That the disease produced upon the cows by the colt and from thence conveyed to those who milked them was the TRUE and not the SPURIOUS cow-pox, there can be scarcely any room for suspicion; yet it would have been more completely satisfactory had the effects of variolous matter been ascertained on the farmer's wife, but there was a peculiarity in her situation which prevented my making the experiment.

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.



II

FURTHER OBSERVATIONS ON THE VARIOLA VACCINAE, OR COW-POX. 1799

Although it has not been in my power to extend the inquiry into the causes and effects of the variolae vaccinae much beyond its original limits, yet, perceiving that it is beginning to excite a general spirit of investigation, I think it of importance, without delay, to communicate such facts as have since occurred, and to point out the fallacious sources from whence a disease imitative of the true variolae vaccinae might arise, with the view of preventing those who may inoculate from producing a spurious disease; and, further, to enforce the precaution suggested in the former treatise on the subject, of subduing the inoculated pustule as soon as it has sufficiently produced its influence on the constitution. From a want of due discrimination of the real existence of the disease, either in the brute or in the human subject, and also of that stage of it in which it is capable of producing the change in the animal economy which renders it unsusceptible of the contagion of the smallpox, unpleasant consequences might ensue, the source of which, perhaps, might not be suspected by one inexperienced in conducting such experiments.

My late publication contains a relation of most of the facts which had come under my own inspection at the time it was written, interspersed with some conjectural observations. Since then Dr. G. Pearson has established an inquiry into the validity of my principal assertion, the result of which cannot but be highly flattering to my feelings. It contains not a single case which I think can be called an exception to the fact I was so firmly impressed with—that the cow-pox protects the human body from the smallpox. I have myself received some further confirmations, which shall be subjoined. I have lately also been favoured with a letter from a gentleman of great respectability (Dr. Ingenhousz), informing me that, on making an inquiry into the subject in the county of Wilts, he discovered that a farmer near Calne had been infected with the smallpox after having had the cow-pox, and that the disease in each instance was so strongly characterized as to render the facts incontrovertible. The cow-pox, it seems, from the doctor's information, was communicated to the farmer from his cows at the time that they gave out an offensive stench from their udders.

Some other instances have likewise been represented to me of the appearance of the disease, apparently marked with its characteristic symptoms, and yet that the patients have afterwards had the smallpox. On these cases I shall, for the present, suspend any particular remarks, but hope that the general observations I have to offer in the sequel will prove of sufficient weight to render the idea of their ever having had existence, but as cases of spurious cow-pox, extremely doubtful.

Ere I proceed let me be permitted to observe that truth, in this and every other physiological inquiry that has occupied my attention, has ever been the object of my pursuit, and should it appear in the present instance that I have been led into error, fond as I may appear of the offspring of my labours, I had rather see it perish at once than exist and do a public injury.

I shall proceed to enumerate the sources, or what appear to me as such, of a spurious cow-pox.

First: That arising from pustules on the nipples or udder of the cow; which pustules contain no specific virus.

Secondly: From matter (although originally possessing the specific virus) which has suffered a decomposition, either from putrefaction or from any other cause less obvious to the senses.

Thirdly: From matter taken from an ulcer in an advanced stage, which ulcer arose from a true cow pock.

Fourthly: From matter produced on the human skin from contact with some peculiar morbid matter generated by a horse.

On these subjects I shall offer some comments: First, to what length pustulous diseases of the udder and nipples of the cow may extend it is not in my power to determine; but certain it is that these parts of the animal are subject to some variety of maladies of this nature; and as many of these eruptions (probably all of them) are capable of giving a disease to the human body, would it not be discreet for those engaged in this investigation to suspend controversy and cavil until they can ascertain with precision what IS and what IS NOT the cow-pox?

For example: A farmer who is not conversant with any of these maladies, but who may have heard of the cow-pox in general terms, may acquaint a neighbouring surgeon that the distemper appears at his farm. The surgeon, eager to make an experiment, takes away matter, inoculates, produces a sore, uneasiness in the axilla, and perhaps some affection of the system. This is one way in which a fallacious idea of security both in the mind of the inoculater and the patient may arise; for a disease may thus have been propagated from a simple eruption only.

One of the first objects then of this pursuit, as I have observed, should be, to learn how to distinguish with accuracy between that peculiar pustule which is the true cow pock, and that which is spurious. Until experience has determined this, we view our object through a mist. Let us, for instance, suppose that the smallpox and the chicken-pox were at the same time to spread among the inhabitants of a country which had never been visited by either of these distempers, and where they were quite unknown before: what confusion would arise! The resemblance between the symptoms of the eruptive fever and between the pustules in either case would be so striking that a patient who had gone through the chicken-pox to any extent would feel equally easy with regard to his future security from the smallpox as the person who had actually passed through that disease. Time and future observation would draw the line of distinction.

So I presume it will be with the cow-pox until it is more generally understood. All cavilling, therefore, on the mere report of those who TELL US they have had this distemper, and are afterwards found susceptible of the smallpox, should be suspended. To illustrate this I beg leave to give the following history:

Sarah Merlin, of the parish of Eastington in this county, when about thirteen or fourteen years of age lived as a servant with farmer Clarke, who kept a dairy consisting of about eighteen cows at Stonehouse, a neighbouring village. The nipples and udders of three of the cows were extensively affected with large white blisters. These cows the girl milked daily, and at the time she assisted, with two others, in milking the rest of the herd. It soon appeared that the disease was communicated to the girl. The rest of the cows escaped the infection, although they were milked several days after the three above specified, had these eruptions on the nipples and udders, and even after the girl's hand became sore. The two others who were engaged in milking, although they milked the cows indiscriminately, received no injury. On the fingers of each of the girl's hands there appeared several large white blisters—she supposes about three or four on each finger. The hands and arms inflamed and swelled, but no constitutional indisposition followed. The sores were anointed with some domestic ointment and got well without ulcerating.

