Popular Science Monthly/Volume 20/December 1881/Disease-Germs

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DISEASE-GERMS.
By Dr. WILLIAM B. CARPENTER.

AMONG the distinguished men who came together at the recent International Medical Congress—a gathering altogether unexampled for its combination of great and varied ability, and worthily representative of almost every country in which medicine is studied—there was no one whose presence was more universally or more cordially welcomed than a quiet-looking Frenchman, who is neither a great physician nor a great surgeon nor even a great physiologist, but who, originally a chemist, has done more for medical science than any savant of his day; and this, not only (probably not so much) through the results already attained by Pasteur himself and by others working on his ideas—great though these results are—but through the entirely new direction he has given to scientific inquiry, the number of new paths of research he has opened out, and of new clews he has afforded to those who will follow them up, and, last but by no means least, by the admirable example he has afforded, in the strictness and severity of his own methods (which have made him almost unerring in his predictions, and have given his conclusions the force of demonstrations), to those who would carry on the same lines of inquiry.

And here I would stop to note, as honorable to the disinterested character of a profession which has been lately the object of violent abuse for its (alleged) selfish and mercenary spirit, that this unique welcome was given, not to a great physician who had discovered a cure for gout, cancer, or consumption, by the use of which it would be enriched—not to a bold surgeon who had brought into vogue some wonderful operation, the success of which would tend to its renown—but to the scientific investigator of the causes of disease, whose work belongs altogether to the domain or preventive medicine, and thus, so far from being likely to benefit its members pecuniarily, tends only to diminish their remunerative employment. I never felt so proud of belonging to the body which still does me the honor to recognize me as one of its members as I did when Sir James Paget, the President of the Congress, paused in his opening address to point out on the platform behind him the greatest living exemplar of the truths he was so admirably enforcing, and when the whole of his vast audience—the like of which had never before been gathered in St. James's Hall, and perhaps never will be again—enthusiastically cheered, not once only, but again and again, the scientific veteran whose renown has spread from his quiet Parisian laboratory over the whole civilized world.

In order that the last of Pasteur's great achievements—which, with some of the ideas it suggests, it is my object now to bring before the readers of "The Nineteenth Century"—may be properly appreciated, it will be well for me to sketch out briefly what has been the nature of his life-work from the time when the singular beauty of some of his chemico-physical researches (which obtained for him in 1856 the Rumford Medal of the Royal Society) marked him out as one likely to attain further distinction.

It seems to have been by his special interest in the chemistry of organic substances that he was early led to examine into the question of fermentation, which had come to present an entirely new aspect through the discovery of Cagniard de la Tour that yeast is really a plant belonging to one of the lowest types of fungi, which grows and reproduces itself in the fermentable fluid, and whose vegetative action is presumably the cause of that fermentation, just as the development of mold in a jam-pot occasions a like change in the upper stratum of the jam, on whose surface and at whose expense it lives and reproduces itself. Chemists generally—especially Liebig, who had a fermentation theory of his own—pooh-poohed this idea altogether; maintaining the presence of the yeast-plant to be a mere concomitant, and refusing to believe that it had any real share in the process. But, in 1843, Professor Helmholtz, then a young, undistinguished man, devised a method of stopping the passage of organic germs from a fermenting into a fermentable liquid, without checking the passage of fluids; and, as no fermentation was then set up, he drew the inference that the "particulate" organic germs, not the soluble material of the yeast, furnish the primum mobile of this change—a doctrine which, though now universally accepted, had to fight its way for some time against the whole force of chemical authority.[1]

A little before Cagniard de la Tour's discovery, a set of investigations had been made by Schulze and Schwann to determine whether the exclusion of air was absolutely necessary to prevent the appearance of living organisms in decomposing fluids, or whether these fluids might be kept free from animal or vegetable life by such means as would presumably destroy any germs which the air admitted to them might bring in from without, such as passing it through a red-hot tube or strong sulphuric acid. These experiments, it should be said, had reference rather to the question of "spontaneous generation," or "abiogenesis," than to the cause of fermentation and decomposition, its object being to determine whether the living things found by the microscope in a decomposing liquid exposed to the air spring from germs brought by the atmosphere or are generated de novo in the act of decay—the latter doctrine having then many upholders. But the discovery of the real nature of yeast and the recognition of the part it plays in alcoholic fermentation gave an entirely new value to Schulze's and Schwann's results, suggesting that putrefactive and other kinds of decomposition may be really due, not (as formerly supposed) to the action of atmospheric oxygen upon unstable organic compounds, but to a new arrangement of elements brought about by the development of germinal particles deposited from the atmosphere.

