330 professor joseph lister. on the relatio...

3 3 0 PROFESSOR JOSEPH LISTER.

On the RELATION of MICRO-ORGANISMS to DISEASE. BYJOSEPH LISTER, F.R.S., Professor of Clinical Surgeryin King's College, London.1

T H E relation of micro-organisms to disease is a subject ofvast extent and importance. If we compare the presentstate of knowledge regarding it with that of twenty years ago,we are astonished at the progress which has been made inthe interval. At that time bacteria were little more thanscientific curiosities; whether they were animal or vegetablefew people knew or cared, but most regarded them as animalson account of the active movements which they often ex-hibited. That they were causes of putrefaction, or otherfermentative changes, was a thing scarcely thought of; audthe notion that they had special relations to disease wouldhave been regarded as the wildest of speculations. Now,however, a mass of information has been accumulated re-garding all these points, of which it would be hopeless forme to attempt to give even a brief sketch in the time at mydisposal, and all that I can do is to present to the pathlo-logical section a few examples illustrating the progress whichis being made in this department of research.

First, I will mention some examples of the labours of Dr.Koch, of Wollstein, in Germany. Though a hard-workedgeneral practitioner, Koch has contrived to devote an im-mense amount of time and energy to his investigations, andby a combination of well-planned experiments, ingeniousmethods of staining bacteria out of proportion to the tissuesamong which they lie, a beautiful adaptation of opticalprinciples to render the coloured objects discernible by thehuman eye, and, further, by a most successful applicationof micro-photography, he has succeeded in demonstratingthe presence of these minute organisms in a manuer neverbefore attained.

The Bacillus anthracis is now universally recognisedamong pathologists as the cause of splenic fever, so fatalamong cattle in this and other countries, and capable ofbeing communicated to various other animals, and, amongthe rest, to the human species, as has been lately illustratedby the so-called woolsorters' disease, in the North ofEngland. The Bacillus anthracis is a large form of bacte-

1 An address delivered before the Pathological Section of the BritishMedical Association at Cambridge, August 12th, 18S0.

THE RELATIONS OF MICRO-ORGANISMS TO DISEASE. 3 3 1

rium, as is shown at a in the accompanying woodcut. It is

there represented magnified 700 diameters, along with redblood-corpuscles of a mouse, and the rods of which it iscomposed are seen to be in diameter nearly one fourth ofthat of the red corpuscles. Koch's method of staining thesections shows in the most beautiful manner that thesebacilli are not only present in the spleen and some otherorgans, but that they people the blood in the minute vesselsof all parts. Koch has thus added to our conviction thatthe bacillus is the cause of the symptoms, seeing that, as heremarks, it is impossible to suppose that an organism candevelop in such enormous numbers at the expense of thevital fluid without exerting a serious influence upon thesystem.

But the most striking and important results of Koch'smethods of investigation are those which relate to organismsof much smaller dimensions. He found that, if putridliquid is injected under the skin of a mouse, the animalmay die in the course of a short time, as the result of thechemically toxic effects of the products of putrefaction ab-sorbed into the circulation ; but, if it survive this primarydisorder, it may succumb in the course of about two days toblood disease. If the point of a lancet be dipped into theblood of the heart of a mouse which has died in this way,and a scratch be made in the skin of a healthy mouse withthe envenomed instrument, the second mouse dies withsimilar symptoms to those of the first, the poison beingabsolutely certain in its virulent operation; and the samething may be continued indefinitely through any series ofanimals. If now sections of the tissues be made and stained,and examined by Koch's procedures, it is found that theentire blood of the diseased animal is peopled with bacteria,resembling those of the Bacillus anthracis in the enormousmultitudes in which they are produced, and also in theirrod-like form, but differing from them in being exquisitelyminute and delicate, as is shown at b (drawn on the samescale as a, as is indicated by the accompanying outlines ofred corpuscles), where it is seen that the diameter can only

3 3 2 PPOFESSOK JOSKPH LISTER.

be represented by a slender streak not one eighth of thediameter of the Bacillus anthracis, and such as, before theintroduction of Koch's method, would have escaped noticealtogether. Now, this disease is totally distinct from pyaemia,being not accompanied with multiple abscesses or embolism;and thus it has been showu by Koch that septicaemia may

exist as a deadly blood disease, caused by the developmentof micro-organisms, equally distinct from pyaemia and fromthe chemically toxic effects of septic products.

