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t o repeat the above examinatioue this year, and to examine these other varieties. The practical results of the above iilveatigations are, that for the production of either syrup or sugar from the sorghums, the cane shoulJ be worked when fully ripe, as evidenced by the seeds having become hard and dry, the lower blades of the stalks drying and falling away, and the appearance of off-shoots from the upper points of the stalks. A t this period, not only is the total amount of sugars, both sucrose and glucose, a t its maximum, thus giving the largest yield of syrup, but the relative proportions of crystallizable sugar to uncrystallizable, is aldo a t its maximum, thus giving the largest yield of sugar.
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~ . - O X VIBIJLEXT DISEASES, AND ESPECIALLY O X T H E DISEASE COMMONLYCALLEDCHICKENCHOLERA. BY M. PASTEUR. Translated from the Comjtrr R m d w d e I’Aco&mir des Sciences, of Feb. Qth, 1880, page by 1’. CASAMAJOR.
039,
Virulent diseases may be ranked among the greatest of the evils that afflict living beings. To prove this, we have merely to name measles, Rcarlatina, variola, s y p h i h , glanders, the carbuncular disease, yellow fever, typhus and the cattle plague. This list is far from being complete ; the pathology of the most important diseases may find a place here. When the ideas of Liebig on the nature of fermente, were in vogue, each virus was considered as a substance undergoing an internal change, which could be communicated to living organisms, turning the constituents of these into a virus of the same nature. Liebig was well aware that the first apparition of ferments, their mull iplication and their power of decomposition, present the greatest analogies with the phenomena of life, but, in the introduction to his Organic Chemistry, he tells us that these analogies may be considered as deceitful illusions. All the experiments which I have communicated t o this Academy for the last twenty-three years, have demonstrated, either directly or indirectly, the inaccuracy of the opinions of Liebig. A single method has guided me in the study of microscopic organisms. This method has been essentially the cultivation of these minute beings in a pure state, that is: by eliminating the heterogenous substances, living or dead, which accompany them. By the use of this method, the most difficult questions are often solved in the easiest and most
decisive manner. I will here recall one of t h e first applications wliich I made of this method ( 1 8 5 i - l S j P j . E'erments, according to Liehig, :Ire tlie nitrogenous substances o f orgariistiis, sticli as tibrine, alburneti, casein, $c., in a state of deconiposition, rcsiilting f r o m contact tvith air. There was 1 1 0 ferrrient'itioii k i i ~ \ v n ,i n which these nitrogenous substanccs were not [JrcseIIt ani1 active. Onc cliaracter of ferrnent:itioris, as well :ts of tliscwes, was tliwt they r n c ~ sporitaiicu~is t ~ i n tlicir origin arid dcvelopn~c~rit.111 order tu sliotv t1i:it the Iiyputliesis of rile 1c:irned German chemiet was, t o use his o w n wurds, '' but a deceitful illusion," 1 made up artificial inistiires who2se only constituents w t w as follows: water, the ixiinetxl cc~iistitiierits essential tu life, fcrriientable substances, and tht> germs of' t l i e ferrnerits which act o i i these suhst:qnc:cs. W i t h these ~nistiircs,ferrneiitation took ~ ) I : t c . ttvitli ~ a regulurity mid a purity, i f I mpy us? tlie word, which art' tiever found i n the spontaneous fermentation (Jf natnre. LIS evcry albliniinoit~ substaticr 113d heen exclutlecl f i - o n i these ~nixtnrt~s, thc. fernient appeared as a living being, t~-Iiichborrowed from the frrmental~lesubstancc all the carbon of its successi\e,getieratioris, arid, from tlie mitiern1 constituents, tlie nitrogen, phosphorus, potassium, n1agriesiiirii--1~leirrents, tlic assimilation of which is an indispensable contlition to the furination of all living beings, l x they great or sniall. After these experiments, not only was the theory of' Liebig left without any foundation, but the plienoineria of Eertneritation presented theinselves as simple plienorneiia of nutrition, taking place in except,ioriiil conditions, the niost extraordinary of which is thc possible a1)senc~eof any contact with xir. 1 Iuni:i1i, :is well :is veterinary, medicine niacle uRe of the light which shone f r o m these new results. Many investigators macle experiinents to Jiscwver if ever)- virus or contagion was not an nnirnated I)eitig. Lh. Davaine, i n l ~ t j : )endeavored , t o show the functions of t h e Irclctwitlitr of c~:irl)uricrilardisease, which lie had discovered in 1850. Iri 1868, I h . C1i:iiive;~utried t o show tlint virulencc was due to the solid particles previously noticed. i n every virus. Dr. Klebs, in 1872, attributed traumatic virus t o microscopic orgaliisrns. In l H i O , Dr. Kock obtained, by artificial cultivation, the germs of bucteritliw, which were similar in evcry respect to those which I had pointed out i i i u / h * i m (1865-187~), and the citusc's of several other diseases were ascribed t o microscopic organisms. To-day those who are ruost opposed to the theory of germs, are wavering. Still the greatest obscurity prevails OII tlie most important points.
