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Watson in these pages-for what was once the most dreaded of themSmall-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 Cow-pox 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 cowpox 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

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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 neighbourhood, and proved to reproduce the characteristic Jennerian vesicle. The circumstances attending this re-introduction of an original vaccinia, which I have recently detailed elsewhere, 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 ; whilst, 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 humanised.' 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 migbt be scientifically expected. A most curious proof of the modification which vaccinia, thus humanised, has undergone, is afforded by the experiments of Dr. Martin (of Roxborough, Massachusetts); who states, that whilst there is no difficulty in keeping up an original vaccinia for any length of time by continuous transmission through heifers, the humanised vaccinia, if re-communicated 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 antivaccinationists as proofs that the alleged protective power of vaccination is a mere assumption, are attributable to this degeneration; the protection diminishing with the humanisation 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 practise a really compulsory vaccination and revaccination), be always found bimself 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

s See the Lancet, May 10.

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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 neighbourhood of Boston (New England) for the last ten years; and he assures me,(1) that vaccination from this heifer-stock, if practised 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 humanisation'; (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.

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 characterised 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 3 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.

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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 re-vaccination 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 dcubt as to the preventive efficacy of vaccination.

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 re-vaccination may be performed (if desired) with lymph derived from the original cow-stock, without any humanisation whatever. 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 “humanised' 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 humanisation, 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 cannot 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 induced. But the evidence in support of this assertion did not command general assent; and it was not until Dr. Thiele of Kasan 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

? 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 practised according to the method which his large experi. ence has led him to adopt as the most effective.

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 afterwards (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 ;

& The only possible fallacy in these experiments, as it seems to me, might lie in his medical friend, Mr. (afterwards 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.

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