It was at this point that Pasteur took up the inquiry, and, for its subsequent complete working-out, science is mainly indebted to him; for, although other investigators—notably Professor Tyndall—have confirmed and extended his conclusions by ingenious variations on his mode of research, they would be the first to acknowledge that all those main positions which have now gained universal acceptance—save on the part of a few obstinate "irreconcilables" have been established by Pasteur's own labors. These positions may be briefly summarized as follows:

1. That no organic fluid undergoes spontaneous fermentation or decomposition, even in the presence of atmospheric air, any such action being originated and maintained only by the developmental action of definite organic germs.

2. That different kinds of fermentation (using that term in its large sense) are produced by organic germs of different species. Thus, while torula sets going the alcoholic fermentation in a saccharine wort, other fungoid germs will set up the acetous, and others, again, the putrefactive fermentation, when introduced into fluids of the same kind.

3. That many different kinds of germs—notably those of the bacteria, which induce putrefactive fermentation—are constantly floating in the ordinary atmosphere, so as to be almost certainly self-sown in any organic fluid freely exposed to it.

4. That, if these germs be removed by mechanical filtration, or be got rid of by subsidence, or be deprived of their potency by chemical agents which destroy their vitality, the most readily decomposable organic fluid may be subjected to the freest contact with the air from which the germs have been thus eliminated without undergoing any change.

5. That, as there is no such thing as fermentation without the presence of germ-particles, so there is no such thing as the spontaneous origination of such germs, each kind, when sown in the liquid, reproducing itself with the same regularity as in higher plants, and thus continuously maintaining its own type.

6. That such germ-particles, when dried up, can not only maintain their germinal power for unlimited periods, starting into renewed activity so soon as the requisite conditions are supplied, but that, in this state of dormant vitality, they can be subjected to influences which would destroy the life of the growing plants—such as very high or very low temperatures, the action of strong acid or alkaline solutions, and the like.[2]

The first application of these doctrines to the study of disease in the living animal was made in a very important investigation, committed to Pasteur by his old master in chemistry (the eminent and eloquent Dumas), into the nature of the pébrine, which was threatening to extinguish the whole silk-culture of France and Italy. It had been previously ascertained that the bodies of the animals affected with this disease (whether in the worm, chrysalis, or moth stage) swarm with peculiar minute corpuscles, which even pass into the undeveloped eggs of the female moth, but there was no evidence that these corpuscles were independent, self-developing organisms introduced from without, many regarding their presence as a mere expression or concomitant of the disorder, not as its cause. It would be too long to detail the steps of this most complicated and difficult inquiry, and I must satisfy myself with the mere statement that it not only proved completely successful as to what may be termed its commercial object, but that, though it concerned only a humble worm, it laid the foundation of an entirely new system and method of research into the nature and causes of a large class of diseases in man and the higher animals, of which we are now only beginning to see the important issues.

Among the most immediately productive of its results may be accounted the "antiseptic surgery" of Professor Lister, of which the principle is the careful exclusion of living bacteria and other germs alike from the natural internal cavities of the body and from such as are formed by disease, whenever these may be laid open by accident or may have to be opened surgically. This exclusion is effected by the judicious use of carbolic acid, which kills the germs without doing any mischief to the patient; and the saving of lives, of limbs, and of severe suffering, already brought about by this method, constitutes in itself a glorious triumph alike to the scientific elaborator of the germ-doctrine and to the scientific surgeon by whom it has been thus applied.

A far wider range of study, however, soon opened itself. The revival by Dr. Farr of the doctrine of zymosis (fermentation), long ago suggested by the sagacity of Robert Boyle, and practically taken up in the middle of the last century by Sir John Pringle (the most scientific physician of his time), as the expression of the effect produced in the blood by the introduction of a specific poison (such as that of small-pox, measles, scarlatina, cholera, typhus, etc.), had naturally directed the attention of thoughtful men to the question (often previously raised speculatively) whether these specific poisons are not really organic germs, each kind of which, a real contagium vivum, when sown in the circulating fluid, produces a definite zymosis of its own, in the course of which the poison is reproduced with large increase, exactly after the manner of yeast in a fermenting wort. Pasteur's success brought this question to the front as one not to talk about but to work at, the lead being taken, I believe, by M. Chauveau, the distinguished Professor of Medicine at Lyons, but other investigators (among them our own Professor Burdon-Sanderson) followed closely in his wake. Pasteur's own attention seems at that time to have been chiefly directed to what may be termed the pathology of beer, wine, and vinegar, and to the fight he had still to maintain with the advocates of abiogenesis. I shall not stop to describe the valuable improvements he has introduced into the manufacture of alcoholic and acetous liquors, with a view of preventing those injurious fermentations which often interfere with the normal processes, and sometimes ruin their results, but shall keep to the object I have specially in view, the exposition of those more recent contributions to "preventive medicine," which constitute him the greatest public benefactor of his time.