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I n the great majority of virulent diseases, the virus has not as yet been isolated, and still less has it been shown, by artificial cultivation, that it is a living organism, and everything contributes to make us regard these ‘‘ unknown quantities ” of pathology as mysterious morbific causes. The study of the diseases which they cause, presents many extraordinary circumstances, among which the most remarkable is their non-recurrence. Human imagination can hardly venture to present a hypothetical explanation having any experimental foundation. Is it not still more surprising to find that vaccine, a virulent but mild disease, is a preventive, not only of vaccine itself, but of a more scrious disease-the small pox 2 These facts were known from the remotest antiquity. Variolisation and vaccination have been practiced in India from immemorial times, and when Jenner demonstrated the efficacy of vaccination, the common people of the locality in which he practiced medicine, knew that cow-pox was a preservative from variola. Vaccination appears as an isolated fact, but the non-recurrence of virulent diseases appears to be general. The organism does not g o twice through measles, scarletina, typhus, the plague, variola, syphilis, &c.; a t least it may be said chat the immunity persists for a certain time. Although in the presence of such mysteries, it behooves us t o b e humble, I dare t o hope that the Academy will find that the facts which I am about t o have the honor of presenting before it, throw unexpected light on the problems raised by the study of virulent d’iseases. There occurs sometimes in poultry yards a fearful disease, commonly called chicken cholera. The victim overtaken by it, locles its strength, and stumbles about with drooping wings, I t s feathers stand on end, and give it the appearance of a ball ; it seems overcome by drowsiness ; if we open its eyes, it seems to awake from profound sleep, and soon its eyelids close again. Generally death comes after a dumb agony, without the victim even moving from the position it has occupied during the last stages of the disease. I n rare cases, it beats its wings for a few seconda. The internal disorders are of t h e most serious nature. This disease is caused by a microscopic organism which, according t o Tundel’s dictionary, was first suspected b y M. Moritz, a veterinary surgeon in upper Alsatia ; which was drawn more accurately, in 1878, b y M. Peroncito, a veterinary surgeon in Turin ; and which was found again, in 1879, by M. Toussaint, professor at the Veterinary School of Alfort, who demonstrated, by cultivation in neutralized urine, that this organism was the cause of the virulence in the blood.
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VIRULENT DISEASES, ETC.
