March

KING ON ANIMAL VACCINE.

1894.]

?riginal (Ccrmnutiriqaiioitr).

?

/

ANIMAL VACCINE: ITS ORIGIN A.ND CULTIVATION. By W. G. King, m.b., c.m., d.p.ii., Aberdeen, Surgeon-Major, Indian Medical Service.

(Continued

from page 218 of

July 1893.)

No. III. The existing difference of opinion as to experiments by various observers would dictate the desirability of an attempt to discover the cause bv comparison of the methods pursued and the results obtained. The material for such an

investigation is, unfortunately, incomplete, as several observers have placed but scanty infor-

on record; but such as is obtained I now propose to note. As a preliminary it may be conceded that there are certain general points In view of the fact on which all critics agree. that the Lyons' Commission, Martin, "Woodhouse, and others have produced small-pox in the human being after attempting to inoculate bovines, it may at once be allowed that disastrous consequences in the hands of certain experimenters have occurred. It may also be conceded that led by experience of the results of sinall-pox inoculation and of cow-pox on the human being, the early observers were predisposed, as shown by the history of their enquiries, to regard vesiculation at the point of insertion as the sign of success; although they, doubtless, also held in view the possibility of a general eruption occurring. Certain observers also believed there was more likelihood of securing results by flooding the animals experimented upon with a quantity of the virus. The favourable sites for inoculation were the teats and vulva of the heifer, and the ears and the scrotum of the Btirlc. Lastly, most observers probably agree that, failing the possibility of it being ultimately shown that certain as yet undetermined conditions will invariably secure success, bovines are not easily infected with small-pox. Perhaps the quickest way to render the accumulated experience available is, first of all, to consider the circumstances under which experimenters gained positive results, and then those under which negative results were secured. Ceely's Experiments. No. I (February 1st, 1839).?a white and red stirh, ten months old, having a thin skin and of gentle disposition, was inoculated with virus from selected plump vesicles in eases of healthy young men, on the seventh or eighth day of the disease. Inoculation was effected twelve hours after collection. I he virus was introduced by punctures on the vulva. Setons saturated with the virus also were used. Result.? Up to the sixth day, there was tumidity at the sites of insertion, although the

mation

81

majority had gradually faded awav. On the ninth day, the experiment being considered of no utility, vaccination on the other side of the vulva

resorted to. One of the trivial spots the small-pox insertions now developed vesicle.

was

denoting into

a

Experiment, No. II (a).?The small-pox virus used was the same as in Experiment No. I; the method of insertion was similar. The subject was a white stirk with thin skin. Result.?Papules advancing up to sixth day, by their gradual decline. Experiment No. II (b).?Re-inoculation was

followed

undertaken with virus of the seventh and

eighth

opaque, some pellncid. This was derived from a case of variola discreta, and had been stored in capillary tubes.

day,? some being

Result.?Papules increasing till the sixth day, when vesicles appeared. From this date, the old papules on site of first inoculation developed till they appeared as oval, circular, solid rings, having central depressions. By the tenth day, these papules had become vesicular also. The lymph derived was used on the human being at the first generation, with the result of producing rashes, but none having the character of smallThe constitutional symptoms of vaccine pox. were severe, but the secondary symptoms were in proportion to the extent of areola only. Ceely concludes from his experience that by preference small-pox lymph should be taken on the fifth or sixth day, and not later than the

seventh or eighth, ami that superficial wounds in the condition of scabbing?practically abrasions ?offer the best mode of infection.

Budcock, as a result of his successful experiments, maintained that variola lymph should be used alone, i.e., not side by side with vaccine; that the virulence of the virus, as judged by

being derived from discrete or confluent cases, is of no importance. That young cows that had recently calved should be preferred, and that the udder should be shaved before inoculation. Badcock inoculated a healthy young cow with small-pox lymph from a strong healthy girl. I have not been able to secure any further details of his mode.

Dr. Cleveland, of the Madras Medical Service, also about the year 1863, seems to have conducted successful experiments, of which also, unfortunately, I can find no record. He, however, states as

follows:?

