cination, Moses Cleaveland, of Canterbury, Connecticut, made his crucial experiment on the banks of the Cuyahoga, by staking out a town plot and risking his reputation, as Jenner did, in an attempt to inoculate the fertile soil of the Erie shore with the germs of modern progress and industry, and so give to this region a new page of history, in which the welfare of mankind should be written over and cover the dark stains of rapine and desolation, with which Shawanees, Wyandottes and Kickapoos had for centuries marked its virgin forests and crystal streams. Not greater are the changes which we behold in looking about to-night, than those which the century has brought in regard to the prevention of that plague referred to by Ben Jonson in an "Epigram to Smallpox :"

Grievous and foul disease, could there not be

One beauty in an age, and free from thee?

It was on May 14, 1796, that Jenner made his famous experiment on the boy James Phipps by inoculating him with lymph taken from a cow pox vesicle on the hand of Sarah Helmes, a dairy maid, in two superficial incisions on the arm, and it was in the following July that Jenner inserted by several incisions virus from a smallpox pustule into the same boy. The miracle was performed, for no disease followed, since the boy had been protected by vaccination.

In 1798, Jenner published his "Enquiry into the Causes and Effects of Variolæ Vaccinæ." In the following years further observations were published. The following extracts from the Life of Jenner published in 1838 by Baron, M. D., F. R. S., late Senior Physician to the General Infirmary, Gloucester, Jenner's own country town, will serve to recall smallpox as it existed in the 18th century.

P. 257. From authentic documents and accurate calculations it has been ascertained that 1 in 14 of all that were born died of smallpox. Of those who recovered very many were permanently disfigured or deprived of eye-sight.

P. 262. It has been proved by the records of the London Institution for the In

digent Blind that three-fourths of the subjects relieved had lost their eye-sight through smallpox.

P. 264. The colonial Government of Spanish-America adopted vaccination with such success that very soon after the arrival of Balmis' celebrated expedition the smallpox was exterminated in the department of Venezuela.

P. 265. Vaccination was introduced into Vienna by Dr. De Carro in May, 1799. In the year 1804 only two persons died of smallpox in that city and these two were imported.

P. 266. Vaccination was introduced into the Royal Military Asylum of England in 1803, and up to 1811 only one child had died of smallpox, and that one had not been vaccinated.

P. 267. Between 1802 and 1810, 128,732 persons were vaccinated in the Island of Ceylon. The consequence was that smallpox was unknown on any part of the island from February, 1808 to 1809, when it was introduced from the Malabar coast, and spread to a few individuals who had not been vaccinated; but its progress was instantly arrested. In Ceylon previous to vaccination, smallpox used to rage with dreadful severity.

P. 271. In 1823 smallpox was epidemic in Prussia, but in Berlin there were but 200 cases and 5 deaths, while in 1801 previous to vaccination 16,000 had smallpox and 1,646 died. The vaccination establishment was instituted in 1802.

These figures possess an extreme interest since they set forth facts relating to conditions, when sanitation, as to-day understood, did not exist, and the social conditions and the crude municipal machinery permitted disease, so far as isolation and disinfection were concerned, to go on unchecked until the fires went out for want of fuel.

De Freycinet of Paris has stated that in 1871 when vaccination in France was not compulsory the French army lost 24,000 from smallpox, while in the German army with compulsory vaccination there were but 459 deaths in two years in a much larger army.

Dr. Farr, Reg. General of England, states that in the periods: 1838–1853, the deaths from smallpox were .5 per 1,000; 1854–1871, .38 per 1,000; 1872-1882 (the period of the severest type of modern times) the deaths from small pox were .26 per 1,000; 18821891, .07 per 1,000.