As this malady was called the cow-pox, and recorded as such in the mind of the patient, she became regardless of the smallpox; but, on being exposed to it some years afterwards she was infected, and had a full burthen.

Now had any one conversant with the habits of the disease heard this history, they would have had no hesitation in pronouncing it a case of spurious cow-pox; considering its deviation in the NUMEROUS blisters which appeared on the girl's hands; their termination without ulceration; its not proving more generally contagious at the farm, either among the cattle or those employed in milking; and considering also that THE PATIENT FELT NO GENERAL INDISPOSITION, ALTHOUGH THERE WAS SO GREAT A NUMBER OF VESICLES.

This is perhaps the most deceptious form in which an eruptive disease can be communicated from the cow, and it certainly requires some attention in discriminating it. The most perfect criterion by which the judgment may be guided is perhaps that adopted by those who attend infected cattle. These white blisters on the nipples, they say, NEVER EAT INTO THE FLESHY PARTS like those which are commonly of a bluish cast, and which constitute the TRUE COW-POX, but that they affect the skin only, quickly end in scabs, and are not nearly so infectious.

That which appeared to me as one cause of spurious eruptions, I have already remarked in the former treatise, namely, the transition that the cow makes in the spring from a poor to a nutritious diet, and from the udder's becoming at this time more vascular than usual for the supply of milk. But there is another source of inflammation and pustules which I believe is not uncommon in all the dairy counties in the west of England. A cow intended to be exposed for sale, having naturally a small udder, is previously for a day or two neither milked artificially nor is her calf suffered to have access to her. Thus the milk is preternaturally accumulated, and the udder and nipples become greatly distended. The consequences frequently are inflammation and eruptions which maturate.

Whether a disease generated in this way has the power of affecting the constitution in any PECULIAR manner I cannot presume positively to determine. It has been conjectured to have been a cause of the true cow-pox, though my inquiries have not led me to adopt this supposition in any one instance; on the contrary, I have known the milkers affected by it, but always found that an affection thus induced left the system as susceptible of the smallpox as before.

What is advanced in my second position I consider also of very great importance, and I could wish it to be strongly impressed on the minds of all who may be disposed to conclude hastily on my observations, whether engaged in their investigation by experiments or not to place this in its clearest point of view (as the similarity between the action of the smallpox and the cow-pox matter is so obvious) it will be necessary to consider what we sometimes observe to take place in inoculation for the smallpox when imperfect variolous matter is made use of. The concise history on this subject that was brought forward respecting what I had observed in this neighbourhood [Footnote: Inquiry into the Causes and Effects of the Variolae Vaccinae, p.56 of the original article]. I perceive, by a reference since made to the Memoirs of the Medical Society of London, may be considered as no more than a corroboration of the facts very clearly detailed by Mr. Kite [Footnote: See an account of some anomalous appearances consequent to the inoculation of the smallpox, by Charles Kite, Surgeon, of Gravesend, in the Memoirs of the Medical Society of London, vol. iv, p. 114.]. To this copious evidence I have to add still more in the following communications from Mr. Earle, surgeon, of Frampton-upon-Severn, in this county, which I deem the more valuable, as he has with much candour permitted me to make them public:

"SIR:

"I have read with satisfaction your late publication on the Variolae Vaccinae, and being, among many other curious circumstances, particularly struck with that relating to the inefficacy of smallpox matter in a particular state, I think it proper to lay before you the following facts which came within my own knowledge, and which certainly tend to strengthen the opinions advanced in pages 56 and 57 of your treatise.

"In March, 1784, a general inoculation took place at Arlingham in this county. I inoculated several patients with active variolous matter, all of whom had the disease in a favourable way; but the matter being all used, and not being able to procure any more in the state I wished, I was under the necessity of taking it from a pustule which, experience has since proved, was advanced too far to answer the purpose I intended. Of five persons inoculated with this last matter, four took the smallpox afterwards in the natural way, one of whom died, three recovered, and the other, being cautioned by me to avoid as much as possible the chance of catching it, escaped from the disease through life. He died of another disorder about two years ago.

"Although one of these cases ended unfortunate, yet I cannot suppose that any medical man will think me careless or inattentive in their management; for I conceive the appearances were such as might have induced any one to suppose that the persons were perfectly safe from future infection. Inflammation in every case took place in the arm, and fever came on with a considerable degree of pain in the axilla. In some of their arms the inflammation and suppuration were more violent than is commonly observed when perfect matter is made use of; in one there was an ulcer which cast off several large sloughs. About the ninth day eruptions appeared, which died away earlier than common without maturation. From these circumstances I should suppose that no medical practitioner would scarcely have entertained a doubt but that these patients had been infected with a true smallpox; yet I must confess that some small degree of doubt presented itself to me at the speedy disappearance of the eruptions; and in order, as far as I could, to ascertain their safety, I sent one of them to a much older practitioner than myself. This gentleman, on hearing the circumstances of the case, pronounced the patient perfectly secure from future infection.

