THE
BACTERIOLOGY
OF
partly on the quantity of the primary infection, a n d partly on the period which has elapsed since its introduction into the system. r 4. Because, farther, in regard to re-vaccination, experience abundantly proves, especially in the case of hospital nurses, medical attendants, and others, who c o m e m u c h into relation with smallpox, that an attack of this disease, either within a certain period after primary vaccination, or after re-vaccination, is so rare, and so trivial when it does occur, as to involve only an infinitesimal risk..~'15. Because, finally, in this, as ia all o t h e r matters, probability must be the guide of life for all o f us ; and every sensible m a n or woman, in deciding on what course they shall pursue in regard to a matter which may involve not only their own health and life, b u t that of others who are near and dear to them, should be guided by the consideration of which of the two sides is probably in the r i g h t - - t h a t which is represented by a comparatively small body o f irresponsible and often a n o n y m o u s persons, the great ma!orvy of whom have had no experience or training which justifies them in ex*"The evidence on this point is so striking that it is weU to summarise a few of the leading points in it, which are taken from the admirable and instructive *' Report on Vaccination as a Branch of Preventive Medicine," by g{r. E~nest Hart, published i~ the Brills'/z 2F[cdical ~ournalin x895 :--In I87I, Dr. Collie, formerly Superintendent of one of the Hospitals of the Metropolilan Asylums Board, states that I to persons were engaged• in the Homerton Fever Hospital in attendance on smali-pox cases. All these, with two exceptions, were re-vaccinated, and all but those two exceptions escaped small-pox.--A Special Committee of the Epidemiotogical Society whLh investigated this question of hospital immunity found that out of 1,5oo persons in attendance on cases of small-pox only 43 contracted the disease, • and not one of these bad been vacciaated.~At Highgate Small-pox Hospital, Dr. Herbert Goude, who was then medical officer, states, in I893 : The statement I made in x885--that no nurse or other official of this hospital had contracted small-pox, wi~h one exception, ~hat of a gardener who had escaped re-vaccination--holds good to the present date, so that now we have an un ~roken record of fifty-eight years, during which no nurse or servant has contracted the disease even in a modified form ; and this, too, though the nurses and attendants have on many occasions accidentally inoculated themselves with variolous matter, thus lmtting the protection afforded by vaccination to a really crucial test. We have had no injurious effects from re-vaccinatlon beyond those apparently inseparable from the operation, such as t;zalaf;~, and occasionally tardy healing of the pesicles."--O~ board the Sm~il-pox Hospital Skips of the Metropolitan Asylums Board, Dr. Ricketts, the medical superintendent, states that, in ~892, out of t,2oI persons. who had been engaged on the ships since I884, only 6 contracted the disease, and all recovered. Not one of these 6 cases had been re-vaccinated before joining the ships. In i893 , again, 6 persons, out of 307 in attendance on the sick, contracted small-pox, none of whom had been vaccinated before joining the ships, but only more or less successfully after coming on board. All recovered. These illustrations might he paralleled by similar ones from all parts of the world, and can leave no doubt upon the mind of any impartial person that the chances of any person who has been properly vaccinated taking small-pox are exceedingly small, and that the chances of death in such a contingency, if it were to occur~ are practically n//.
VACCINIA
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pressing a positive opinion in this m a t t e r - - o r the side which is represented by a large body o f professional men, who have b e e n specially trained to investigate such problems as this, who have more or less frequent opportunities for personally testing their opinions by practical observation of the effects o f vaccination on small-pox, and who c a n n o t but feel the grave responsibility under which they would lie if they were to r e c o m m e n d a proceeding in regard to the safety o f which they had any doubt ?
THE
BACTERIOLOGY OF AND VARIOLA.