On some occasions, as the result of the introduction ofputrid fluid under the mouse's skin, Koch found, besidessepticaemia, a local affection of the seat of inoculation, in theform of spreading gangrene ; and, on investigating the part,he discovered in it, exactly corresponding with the extent ofthe local affection, another organism very differently formedfrom that of the septicaemia, viz. a micrococcus, consistingof minute spherical granules arranged in linear series, likestrings of exquisitely minute beads, as represented at c in

H

the woodcut. Believing that this locally developing or-ganism must be the cause of the gangrene, he tried to sepa-rate it from the bacillus of the septicaemia, and succeededthrough an accidental observation of great interest. Havingtill that time employed the house mouse in his experiments,be happened to try the inoculation of a field mouse. Thisanimal, though so closely allied, proved not susceptible ofthe septicaemia. The bacillus of that disease was unable togrow in the blood of the field mouse, but the micrococcus ofthe gangrene could develop among its tissues. The neworganism was thus obtained in an isolated form, and, whennow inoculated into the house mouse, produced in thatanimal gangrene pure and simple, extending for an inde-finite period among its tissues.

Thus the animal body, which had previously been anobscure field of labour in this department, in which the


pathologist did little more than grope in the dark, was con-verted by Koch into a pure cultivating apparatus, in whichthe growth and effects of the micro-organisms of variousinfective diseases could be studied with the utmost sim-plicity and precision.

One more example I must take from Koch's work. Onone occasion, as the result of inoculating putrid liquid intoa rabbit, he observed a spreading inflammation having allthe clinical characters of erysipelas; and, on examiningstained sections of the part, he discovered another exqui-sitely delicate bacillus resembling the micrococcus of thegangrene in being local in its development, while its exactcorrespondence in extent with that of the disease led fairlyto the conclusion that it constituted the materies morbid

I will next refer. to a disease occasioned by a micro-organism discovered by the eminent pathologist, ProfessorToussaint, of Toulouse, whom I am proud to see present inthis Section to-day. This disease has been somewhat in-appropriately termed Cholera des poules, or fowl cholera,for it is not attended with diarrhoea or any other of thesymptoms of cholera; but, as it happened to be extremelydestructive among the poultry-yards of Paris at the sametime that an epidemic of cholera was raging in the city, thedisorder that prevailed among the fowls was also given thename of cholera. The lesions by which it is chiefly cha-racterised are great swelling of the chains of lymphaticglands in the vicinity of the trachea, pericarditis accom-panied with great effusion, and congestion, and it may beulceration, of the mucous membrane of the duodenum. Itis a blood disease, and highly infectious. If some of theblood of a chicken that has died of it be mixed with the oatswith which healthy chickens aro fed, a considerable propor-tion, perhaps four out of six, are affected and die; andsimilar results are produced by mixing the intestinal ex-creta of diseased fowls with the food. It is an interestingquestion how the virus thus administered enters the circu-lation. The invariable affection of the lymphatic glands ofthe throat suggests to M. Toussaint the idea that someaccidental abrasion of the epithelium in the mouth orpharynx is probably the channel; and this view is con-firmed by the fact that a similar affection of the lymphaticglands, together with other symptoms of the disease, is pro-duced by inoculating the chicken in the mouth ; and fur-

1 See ' Untersucliungen iiber die iEtioiogie der Wundinfectionskrank-heilen,' von Robert Dr. Koch, Leipzig, 1S7S. A translation has just beenissued bj the Sjdenham Society.