"

That vaccine lymph speedily degenerates, so that its prophylactic virtues are weakened and its protective power over the system diminished, lias been much noticed of late years amongst medical officers serving in damp tropical climates, as in Burmah and the Western Coast. Lymph obtained from the best sources has been hermetically sealed and preserved in other respects 16

82

INDIAN MEDICAL GAZETTE.

with every possible precaution, ami in these countries found to be inefficient after a brief use. "In the usual peripatetic career of an Assistant Surgeon on the Madras Establishment, it has been my lot to vaccinate during the last, ten years, at several stations in Southern India, on the Eastern and Western Coast, and inland, as well as at every station on the Sitang iti Bunnah, and my observation corresponds with that of The same lymph successfully used in others. Tanjore and Tinnevelly, was soon found inefficient in Travancore and Malabar. " There is little doubt, however, that we have the remedy at hand, and that the inoculation of with variolous lymph a cow in a fit condition from the human subject at a fit stage will furnish us at. a definite period with vaccine lymph, fresh The scepand effective, genuine and protective. tical mind may not be readily disposed to accept the experiments of Ceely and others on this point,?perhaps not admit the established facts (Wilson," Skin Diseases," page 507) of the transmission by inoculation of the small-pox to cattle and the consequent development of cow-pox in those animals, and of the transmission by inoculation of the cow-pox to man, and the consequent development of a pustule similar in character to the vaccine-pox of the cow. " The test only requires, like all others, to be rightly exercised,?the first step of which, the condition of the animal t be inoculated, should be left to the judgment of the Veterinarian ; for the second, my own experiments lead me to believe that we should take the variolous lymph from the human subject at the proper vesicular stage of the disease, or about the fifth day." Shortt's Experiments.?Experiment No. I (at. Simrnery, North Arcot District, October 1866.) Small-pox virus of the 17th to the 19th day was obtained from a boy 14 years old. Dr. Shortt " speaks of this virus as pus." A heifer 18 months old was inoculated by punctures on the teats On the sixth day, a papule containing and ears. clear lymph was used for transfer to three cases; all gave characteristic vaccine vesicles. Three cases were subsequently vaccinated at Madras Town with the same lymph sent there in tubes. In all, characteristic vaccine vesicles without secondary results occurred. Experiment No. I (a).?On inoculation of a bull calf with this same lymph, glandular enlargement and very numerous small tumours were produced throughout the body. Dr. Shortt does not say whether he opened these tumours The animal was apto ascertain their contents. parently discharged without any transfer being made. Experiment No. II.?A heifer two years old was inoculated direct with was selected, and of the virus seventh day, which is stated small-pox On the sixth day, there reto have been clear. sulted an umbilicnted papule, and on the seventh

[Marcs

1894.

became vesicular. " One or two " additional vesicles also appeared over other sides of inserThis lymph was not transferred to human tion. beings; but the experiment was noteworthy. Dr. Shorrt mentions speciiically that vesicles resulted, although in Experiment No. I he mentions that he took the lymph from " papules." tins

No. III.? A black bull, two years the subject; the lymph was of the fourth morning of the eruption. On the thirteenth day the papule was broken and clear lymph was obtained. Dr. Shortt was long known in the Madras Presidency as an earnest worker, and whatever subject, he put his hand to was laboriously investigated. In these experiments he iuoculateil and vaccinated dogs, goats, donkeys and ponies. In fact, lie pressed into his service every representative of the live-stock usually to be found in villages. Possibly, the choice was made at times on the spur of the moment; for, with considerable naivete, he explains to his readers his reason for not being able to record the result of the inoculation of a certain pony, as due to the circumstance that the pony happened to be a traveller's of which he was not aware at the time, and that, consequently, lie was not in a position to give the further history ! With the exception of the first three cases, Dr. Shortt's transfers to the h uman body which were conducted personally, were followed by secondary eruptions of the character of small-pox; but, as already stated, when the same variola-vaccine lymph was sent to Madras for trial at the Vaccine Depot, 110 untoward effect followed. Dr. Sliortt attempts to explain this difference of results to "epidemic influence" intensifying the action of the vaccine amongst the subjects of the experiment at Arcot when small-pox was present, whilst this condition was absent in Madras. It is, however, much more reasonable to believe that either he used instruments indifferently for vaccination and inoculation without due precaution as to their sterilization, or that his subjects 011 the spot were infected naturally?a very likely result in the case of a people who not only do not fear small-pox, but superstitiously court infection. It seems unlikely in the extreme that lymph capable in one locality of conveying small-pox, would not have conveyed it equally in any If this view of the matter be taken, other. Dr. Shortt must be regarded as having succeeded in securing vaccine. Voigt.?In 1881, Voigt used variolous lymph of the fourth day of eruption; at the same time he inserted ordinary vaccine lymph in parts of the body well removed from the sites of inoculation with variola. Four of the insertions of variolous virus failed; but, on the fifth spot, he secured a round greyish but not umbilicated On the sixth day lie used the lymph vesicle. from this vesicle direct upon a scrofulous child