VACCINIA
BY
S, MONCKTONCi~Im~tAN,M.A., M.D.(Cantab.),M.R.C.P , Lecturer on Hyglene and Pubhc Health in the Medical School of Westminster ttospital. T ~ E occurrence of t h e centenary o f the first vaccinations carried out by J e n n e r affords fitting occasion for a brief account of t h e present state of our knowledge o f the pathology of vaccinia and small-pox resL,ectively, and especially of the light which bacteriology has thrown on the value of the operation of vaccination as a prophylactic against subsequent invasion of the system by small-pox, and on the question of the best m e t h o d s of carrying out the process. Since the days when C h a u v e a u and BurdonSanderson demonstrated, almost concurrently, the probability of the particulate n a t u r e of the specific virus of vaccine lymph, a great n u m b e r o f bacteriologists have d e v o t e d themselves to the search in this l y m p h for a micro-organism, to which the special and peculiar effect resulting o n the inoculation of such lymph was due. At various times numerous micro-organisms have b e e n isolated and described, of which s o m e have been regarded by their discoverers as the active contagium, but on further investigation, this has agmn and again been found not to be the case. Pfeiffer, and many other observers, h a v e i n d e e d shown that bacteria of different species can be grown in various nutrient media from specimens of vaccine lymph obtained in the ordinary way, but to none of them can be assigned the r61e of the actual vaccine virus ; for which reason I have applied t h e t e r m " extraneous " to these bacteria, signifying thereby that their presence is not in any way essential to the successful action of the vaccine lymph. C r o o k s h a n k states, in reference to this matter, in a Communication to the International Congress o f H y g i e n e , o f 189I , that, i..~ his ~pinion, n o n e o f the different species o f bacteria, which he had isolated from vaccine lymph, are peculiar to i t ; that there is no bacterium constantly present in h u m a n and calf vaccine, and that there is not one which can be r e g a r d e d as the contagium. Most of them, indeed, are welt-known saprophytic bacteria,
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and some are identical with bacteria commonly found in suppuration. He adds that vaccine lymph is a most suitable cultivating medium for ,micro-organisms, and bacteria almost invariably get access to the contents of the vaccine vesicle. I-Ie gives a lengthy list, in the paper referred to, of the various bacteria which may be isolated from human or calf lymph by the method of plate cultivation, but no statement is made as to Whether any and, if so, what precautions had been taken with regard to the collection of the lymph; neither is any attempt made to distinguish between those bacteria which are commonly to be found, and those whose presence is exceptional. It would appear, however, that there are at least three species of micro-organisms--Staphylococcus albus epidermidis, Staphylococcus pyogenes aureus, Staphylococcus cereus fiavus, one or more of which are almost universally to be found in every specimen of vaccine lymph examined. O f these the Staphylococcus albus epidermidis is usually to be found in the upper layers of healthy skin. Of more importance is the fact that in certain cases, though rarely, the Streptococcus of erysipelas has also been isolated from a specimen of vaccine lymph. That untoward results should occasionally, in certain cases, follow the inoculation during tile act of vaccination of one or other of the various extraneous organisms which may be present in the lymph employed, is not to be wondered at ; indeed, it would appear rather a matter for wonder that the evil results following t h e present somewhat empirical practice of vaccination have been, in the past, so few in proportion to the vast numbers that have undergone the operation. In this connection, however, attention may be called to the fact that recently it has been found possible, by certain staining methods, to demonstrate, both in vaccine and in variolous lymph, the presence of a small spore-bearing bacillus, some. times in considerable numbers. This bacillus is to be found most readily in lymph taken on the fourth or fifth day (seventytwo to ninety-six hours) in the calf, and in the human vaccine (or variolous) vesicle about the fifth day of eruption, while later lymph, such as that obtained at the ordinary period for purposes of vaccination, contains but a few at the most. This fact, which not unlikely has relation to sporeformation by the bacilli at about the time of maturity of the vesicle, probably accounts for their presence having been overlooked by previous workers in this field. If proper precautions as to time and method be taken in the collection of lymph, it is usually found that although these bacilli are present, often in extraordinary rmmbers~ other bacteri,~ are conspicuous by their absence. The fact that these apparently identical bacilli are to be found both in vaccine and in variolous lymph of about t h e fifth day of eruption, tends
to support the hypothesis that they in reality constitute the active cor~tagium of the diseases in question ; and the further fact that it has not been found possible to cultivate them in any of the artificial media ordinarily employed, renders it practically certain that they are not merely "extraneous" saprophytic orgamsms. Although not capable o f growth on gelatine, agar, etc., the writer has succeeded by employing for the purpose the hen's egg inoculated with an emulsion of small-pox crusts in normal saline solution and incubated for about a month at the body temperature. With material obtained from such an egg, a series of calves have been inoculated, and with lymph of the third remove from the egg numbers of children have been successfully vaccinated. Without resorting to cultivation experiments, however, it is possible to prepare, with ease and certainty, from vaccine lymph, a material containing what must be regarded as a pure culture of the organism peculiar to vaccinia, and which, therefore, is of special value for purposes of vaccination. As already stated, it has been a~mndantly demonstrated that vaccine lymph, as. ordinarily obtainedi gives rise, when inoculated into various nutrient media, of which plate cultivations are subsequently made, to growths of various "extraneous" saprophytic organisms. If, however, previous to making a plate cultivation the lymph has been intimately mixed with equal parts of a sterilized 5 ° per cent. solution of chemically pure glycerine in water, and subsequently kept protected from the air and light in hermetically sealed capillary tubes for a