"The following facts are also a striking proof of the truth of your observations on this subject:

"In the year 1789 I inoculated three children of Mr. Coaley, of Hurst farm in this county. The arms inflamed properly, fever and pain in the axillae came on precisely the same as in the former cases, and in ten days eruptions appeared, which disappeared in the course of two days. I must observe that the matter here made use of was procured for me by a friend; but no doubt it was in an improper state; for, from the similarity of these cases to those which happened at Arlingham five years before, I was somewhat alarmed for their safety, and desired to inoculate them again: which being permitted, I was particularly careful to procure matter in its most perfect state. All the children took the smallpox from this second inoculation, and all had a very full burthen. These facts I conceive strikingly corroborate your opinion relative to the different states of matter; for in both instances that I have mentioned it was capable of producing something strongly resembling the true smallpox, although it afterwards proved not to be so.

"As I think the communication of these cases is a duty I owe to the public, you are at liberty to make what use you please of this letter. I remain, &c.,

"John Earle.

"FRAMPTON-UPON SEVERN, GLOUCESTERSHIRE, November 10, 1798.

"P. S. I think it necessary to observe that I can pronounce, with the greatest certainty, that the matter with which the Arlingham patients were inoculated was taken from a true smallpox pustule. I took it myself from a subject that had a very full burthen."

Certain then it is that variolous matter may undergo such a change from the putrefactive process, as well as from some of the more obscure and latent processes of nature, as will render it incapable of giving the smallpox in such a manner as to secure the human constitution from future infection, although we see at the same time it is capable of exciting a disease which bears so strong a resemblance to it as to produce inflammation and matter in the incised skin (frequently, indeed, more violent than when it produces its effects perfectly), swelling of the axillary glands, general indisposition, and eruptions. So strongly persuaded was the gentleman, whose practice I have mentioned in page 56 of the late treatise, that he could produce a mild smallpox by his mode of managing the matter, that he spoke of it as a useful discovery until convinced of his error by the fatal consequence which ensued.

After this ought we to be in the smallest degree surprised to find, among a great number of individuals who, by living in dairies, have been casually exposed to the cow-pox virus when in a state analogous to that of the smallpox above described, some who may have had the disease so imperfectly as not to render them secure from variolous attacks? For the matter, when burst from the pustules on the nipples of the cow, by being exposed, from its lodgment there, to the heat of an inflamed surface, and from being at the same time in a situation to be occasionally moistened with milk, is often likely to be in a state conducive to putrefaction; and thus, under some modification of decomposition, it must, of course, sometimes find access to the hand of the milker in such a way as to infect him. What confusion should we have were there no other mode of inoculating the smallpox than such as would happen from handling the diseased skin of a person labouring under that distemper in some of its advanced and loathsome stages! It must be observed that every case of cow-pox in the human species, whether communicated by design or otherwise, is to be considered as a case of inoculation. And here I may be allowed to make an observation on the case of the farmer communicated to me by Dr. Ingenhousz. That he was exposed to the matter when it had undergone the putrefactive change is highly probable from the doctor's observing that the sick cows at the farm gave out an OFFENSIVE STENCH FROM THEIR UDDERS. However, I must remark that it is unusual for cattle to suffer to such an extent, when disordered with the cowpox, as to make a bystander sensible of any ill smell. I have often stood among a herd which had the distemper without being conscious of its presence from any particular effluvia. Indeed, in this neighbourhood it commonly receives an early check from escharotic applications of the COW LEECH. It has been conceived to be contagious without contact; but this idea cannot be well founded because the cattle in one meadow do not infect those in another (although there may be no other partition than a hedge) unless they be handled or milked by those who bring the infectious matter with them; and of course, the smallest particle imaginable, when applied to a part susceptible of its influence, may produce the effect. Among the human species it appears to be very clear that the disease is produced by contact only. All my attempts, at least, to communicate it by effluvia have hitherto proved ineffectual.

As well as the perfect change from that state in which variolous matter is capable of producing full and decisive effects on the constitution, to that wherein its specific properties are entirely lost, it may reasonably be supposed that it is capable of undergoing a variety of intermediate changes. The following singular occurrences in ten cases of inoculation, obligingly communicated to me by Mr. Trye, Senior Surgeon to the Infirmary at Glocester, seem to indicate that the variolous matter, previously to its being taken from the patient for the intended purpose, was beginning to part with some of its original properties, or, in other words, that it had suffered a partial decomposition. Mr. Trye says: "I inoculated ten children with matter taken at one time and from the same subject. I observed no peculiarity in any of them previously to their inoculation, nor did any thing remarkable appear in their arms till after the decline of the disease. Two infants of three months old had erysipelas about the incisions, in one of them extending from the shoulders to the fingers' ends. Another infant had abscesses in the cellular substance in the neighbourhood of the incisions, and five or six of the rest had axillary abscesses. The matter was taken from the distinct smallpox late in its progress, and when some pustules had been dried. It was received upon glass and slowly dried by the fire. All the children had pustules which maturated, so that I suppose them all secure from future infection; at least, as secure as any others whom I have ever inoculated. My practice never afforded a sore arm before."