An epizoötic malady extensively prevails on the Continent of Europe, though fortunately but little known in this country, which is sometimes designated "splenic fever," and sometimes "anthrax" or "carbuncular" disease, while it is known in France as "charbon" or "pustule maligne." In its most malignant form, it causes the death of the horses, cattle, and sheep affected by it, in the course of four-and-twenty hours. In the less severe form of anthrax disease, it occasions great and prolonged suffering, even when final recovery takes place. Both forms seem propagable to man. Between the years 1867 and 1870, above 56,000 deaths from this disease are recorded as having occurred among horses, cattle, and sheep, and 528 deaths among the human population, in the single district of Novgorod in Russia. It appears to be scarcely ever absent from France, and is estimated to involve an annual loss of many millions of francs on the part of breeders in that country, whole flocks and herds being carried off at once, and their proprietors ruined. A mild epizoötic of this type seems to have prevailed in this country between 1850 and 1860; while the "plague of boils," under which many of our human population (my unhappy self among the rest) suffered during some part of that decennium, was probably brought on us by infection from animals. Attention has lately been drawn to a severe and often fatal malady occurring among the "wool-sorters" at Bradford, which is pretty certainly a modification of "splenic fever," communicated by the wool of sheep infected with that disease.

As far back as 1850 it was observed by two distinguished French pathologists, MM. Bayer and Davaine, that the blood of animals affected with splenic fever contained minute, transparent rods; but their fungoid nature and life-history were first worked-out a few years since by a young German physician named Koch, whose account of it was soon confirmed by Cohn, the eminent Botanical Professor of Breslau, and afterward in this country by Mr. Ewart, all of whom "cultivated" the plant in aqueous humor, or some other organic liquid of suitable character, kept at nearly blood-heat. They found the "rods" to be produced by progressive extension from germ-particles of extreme minuteness. At first they are simple tubes divided at intervals by transverse partitions, but after a time minute dots are seen within these tubes, which gradually enlarge into ovoid bodies that lie in rows within the rods, and at last the rods fall to pieces, liberating the germ-particles they included. The minutest drop of the fluid containing these germs, if conveyed into another portion of cultivated fluid, initiates the same process of growth and reproduction, and this may be repeated many times without any impairment of the potency of the germs, which, when introduced by inoculation into the bodies of rabbits, Guinea-pigs, and mice, develop in them all the characteristic phenomena of splenic fever. Koch further ascertained that the blood of animals that succumbed to this disease might be dried and kept for four years, and might be even pulverized into dust, without losing its power of infection.

Here I would stop to cite the prophetic words used by Professor Tyndall, when giving an account to a Glasgow audience, in 1876, of Koch's then recent researches: "The very first step toward the extirpation of those contagia is the knowledge of their nature; and the knowledge brought to us by Dr. Koch will render as certain the stamping out of splenic fever as the stoppage of the plague of pébrine by the researches of Pasteur."

It was but fitting that the complete verification of this prediction should be the direct result of the labors of the illustrious man on whose previous work it was based, although others were at work, more or less successfully, in the same direction.

One of the first questions examined by Pasteur was the cause of outbreaks of "charbon" in its most deadly form among flocks of sheep feeding in what appeared to be the healthiest pastures, far removed from any obvious source of infection. Learning by the inquiries he instituted that special localities seemed haunted, at distant intervals, by this plague, he inquired what had been done with the bodies of the animals that had died of it, and learned that it had been customary to bury them deep in the soil, and that such interments had been made, it might have been ten years before, beneath the surface of some of the very pastures in which the fresh outbreaks took place. Notwithstanding that the depth (ten or twelve feet) at which the carcasses had been buried seemed to preclude the idea of the upward traveling of the poison-germs, the divining mind of Pasteur found in earth-worms a probable means of their conveyance, and he soon obtained an experimental verification of his idea, which satisfied even those who were at first disposed to ridicule it. Collecting a number of worms from these pastures, he made an extract of the contents of their alimentary canals, and found that the inoculation of rabbits and Guinea-pigs with this extract gave them the severest form of "charbon," due to the multiplication in their circulating current of the deadly anthrax-bacillus, with which their blood was found after death to be loaded.

Another mode in which the disease-germs of anthrax may be conveyed to herds of cattle widely separated from, each other and from any ostensible source of infection was discovered by the inquiries prosecuted, a few years ago, by Professor Burdon-Sanderson at the Brown Institution, in consequence of a number of simultaneous outbreaks which occurred in different parts of the country. It was found that all the herds affected had been fed with brewers' grains supplied from a common source; and, on examining microscopically a sample of these grains, they were seen to be swarming with the deadly bacillus, which, when it has once found its way among them, grows and multiplies with extraordinary rapidity.