334 PROFESSOR JOSEPH LISTER.

ther, by the circumstance that such chickens as fail to takethe disease when fed with the infected food are liable to itwhen inoculated, implying that it was merely some acci-dental circumstance which secured their previous immunity.This disease has been made the subject of special investiga-tion by M. Pasteur. He found that the micro-organismcould be readily cultivated outside the body of the fowl. Itwas, indeed, somewhat particular as regards the fluid inwhich it would grow; thus yeast-water, in which theBacillus anthracis grows readily, proved an unsuitablemedium for this organism, but it grew luxuriantly inchicken broth, and, indeed, in infusion of other kinds ofmeat; but chicken broth proved peculiarly convenient forthe purpose. M. Pasteur has been so kind as to send mesome tubes in which the organism has been cultivated, anda drop of the liquid has been placed under a microscope onthe table. It will be seen that the organism is a minuteform of bacterium, oval-shaped, tending to multiplication bytransverse constriction, and very frequently seen in pairs,and occasionally in chains. Its transverse diameter is froml-50,000thto l-25,000thof an inch, so that it resembles veryclosely the Bacterium lactis. The woodcut d represents a

d

** *.

camera lucida sketch of the organism sent by M. Pasteur.So far as I am aware, this is the first time this bacteriumhas been shown in this country. Now, it was found byPasteur that the organism could be produced in chickenbroth, in any number of successive cultivations, and to thelast retain its full virulence, so that, if a healthy chicken beinoculated with it, the fatal diseade was produced as surelyas by inoculation with the blood of a fowl that had died ofthe complaint. This was pretty conclusive evidence thatthe organism was the cause of the disease, and that it con-stituted the true infective element; because auy other mate-rial that might be supposed to accompany it in the blood ofthe diseased animal must have been got rid of by the suc-cessive cultivations in chicken broth.

The growth of the organism occasions no putrefaction inthe liquid ; so that this is a good example of a bacteriumwhich is most destructive as a disease, but which is at thesame time entirely destitute of septic property, in the primi-tive sense of that term as equivalent to putrefactive. After

THE RELATIONS OF MICKO-ORGANISMS TO DISEASE. 3 3 5

the bacterium has grown for a certain time in a given por-tion of chicken broth, it ceases to develop further; and whenthis is the ease, although the broth has lost only a verysmall proportion of its substance by weight, and although,as aforesaid, it has not undergone putrefaction, and stillconstitutes an excellent pabulum for ordinary forms ofbacteria, the bacterium of the fowl-cholera, though intro-duced from some new source, is incapable of growing in it.This fact seems highly suggestive of an analogy with theeffects of vaccination, or those of an attack of measles orscarlatina in securing immunity from the disease for thefuture. Here we have a certain medium invaded by a viruscapable of self-multiplication, as is the case with those dis-eases in the animal body; the medium itself little affectedchemically by the growth of the virus within it, but never-theless rendered unfit for the development of that virus forthe future. But something more than the suggestion ofanalogy with vaccination has been effected by M. Pasteur.By cultivating this bacterium in a particular manner, whichhe has not yet published, he enfeebles the organism, as hebelieves, and produces such an alteration in it that, wheninoculated into a healthy fowl, it produces only a modified,and no longer fatal form of complaint, but the bird isthereby rendered secure against taking the ordinary form ofthe disease. It has been really vaccinated, if we adopt M.Pasteur's extension of the term vaccination to other similarcases ; for just as we speak of an iron milestone, we may, ifwe please, apply the term vaccination to the use of a virusother than the vaccine obtained from a heifer. But thoughthe vaccination with the modified bacteria of the fowl-cholera does not occasion the fatal disease, it producespretty severe local effects. If inoculated on the breast ofthe fowl, it causes a limited gangrene of the pectoral muscle,the affected part falling off in due time as a dry slough.Through the great kindness of M. Pasteur, I have now theopportunity of showing to the Section a hen which hasbeen treated in this way. You observe a slough on thebreast of the bird about as large as a penny piece; it is dry,and obviously old. The fowl has been some days in mypossession subsequently to its journey from Paris; butthough more than enough time has elapsed since the inocu-lation to have caused its death, had the dieease been in theordinary form, it is, you see, in good health, bright andactive, and it both eats and sleeps well.1

1 M. Pasteur's researches on this subject are related in the ' ComptesReudus de l'Academie des Sciences,' February, April, and May, 1880.