Experiment

old,

was

March

KING ON ANIMAL VACCINE.

1894.]

with the result that considerable fever and auxithe vaccine vesicles were typical. From the produced, however, he started a new child this from taken lymph stock upon calves.

liary enlargement, followed;

of the Royal Commission stated that now sitting, it is on Vaccination Voigt's stock was lost on account of degeneration occurring following the retention of the animals in ill-ventilated sheds. On the other hand, Professor Crookshanks gives the following version of the supposed loss of this stock :? In the Second

Report

" From the mere resemblance which existed between late removes of 'variola-vaccine' and ordinary vaccine, Voigt believed that he had succeeded in transforming small-pox into cow-pox. Voigt was misled by appearances in precisely the same way as Ceely and others who have succeeded in reducing small-pox to the appearThe true variolous ances of a vaccine vesicle. character of the 'variola-vaccine' lymph, and the tendency, in less early removes, to produce small-pox, is probably the reason why Voigt has abandoned its use in favour, as I am informed by M. Lnyet, of the ordinary spontaneous cow-pox lymph, from the Vaccination Station at Rotterdam." The following information has been courteously placed sit. my disposal by Dr. Voigt. in a letter dated 20th May 1893, showing that, another instance of reversion upon which the followers of Chauveav have relied, never existed : ?

"I got my variola-vaccine stock in 1881. From that time until now this lymph stock has

83

"During :il 1 these twelve years, there was not to be found the slightest trace of its origin from

small-pox. "

Mv

new

variola-vaccine stock

was,

in the year

1882, when I used it first for

public vaccination, the Beaugency stock,

much more vigorous than which I used previously ; not only the security of successful vaccination of children and animals by inoculating from body to body was much improved, but also the duration of the stored lymph much more insured. Afterwards it has since maintained only the value of ordinary good vaccine, not better and not weaker than the lymph, that is propagated in other countries." Simpson'sExperiments.?In 1884, Dr. Simpson, using small-pox virus, raised a vesicle upon a ewe lamb. In 1885, he produced a vesicle upon a cow and a sheep. For the cow fifth-day, for the sheep eighth-day, small-pox virus had been employed; again, in 1886, he raised vesicles on a cow and ewe. The lymph from the cow was forwarded to Dr. Cory, and was used freely, as already stated, with safety at the Animal Vaccination Station, London. These several experiments were conducted in Aberdeen. At Calcutta, on March 4th, 1892, he inoculated a calf by punetures and incisions, with small-pox virus of the fifih day of eruption by direct transfer. This experiment was of the most, convincing nature, and it ought to be impossible for the The followers of Chauveau to point to a flaw. experiment was conducted in the presence of On the sixth numerous professional witnesses. three of there inoculation, papules day appeared on the groin; by the seventh day these had become vesicles and continued to develop till the 10th day. Vesicles were also found at the sites of inoculation. By the tenth day successive crops of secondary vesicles on the thigh and groins made their appearance. The lymph was used successfully on the human being in the fifth generation. He has since used lymph of the second generation without any but satisfactory results. JEternod and Huccins, in December 1890, announced in the Semuine Medicale that they had successfully cultivated lymph from vaccine from small-pox virus, but refrained from giving a detailed description of their experiments which they promised to afford subsequently. In May 1891, Dr. Eternod replied to Chauveau's objections at. the Society Vendoise de Medicine. In 1892, they published a brochure giving a detailed account of their experiment as promised. They employed calves of three to four months All the usual precautions as to sterilizaold. tion of instruments were carefully exercised. virus of various days' duraThey used