The next important step in this investigation was the discovery of the modification in the potency of the poison, which can be produced by the "cultivation" of this bacillus. Every one knows that some of our most valued esculent plants and fruits are the "cultured" varieties of types which man would scarcely care to use in their original state, on account of the unpleasantness of their flavor or their semi-poisonous qualities. And, now that we know that these disease-germs are really humble types of vegetation, the idea naturally suggests itself whether they, too, may not be so far modified, by the "environment" in the midst of which they are developed, as to undergo some analogous modification. Two modes of such "culture" suggest themselves: the introduction of the germs into the circulating current of animals of a different type, and its repeated transmission from one such animal to another; and cultivation carried on out of the living body, in fluids (such as blood-serum or meat-juice) which are found favorable to its growth, the temperature of the fluid in the latter case being kept up nearly to blood-heat. Both these methods have been used by Pasteur himself and by Professor Burdon-Sanderson; and the latter especially by M. Toussaint, of Toulouse, who, as well as Pasteur, has experimented also on another bacillus which he had found to be the disease germ of a malady termed "fowl-cholera," which proves very fatal among poultry in France and Switzerland.[3] It has been by Pasteur that the conditions of the mitigation of the poison by culture have been most completely determined, so that the disease produced by the inoculation of his "cultivated" virus may be rendered so trivial as to be scarcely worth notice. His method consists in cultivating the bacillus in meat-juice or chicken broth, to which access of air is permitted while dust is excluded, and then allowing a certain time to elapse before it is made use of in inoculation experiments. If the period does not exceed two months, the potency of the bacillus seems but little diminished; but, if the interval be extended to three or four months, it is found that, though animals inoculated with the organism take the disease, they have it in a milder form, and a considerable proportion recover; while, if the time be still further prolonged, say to eight months, the disease produced by it is so mild as not to be at all serious, the inoculated animals speedily regaining perfect health and vigor.[4]

Thus, then, it becomes possible to affect sheep and cattle with a form of anthrax-disease so mild as to bear much the same relation to the severer forms that cow-pox bears to small-pox; and for this artificial affection with the mitigated disorder, Pasteur uses the term "vaccination." The question that now arises—to which the whole previous investigation has led up—is the most important of all: Does this "vaccination" with the mild virus afford the same protection against the action of the severe, that is imparted by cow-pox vaccination against small-pox? To this question affirmative answers were last year obtained by Professor Greenfield (on Professor Burdon-Sanderson's suggestion) in regard to bovine animals, and by M. Toussaint in regard to sheep and dogs; the former, when "vaccinated" from rodents, and the latter from fluids "cultivated" outside the living body after a method devised by M. Toussaint, proving themselves incapable of being infected with any form of anthrax-disease, though repeatedly inoculated with the malignant virus, and remaining free from all disorder, either constitutional or local. The same result having been obtained from experiments made by Pasteur himself, probably about the same date, with charbon-virus cultivated in the manner previously described, it was deemed expedient by one of the Provincial Agricultural Societies of France that this important discovery should be publicly demonstrated on a great scale. Accordingly, a farm and a flock of fifty sheep having been placed at M. Pasteur's disposal, he "vaccinated" twenty-five of the flock (distinguished by a perforation of their ears) with the mild virus on the 3d of May last, and repeated the operation on the 17th of the same month. The animals all passed through a slight indisposition, but at the end of the month none of them were found to have lost either fat, appetite, or liveliness. On the 31st of that month, all the fifty sheep, without distinction, were inoculated with the strongest charbon-virus, and M. Pasteur predicted that on the following day the twenty-five sheep inoculated for the first time would all be dead, while those protected by previous "vaccination" with the mild virus would be perfectly free from even slight indisposition. A large assemblage of agricultural authorities, cavalry-officers, and veterinary surgeons having met at the field the next afternoon (June 1st), the result was found to be exactly in accordance with M. Pasteur's predictions. At two o'clock twenty-three of the "unprotected" sheep were dead; the twenty-fourth died within another hour, and the twenty-fifth an hour afterward. But the twenty-five "vaccinated" sheep were all in perfectly good condition; one of them, which had been designedly inoculated with an extra dose of the poison, having been slightly indisposed for a few hours, but having then recovered. The twenty-five carcasses were then buried in a selected spot, with a

view to the further experimental testing of the poisonous effect produced upon the grass which will grow over their graves. But the result, says the reporter of the "Times" (June 2d), "is already certain; and the agricultural public now know that an infallible preventive exists against the charbon-poison, which is neither costly nor difficult, as a single man can inoculate a thousand sheep in a day." I have since learned that this protection is being eagerly sought by the French owners of flocks and herds; and, if any severe epidemic of the same kind were to break out in this country, our own agriculturists would probably show themselves quite ready to avail themselves of it. To the "wool-sorters" of Bradford it must prove a most important boon, if they can be led to understand its value.

That this is not to remain an isolated fact, but will be the first of a series of discoveries of surpassing importance (some of them already approaching maturity), is shown by the fact that Pasteur has found himself able to impart a like protection against fowl-cholera by "vaccinating" chickens with its cultivated bacillus.