In regard to my former observation on the improper and dangerous mode of preserving variolous matter, I shall here remark that it seems not to have been clearly understood. Finding that it has been confounded with the more eligible modes of preservation, I will explain myself further. When the matter is taken from a fit pustule and properly prepared for preservation, it may certainly be kept without losing its specific properties a great length of time; for instance, when it is previously dried in the open air on some compact body, as a quill or a piece of glass, and afterwards secured in a small vial. [Footnote: Thus prepared, the cow-pox virus was found perfectly active, and possessing all its specific properties, at the end of three months.] But when kept several days in a state of moisture, and during that time exposed to a warm temperature, I do not think it can be relied upon as capable of giving a perfect disease, although, as I have before observed, the progress of the symptoms arising from the action of the imperfect matter bear so strong a resemblance to the smallpox when excited completely.

Thirdly. That the first formed virus, or what constitutes the true cow-pox pustule, invariably possesses the power I have ascribed to it, namely, that of affecting the constitution with a specific disease, is a truth that no subsequent occurrence has yet led me to doubt. But as I am now endeavouring to guard the public as much as possible against erroneous conclusions, I shall observe that when this pustule has degenerated into an ulcer (to which state it is often disposed to pass unless timely checked), I suspect that matter possessing very different properties may sooner or later be produced; and although it may have passed that stage wherein the specific properties of the matter secreted are no longer present in it, yet when applied to a sore (as in the casual way) it might dispose that sore to ulcerate, and from its irritation the system would probably become affected; and thus, by assuming some of its strongest characters, it would imitate the genuine cow-pox.

From the preceding observations on the matter of smallpox when decomposed it must, I conceive, be admitted that cow-pox matter in the state now described may produce a disease, the effects of which may be felt both locally and generally, yet that the disease thus induced may not be effectual in obviating the future effects of variolous contagion. In the case of Mary Miller, related by Mr. Kite in the volume above alluded to, it appears that the inflammation and suppuration of the inoculated arm were more than usually severe, although the system underwent no specific change from the action of the virus; which appears from the patient's sickening seven weeks afterwards with the natural smallpox, which went through its course. Some of the cases communicated by Mr. Earle tend further to confirm this fact, as the matter there manifestly produced ulceration on the inoculated part to a considerable extent.

Fourthly. Whether the cow-pox is a spontaneous disease in the cow, or is to be attributed to matter conveyed to the animal, as I have conceived, from the horse, is a question which, though I shall not attempt now fully to discuss, yet I shall digress so far as to adduce some further observations, and to give my reasons more at large for taking up an opinion that to some had appeared fanciful. The aggregate of these observations, though not amounting to positive proof, forms presumptive evidence of so forcible a kind that I imagine it might, on any other person, have made the same impression it did on me, without fixing the imputation of credulity.

First: I conceived this was the source, from observing that where the cow-pox had appeared among the dairies here (unless it could be traced to the introduction of an infected cow or servant) it had been preceded at the farm by a horse diseased in the manner already described, which horse had been attended by some of the milkers.

Secondly: From its being a popular opinion throughout this great dairy country, and from its being insisted on by those who here attend sick cattle.

Thirdly: From the total absence of the disease in Ireland and Scotland, where the men-servants are not employed in the dairies. [Footnote: This information was communicated to me from the first authority.]

Fourthly: From having observed that morbid matter generated by the horse frequently communicates, in a casual way, a disease to the human subject so like the cow-pox that, in many cases, it would be difficult to make the distinction between one and the other. [Footnote: The sound skin does not appear to be susceptible of this virus when inserted into it, but, when previously diseased from little accidents, its effects are often conspicuous.]

Fifthly: From being induced to suppose, from experiments, that some of those who had been thus affected from the horse resisted the smallpox.

Sixthly: From the progress and general appearance of the pustule on the arm of the boy whom I inoculated with matter taken from the hand of a man infected by a horse; and from the similarity to the cow-pox of general constitutional symptoms which followed. [Footnote: This case (on which I laid no inconsiderable stress in my late treatise, as presumptive evidence of the fact adduced) seems to have been either mistaken or overlooked by those who have commented upon it. (See Case XVIII, p. 36.) The boy, unfortunately, died of a fever at a parish workhouse before I had an opportunity of observing what effects would have been produced by the matter of smallpox.]

I fear it would be trespassing too far to adduce the general testimony of our farmers in support of this opinion; yet I beg leave to introduce an extract of a letter on this subject from the Rev. Mr. Moore, of Chalford Hill, in this county:

"In the month of November, 1797, my horse had diseased heels, which was certainly what is termed the grease; and at a short subsequent period my cow was also affected with what a neighbouring farmer (who was conversant with the complaints of cattle) pronounced to be the cow-pox, which he at the same time observed my servant would be infected with: and this proved to be the case; for he had eruptions on his hands, face, and many, parts of the body, the pustules appearing large, and not much like the smallpox, for which he had been inoculated a year and a half before, and had then a very heavy burthen. The pustules on the face might arise from contact with his hands, as he had a habit of rubbing his forehead, where the sores were the largest and the thickest.

"The boy associated with the farmer's sons during the continuance of the disease, neither of whom had had the smallpox, but they felt no ill effects whatever. He was not much indisposed, as the disease did not prevent him from following his occupations as usual. No other person attended the horse or milked the cow but the lad above mentioned. I am firmly of opinion that the disease in the heels of the horse, which was a virulent grease, was the origin of the servant's and the cow's malady."

But to return to the more immediate object of this proposition.