In the study of ttiicroscopic pprasites, the first, arid most useful, condition to fulfil, is to obtain a liquid ill wl~ichthe infectious organism may be cultivated with ease, and without a n y admixture of other organisms of different species. Seutralized urine, wIiicIi I have used with so inucli success to show that the product obtained by t'he cultivation of the bacteriiliu of Daraine, is ideiitic:il with the virus of carbuncular disease ( 1 s i ; , Pasteur and Jaiibert), does iiot fulfil the double end iu view. But A liqniil ni,trvello:i-;y acla\,tcll t o the life of the germ o f chicken c:lioler;t, is it hrL)th ni,t,Ie fi.uin vliicken's muscles, neutralized with pot sa, ant1 iii:tde sterilc b y :i teiiiperature superior t o ~ U U "C. ( 1 1 ~ to" 115,'). The case \\.ith ~ . h i c i ithe microscopic organism inultiplie?, i n this liquid, seeins prodigious. 111 a few hours, the most limpid broth 1)euoriies turbid, aiitl is tillw.l with an infinite multitude of sniull artirulatioris of extreme-tcrruity,slightly t h i n n e ~i n~ the middle, and wliicli a t first sight Iinvta tliri :qjpea-aiiw of isolated dots. 'l'hese small articulatioiis have n o inotiori of their O W I I , aiitl they certainly belong to a very different group frorti that of uihriox. I imagine that they will be classified some day with other forrns of virus, now unknown, when we cultivate these, as I hope we are on the eve of doing. 1 lie cultivation of this microscopic organism presents some very ititeresting peculiarities. I n my former researches, one of the liquids which I used with the greatest success, was a decoction of beer-yeast i i i water, after filtering it to obtain it perfcc:tly limpid, and after reiidering it sterile by a temperature superior to 100' C. T h e most various microscopic organisms thrive 011 the food presented by this liquid, particularly after being neutralized. F o r instance, the Dwteridiu of carbuncular disease miiltipliev surprisingly in a few hours. It is a strange thing that this liquid is entirely unsuited to the life of the orgaiiisni of chicken cholera, whicli dies in it in less thari forty-eight hours. Is not, this entirely analogous to what happens when a microscopic organism is entirely inocrious towards an animal on which it has beeti i1ioc.ulated ? It remains inoffensive because it does not develop in the body of the animal, and it does not reach t h e organs essential t o life. T h e sterility of the decoction of yeast, with respect t o the microscopic organism of chicken cholera, affords us an excellent criterion for the purity of the cultivation of this organism in chicken broth. If the cultivation be pure, upon transferring it t o a decoction of yeast, no development takes place, and the yeast solution reniainv limpid. If,however, other organisms are present, they are developed, and the r ,
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solution becomes turbid. I will, in the next place, call your attention t o a still more extraordinary pccnliarity of the cultivation of the germ of chicken cholera. T h e inoculation of this organism on Guinea pigR is not so surely fatal as in the case of chickens. In Guinea pigs, particularly in t8he older animals, the only thing that can be observed is a load lesion, at the point of inoculation, which ends in an abcess, of greater or lesser volume. This abcess opens spontaneously and heals, and meanwhile tbe Guinea pig eats his food au usual, and seems t o possess all the characteristics of health. These abcesses last sometimes for several weeks before discharging, being surrounded by a membrane full of creamy pus, in which the microscopic organism exists in infinite numbers, side b y side with the globules of pus. It is the life of the inoculated organisms which causes the abcess, which is as a cloRed vessel, from which we may obtain the organisni without endangering the life of the animal. T h e microscopic organism remains, mixed with p u ~ in , a great state of purity, without losing its vitality. This may be proved by inoculating on chickens a small portion of the contents of the abcess. From the effect of these inoculations, the chickens very soon die, while the Guinea pig, which haR furnished the virus, is entirely cured after a short time. This is an instance of the localized evolution of a niicroscopic organkm, which causes the formation of pus and of a closed abcess, without, a t the same time, causing internal disturbances or the death of the animal on which it exists. I t is, however, always able to cause the death of other species on which i t may be inoculated, and even the death of the animal on which it exists in a closed abcesu, if through some fortuitous circumstances, i t should pass into the blood or into the viscera. Chickens and rabbits, living in company with Guinea pigs, affected with abcesses of this kind, might, all at once, sicken and die, without any great change being observable in the health of the Guinea pigs. This could easily happen if the abcesses of the Guinea pigs discharged a small portion of their contents on the food of the chickens and rabbits. An observer who witnessed these facts, and was ignorant of all the points, might well be astonished t o see chickens and rabbits die in great numbers, without any apparent cause, and he would be apt t o believe in some spontaneous disease. Certainly, he would not suppose that the Guinea pigs were the cause of all the trouble, when he saw them all in good health, and particularly if he knew that the Guinea pigs themselves often suffer from the same disease. Many of the mysteries in the history of contagions will some day be solved in easier ways than the one I have just mentioned. W e may reject
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T'IRVLEXT DIGEABER, ETC.
