The deviation of man from the state in which he was originally placed by nature seems to have proved to him a prolific source of diseases.  From the love of splendour, from the indulgences of luxury, and from his fondness for amusement he has familiarised himself with a great number of animals, which may not originally have been intended for his associates.

The wolf, disarmed of ferocity, is now pillowed in the lady's lap.  The cat, the little tiger of our island, whose natural home is the forest, is equally domesticated and caressed.  The cow, the hog, the sheep, and the horse, are all, for a variety of purposes, brought under his care and dominion.

There is a disease to which the horse, from his state of domestication, is frequently subject.  The farriers [blacksmiths who shoe horses; in the past, farriers treated the diseases of horses as well] have called it the Grease.  It is an inflammation and swelling in the heel, from which issues matter possessing properties of a very peculiar kind, which seems capable of generating a disease in the human body (after it has undergone the modification which I shall presently speak of), which bears so strong a resemblance to the smallpox that I think it highly probable it may be the source of the disease.

In this dairy country a great number of cows are kept, and the office of milking is performed indiscriminately by men and maid servants.  One of the former having been appointed to apply dressings to the heels of a horse affected with the Grease, and not paying due attention to cleanliness, incautiously bears his part in milking the cows, with some particles of the infectious matter adhering to his fingers.  When this is the case, it commonly happens that a disease is communicated to the cows, and from the cows to the dairy maids, which spreads through the farm until the most of the cattle and domestics feel its unpleasant consequences.

These symptoms, varying in their degrees of violence, generally continue from one day to three or four, leaving ulcerated sores about the hands, which, from the sensibility of the parts, are very troublesome, and commonly heal slowly, frequently becoming phagedenic, like those from whence they sprung.  The lips, nostrils, eyelids, and other parts of the body are sometimes affected with sores; but these evidently arise from their being heedlessly rubbed or scratched with the patient's infected fingers.

No eruptions on the skin have followed the decline of the feverish symptoms in any instance that has come under my inspection, one only excepted, and in this case a very few appeared on the arms:  they were very minute, of a vivid red colour, and soon died away without advancing to maturation; so that I cannot determine whether they had any connection with the preceding symptoms.

Thus the disease makes its progress from the horse to the nipple of the cow, and from the cow to the human subject.

[NOTE:  Although Jenner was incorrect in suggesting that cows may contract cow-pox after exposure to the equine infection called "the Grease," he was correct in his assessment of the relationship between cow-pox and smallpox.]

In support of so extraordinary a fact, I shall lay before my Reader a great number of instances.

[It is necessary to observe that pustulous sores frequently appear spontaneously on the nipples of cows, and instances have occurred, though very rarely, of the hands of the servants employed in milking being affected with sores in consequence, and even of their feeling an indisposition from  absorption.  These pustules are of a much milder nature than those which arise from that contagion which constitutes the true cow-pox.  They are always free from the bluish or livid tint so conspicuous in the pustules in that disease.  No erysipelas attends them, nor do they shew any phagedenic disposition as in the other case, but quickly terminate in a scab without creating any apparent disorder in the cow.  This complaint appears at various seasons of the year, but most commonly in the spring, when the cows are first taken from their winter food and fed with grass.  It is very apt to appear also when they are suckling their young.  But this disease is not to be considered as similar in any respect to that of which I am treating, as it is incapable of producing any specific effects on the human constitution.  However, it is of the greatest consequence to point it out here, lest the want of discrimination should occasion an idea of security from the infection of the smallpox, which might prove delusive.]

It is necessary to observe that the utmost care was taken to ascertain, with the most scrupulous precision, that no one whose case is here adduced had gone through the smallpox previous to these attempts to produce that disease.

Had these experiments been conducted in a large city, or in a populous neighbourhood, some doubts might have been entertained; but here, where population is thin, and where such an event as a person's having had the smallpox is always faithfully recorded, no risk of inaccuracy in this particular can arise.

[I have purposely selected several cases in which the disease had appeared at a very distant period previous to the experiments made with variolous matter, to shew that the change produced in the constitution is not affected by time.]

[It is remarkable that variolous matter, when the system is disposed to reject it, should excite inflammation on the part to which it is applied more speedily than when it produces the smallpox.  Indeed, it becomes almost a criterion by which we can determine whether the infection will be received or not.  It seems as if a change, which endures through life, had been produced in the action, or disposition to action, in the vessels of the skin; and it is  remarkable, too, that whether this change has been effected by the smallpox or the cow-pox that the disposition to sudden cuticular inflammation is the same on the application of variolous matter.]

It is a fact so well known among our dairy farmers that those who have had the smallpox either escape the cow-pox or are disposed to have it slightly, that as soon as the complaint shews itself among the cattle, assistants are procured, if possible, who are thus rendered less susceptible of it, otherwise the business of the farm could scarcely go forward.