From the similarity of symptoms, both constitutional and local, between the cow-pox and the disease received from morbid matter generated by a horse, the common people in this neighbourhood, when infected with this disease, through a strange perversion of terms, frequently call it the cow-pox. Let us suppose, then, such a malady to appear among some of the servants at a farm, and at the same time that the cow-pox were to break out among the cattle; and let us suppose, too, that some of the servants were infected in this way, and that others received the infection from the cows. It would be recorded at the farm, and among the servants themselves wherever they might afterwards be dispersed, that they had all had the cow-pox. But it is clear that an individual thus infected from the horse would neither be for a certainty secure himself, nor would he impart security to others were they inoculated by virus thus generated. He still would be in danger of taking the smallpox. Yet were this to happen before the nature of the cowpox be more maturely considered by the public my evidence on the subject might be depreciated unjustly. For an exemplification of what is here advanced relative to the nature of the infection when received directly from the horse see Inquiry into the Causes and Effects of the Variolae Vaccinae, pp. 27, 28, 29, 30, and p. 35; and by way of further example, I beg leave to subjoin the following intelligence received from Mr. Fewster, Surgeon, of Thornbury, in this county, a gentleman perfectly well acquainted with the appearances of the cow-pox on the human subject:

"William Morris, aged thirty-two, servant to Mr. Cox of Almondsbury, in this county, applied to me the 2d of April, 1798. He told me that, four days before, be found a stiffness and swelling in both his hands, which were so painful it was with difficulty he continued his work; that he had been seized with pain in his head, small of the back, and limbs, and with frequent chilly fits succeeded by fever. On examination I found him still affected with these symptoms, and that there was a great prostration of strength. Many parts of his hands on the inside were chapped, and on the middle joint of the thumb of the right hand there was a small phagedenic ulcer, about the size of a large pea, discharging an ichorous fluid. On the middle finger of the same hand there was another ulcer of a similar kind. These sores were of a CIRCULAR form, and he described their first appearance as being somewhat like blisters arising from a burn. He complained of excessive pain, which extended up his arm into the axilla. These symptoms and appearances of the sores were so exactly like the cow-pox that I pronounced he had taken the distemper from milking cows. He assured me he had not milked a cow for more than half a year, and that his master's cows had nothing the matter with them. I then asked him if his master had a GREASY horse, which he answered in the affirmative, and further said that he had constantly dressed him twice a day for the [Footnote: HC—Vol.88] last three weeks or more, and remarked that the smell of his hands was much like that of the horses's heels. On the 5th of April I again saw him, and found him still complaining of pain in both hands, nor were his febrile symptoms at all relieved. The ulcers had now spread to the size of a seven-shilling gold coin, and another ulcer, which I had not noticed before, appeared on the first joint of the forefinger of the left hand, equally painful with that on the right. I ordered him to bathe his hands in warm bran and water, applied escharotics to the ulcers, and wrapped his hands up in a soft cataplasm. The next day he was much relieved, and in something more than a fortnight got well. He lost his nails from the thumb and fingers that were ulcerated."

The sudden disappearance of the symptoms in this case after the application of the escharotics to the sores is worthy of observation; it seems to show that they were kept up by the irritation of the ulcers.

The general symptoms which I have already described of the cow- pox, when communicated in a casual way to any great extent, will, I am convinced, from the many cases I have seen, be found accurate; but from the very slight indisposition which ensues in cases of inoculation, where the pustule, after affecting the constitution, quickly runs into a scab spontaneously, or is artificially suppressed by some proper application, I am induced to believe that the violence of the symptoms may be ascribed to the inflammation and irritation of the ulcers (when ulceration takes place to any extent, as in the casual cow-pox), and that the constitutional symptoms which appear during the presence of the sore, while it assumes the character of a pustule only, are felt but in a very trifling degree. This mild affection of the system happens when the disease makes but a slight local impression on those who have been accidentally infected by cows; and, as far as I have seen, it has uniformly happened among those who have been inoculated, when a pustule only and no great degree of inflammation or any ulceration has taken place from the inoculation. The following cases will strengthen this opinion.

The cow-pox appeared at a farm in the village of Stonehouse, in this county, about Michaelmas last, and continued gradually to pass from one cow to another till the end of November, On the twenty-sixth of that month some ichorous matter was taken from a cow and dried upon a quill. On the 2d of December some of it was inserted into a scratch, made so superficial that no blood appeared, on the arms of Susan Phipps, a child seven years old. The common inflammatory appearances took place in consequence, and advanced till the fifth day, when they had so much subsided that I did not conceive any thing further would ensue.

6th: Appearances stationary.

7th: The inflammation began to advance.

8th: A vesication, perceptible on the edges, forming, as in the inoculated smallpox, an appearance not unlike a grain of wheat, with the cleft, or indentation in the centre.

9th: Pain in the axilla.

10th: A little headache; pulse, 110; tongue not discoloured; countenance in health.

11th, 12th: No perceptible illness; pulse about 100.

13th: The pustule was now surrounded by an efflorescence, interspersed with very minute confluent pustules to the extent of about an inch. Some of these pustules advanced in size and maturated. So exact was the resemblance of the arm at this stage to the general appearance of the inoculated smallpox that Mr. D., a neighbouring surgeon, who took some matter from it, and who had never seen the cow-pox before, declared he could not perceive any difference. [Footnote: That the cow-pox was a supposed guardian of the constitution from the action of the smallpox has been a prevalent idea for a long time past; but the similarity in the constitutional effects between one disease and the other could never have been so accurately observed had not the inoculation of the cow-pox placed it in a new and stronger point of view. This practice, too, has shewn us, what before lay concealed, the rise and progress of the pustule formed by the insertion of the virus, which places in a most conspicuous light its striking resemblance to the pustule formed from the inoculated smallpox.] The child's arm now shewed a disposition to scab, and remained nearly stationary for two or three days, when it began to run into an ulcerous state, and THEN commenced a febrile indisposition accompanied with an increase of axillary tumour. The ulcer continued spreading near a week, during which time the child continued ill, when it increased to a size nearly as large as a shilling. It began now to discharge pus; granulations sprang up, and it healed. This child had before been of a remarkably sickly constitution, but is now in very high health.