These wonderful results obviously hold out an almost sure hope of preventing the ravages, not merely of the destructive animal plagues that show themselves from time to time among us, but of doing that for some of the most fatal forms of human infectious disease which Jennerian vaccination has already done—as shown by Sir Thomas Watson in these pages—for what was once the most dreaded of them—small-pox. It is unfortunately too true that, with the reduction of small-pox mortality, there has been an increase in the mortality from measles and scarlatina exceeding that which increase of population would account for, the number of deaths in England and Wales from the former of these diseases frequently exceeding 10,000 in the year, while the annual mortality from the latter averages nearly 20,000, sometimes exceeding 30,000. It scarcely seems too much to expect that before long, as Professor Lister last year suggested, "an appropriate 'vaccine' may be discovered for measles, scarlet fever, and other acute specific diseases in the human subject"; for already, as I have been informed by one of the most distinguished of the United States members of our Congress, researches have been there made, with very promising results, on the "cultivation" of the diphtheritic virus—the mortality from which, in England and Wales, during the last decade, has averaged nearly 3,000 annually, being, for the seven years, 1873-'79, half as great again as the mortality from small-pox during the same period.

Another important line of inquiry, which was supposed by many able pathologists to have been closed by the negative results of previous investigations, has now to be reopened under the new light shed upon it by Pasteur's discoveries: I refer to the relation between cowpox and small-pox. It is well known that Jenner himself, struck with the fact that the protective influence of successful vaccination against the occurrence of small-pox is about the same as that of a first attack of small-pox against its recurrence, suspected that cow-pox might really be small-pox modified by passing through the living body of the cow; and attempts have been made, at different times and in various places, to test the truth of this hypothesis. Before proceeding, however, to discuss that question, it will be advantageous to consider what new light is cast, by recent scientific discovery, on the nature of the protection afforded by successful vaccination.

Notwithstanding the "strong assurance of faith," on the part of Jenner and his immediate disciples, in regard to the permanent efficacy of vaccination, it is certain that, as time went on, a suspicion grew up among vaccinators of long experience, that vaccinia has a tendency to degenerate—i. e., to lose its protective power—in proportion to the remoteness of its derivation from the original (cow) stock. During my own early professional life (1830-'40) in Bristol, this conviction was prevalent among the older practitioners, who recollected the early Jennerian cow-pock. The vesicle (they said) was smaller than the original, and ran its course more quickly; and the want of the slight constitutional disturbance formerly observable at its maturity showed that the body of the subject was not thoroughly affected by the disorder. Hearing in 1838 of a renewed outbreak of cow-pox among cows at Berkeley, Mr. J. B. Estlin (whose pupil I had been) went down thither, and brought back a supply of original vaccine lymph, which (with the assistance of his brother practitioners) was soon diffused through Bristol and its neighborhood, and proved to reproduce the characteristic Jennerian vesicle. The circumstances attending this reintroduction of an original vaccinia, which I have recently detailed elsewhere,[5] strongly impressed me with the idea that the vaccine virus became "tempered" (so to speak) by passing through the human body, its original potency suffering diminution with the increase in the number of subjects through which it had been transmitted; while, at the same time, the proportion of subjects in whom the vaccination "took," which had been small with the original "vaccine," increased when it had (so to speak) become "humanized." This gradual modification we now understand to be the natural result of the continued "cultivation" of vaccinia in the human body; so that the diminution of the protective power of vaccination by such "cultivation" through a long succession of generations is just what might be scientifically expected. A most curious proof of the modification which vaccinia, thus humanized, has undergone, is afforded by the experiments of Dr. Martin (of Foxborough, Massachusetts), who states that, while there is no difficulty in keeping up an original vaccinia for any length of time by continuous transmission through heifers, the humanized vaccinia, if recommunicated to heifers, soon dies out, this retro-vaccination (as Dr. Martin terms it) never succeeding beyond the third remove from the human into the bovine subject.

There can now, therefore, be no reasonable doubt that a very large proportion of the failures, triumphantly adduced by anti-vaccinationists as proofs that the alleged protective power of vaccination is a mere assumption, are attributable to this degeneration, the protection diminishing with the "humanization" of the virus employed, and this being proportional to the remoteness of its derivation from the bovine stock.