been in common public use, as well in Hamburg in great part, of Germany, and now also during many years in the Royal Central Vaccination Institute of Denmark at Vyobenhaon. All contrary assertions concerning this variola-vaccine stock, as given by Layet, ' Traite de la vaccine animale,' page 103, and by Crookshanks in liia * Pathology of Vaccination,' are merely erroneous, and I do not, know why, or in what manner, these gentlemen got this and much other erroneous information. 1 have propagated my lymph always from one calf to the other except in the years 18^6 and 1887. At that time the Vaccination Commission in Berlin directed that the shaved area of the animals, previous to inoculation, be washed with a solution ot sublimate of In consemercury 1 : 10000. quence of this treatment, my lymph stock lost, at. that time some of its vigour, and I was compelled (1 believe four times) to let one generation of this vaccine pass through a human being for the sake of maintaining the vigour of it. In small-pox the autumn of 1887 I stopped treating the fion. more or less clear and often purulent. shaved area of the animals with sublimate, and Experiment No. I.?Two tubes of clear lymph since then I have been able to were variolathis plant employed by punctures, scarifications and vaccine lymph A vesicle appeared on the sixth day up to date without difficulty from abrasions. one animal on to the other. at the site of insertion.

as

INDIAN MEDICAL GAZETTE.

84

Experiment No. II.? A male calf was inoculated with the contents of three tube* of variola virus slightly opaque from a male 28 years old vaccinated in childhood, hut suffering from a confluent attack. On the fourth day, a small vesicle ?was obtained on the abrasion near scrotum ; on the fifth day, a second vesicle appeared. In the fourth generation of cultivation oil the calf, secondary vesicles were produced. No. III.?Virus from a case of small-pox in an unvaccinated child was employed on the posterior part of the scrotum of the calf; a typical vaccine vesicle developed. The sites of inoculation gave no results beyond the usual papular elevation.

Experiment

confluent

January several Professors of who had been invited to an inspection of results 011 a calf inoculated in part with variola-vaccine and with ordinary vaccine, stated they could not distinguish them. M. Haccius makes the following deductions from their experiOn the 27th

Medicine,

ments

:?

"From the preceding remarks, we are authorized to conclude that the variola virus by its passage through the animals undergoes a transformation or at least a modification in its nature. Favoured by these successive passages, it loses its malignity and acquires the mild character of vaccine in producing a vesiculation localized at To arrive at the experithe points of insertion. mental proof it is necessary to observe a particular technical operation, otherwise the result * will be nil * * If we had not taken care to use scarified and abraded surfaces it is probable that our inoculations of variola would not have been successful. This procedure is a most important factor for securing success."

Ilime.?On the 16th

May 1892, Dr. Hime, of used variola lymph that was perfectly limpid, transparent and translucent,from a severe case of semi-confluent eruption in a woman aged thirty-seven years. The calf chosen was ten weeks old. Three abrasions and fourteen incisions were made. On the fourth day, all points of insertions having faded away without apparent action, four papules, otherwise than on the site of insertion, appeared. On the fifth day, two more papules of the same description made their appearance. By the eighth day, these papules had become vesicular. The lymph obtained was scanty, but perfectly clear and limpid. Two vesicles had also developed 011 the site of insertions. This first generation was used upon Dr. Hime'sown person and upon a friend ; and, although both had been " " effectually re-vaccinated, the insertions took. A child was vaccinated also with the second reBradford,

move

successfully.

Dr. Hime,

011

remarking

the results obtained, lays stress on his choaeu the calf instead of the cow.

(To

be

continued.)

on

having

/

TMarch 1894.

Animal Vaccine: Its Origin and Cultivation.

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