These figures have been quoted again and again, but they must ever have the same value as illustrating the change which a century of science has wrought. It is, gentlemen, more than twenty years during which it has been my duty as a provincial officer to deal with this disease in a population of over 2,000,000, and I may here be pardoned if in order to illustrate this story yet more I refer to a single epidemic, which raged for months in the Province of Quebec, more furiously than had any epidemic of the 19th century in America. Apart from the deaths in the whole Province, this outbreak occurring in 1885, caused 3,175 deaths in seven months in Montreal; while in the Province of Ontario, daily receiving travelers by train and boat from that city, through compulsory vaccination and inspection of all travelers, amounting on trains alone during the four months of inspection to 112,320, added to an unusual activity of local Boards of Health in the matter of general vaccination, there resulted from 42 distinct importations of the disease from Montreal but 146 cases. Some 17 of these occurred in the early part of the epidemic before inspection began. As a result of the efforts put forth, the Province of Ontario with a generally vaccinated population had but 23 deaths during 1885, while more than 7,000 occurred in the French Province, where an anti-vaccination propaganda had flourished for years and where many people gave way to a fatalistic belief that it was the will of God.

With such personal experience many years ago of smallpox epidemics, one may be forgiven, gentlemen, in spite of all which has been said and written during the past three years, concerning a type of smallpox which has been present of a mildness unprecedented in temperate climates since the time of Sydenham who described

its prototype in 1771, if he adopt as a motto the words of the prophet of old, "Stand ye in the ways and seek and ask for the old paths, where is the good way and walk therein."

Now though it is an historical as well as a modern scientific fact that vaccination has protected and will protect to-day against smallpox, it nevertheless becomes incumbent upon us to precisely understand just what Jenner meant by vaccination, and what has been implied in the term by all the great teachers and practisers of the art during the past century, and what we understand by it to-day. Without going greatly into detail it may be said that what Jenner did, and what he taught, was to introduce by inoculation a disease, which causes a vesicle of a particular character on the teats of a cow, or on the tender skin of the belly or flanks of a calf, the virus of which when inoculated into a person, produces a vesicle of a similar character. The vesicle can be produced through inoculating several calves in a series with virus from a smallpox patient, and that smallpox virus thus modified produces in other calves, in man and monkeys a disease, vaccinia, which protects against smallpox completely, in practically all cases for 10 years, in a great percentage for 20 years and which, though the protection decreases with the distance of years from primary vaccination, yet always produces a marked effect in lessening the virulence of smallpox, should a person once vaccinated take the disease.

The experiments of Pearson, Tanner and Barry had fully proved by 1801 Jenner's teaching that cow-pox and grease, or true horse-pox, were sources of a vaccine protective against smallpox; while it is of much practical interest to remember that Drs. Pearson and Woodville of London, physicians to the smallpox hospital, obtained their first lymph in 1799, not from Jenner, but from an outbreak of cow-pox in a dairy in Grey's Inn, and from another at Marylebone. We are informed that these as well as Jenner often went back to the cow for fresh lymph. These early experimenters were anxious to deter

mine all the problems, connected with vaccine from different sources, whether all were the same or different; and also whether they were altered by continuous transmission from arm to arm. It is related that Woodville's first results were milder than those of Jenner who wrote of the inflammatory results as regards the auxiliary glands and the formation of an ulcer on the pock. The efficacy of a lymph in those early days was also tested by the variolous test. Willan writing in 1806, mentions, that from personal inquiries amongst eighty-six medical men whom he had met during the course of the previous three months, he had been made aware of over 18,000 vaccinations done by them, all the cases having remained free from smallpox, though most of them were either inoculated with variolous matter or exposed at different periods to contagion. At the same time it was no uncommon thing for parents to hesitate between the old practice and the new, to have some of their children vaccinated and some variolated; and Willan states that Wachsel, of the smallpox hospital, had noted this in more than an hundred families, without observing an instance of variolous fever and eruption among vaccinated children. Abundant evidence was soon obtained from every country to which the marvelous discovery rapidly spread, of the protective effects of vaccination against direct inoculation as well as exposure to smallpox. Published plates of Jenner, Aiken, Bell and others show vaccinia 100 years ago exactly as we know it at the present day.