During the war between the Northern and Southern States, Dr. Martin (who had previously acquired a reputation for special knowledge of this subject) was specially employed by the Government of the North to proceed to the various localities in which severe outbreaks of small-pox were from time to time taking place, and he most commonly found that there had either been no previous vaccination at all or vaccination with degenerate virus. Armed with a supply of good lymph, and with military authority (which enabled him to practice a really compulsory vaccination and revaccination), he always found himself able to control these outbreaks, and to prevent their recurrence. Anxious, however, to obtain (if possible) a fresh primary stock of vaccine, he advertised extensively for information as to any original case of cow-pock, but could hear of none. And he then imported from France some dried lymph of what is known as the "Bougival" stock, which had been continuously transmitted, through a long succession of heifers, from its original bovine parentage in that place. This transmission he has himself kept up in the neighborhood of Boston (New England) for the last ten years; and he assures me—1. That vaccination from this heifer-stock, if practiced according to his instructions, is quite as successful (in regard to the proportion of cases in which it "takes") as vaccination from the human arm; 2. That the vesicle produced by it is always of the true old Jennerian type, no deterioration having taken place in its long descent from the original stock, such as is produced by "humanization"; 3. That he has never seen either erysipelas or any other of the "accidents" which sometimes (as in my own Bristol experience in 1838) attend the direct vaccination from the original cow-stock; and, 4. That, having offered a considerable reward in all the principal towns of the Union for information as to the occurrence of any case of small-pox within ten years after thorough vaccination with his heifer-lymph, this reward has never been claimed; although, since its introduction, the United States have been traversed (in the years 1874-'76) by an epidemic of small-pox, which will be long remembered there for its peculiar virulence and the wide-spread mortality it occasioned.[6]

This epidemic was clearly the same as that which, had prevailed, with somewhat of the same severity, not only in this country, but also over the greater part of the Continent of Europe, two years previously; and hence there can be little doubt that the high rate of mortality by which it was everywhere characterized must have been due to general rather than to local causes. It had the good effect of frightening many of our local health authorities into a more efficient observance of their duty in regard to vaccination; and the result has been that, during the last two years, the reports of the Registrar-General show an almost complete extinction of small-pox in the nineteen great towns, whose aggregate population (about three and three quarter millions) equals that of the metropolis. The fresh outbreak which has taken place during the first half of the present year has been almost entirely restricted to the London area, and evidently points to the importance of a more strict enforcement of the vaccination law, which is at present rendered nugatory, as regards no inconsiderable proportion of the metropolitan population, by the migration of families from one district to another.

The prolonged experience of Dr. Martin, in regard to the facility of keeping up heifer-vaccination continuously from the original stock, altogether confirmatory as it is of what has been reported on this subject from France, Belgium, and St. Petersburg, seems to me to justify the demand that our Government should maintain the requisite establishment on a sufficient scale to meet the requirements of the whole country, so that every vaccination and revaccination may be performed (if desired) with lymph derived from the original cow-stock, without any humanization whatever.[7] The vaccinia of Jenner may be thus maintained in its original efficacy, without the impairment of its protective influence by prolonged "cultivation" in the human subject, and thus only can it be secured against the contaminating influence of human disease, the liability to which furnishes the anti-vaccinationists with their strongest weapon.

No benefit can be reasonably expected from the adoption of any system which is based on the induction of vaccinia in a calf or

heifer, by inoculation with lymph which has been "humanized" by long transmission through a succession of human beings. For, as is proved by Dr. Martin's experiments on this retro-vaccination, such lymph has been so altered by "humanization" that the germs it contains do not properly reproduce themselves in the system of the calf, thus showing that it no longer possesses the attributes of true vaccinia. And, although the liability to contamination from human disease may be thus greatly diminished, it can not be certainly said to have been destroyed.

We now come to the bearing of Pasteur's researches on the question of the fundamental identity of small-pox and cow-pox, originally mooted by Jenner. Attempts at its solution were made, early in the present century, by the inoculation of bovine animals with small-pox virus; and it was asserted that in this way true vaccinia had been artificially produced. But the evidence in support of this assertion did not command general assent; and it was not until Dr. Thiele, of Kazan, published, about forty years ago, an account of his experiments, that the doctrine obtained any considerable amount of acceptance. According to the citations given by Mr. Simon, in his valuable "Report on Small-pox and Vaccination," issued under Government authority, in 1857, Dr. Thiele not only repeatedly succeeded in producing a genuine vaccinia by inoculating bovine animals with small-pox virus, but himself used this artificial vaccine largely and successfully in human vaccination, and propagated it extensively by the instrumentality of other vaccinators, its protective power being found to be fully equal to that of the natural vaccinia. But, further, Dr. Thiele asserted that he could produce this artificial vaccine without the use of the cow at all, by diluting the small-pox virus with warm milk, or, as we should now term it, "cultivating" its living germs in that fluid. I can scarcely help thinking that the great improbability as it then seemed—of such a conversion has thrown a discredit upon the whole of Dr. Thiele's statements, which has caused them to be ignored by most subsequent workers on this subject. But, should that part of his results be ever confirmed, he must be accorded the credit of having anticipated in a most remarkable way one of the most important of Pasteur's methods, though, it is pretty certain, without knowing, or even guessing, their true rationale; for it must have been not by dilution of the virus (like that of a chemically acting fluid), but by a modification in the character of the disease-germs resulting from their development in milk, that this part of Thiele's results (supposing them to be genuine) was produced.