Mary Hearn, twelve years of age, was inoculated with matter taken from the arm of Susan Phipps.

6th day: A pustule beginning to appear, slight pain in the axilla.

7th: A distinct vesicle formed.

8th: The vesicle increasing; edges very red; no deviation in its appearance at this time from the inoculated smallpox.

9th: No indisposition; pustule advancing.

10th: The patient felt this evening a slight febrile attack.

11th: Free from indisposition.

12th, 13th: The same.

14th: An efflorescence of a faint red colour extending several inches round the arm. The pustule, beginning to shew a disposition to spread, was dressed with an ointment composed of hydrarg. nit. rub. and ung. cerce. The efflorescence itself was covered with a plaster of ung. hydr. fort. In six hours it was examined, when it was found that the efflorescence had totally disappeared.

The application of the ointment with the hydr. nit. rub. was made use of for three days, when, the state of the pustule remaining stationary, it was exchanged for the ung. hydr. nit. This appeared to have a more active effect than the former, and in two or three days the virus seemed to be subdued, when a simple dressing was made use of; but the sore again shewing a disposition to inflame, the ung. hydr. nit. was again applied, and soon answered the intended purpose effectually. The girl, after the tenth day, when, as has been observed, she became a little ill, shewed not the least symptom of indisposition. She was afterwards exposed to the action of variolous; matter, and completely resisted it. Susan Phipps also went through a similar trial. Conceiving these cases to be important, I have given them in detail: first, to urge the precaution of using such means as may stop the progress of the pustule; and, secondly, to point out (what appears to be the fact) that the most material indisposition, or at least that which is felt most sensibly, DOES NOT ARISE PRIMARILY FROM THE FIRST ACTION OF THE VIRUS ON THE CONSTITUTION, BUT THAT IT OFTEN COMES ON, IF THE PUSTULE IS LEFT TO CHANCE, AS A SECONDARY DISEASE. This leads me to conjecture, what experiment must finally determine, that they who have had the smallpox are not afterwards susceptible of the primary action of the cow-pox virus; for seeing that the simple virus itself, when it has not passed beyond the boundary of a vesicle, excites in the system so little commotion, is it not probable the trifling illness, thus induced may be lost in that which so quickly, and oftentimes so severely, follows in the casual cow- pox from the presence of corroding ulcers? This consideration induces me to suppose that I may have been mistaken in my former observation on this subject.

In this respect, as well as many others, a parallel may be drawn between this disease and the smallpox. In the latter, the patient first feels the effect of what is called the absorption of the virus. The symptoms then often nearly retire, when a fresh attack commences, different from the first, and the illness keeps pace with the progress of the pustules through their different stages of maturation, ulceration, etc. Although the application I have mentioned in the case of Mary Hearn proved sufficient to check the progress of ulceration and prevent any secondary symptoms, yet, after the pustule has duly exerted its influence, I should prefer the destroying it quickly and effectually to any other mode. The term caustic to a tender ear (and I conceive none feel more interested in this inquiry than the anxious guardians of a nursery) may sound harsh and unpleasing, but every solicitude that may arise on this account will no longer exist when it is understood that the pustule, in a state fit to be acted upon, is then quite superficial, and that it does not occupy the space of a silver penny. [Footnote: I mention escharotics for stopping the progress of the pustule because I am acquainted with their efficacy; probably more simple means might answer the purpose quite as well, such as might be found among the mineral and vegetable astringents.]

As a proof of the efficacy of this practice, even before the virus has fully exerted itself on the system, I shall lay before my reader the following history:

By a reference to the treatise on the Variolae Vaccinae it will be seen that, in the month of April, 1798, four children were inoculated with the matter of cow-pox, and that in two of these cases the virus on the arm was destroyed soon after it had produced a perceptible sickening. Mary James, aged seven years, one of the children alluded to, was inoculated in the month of December following with fresh variolous matter, and at the same time was exposed to the effluvia of a patient affected with the smallpox. The appearance and progress of the infected arm was, in every respect similar to that which we generally observe when variolous matter has been inserted into the skin of a person who has not previously undergone either the cow-pox or the smallpox. On the eighth day, conceiving there was infection in it, she was removed from her residence among those who had not had the smallpox. I was now anxiously waiting the result, conceiving, from the state of the girl's arm, she would fall sick about this time. On visiting her on the evening of the following day (the ninth) all I could learn from the woman who attended her was that she felt somewhat hotter than usual during the night, but was not restless; and that in the morning there was the faint appearance of a rash about her wrists. This went off in a few hours, and was not at all perceptible to me on my visit in the evening. Not a single eruption appeared, the skin having been repeatedly and carefully examined. The inoculated arm continued to make the usual progress to the end, through all the stages of inflammation, maturation, and scabbing.

On the eighth day matter was taken from the arm of this girl (Mary James) and inserted into the arms of her mother and brother (neither of whom had had either the smallpox or the cow-pox), the former about fifty years of age, the latter six.