I will now return to the Bacillus anthracis, with regardto which I shall have again to refer to the labours of M.Toussaint. First, however, I must allude to the work ofsome of my own countrymen. In March, 1878, an experi-ment was made at the Brown Institution, at the suggestionof Dr. Burdon Sanderson, of inoculating a calf with theblood of a guinea-pig which had died of splenic fever, whichis exceedingly fatal to rodentia. The result was that thecalf took the disease, but in a mild form, and recoveredfrom i t ; and a similar fact was observed in two heiferstreated in the same way.1

This line of inquiry has since been followed up by Dr.Sanderson's successor at the Brown Institution, Dr. Green-field, with a view of ascertaining whether the milder form ofthe disease in cattle, resulting from inoculation with theblood of rodentia affected with it, confers upon the cattleimmunity from the complaint in its fatal form; or, to useagain M. Pasteur's expression, whether the cattle have beenvaccinated with reference to anthrax. And I have greatpleasure in being able to inform the Section, by Dr. Green-field's permission, that the question has been answered inthe affirmative; and that one bovine animal, inoculatedseven months ago with virus from a rodent, has proveditself, on repeated inoculations, entirely incapable of con-tracting splenic fever, remaining free from either constitu-tional or local manifestations of it.

And now to return to M. Toussaint, who has made obser-vations with regard to this same subject of vaccinationagainst anthrax fraught with the very deepest interest.The question arises with regard to effective vaccination,using the term in Pasteur's general sense: Is it essentialthat micro-organisms should develop in the blood of theanimal in which immunity from further attacks of the dis-ease is to be secured ? Or is it possible that the necessaryiufluence upon the system may be exerted by merely chemi-cal products of the growth of that organism in some othermedium ? With the view of approaching the solution ofthis question, M. Toussaint has performed experiment ofinjecting into the blood of healthy sheep blood taken froman animal affected with splenic fever, but deprived of theBacillus anthracis. Taking blood from a sheep just on thepoint of death, when the bacillus has presumably producedall its possible effect upon the vital fluid, M. Toussaint pro-ceeds to deprive it of the living bacillus in either of two

1 See "Report on Experiments on Anthrax," by Dr. Sanderson ('Journalof the Royal Agricultural Society of England,' vol. xvi, s.s., part i).

THE RELATIONS OP MICRO-ORGANISMS TO DISEASE. 3 3 7

ways—by filtration, or by destroying the vitality of theorganism. The former he effects by mixing the blood withthree or four parts of water, and then passing it throughabout twelve layers of ordinary filter-paper. The bacillus,in consequence of its large dimensions, is entirely retainedby this form of filter, as is proved by the fact that thefiltrate no longer gives rise to the organism in a cultivatingliquid or in a living animal. Nevertheless, if injected inconsiderable quantity into the circulation of a healthy sheep,it produces a true vaccinating influence, that is to say,secures immunity from splenic fever. But, what is furtherextremely interesting, in order that this change in the con-stitution of the sheep may be brought about, the lapse of acertain time is essential. If a vaccinated sheep be inocu-lated with anthrax within a few days of the operation, itwill die of splenic fever ; but if from twelve to fifteen daysbe allowed to elapse, complete immunity is found to havebeen produced. Similar results followed from the injectionof anthrax blood treated by Mr. Toussaint's other method,which consists of maintaining it for a considerable time ata temperature of 55° C. (131° P.), which has the effect ofkilling the bacillus; after which one half per cent, of car-bolic acid is added, to prevent putrefaction of the liquid.The blood treated in this way having been proved to befree from living bacilli by negative results of an experimentupon a rodent, about four cubic centimetres are injected intothe venous system of a sheep, with the effect of producingthe same protective influence against splenic fever as isensured by the filtered blood. These experiments are stillin progress; but M. Toussaint informs me that he hasalready ascertained the existence of immunity against an-thrax for three months and a half in both sheep and dogtreated in this way.