tbeories which are i n cont,radiction with known facts, bnt we must not reject them solely because some of their applications olude our grasp. T h e combinations of nature are both simpler and more varied than those of human imagination. I may easily convince you of the truth of these statements, if I add that, if a few drops from a cultivation of our microscopic organism, be placed 011 bread or meat given t o chickens, they are sufficient to propagate the evil to their intestines, i n which tlie little organism p r o p a p t e s with siic*h remitrkable rapidity, that the e x c i x ~ m c n t s of chickens so puisonecl C ; L I I S C tlie death of those on whoin they are i n oculatcd. ' l ' l i ~ w facts etiable 11s to understand thc ninnner i n which this fcarful disense develop; i i i poiiltry y;i~"ls. Evidently, the exoremerits of the diseased chickens hitve nioht to do with t h c h contagion. Kothing woriltl be easier than t o prevent the spreacl o f the disease by isolating the chickens for only :i fciv clays ; b y ~vashingthe poultry yard with plenty of water, ai111particularly with water containitig it little sulphriric acid, which kills the perm of' this disease. The c~xcrenieritsshould be carried off to distance. After a f e w days, the chickens t h : ~ tare still alive could be brought together again with perfert safety, hecause this disease is so rapidly fatal that in a short timz all the diseased animals woiild be dead. IC the cultivation o f the infttctious ovganisin in chicken broth is repeirted inany titiles over, I)> passing f r o m one cultivation to the next by sowing an infinitely sinall qwtntity, such as niay he gathered on the point of a neetflz, the vitxlencr~of the germ is not w a k e n e d by the process. This is analogous to the O:~HC with whirh it rnultiplies in the bodies of the C A d Z h w c ~ e . Tliis virulence is so great, that the inoculation of a rniriiitcl fraction of :i drop will c:nuse death i l l two or three days, and most generally i n less than twenty-foiir hor1rs. liaving est.ablished these preliminaries, I now come t o the most important portion of this communication. 12; operating. certain changes i n the process of cultivation, t h e viruleiice of the infectious germ may be much lessened. This is the vital part of the subject. I beg the Academy's permission t o withhold a description of the processes by means of which I determine this diminution of virulence. My object is t o insure independence in m y studies. The diminution of virulence is seen in cultivations by a slower development of the infectious organism, but, in reality, t,he t w o varieties of virus are identical. I n the first or very infectious state,
VIKULENT DISEABRE, ETC.
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the inoculated germ may kill twenty times in twenty. In the milde r state, it may twenty times in twenty give rise to illness, but not t o death. These facts have an importance which is easily understood, a s they allow us t o form an opinion, in this particular disease, of the problem of its recidivation or non-recidivation. If we take forty chickens, and inoculate twenty of them with the very virulent virus, these twenty will die. If we inoculate the other twenty with attenuated virus, these will all be ill, but they will not die. W e let the twenty chickens be entirely cured, and then if we inoculate them with the very infectious virus, they will not die. T h e conclusion from this is evident. The disease is its own preventive. It has the character of virulent diseases, which do not recidivate. Let us not be astonished a t the singularity of this result. All things are not here as new as they appear at first. In one important particular, however, there is a rlovelty which will he pointed out. Before the time of Jenner, who himself practiced this method, as I have already mentioned, there was a practice of inoculating variola t o preserve from variola. I n our day, sheep are inoculated with murrain to preserve them from murrain, and cattle are inoculated with peripneumonia to preserve from this fearful disease. Chicken cholera shows us an immunity of the same kind. I t is an interesting fact, but it does not show any theoretical novelty. There is, however, an important novelty in the preceding observations, a novelty which gives food for reflection on the nature of virus. I t consists in this, that we have here a disease whose virulent cause is a microscopic parasite, which may be cultivated outside of the animal economy. The virus of variola, the virus of vaccine, those of glanders, syphilis, the plague, &e., are unknown in thei;. nature. This new virus is n living organism, and the disease to which it gives rise has one thing in common with virulent diseases, properly so called, a quality heretofore unknown in virulent diseases, caused by microscopic parasites: i t is, that it does not recidivate. The existence of this disease is a connecting link between virulent diseases caused b y a living virus, and other diseases, in the virus of which life has never been recognized. I would not have it believed that the facts present the constancy and mathematical regularity which I have mentioned. 9’0 believe this would be t o ignore the great variability in the constitution of animals, taken at hap hazard from among domestic animals, and also the variability in the manifestations of life in general. The very virulent virus of chicken cholera does not always kill twenty times
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YIKULENT D18EA8E8, ETC.