Some years after Jenner's death a new spirit of inquiry arose regarding cow-pox as the source of vaccine lymph, many believing that the vesicles being produced by vaccination were not comparable with those of early times, and that the protection afforded by vaccination was not so great. Their experiments were important in showing the need of taking lymph from the vesicles before they had broken and had been subjected to secondary pus infection, corroborating Jenner's opinion, "That the most material indisposition, or

at least that which is felt most sensibly, does not come primarily from the first action of the virus on the constitution, but that it often comes on if the pustules be left to chance as a secondary disease;” and again he says, "I am more and more convinced of the extreme mildness of the symptoms merely from the primary action of the virus in the constitution."

As we read these words of that marvelous old-time experimenter and clinician, which, in these days, glorious with the victories of aseptic surgery, could not be improved upon in describing the vaccine vesicle previous to secondary infection, we are forced to use the words of Horace, "Justum et tenaceum propositi virum."

The accuracy and comprehensiveness of the work done by Jenner and his contemporaries is best measured by the fact that not till the last twenty years of the century when bacteriology had begun to take its place as the most important application of experimental science to medicine, did the real nature of vaccine become a matter

of renewed investigation. With the appearance of an epidemic of smallpox in 1870 of world-wide extent and of unexampled severity, vaccination was made compulsory in England and most European countries; vaccination stations and regularly appointed public vaccinators became a routine measure and the epidemic was stayed. The disease reappeared in many quarters in 1881, but during the interval in England especially, a certain amount of agitation against the compulsory operation of the Act had developed, the chief reason being that certain diseases as syphilis had been, it was affirmed, introduced with the vaccine. As an outcome of this, Dr. Robt. Cory submitted himself to direct inoculation with lymph taken from syphilitic children, and on four different occasions, once in 1878, in 1879, in May, 1881, and in July, 1881, and in the last experiment, was inoculated with the disease. The conclusion arrived at was that the disease was to a limited extent capable of being transmitted when the virus is taken from a vesicle in a child suffering from the disease in its primary stage. It is not to be for

gotten, however, that the disease in the children was in so acute a stage that no physician would have thought of using them as a source of vaccine lymph.

It was, however, as the result of these discussions and experiments that the question of returning to the cow as a source of vaccine came into prominence.

In the 1883 Report of the Local Government Board is described the Vaccine Station of the Board, as being situated at 95 Lamb's Conduit Street, London, on the ground floor of the house.

It consisted of Beyond this

a waiting-room 32x29 feet. was another room 25x30 feet, divided by a screen, on either side of which the vaccination of children and calves was performed. Beyond this room was the stable for calves. There was stabling for four calves, each having a floor space of 36.7 feet or 72x5.

The then practice was to vaccinate a calf on Saturday with lymph stored in tubes. This calf supplied lymph on the following Thursday, which was used as follows to (1) Vaccinate children brought to the station; (2) to supply lymph to the National vaccine establishment; (3) for the direct vaccination of another calf; (4) for the vaccination from tube of another calf the next Saturday; (5) the calf vaccinated on Thursday supplied lymph for vaccinating children on the following Tuesday, and (6) for supplying tubes for the National Vaccine Establishment.

Such is the beginning of the supply of bovine lymph in England, and how small this beginning, is gathered from the reports which show that from the Animal Vaccine Station of the Local Government Board there were sent out:

perfectly fresh lymph 990 primary vaccinations in 1,000 were successful; and with perfectly fresh lymph, human or bovine, 99 primaries were successful at the National Vaccine Stations. The Report of the British Army Medical Department of 1882 showed that only 40 per cent. of primary vaccinations were thoroughly successful with stored lymph, mostly all of which was humanized lymph in tubes.

While in a very remarkable manner, the routine of 1883, is found continued in the Report of the Local Government Board for 1900, and while the station is situated in the same place, the extension of the work may be gauged by the fact that although there was almost no smallpox in the United Kingdom in 1900, vaccine was supplied to the extent of 444,221 charged capillary tubes of glycerinated vaccine, sent in response to 50,512 applications from Public Vaccinators; while there were in addition to the Animal Vaccine Station 22 other stations throughout the Kingdom, known as Educational Vaccination Stations.