Simultaneously with those of Dr. Thiele, a set of experiments of the same kind was being carried on in our own country by Mr. Ceely, of Aylesbury; the results of which, however, were not equally satisfactory. He did, it is true, produce an eruption in cows inoculated with small-pox virus, which was transmissible by inoculation to the human subject, but this eruption seems to have had rather the character of a modified variola than that of a true vaccinia; and, as its transmission by inoculation through a succession of human subjects did not produce what the best judges considered a genuine cow-pock, it was allowed to die out. The case was very different, however, with another set of experiments made a few years afterward (in ignorance of Mr. Ceely's) by Mr. Badcock, a druggist at Brighton, who was led to institute them through having himself suffered an attack of small-pox, though vaccinated in early life, and having been thus led to suspect that the protective power of vaccination had undergone deterioration. From the account he gave of his work in a small pamphlet published in 1845 (for a sight of which I am indebted to his son), it appears—1. That he inoculated his cows with small-pox virus furnished to him from an unquestionable source;[8] 2. That this inoculation produced vesicles which were pronounced by some of the best practitioners of Brighton to have the characters of genuine vaccinia; 3. That lymph drawn from these vesicles, and introduced by inoculation into the arms of children, produced in them vaccine vesicles of the true Jennerian type; 4. That free exposure of some of these children to small-pox infection showed them to have acquired a complete protection; and, 5. That this new stock of "vaccine" had been extensively diffused through the country, and had been fully approved by the best judges of true vaccinia, both in London and the provinces.

Mr. Simon, writing in 1857, stated that, from the new stock thus obtained by Mr. Badcock (not once only, but repeatedly), more than 14,000 persons had been vaccinated by Mr. Badcock himself, and that he had furnished supplies of his lymph to more than 4,000 medical practitioners. And I learn from Mr. Badcock, junior, who is now a public vaccinator at Brighton, that this stock is still in use in that town and neighborhood.

Against these positive results are to be set the negative results of attempts made in the same direction by many other able experimenters, such as Professor Chauveau and his coadjutors, the recent Belgian Commission, and Professor Burdon-Sanderson, as well as the unsatisfactory results obtained by Ceely. But I can not see that their non-successes are in any way contradictory of the absolute and complete successes which, if testimony is to be trusted, were obtained by Thiele and Badcock. The lesson taught by the failures appears to me to be the careful imitation of the conditions under which the successes were obtained; and, as Mr. Badcock, senior, is still living, and is said to be both able and willing to give all needful information, it is the intention of Professor Burdon-Sanderson and myself to take an early opportunity of personally obtaining this from him, with a view to a careful and thorough testing of his experiments, with every precaution that experience can devise.

The recent meeting of the Medical Congress has given me the opportunity of personal communication on this subject both with M. Pasteur and M. Chauveau. From the former I learned that his use of the term "vaccination" in connection with his employment of the mitigated virus of "charbon" and "chicken-cholera," as a protective against the malignant forms of those diseases, was intended rather as a compliment to Jenner than as expressive of any belief in the identity of vaccinia and variola. This question, he said, was one which he had not himself investigated, and on which he did not feel himself justified in forming an opinion. But, when I asked him whether he considered it to have been already decided in the negative, and further informed him of the positive evidence afforded by Mr. Badcock's experiments, he expressed himself strongly in favor of regarding the question as still open, to be decided by further researches carried on under the new light afforded by the results of his own recent investigations. I found M. Chauveau himself not less willing to admit the force of the strong analogy between the protective agency of the Jennerian and what I may term the Pastorian "vaccination," and not less ready to accept the results of any thorough reinvestigation of the subject. Such a reinvestigation I hope shortly to see carried out at the Brown Institution by the accomplished young successor to Professor Greenfield, under the superintendence and with the co-operation of Professor Burdon-Sanderson, in whose great knowledge, long experience, and wise judgment, all who know him and his pathological work have the fullest confidence.

 

Now, putting altogether on one side the purely scientific interest of this investigation, let us see in what position we shall be, if it should issue in the confirmation of Jenner's view of the fundamental identity of vaccinia and variola, proving cow-pox to be not a disease sui generis, but small-pox modified by passing through the cow.

In the first place, we shall have the scientific basis for the practice of vaccination, which it has never yet possessed; for it will be then clear that the protective power of vaccination is exactly the same in kind—as it has long been known to be about the same in degree—as that of a first attack of small-pox.

Secondly, the "common-sense" argument in favor of vaccination will be greatly strengthened by the proof that we are not poisoning the blood of our children with a new disease (which some of the most vehement of the anti-vaccinationists maintain to be already destroying the vitality of the nation), but are merely imparting to them in its mildest form a disease which every one is liable, without such protection, to take at any time. Those who would hasten to protect their flocks and herds by Pastorian "vaccination" against a deadly "charbon" raging in their neighborhood—as who would not?—can not, in common consistency, refuse Jennerian vaccination for their children.