in twenty. Sometinies this virus only kills eighteen times in twenty, but generally twenty times in twenty. W e may alsoremark that t h e virus, when reduced in virulence, does not save life twenty times in twenty. Sometimes this happens only eighteen times in twenty and even sixteen times in twentj-. Neither is it an ubsolute preservative by one inoculation. W e may more surely prevent recidivation b y two than by qne inoculation. If we compare the results above stated with what is known of vaccine and its relations t o variola, we may nee that the less vigorous organism which does uot cause death, is analogous t o a vaccine, relatively t o the one that kills, for it gives rise t o a disease which may be called mild, a8 it does not cause death, and, at the same time, it preserves from the disease in its most deadly shape. W h a t other condition must this organism fulfil t o be a true vaccine like t h a t of cow-pox ? This condition iq that it ahould he a definite variety, and that we should not be obliged t o prepare it d e )iouo, when we wish to use it. W e find here the same difficulty which presented itself to Jenner. After he had demonstrated that inoculated cow-pox is a preservative against variola, he thought that it was necessary t o start from the cow-pox of a cow. Jenner soon discovered, however, that he could get along without cows, and make vaccine l a s s from one a n n t o another. W e may try t o d o the same by causirig our germ to pass from one cultivation t o another. Under these circunistances, will the germ become actively virulent or will it remain moderately so? Although this may appear very astonishing, I can say that the last supposition is the correct one. The virulence of the germ, in the small number of cultivations which I have attempted, has not increased, and everything seems t o point t o the existence of a true vac~ ~ add that one or two trials favor the idea that t h e cine. 1 I T I even attenuated virus keeps its character of mildness after passing through the bodies of Guinea pigs. W i l l the same thing happen after repeated cultivations and repeated inoculations ? Only by experiments call such a quevtion be answered. At an! rate, we now know of a disease caused by a microscopic parasite, which may be obtained in such a condition, that it does not recidivate, as other diseases caused b y similar parasites. Rloreorer, we have a variety of its virus, which behaves towards it as vaccine towards variola. The Academy may allow me a digression worthy of attention. From what has been said, we can easily obtain chickens affected with the disease called chicken cholera, in which death is not a necessary
V I R U L E N T DISEASES, ETC.
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consequence of the disease. W e may then witness as many cases of cure as we may wish. Now, I d o not believe that experimental surg e r y has ever niet with more curious phenomena than those which are present when the animal returns t o health, after inoculations have been made in the large pectoral muscles. T h e germ of the disease multiplies in the substance of the muscle as it would in a vessel. At t h e same time, the muscle swells, hardens, and becomes bleached at t h e surface and below the surface. I t becomes filled with globules of pus, but does not suppurate. I t s histological elements are easily torn, because the parasitical germ is scattered through them in niimerous pockets, and it feeds on a portion of their substance. I will, later on, exhibit colored figures, showing the disorders caused by the parasitical germ in vase of cure. T h e parasite is gradually arrested in its development and disappears, while a t the same time t h e portion of muscle which has been attacked, unites, hardens and l d g e s itself in a cavity whose surface resembles that of a healthy granulating wound. The portion which has suffered from the disease finally forms a sequestrum, and is SO well isolated in the cavity that holds it, that it may be felt by the finger under the skin, and, hy t h e least iocision, it may be seized with forceps and extracted. T h e small wound left in the skin heals immediately, and the cavity is gradually fllled by the renewed elements of the muscle. I will now place some of these demonstrations before the Academy.