period of from a few days to a couple of months, it is found that all "extraneous ~' organisms have now been killed out and no growth occurs in gelatine or agar plates. At the same time, the mixture of lymph with glycerine will be found to have gained in efficiency as vaccine rather than the reverse. Since I first published the results of this investigation, ample corroboration of my work has been afforded by certain French and Italian observers who have published their experience of the use ofglycerinated vaccinal lymph when kept for a long time in capillary glass tubes previously sterilized and closed by the blowpipe. The results obtained by Chambon and M6nard, for instance, with lymph originally good, were, as they state, highly satisfactory, and even lymph, which in its fresh state gave mediocre results, in the course of fifteen days after such admixture produced a passable vesicle, after forty, fifty, or sixty days a typical one. The improvement in their opinion seemed due to the gradual extinction of parasitic microbes under the influence of glycerine and time. Professor Straus made plate cultures with their glycerinated lymph, which showed that when fresh it gave rise to numerous colonies of various microbes, especially Staphylococcus albus, while the glycerine lymph, fifty to sixty days old, remained
S C I E N T I F I C INVESTIGATIONS OF T H E LOCAL GOVERNMENT BOARD. absoluteIy sterile, intermediate specimens presenting fewer and fewer microbes as they became older. These experiments were repeated many times, and invariably with similar results. Glycerine has, of course, been employed for some time past for the multiplication and preservation of vaccine lymph, but the peculiar action exerted by it, when used after the fashion advocated, in the elimination of "extraneous " organisms had not, as far as I am aware, been appreciated until within the last few years. Such glyeerinated lymph would appear, therefore, to offer the most favourable opportunity for the further study of the specific organism of vaceinia and variola, as possible fallacies induced by the presence of'" extraneous" organisms of any kind would thus be obviated. It may be mentioned that in 189o Pfeiffer described certain protozoa and zoospores as found by him in the vaccine "vesicle "--as in all other vesicular eruptions in man and the lower animals-mainly within the epithelial cells. Pfeiffer has since published a further account of these supposed organisms, while the presence of protozoa has also been described by Van der Loeft, Guarnieri, and Doehle. In this country both Ruffer and Jackson Clarke have called attention to the fact that they have been able to demonstrate similar bodies in and among the epithelial cells of an inoculated area. It should be remembered, however, that the most recent experiments in this direction have been carried out on the cornea of the rabbit, an animal which is generally believed to be insusceptible to vaecinia. It may be added also that no such bodies have been satisfactorily demonstrated in vaccine lymph itself. It is therefore conceivable that the "parasites" in question may represent merely the result of epithelial irrition caused by the scarification, together withthat--of a non-specific nature however,--set up by the vaccine lymph employed. On the other hand there appears good reason for believing that the bacillus demonstrated by Klein and myself, and which I have succeeded in cultivating outside the body, in reality constitutes the specific virus of small-pox and vaccinia respectively. It is consequently of interest to note that the operation of vaccination is probably one of the earliest instances on record of the employment of a bacterial inoculation; although', of course, its true nature was not appreciated at the time of its introduction. Almost from Jenner's day, however, the value of the practice has, by some, been impugned on the plea that inoculation of one disease, "cow-pox," could not be expected to exert any really protective action against the supposed totally different disease of small-pox. And if the thesis of essential difference between these maladies were only capable of scientific demonstrations no doubt such objection
275
would be of considerable weight, seeing that, as far as I am aware, there exists no well-authenticated evidence as to the living virus of one disease being capable, when inoculated into an animal, of affording protection to the system from the effects of inoculation of the virus of a totally different disease, although in such a case the incubation period of the second infection may be somewhat delayed. That some such thought was possibly present to the mind of Jenner may be gathered from the fact of his employing, in reference to vaccinia, the alternative term variola vaccin~e, or "small-pox of the cow." His use of this term would indeed appear to indicate his belief that vaccinia was really nothing more nor less than small-pox which had in some way become modified by residence in the organism of the cow. However imperfect in the first instance may have been the experimental methods on which such theory was based, it has, nevertheless, in my opinion, become, during the century which has elapsed since Jenner wrote, and more particularly during the last few years, increasingly apparent that he was amply justified in this belief.
S C I E N T I F I C INVESTIGATIONS OF T H E LOCAL GOVERNMENT BOARD, 1893-4. BY R. THORNZ THORNE, M.B., F.R.S., Medical Officer to the Board.
(Continued from p. 172.) CHEMICAL PATHOLOGY OF TETANtlS. Dr. Sidney Martin's investigation of the chemical pathology of tetanus, referred to in my last report as then in progress, has advanced on lines indicated by his previous researches respecting anthrax and diphtheria. The preliminary report now sub* mitred by him, gives account of his chemical examination of the tissues of persons dead of tetanus, of the albumoses and acid organic substances thus obtained by him from their blood and from their spleens, and of the physiological effect of these upon rodents. As yet, Dr. Martin has not ascertained whether similar albumoses and acid organic bodies are obtainable from animals in which tetanus has been experimentally induced, or from culture media in which the tetanus bacillus has been artificially grown ; nor indeed whether any other tissues of the tetanus subject, as, for instance, the spinal cord, contain, in greater amount than the blood and spleen, those metabolic products of this bacterium upon which the disease tetanus would seem to depend. The result of Dr. Martin's further research in these directions, will form the subject of an additional report. The albumoses obtained by Dr. Martin from the blood and spleen of tetanus when intravenously