On the eighth day after the insertion the boy felt indisposed, and continued unwell two days, when a measles-like rash appeared on his hands and wrists, and was thinly scattered over his arms. The day following his body was marbled over with an appearance somewhat similar, but he did not complain, nor did he appear indisposed. A few pustules now appeared, the greater part of which went away without maturating.

On the ninth day the mother began to complain. She was a little chilly and had a headache for two days, but NO PUSTULE APPEARED on the skin, nor had she any appearance of a rash.

The family was attended by an elderly woman as a nurse, who in her infancy had been exposed to the contagion of the smallpox, but had resisted it. This woman was now infected, but had the disease in the slightest manner, a very few eruptions appearing, two or three of which only maturated.

From a solitary instance like that adduced of Mary James, whose constitution appears to have resisted the action of the variolous virus, after the influence of the cow-pox virus had been so soon arrested in its progress, no positive conclusion can be fairly drawn; nor from the history of the three other patients who were subsequently infected, but, nevertheless, the facts collectively may be deemed interesting.

That one mild variety of the smallpox has appeared I have already plainly shewn; [Footnote: See Inquiry into the Causes and Effects of the Variolae Vaccinae, p. 54 (of original article)], and by the means now mentioned we probably have it in our power to produce at will another.

At the time when the pustule was destroyed in the arm of Mary James I was informed she had been indisposed about twelve hours; but I am now assured by those who were with her that the space of time was much less. Be that as it may, in cases of cow-pox inoculation I would not recommend any application to subdue the action of the pustule until convincing proofs had appeared of the patient's having felt its effects at least twelve hours. No harm, indeed, could ensue were a longer period to elapse before the application was made use of. In short, it should be suffered to have as full an effect as it could, consistently with the state of the arm.

As the cases of inoculation multiply, I am more and more convinced of the extreme mildness of the symptoms arising merely from the primary action of the virus on the constitution, and that those symptoms which, as in the accidental cow-pox, affect the patient with severity, are entirely secondary, excited by the irritating processes of inflammation and ulceration; and it appears to me that this singular virus possesses an irritating quality of a peculiar kind, but as a single cow-pox pustule is all that is necessary to render the variolous virus ineffectual, and as we possess the means of allaying the irritation, should any arise, it becomes of little or no consequence.

It appears then, as far as an inference can be drawn from the present progress of cow-pox inoculation, that it is an accidental circumstance only which can render this a violent disease, and a circumstance of that nature which, fortunately, it is in the power of almost every one to avoid. I allude to the communication of the disease from cows. In this case, should the hands of the milker be affected with little accidental sores to any extent, every sore would become the nidus of infection and feel the influence of the virus; and the degree of violence in the constitutional symptoms would be in proportion to the number and to the state of these local affections. Hence it follows that a person, either by accident or design, might be so filled with these wounds from contact with the virus that the constitution might sink under the pressure.

Seeing that we possess the means of rendering the action of the sores mild, which, when left to chance, are capable of producing violent effects; and seeing, too, that these sores bear a resemblance to the smallpox, especially the confluent, should it not encourage the hope that some topical application might be used with advantage to counteract the fatal tendency of that disease, when it appears in this terrific form? At what stage or stages of the disease this may be done with the most promising expectation of success I will not pretend now to determine. I only throw out this idea as the basis of further reasoning and experiment.

I have often been foiled in my endeavours to communicate the cow- pox by inoculation. An inflammation will sometimes succeed the scratch or puncture, and in a few days disappear without producing any further effect. Sometimes it will even produce an ichorous fluid, and yet the system will not be affected. The same thing we know happens with the smallpox virus.

Four or five servants were inoculated at a farm contiguous to this place, last summer, with matter just taken from an infected cow. A little inflammation appeared on all their arms, but died away without producing a pustule; yet all these servants caught the disease within a month afterwards from milking the infected cows, and some of them had it severely. At present no other mode than that commonly practiced for inoculating the smallpox has been used for giving the cow-pox; but it is probable this might be varied with advantage. We should imitate the casual communication more clearly were we first, by making the smallest superficial incision or puncture on the skin, to produce a little scab, and then, removing it, to touch the abraded part with the virus. A small portion of a thread imbrued in the virus (as in the old method of inoculating the smallpox) and laid upon the slightly incised skin might probably prove a successful way of giving the disease; or the cutis might be exposed in a minute point by an atom of blistering plaster, and the virus brought in contact with it. In the cases just alluded to, where I did not succeed in giving the disease constitutionally, the experiment was made with matter taken in a purulent state from a pustule on the nipple of a cow.

Is PURE PUS, though contained in a smallpox pustule, ever capable of producing the smallpox perfectly? I suspect it is not. Let us consider that it is always preceded by the limpid fluid, which, in constitutions susceptible of variolous contagion, is always infectious; and though, on opening a pustule, its contents may appear perfectly purulent, yet a given quantity of the limpid fluid may, at the same time, be blended with it, though it would be imperceptible to the only test of our senses, the eye. The presence, then, of this fluid, or its mechanical diffusion through pus, may at all times render active what is apparently MERE PUS, while its total absence (as in stale pustules) may be attended with the imperfect effects we have seen.