I have now to close by an explanation relating t o the non-recidivation of the disease which occupies our attention. Let us take a chicken thoroughly vaccinated b y one or more previous inoculations o f the enfeebled virus. W h a t will happen if we inoculate the same chicken again ? T h e local lesion will be insignificant, while the first inocwlations, and in particular, the very first, had been the cause of such marked change in the miiscle, that a large sequestrum can be easily felt by the touch. T h e cause of the difference in the effects of these inoculations, is t o be found entirely in a greater relative facility of the development of the germ of the disease at the first inoculations, and, in the last inoculation, in the development being either entirely wanting or very feeble and promptly stopped. T h e consequence of this seems evident, and i t is that the muscle, which has been seriously diseased, has become, even after it has been cured, unfit for the cultivation of the germ of the disease, as if this germ, by a preceding cultivation, had suppressed some principle which life does not bring back, and whose absence prevents the development of the microscopic organism. I have no doubt that this
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ABSTRACTS
:
BL‘LLETIN DE: L A BOCIiTk CHINIQUE DE I’AKIS.
explanation, to which we are led b s palpable facts iii this case, will be found to bc generally applicable to all virulent diseases. I t must appear siiperflaous t o 1)oint out the priricipal con~eqiiences of the facts which I hnvc had the honor to 1)rehent 1)efoi.e this Acadern). Tlicve are, I i o c~\ w, two o f tliew M hicli n i a ~lw rnentioried. One is, that we niay hope t o otitain aititicial ciiltivaticm of e\ ery virus, aritl tlie other is, tlie idea of olitaiiiing baeciiieb uf the \ irulrnt diseases which afflict humanity, aiici which are the greateht iilagiie of agriculture, ill the 1)rceding of doniestic aiiirrials. It i3 R d u t y and n pleasiire for rne 1 0 add, that 111 these delicate and lengthened researelies, I have Letli ‘i ted with great zeal aiid iiitelligeiict~by llfesvrn Chaniberlantl : ~ t i c l Kour.
Abstracts from American and Foreign Journals.
Bulletin de la Societe Chirnique de Paris. Abstractor. E H S BAILEY,PH B
Various Thermochemical Data, EERTHELOT (32,385).-Fron1 his recently published work, the author gives various data, the result of careful experiments, in regard to the heat of formation of cyanogen, of diainylene in the gaseous state, and the heat of fusion of glycerine, and its specific heat. O n tlhe Elimination of’ Bromine f r o m Brovnocitruconic Acid, a n d on u Xew Organic A c i d , E. BOURGOIN (32,386).--]3j’ partially saturating a solution of bromocitraconic acid with caustic potash, and slowly evaporating the solution, crystals of bromide of potassium separate out, and the mother liquor consists of a new acid corrwponding t o the fcrmula C10H108. It appears t o be related to pyrotartaric acid (C,,H,O,), and also t o citraconio acid (C,oH608). Note u]?on thZ Solubility of Benzoic and Sulicylic Acids, E. BOURGOIN (32,390).-~\ re-assertion of facts previously stated, and a description of the methods used (see Bull. SOC.Chim., 31, 53, and this JOURNAL, I, 2 7 2 ) On the CMorhydrafe of Phosphoretted Hydrogen. J. OGIER (32,483).--In the apparatus devised by M.Cailletet, a t a temperature of 14‘, hydrochloric acid combines with phosphoretted hydrogen, producing hydrochlorate of phosphoretted hydrogen. I t appears in the shape of small, snowy flakes. At a little higher temperature it ia a liquid.