I need hardly remark on the surpassing importance ofresearches such as these. No one can say but that, if theBritish Medical Association should meet at Cambridge againten years hence, some one may be able to record the dis-covery of the appropriate vaccine for measles, scarlet fever,and other acute specific diseases of the human subject. Buteven should nothing more be effected than what seems to bealready on the point of attainment, the means of securingpoultry from death by fowl-cholera, and cattle from theterrible destructive splenic fever, it must be admitted thatwe have an instance of a most valuable result from the much-reviled vivisection.

I have yet one more example to give of researches in this


domain of pathology; and this also has reference to theBacillus anthracis. The investigator in this instance is Dr.Buchner, assistant physioan in Munich. It is well knownthat the Bacillus anthracis is morphologically identical withan organism frequently met with in infusion of hay,which may be termed hay-bacillus. Such being the case, itoccurred to Dr. Buchner that they might be merely oneand the same organism modified by circumstances. For myown part, I am quite prepared to hear of such modifyinginfluence being exerted upon bacteria, having made theobservation several years ago that, when the Bacteriumlactis had been cultivated for some time in unboiled urine,it proved but a feeble lactic ferment when introduced againinto milk. Its power of producing the lactic fermentationhad been impaired by residence in the new medium. In thecase before us, indeed, the physiological difference betweenthe two organisms seems, at first sight, so great as to forbidthe idea of anything other than a specific difference. TheBacillus anthracis refuses to grow in hay-infusion, in whichthe hay-bacillus thrives with the utmost lnxuriance; andconversely, the hay-bacillus is utterly incapable of growingin the blood of a living animal, whether introduced in smallor in large quantities. The hay-bacillus is remarkable forits power of resistance to high temperatures, which is notthe case with the Bacillus anthracis. The latter is destroyedby a very slight acidity of the liquid of cultivation, or byany considerable degree of alkalinity, whereas the formersurvives under such conditions. Both will grow in dilutedpxtract of meat, but their mode of growth differs greatly.The hay-bacillus multiplies rapidly, and forms a dry andwrinkled skin upon the surface, while the Bacillus anthracisproduces a delicate cloud at the bottom of the vessel, in-creasing slowly. Nothing daunted by these apparentlyessential differences, Dr. Buchner has laboured with indo-mitable perseverance, by means of experiments carried onin Professor Nageli's laboratory, to solve the double problemof changiug the Bacillus anthracis into hay-bacillus, and theconverse. Having devised an ingenious apparatus by whicha large reservoir of pure cultivating liquid was placed incommunication with a cultivating vessel, so that any culti-vation could be drawn off by simply turning a stop-cock,and further cultivating liquid supplied to the organismsremaining in the vessel by a mere inclination of the appa-ratus, Buchner proceded to cultivate the isolated Bacillusanthracis in extract of meat for several hundred successivegenerations. As an early result of these experiments, he