Although the preceding history pretty clearly evinces that the constitution is far less susceptible of the contagion of the cow-pox after it has felt that of the smallpox, and although in general, as I have observed, they who have had the smallpox, and are employed in milking cows which are infected with the cow-pox, either escape the disorder, or have sores on the hands without feeling any general indisposition, yet the animal economy is subject to some variation in this respect, which the following relation will point out:

Although the cow-pox shields the constitution from the smallpox, and the smallpox proves a protection against its own future poison, yet it appears that the human body is again and again susceptible of the infectious matter of the cow-pox, as the following history will demonstrate.

One instance has occurred to me of the system being affected from the matter issuing from the heels of horses, and of its remaining afterwards unsusceptible of the variolous contagion; another, where the smallpox appeared obscurely; and a third, in which its complete existence was positively ascertained.

[It is a remarkable fact, and well known to many, that we are frequently foiled in our endeavours to communicate the smallpox by inoculation to blacksmiths, who in the country are farriers.  They often, as in the above instance, either resist the contagion entirely, or have the disease anomalously.  Shall we not be able to account for this on a rational principle?]

Although in the former instances the system seemed to be secured, or nearly so, from variolous infection, by the absorption of matter from the sores produced by the diseased heels of horses, yet the following case decisively proves that this cannot be entirely relied upon until a disease has been generated by the morbid matter from the horse on the nipple of the cow, and passed through that medium to the human subject.

Here my researches were interrupted till the spring of the year 1798, when, from the wetness of the early part of the season, many of the farmers' horses in this neighbourhood were affected with sore heels, in consequence of which the cow-pox broke out among several of our dairies, which afforded me an opportunity of making further observations upon this curious disease....

This experiment was made to ascertain the progress and subsequent effects of the disease when thus propagated.  We have seen that the virus from the horse, when it proves infectious to the human subject, is not to be relied upon as rendering the system secure from variolous infection, but that the matter produced by it upon the nipple of the cow is perfectly so.  Whether its passing from the horse through the human constitution, as in the present instance, will produce a similar effect, remains to be decided.  This would now have been effected, but the boy was rendered unfit for inoculation from having felt the effects of a contagious fever in a workhouse soon after this experiment was made.

After the many fruitless attempts to give the smallpox to those who had the cow-pox, it did not appear necessary, nor was it convenient to me, to inoculate the whole of those who had been the subjects of these late trials; yet I thought it right to see the effects of variolous matter on some of them, particularly William Summers, the first of these patients who had been infected with matter taken from the cow.  He was, therefore, inoculated with variolous matter from a fresh pustule; but, as in the preceding cases, the system did not feel the effects of it in the smallest degree.

I had an opportunity also of having this boy and William Pead inoculated by my nephew, Mr. Henry Jenner, whose report to me is as follows:

"I have inoculated Pead and Barge, two of the boys whom you lately infected with the cow-pox.  On the second day the incisions were inflamed and there was a pale inflammatory stain around them.  On the third day these appearances were still increasing and their arms itched considerably.  On the fourth day the inflammation was evidently sudsiding, and on the sixth day it was scarcely perceptible.  No symptom of indisposition followed.

"To convince myself that the variolous matter made use of was in a perfect state I at the same time inoculated a patient with some of it who never had gone through the cow-pox, and it produced the smallpox in the usual regular manner."

Although I presume it may be unnecessary to produce further testimony in support of my assertion "that the cow-pox protects the human constitution from the infection of the smallpox," yet it affords me considerable satisfaction to say that Lord Somerville, the President of the Board of Agriculture, to whom this paper was shewn by Sir Joseph Banks, has found upon inquiry that the statements were confirmed by the concurring testimony of Mr. Dolland, a surgeon, who resides in a dairy country remote from this, in which these observations were made.  With respect to the opinion adduced "that the source of the infection is a peculiar morbid matter arising in the horse," although I have not been able to prove it from actual experiments conducted immediately under my own eye, yet the evidence I have adduced appears sufficient to establish it.

They who are not in the habit of conducting experiments may not be aware of the coincidence of circumstances necessary for their being managed so as to prove perfectly decisive; nor how often men engaged in professional pursuits are liable to interruptions which disappoint them almost at the instant of their being accomplished:  however, I feel no room for hesitation respecting the common origin of the disease, being well convinced that it never appears among the cows (except it can be traced to a cow introduced among the general herd which has been previously infected, or to an infected servant) unless they have been milked by some one who, at the same time, has the care of a horse affected with diseased heels....

• May it not ... be reasonably conjectured that the source of the smallpox is morbid matter of a peculiar kind, generated by a disease in the horse, and that accidental circumstances may have again and again arisen, still working new changes upon it until it has acquired the contagious and malignant form under which we now commonly see it making its devastations amongst us?

