corpuscles matter is absorbed, as I have represented itformerly in one of the plates of my work on the diseases ofsilkworms. Little by little all connexion between themdisappears, and presently they are reduced to nothing morethan germ dust. If you make these corpuscles germinate,the new culture reproduces the virulence peculiar to thethready form which has produced these corpuscles, andthis result is seen even after a long exposure of these germsto contact with air. Recently we discovered them in pitsin which animals dead of splenic fever had been buried fortwelve years, and their culture was as virulent as that fromthe blood of an animal recently dead. Here I regret ex-tremely to be obliged to shorten my remarks. I should havehad much pleasure in demonstrating that the anthracoidgerms in the earth of pits in which animals have been buriedare brought to the surface by earthworms, and that in thisfact we may find the whole etiology of disease, inasmuch asthe animals swallow these germs with their food. A greatdifficulty presents itself when we attempt to apply ourmethod of attenuation by the oxygen of the air to theanthracoid microbes. The virulence establishing itselfvery quickly, often after four-and-twenty hours in an ianthracoid germ which escapes the action of the air, it was Iimpossible to think of discovering the vaccine of splenicfever in the conditions which had yielded that of chicken Icholera. But was there, after all, reason to be discouraged ?Certainly not; in fact, if you observe closely, you will findthat there is no real difference between the mode of the gene-ration of the anthracoid germ by scission and that of chickencholera. We had therefore reason to hope that we mightovercome the difficulty which stopped us by endeavouring toprevent the anthracoid microbe from producing corpusclegerms and to keep it in this condition in contact with oxygenfor days, and weeks, and months. The experiment fortunatelysucceeded. In the ineffective (neutre) bouillon de pottlethe anthracoid microbe is no longer cultivable at 45° C.

Its culture, however, is easy at 42° or 43°, but inthese conditions the microbe yields no spores. Consequentlyit is possible to maintain in contact with the pure air at 42°or 43° a mycélienne culture of bacteria entirely free ofgerms. Then appear the very remarkable results whichfollow. In a month or six weeks the culture dies-that isto say, if one impregnates with it fresh bonillon, the latteris completely sterile. Up till that time life exists in thevase exposed to air and heat. If we examine the virulenceof the culture at the end of two days, four days, six days,eight days, &c., it will be found that long before the deathof the culture the microbe has lost all virulence, althoughstill cultivable. Before this period it is found that theculture presents a series of attenuated virulences. Every-thing is similar to what happens in respect to the microbe inchicken cholera. Besides, each of these conditions ofattenuated virulence may bs reproduced by culture; in fact,since the charbon does not operate a second time (nerécidive pas), each of our attenuated anthracoid microbesconstitutes for the superior microbe a vaccine-that is to say,a virus capable of producing a milder disease. Here,then, we have a method of preparing the vaccine ofsplenic fever. You will see presently the practical im-portance of this result, but what interests us more par-ticularly is to observe that we have here a proof that

we are in possession of a general method of preparingvirus vaccine based upon the action of the oxygen and theair-that is to say, of a cosmic force existing everywhereon the surface of the globe. I regret to be unable fromwant of time to show you that all these attenuatedforms of virus may very easily, by a physiological artifice,be made to recover their original maximum virulence.The method I have just explained of obtaining thevaccine of splenic fever was no sooner made knownthan it was very extensively employed to prevent the splenicaffection. In France we lose every year by splenic feveranimals of the value of 20,000,000f. I was asked to give apublic demonstration of the results already mentioned.This experiment I may relate in a few words, Fifty sheepwere placed at my disposition, of which twenty-five werevaccinated. A fortnight afterwards the fifty sheep wereinoculated with the most virulent anthracoid microbe. Thetwenty-five vaccinated sheep resisted the infection ; thetwenty-five unvaccinated died of splenic fever within fiftyhours. Since that time my energies have been taxed tomeet the demands of farmers for supplies of this vaccine.In the space of fifteen days we have vaccinated in the de-partments surrounding Paris more than 20,000 sheep and alarge number of cattle and horses. If I were not pressedfor time I should bring to your notice two other kinds ofvirus attenuated by similar means. These experiments willbe communicated by-and-by to the public. I cannot con-clude, gentlemen, without expressing the great pleasure Ifeel at the thought that it is as a member of an internationalmedical congress assembled in England that I make knownthe most recent results of vaccination upon a disease more

terrible, perhaps, for domestic animals than small-pox is forman. I have given to vaccination an extension whichscience, I hope, will accept as a homage paid to the meritand to the immense services rendered by one of the greatestmen of England, Jenner. What a pleasure for me to do,honour to this immortal name in this noble and hospitablecity of London!

General AddressON

THE CONNEXION OF THE BIOLOGICALSCIENCES WITH MEDICINE.

Delivered at the Meeting of the International MedicalCongress.

BY T. H. HUXLEY, LL.D.,SECRETARY TO THE ROYAL SOCIETY, AND VICE-PRESIDENT OF

THE CONGRESS.

THE great body of theoretical and practical knowledgewhich has been accumulated by the labours of some eightygenerations, since the dawn of scientific thought in Europe,has no collective English name to which an objection maynot be raised; and I use the term "medicine " as that which