found that the bacillus lost its power of producing disease inan animal inoculated with it. Up to this point he is con-firmed by Dr. Greenfield, who has found that, when theSacillus anthrads is cultivated in aqeous humour, after aboutsix generations it loses its infective property. Then asBuchner's experiments proceeded the appearance of thegrowing organism was found to undergo gradual modifica-tion. Instead of a cloud at the bottom of the vessel, ascum began to make its appearance—at first greasy-lookingand easily broken up—constituting, so far as appearanceswent, an intermediate form between the two organisms ; andin course of time the scum became drier and firmer, and atlength the modified Bacillus anthrads was found to becapable of growing in an acid hay infusion, and to presentin every respect the characters of the hay-bacillus. Theconverse feat of changing the hay-bacillus into the Bacillusanthrads proved very much more difficult. A great numberof ingenious devices were adopted by Buchner, who was,nevertheless, continually baffled, till at last he attained suc-cess in the following manner:—Having obtained the bloodof a healthy animal under antiseptic precautions, and defi-brinated it also antiseptically, and having arranged hisapparatus so that the pure defibrinated blood, which was to bethe cultivating medium, should be kept in constant move-ment, so as to continually break up the scum, and also keepthe red corpuscles in perpetual motion so as to conveyoxygen to all parts of the liquid—in this way imitating, toa certain extent, the conditions of growth of the Bacillusanthrads outside the animal body, within which the hay-bacillus could not be got by any means to develope—lieproceded to cultivate through numerous successive genera-tions. A transitional form soon made its appearance; butthe change advanced only to a limited degree, so that furtherprogress by this method became hopeless. The modifiedform hitherto obtained failed entirely to grow when injectedinto the blood of an animal. On the contrary, it was in ashort time completely eliminated from the system, just likethe ordinary hay-bacillus. It had, however, been observedby Buchner that spores had never been formed by thebacillus growing in the defibrinated blood; and it occurredto him that, perhaps, if it were transferred to extract ofmeat, and induced to form spores there, the modifiedorganism might yet grow in the blood of a living animal.The carryiug out of this idea was crowned with success ;and, by injecting various different quantities of the liquidcontaining the organism into different individuals, Buclmer


at length succeeded, both in the mouse and in the rahbit, indeveloping true Bacillus anthrads out of the progeny of thehay-bacillus. When large quantities were introduced, theanimals died rapidly from the merely chemical toxic effectsof the injected liquid; but, in some instances in which asmaller amount was injected, after the period for these pri-mary effects had passed, a fatal disease supervened—attended,as in anthrax, with great swelling of the spleen, the bloodof which was found peopled, as in that affection, with newlyformed bacilli; and the spleens affected in this way werefound to communicate anthrax to healthy animals, justlike those of animals which have died of ordinary splenicfever.1

Supposing these results to be trustworthy (and the recordof them bears the stamp of authenticity) I need scarcelypoint out to a meeting like the present their transcendantimportance as bearing upon the origin of infective diseases,

' and their modifications as exhibited in epidemics.I trust that these examples may suffice to convey some

idea of the work now going on with reference to the rela-tions of micro-organisms to disease.

Since the address was delivered M. Pasteur has publishedthe method by which he produces the " attenuation " of thevirus, or in other words, the enfeeblement of the organism offowl-cholera which fits it for securing immunity from thefatal form of the disease. This method consists in cultivat-ing the organism, pure and unmixed, in chicken broth, towhich access of air is permitted while dust is excluded, andsimply allowing some months to elapse before it is employed.If the period does not amount to more than about twomonths, the organism retains its virulence little abated, butif the period is extended to three or four months it is foundthat animals inoculated with the organism take the disease,but have it in a milder form, and a considerable proportionrecover; and if the time is made still greater, as, for ex-emple, eight months, the organism has so far lost its potencythat though chickens inoculated with it still go through anattack of the disease all recover. If the period is sufficientlyprolonged, there comes a time when the organism is foundto have lost its vitality altogether, so that it will no longergive rise to new development when introduced into freshcultivating liquid.

Iu considering by what agency this enfeeblement of theorganism and ultimate extinction of its vitality was brought