• And, from a consideration of the change which the infectious matter undergoes from producing a disease on the cow, may we not conceive that many contagious diseases, now prevalent among us, may owe their present appearance not to a simple, but to a compound, origin?

• For example, is it difficult to imagine that the measles, the scarlet fever, and the ulcerous sore throat with a spotted skin have all sprung from the same source, assuming some variety in their forms according to the nature of their new combinations?

But what was this disease?

Certainly not the smallpox; for the matter having from putrefaction lost or suffered a derangement in its specific properties, was no longer capable of producing that malady, those who had been inoculated in this manner being as much subject to the contagion of the smallpox as if they had never been under the influence of this artificial disease; and many, unfortunately, fell victims to it, who thought themselves in perfect security....

Whether it be yet ascertained by experiment that the quantity of variolous matter inserted into the skin makes any difference with respect to the subsequent mildness or violence of the disease, I know not; but I have the strongest reason for supposing that if either the punctures or incisions be made so deep as to go through it and wound the adipose membrane, that the risk of bringing on a violent disease is greatly increased.

I have known an inoculator whose practice was "to cut deep enough (to use his own expression) to see a bit of fat," and there to lodge the matter.  The great number of bad cases, independent of inflammations and abscesses on the arms, and the fatality which attended this practice, was almost inconceivable; and I cannot account for it on any other principle than that of the matter being placed in this situation instead of the skin.

It was the practice of another, whom I well remember, to pinch up a small portion of the skin on the arms of his patients and to pass through it a needle, with a thread attached to it previously dipped in variolous matter.  The thread was lodged in the perforated part, and consequently left in contact with the cellular membrane.  This practice was attended with the same ill success as the former....

A very respectable friend of mine, Dr. Hardwicke, of Sodbury in this county, inoculated great numbers of patients ... and with such success that a fatal instance [rarely] occurred....  It was the doctor's practice to make as slight an incision as possible upon the skin, and there to lodge a thread saturated with the variolous matter.  When his patients became indisposed, agreeably to the custom then prevailing, they were directed to go to bed and were kept moderately warm.

Is it not probable then that the success of the modern practice may depend more upon the method of invariably depositing the virus in or upon the skin, than on the subsequent treatment of the disease?...

I cannot account for the uninterrupted success, or nearly so, of one practitioner, and the wretched state of the patients under the care of another, where, in both instances, the general treatment did not differ essentially, without conceiving it to arise from the different modes of inserting the matter for the purpose of producing the disease....

These circumstances must naturally create in every instance some degree of painful solicitude for its consequences.  But as I have never known fatal effects arise from the cow-pox, even when impressed in the most unfavourable manner, producing extensive inflammations and suppurations on the hands; and as it clearly appears that this disease leaves the constitution in a state of perfect security from the infection of the smallpox, may we not infer that a mode of inoculation may be introduced preferable to that at present adopted, especially among those families which, from previous circumstances, we may judge to be predisposed to have the disease unfavourably?

It is an excess in the number of pustules which we chiefly dread in the smallpox; but in the cow-pox no pustules appear, nor does it seem possible for the contagious matter to produce the disease from effluvia, or by any other means than contact, and that probably not simply between the virus and the cuticle; so that a single individual in a family might at any time receive it without the risk of infecting the rest or of spreading a distemper that fills a country with terror.

A young woman who had the cow-pox to a great extent, several sores which maturated having appeared on the hands and wrists, slept in the same bed with a fellow-dairymaid who never had been infected with either the cow-pox or the smallpox, but no indisposition followed.

Another instance has occurred of a young woman on whose hands were several large suppurations from the cow-pox, who was at the same time a daily nurse to an infant, but the complaint was not communicated to the child.

In constitutions predisposed to scrophula [swellings of the neck often associated with tuberculosis], how frequently we see the inoculated smallpox rouse into activity that distressful malady!  This circumstance does not seem to depend on the manner in which the distemper has shewn itself, for it has as frequently happened among those who have had it mildly as when it has appeared in the contrary way.

There are many who, from some peculiarity in the habit, resist the common effects of variolous matter inserted into the skin, and who are in consequence haunted through life with the distressing idea of being insecure from subsequent infection.  A ready mode of dissipating anxiety originating from such a cause must now appear obvious.  And, as we have seen that the constitution may at any time be made to feel the febrile attack of cow-pox, might it not, in many chronic diseases, be introduced into the system, with the probability of affording relief, upon well-known physiological principles?...

Thus far have I proceeded in an inquiry founded, as it must appear, on the basis of experiment; in which, however, conjecture has been occasionally admitted in order to present to persons well situated for such discussions, objects for a more minute investigation.  In the mean time I shall myself continue to prosecute this inquiry, encouraged by the hope of its becoming essentially beneficial to mankind.