The Report states further that 155 calves were vaccinated during the year, having a total weight on reception at the Station of 43,964 lbs. and on dismissal 45,301 or an average gain of 8.62. Of these 142 were vaccinated direct from other calves and thirteen from stored lymph. Insertions to the number of 6,697 in calf-to-calf operations produced 6.521 vesicles; in the 13 vaccinated with lymph stored in tubes of 513 insertions 440 gave vesicles; or in the two methods a percentage insertion success of 97.37 and 85.77 per cent, respectively. No material difference resulted whether the lymph was taken 96 or 120 hours after vaccination.

The remaining primary vaccinations were done with stored glycerinated lymph. There were 11 cases brought back after first inspection on account of some abnormal cause of their vaccination. In most the abnormal condition consisted of "sore arm," caused, in most cases, by domestic maltreatment.

Dr. Frank Blaxall, an old officer of the Local Government Board, in the 1900 Report reports on the Glycerinated Calf Lymph Establishment. The stables in Little James Street are new and extended, and the Laboratory is at the Jenner Institute of Preventive Medicine. The results

of the reports on the 420,425 cases vaccinated with glycerinated lymph and reported upon, show 97.7 per cent. of case successes and 91.2 per cent. of insertion successes. The lymph was from 362 calves. All were examined at slaughter by a veterinary surgeon and declared to be healthy. Four other calves apparently healthy, were on examination found slightly tubercular and the lymph taken from them was destroyed.

These statistical results are of much im. portance, since they indicate that year after year as these Government Reports have shown, the production of normal vaccine is capable of being accurately carried out, since successive reports have told the same story. Similarly these results show that vaccine taken 120 hours after inoculation always shows the presence of a non-sporing series of bacteria, known as "staphylococci" and popularly those present in laudable pus, as the old authors described a healthy suppurating wound. These are such as are found on the skin of men and animals, in the hair depressions and sweat follicles, and when so found do not possess any specific pathological significance when injected into rabbits or guineapigs, though first grown in bouillon. Practically the only other form occasionally found is a spore-bearing form-B. Mesentericus, from the bowel contents of the animals. Although as seen in the report quoted, the use of lymph directly from the calf to the arın is not shown to have any but the best results, yet in view of

the fact of the number of such forms possibly present in the vaccine vesicle where some carelessness in handling animals has existed, it has after ten years' experience become the practice to send out vaccine after a month's treatment in glycerine, by which the extraneous organisms are killed. The lymph taken from a series of animals inoculated from the same stock lymph is found to vary both in quality and amount. Report after report of the National Vaccine Establishment in London. refers to the common experience that in any considerable number of calves, all seemingly healthy, some do not take and are said to be "out of condition;" while others do not produce vesicles to the same extent or supply the same amount or quality of lymph. A very extended physiological study of 25 calves by Dr. Alan B. Greene failed to find any such distinctive blood conditions as would explain why 14 of these yielded vesicles of good quality, while the remaining 6 gave vesicles of poor quality or none at all.

The same experience is obtained at Vaccine Farms everywhere on this Continent; and indeed those in the most southerly localities find that their calves fail largely to respond in periods of continued hot weather. These facts are wholly in keeping with the differences which are known to occur in the severity of smallpox in different individuals, even of the same family, where exposed, though unvaccinated, to a case of smallpox, or indeed to almost any infectious disease; and also illustrates how vaccine produces a more severe reaction in one person than another, quite apart from the secondary effects or pustulation.

Our studies have therefore brought us to several quite obvious conclusions regarding vaccination. Summed up briefly

these are:

1st. That it is variola modified by being transmitted in either some accidental or experimental manner from man, its normal host, to some animal of the bovine species.

2nd. That in common with other microbic diseases, its germ has an optimum temperature at which it grows best and