And, thirdly, we shall be furnished with the means of obtaining, at any time, an original stock of vaccinia, the continuous transmission of which through a succession of heifers will at the same time secure the maintenance of its potency, and exclude the chance of human contamination.

 

Among the numerous other researches now being followed out on the Pastorian lines, I may notice two as likely to prove of the highest practical importance: those which, in the hands of Drs. Klebs and Tommasi Crudeli, seem likely to demonstrate that marsh-malaria derive their potency from organic germs (an idea that singularly harmonizes with the periodicity which is the special character of the varied forms of disease they induce), and those which, based on the original discovery of Villemin (in 1865) as to the communicability of tubercle by inoculation, are rendering it probable that this terrible scourge (including not only pulmonary consumption, but scrofulous disease in all its varied forms) really depends on the presence of a microphyte, which may be introduced into the body, not merely by direct passage into the blood-current (as in inoculation), but also through the alimentary canal, or even through the lungs. This doctrine, which was first advanced by Professor Klebs four years ago, has lately been the subject of most careful research by Dr. Schüller, of Greifswald, who has shown that every form of tuberculosis can thus be artificially induced, the characteristic micrococcus spreading rapidly in the blood and tissues of the animal inoculated with it; and that if, in an animal so infected, any joint is experimentally injured, that joint at once becomes a place of preferential resort to the micrococcus, and the special or exclusive seat of characteristic tubercular changes—a fact of the utmost practical interest in its relation to human joint-diseases. Another line of inquiry, which has obviously the most important bearing upon human welfare, is the propagability of the micrococcus of tubercle by the milk of cows affected with tuberculosis, a question in regard to which some very striking facts were brought before the Medical Congress by a promising young pathologist, Dr. Creighton.

Well might Mr. Simon conclude his admirable address as President of the Public Health Section of the Congress with these pregnant words: "I venture to say that in the records of human industry it would be impossible to point to work of more promise to the world than these various contributions to the knowledge of disease, and of its cure and prevention; and they are contributions which, from the nature of the case, have come, and could only have come, from the performance of experiments on living animals."—Nineteenth Century.

  1. It was, I remember, in or about that year that Professor Liebig's visit to England gave me the opportunity of showing him some yeast under a high power of the microscope. He said that he had not before seen its component cells so distinctly.
  2. The evidence on which these conclusions rest is fully stated in Professor Tyndall's recently published treatise on the "Floating Matter of the Air."
  3. I have seen notices of its serious prevalence during this very summer in some of the localities most frequented by tourists.
  4. It is not a little curious that as culture of one kind can mitigate the action of the poison-germs, so culture of another kind may restore, or even increase, their original potency. It has been found by Pasteur that this may be effected by inoculating with the mitigated virus a new-born Guinea-pig, to which it will prove fatal; then using its blood for the inoculation of a somewhat older animal; and repeating this process several times. In this way a most powerful virus may be obtained at will a discovery not only practically valuable for experimental purposes, but of great scientific interest, as throwing light upon the mode in which mild types of other diseases may be converted into malignant. By Dr. Grawitz, indeed, it has been recently asserted that even some of the most innocent of our domestic microphytes maybe changed by artificial culture into disease-germs of deadly infectiveness.
  5. See the "Lancet," May 10th.
  6. The distinguished American physicians, whose attendance at the recent Congress gave me the opportunity of conversing with them on this subject, entirely confirmed Dr. Martin's account of the severity of that epidemic, which, in some respects, bore such a resemblance to the "Black Death" that carried off what was estimated at one third of the population of Europe in the fourteenth century, as to suggest that the latter may have been really a peculiarly malignant small-pox. My friends greatly regretted the want in the United States of a system of "compulsory" vaccination; but said that, when outbreaks of small-pox occurred in their towns, the municipal authorities took the matter in hand, and insisted on the immediate vaccination and revaccination of all dwellers in the infected localities, by which means these outbreaks were brought under control. As there is no registration system in the American Union, I could not obtain any definite information as to the amount of its small-pox mortality; but no one seemed to entertain the least doubt as to the preventive efficacy of vaccination.
  7. I am assured by Dr. Martin that vaccination with heifer-lymph dried on ivory "points" succeeds in as large a proportion of cases as vaccination with fresh human lymph, provided that it be practiced according to the method which his large experience has led him to adopt as the most effective.
  8. The only possible fallacy in these experiments, as it seems to me, might lie in his medical friend, Mr. (afterward Sir J.) Cordy Burrows, having supplied him with vaccine lymph, instead of with variolous virus. But, though this might have been the case once or twice, it could scarcely have happened several times, except by design, which is scarcely to be thought of.