1 See ' Ueber die experimentelle Erzeugung des Milzbrandcontagiumaaus den Heupilzeu/ vim linns BucLmer, MiincUeu, 1880.


about under the circumstances referred to, it occurred to M.Pasteur that it might perhaps be the oxygen of the airadmitted to the vessels. Oxygen is essential to the growthof the organism, but it might, as M. Pasteur thought, be,nevertheless, in long-continued action upon it, a cause ofweakness. With a view of testing this idea he instituted culti-vations of the bacterium in broth contained in tubes partiallyfilled with the liquid, that is to say, containing a certainproportion of their volume of air, but sealed hermetically.The result was a growth of the organism, indicated by tur-bidity of the clear fluid, attaining a degree proportioned tothe amount of air present in the tube, but soon comingto an end when that air was exhausted, so that the littleorganism, no longer growing throughout the liquid, fell tothe bottom of the vessel, leaving the fluid again clear. Theorganism having now exhausted all the free oxygen, wasfrom this time forth presumably protected from the influenceof that element, and, in exact accordance with M. Pasteur'stheory, it was found that no matter how long these closedtubes were kept, the organism retained not only its vitality,but its full virulence, as tested by inoculation of healthychickens.1

These facts are certainly fraught with the deepest interest,and the medical world must for ever remain deeply indebtedto M. Pasteur for eliciting them. Doubts may, however, beentertained regardiag the interpretation of the phenomena.Thus Dr. Greenfield, whose own researches have had specialreference to the modifying influence exerted upon bacteriaby the medium in which they grow, has thrown out thesuggestion that the enfeeblement of the organisms of fowlcholera grown with free access of air may be due to altera-tions in the fluid which they inhabit rather than to theeffect of oxygen upon them. When free access of oxygen ispermitted, the organism, he contends, will continue to growtill all the material suitable for its nutrition is exhausted,and as the nutriment becomes defective the progeny will befeeble. At the same time this exhaustive development ofthe organism will be attended by the full measure of possiblealteration in the quality of the liquid which the growth ofthe organism can effect, and this alteration will naturallyinvolve the production of substances which may exert aprejudical influence upon the organism itself. On the otherhand, the bacterium, when growing in a sealed tube withlimited supply of oxygen, has its development brought to astand by the exhaustion of that gas, while the organism is

1 See ' Comptes Rendus,' 26th Oct., 1880.


in full vigour and in a fluid but slightly changed from itsoriginal wholesome condition. It thus remains like a vigorousseed, ready to start into energetic growth when the con-ditions for its germination are supplied.1 The essentialdifference between the two views may be stated shortlythus: M. Pasteur regards oxygen as a slow poison of thebacterium ; Dr. Greenfield seeks for the slow poison in theproducts of the fermentative agency of the organism.

The time which has passed since the delivery of thisaddress, has brought out facts which have led M. Toussaintto take a different view of the nature of the liquid used inhis " vaccinations " against anthrax above referred to. Ina letter which he had the kindness to write to me on thesubject, he informs me that on two different occasions in-jections of anthrax blood treated by one of his methods hasled to the death of the animal from anthrax ; and in oneinstance, a similar injection induced a local affection whichappeared to have the characters of malignant pustule. Hehas hence been led to the conclusion that the diseasedblood treated by his methods, instead of being (as he atfirst believed) free from the living bacillus, contained theorganism in an "attenuated " form.

Thus it would appear that the observations of Pasteur,Toussaint, and Greenfield, agree in ascribing the "'vacci-nating " influence to a modified form of the diseaseconcerned.

At the same time some other observations have been madewhich tend to justify the original line of inquiry pursuedby Toussaint. Chauveau has found that if ewes inoculatedwith anthrax in the last months of gestation recover fromthe disease, not only are the mothers no longer susceptible,but the lambs enjoy similar immunity.2 Further, it hasbeen ascertained by others, including Dr. Greenfield, thatthe blood and tissues of the foetus of an animal dying ofanthrax contain no bacilli, while those of the mother swarmwith them. Putting these two observations together we areled to the inference that while the integrity of the placentalvessels prevents the bacilli from entering the foetal circula-tion, the foetus is so dosed with soluble products of thedevelopment of the bacilli in the maternal blood as to berendered proof against the disease.

1 See "The Brown Lectures," by W. S. Greenfield, &c.; Lecture II,' Tlie Lancet,' Jan. 1st, 1881.3 See Dr. Greenfield's 1st "Brown Lecture," 'The Lancet/ 18iliDec., 1880.

330 professor joseph lister. on the relatio...

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