It would be digressing too widely to go far into the doctrine of secretion, but as it will not be quite extraneous, I shall just observe that I consider both the pus and the limpid fluid of the pustule as secretions, but that the organs established by nature to perform the office of secreting these fluids may differ essentially in their mechanical structure. What but a difference in the organization of glandular bodies constitutes the difference in the qualities of the fluids secreted? From some peculiar derangement in the structure or, in other words, some deviation in the natural action of a gland destined to create a mild, innoxious fluid, a poison of the most deadly nature may be created; for example: That gland, which in its sound state secretes pure saliva, may, from being thrown into diseased action, produce a poison of the most destructive quality. Nature appears to have no more difficulty in forming minute glands among the vascular parts of the body than she has in forming blood vessels, and millions of these can be called into existence, when inflammation is excited, in a few hours. [Footnote: Mr. Home, in his excellent dissertation on pus and mucus, justifies this assertion.]

In the present early stage of the inquiry (for early it certainly must be deemed), before we know for an absolute certainty how soon the virus of the cow-pox may suffer a change in its specific properties, after it has quitted the limpid state it possesses when farming a pustule, it would be prudent for those who have been inoculated with it to submit to variolous inoculation. No injury or inconvenience can accrue from this; and were the same method practiced among those who, from inoculation, have felt the smallpox in an unsatisfactory manner at any period of their lives, it might appear that I had not been too officious in offering a cautionary, hint in recommending a second inoculation with matter in its most perfect state.

And here let me suppose, for argument's sake (not from conviction), that one person in an hundred after having had the cow-pox should be found susceptible of the smallpox, would this invalidate the utility of the practice? For, waiving all other considerations, who will deny that the inoculated smallpox, although abstractedly it may be considered as harmless, does not involve in itself something that in numberless instances proves baneful to the human frame.

That in delicate constitutions it sometimes excites scrofula is a fact that must generally be subscribed to, as it is so obvious to common observation. This consideration is important.

As the effects of the smallpox inoculation on those who have had the cow-pox will be watched with the most scrupulous eye by those who prosecute this inquiry, it may be proper to bring to their recollection some facts relative to the smallpox, which I must consider here as of consequence, but which hitherto seem not to have made a due impression.

It should be remembered that the constitution cannot, by previous infection, be rendered totally unsusceptible of the variolous poison; neither the casual nor the inoculated smallpox, whether it produces the disease in a mild or in a violent way, can perfectly extinguish the susceptibility. The skin, we know, is ever ready to exhibit, though often in a very limited degree, the effects of the poison when inserted there; and how frequently do we see, among nurses, when much exposed to the contagion, eruptions, and these sometimes preceded by sensible illness! yet should any thing like an eruption appear, or the smallest degree of indisposition, upon the insertion of the variolous matter on those who have gone through the cow-pox, my assertions respecting the peculiarities of the disease might be unjustly discredited.

I know a gentleman who, many years ago, was inoculated for the smallpox, but having no pustules, or scarcely any constitutional affection that was perceptible, he was dissatisfied, and has since been repeatedly inoculated. A vesicle has always been produced in the arm in consequence, with axillary swelling and a slight indisposition; this is by no means a rare occurrence. It is probable that fluid thus excited upon the skin would always produce the smallpox.

On the arm of a person who had gone through the cow-pox many years before I once produced a vesication by the insertion of variolous matter, and, with a little of the fluid, inoculated a young woman who had a mild, but very efficacious, smallpox in consequence, although no constitutional effect was produced on the patient from whom the matter was taken. The following communication from Mr. Fewster affords a still clearer elucidation of this fact. Mr. Fewster says: "On the 3d of April, 1797, I inoculated Master H—, aged fourteen months, for the smallpox. At the usual time he sickened, had a plentiful eruption, particularly on his face, and got well. His nursemaid, aged twenty-four, had many years before gone through the smallpox, in the natural way, which was evident from her being much pitted with it. She had used the child to sleep on her left arm, with her left cheek in contact with his face, and during his inoculation he had mostly slept in that manner. About a week after the child got well she (the nurse) desired me to look at her face, which she said was very painful. There was a plentiful eruption on the left cheek, BUT NOT ON ANY OTHER PART OF THE BODY, which went on to maturation.

"On enquiry I found that three days before the appearance of the eruption she was taken with slight chilly fits, pain in her head and limbs, and some fever. On the appearance of the eruption these pains went off, and now, the second day of the eruption, she complains of a little sore throat. Whether the above symptoms are the effects of the smallpox or a recent cold I do not know. On the fifth day of the eruption I charged a lancet from two of the pustules, and on the next day I inoculated two children, one two years, the other four months old, with the matter. At the same time I inoculated the mother and eldest sister with variolous matter taken from Master H—. On the fifth day of their inoculation ALL their arms were inflamed alike; and on the eighth day the eldest of those inoculated from the nurse sickened, and the youngest on the eleventh. They had both a plentiful eruption, from which I inoculated several others, who had the disease very favourably. The mother and the other child sickened about the same time, and likewise had a plentiful eruption.

"Soon after, a man in the village sickened with the smallpox and had a confluent kind. To be convinced that the children had had the disease effectually I took them to his house and inoculated them in both arms with matter taken from him, but without effect."

These are not brought forward as uncommon occurrences, but as exemplifications of the human system's susceptibility of the variolous contagion, although it has been previously sensible of its action.

Happy is it for mankind that the appearance of the small-pox a second time on the same person, beyond a trivial extent, is so extremely rare that it is looked upon as a phaenomenon! Indeed, since the publication of Dr. Heberden's paper on the Varicellae, or chicken-pox, the idea of such an occurrence, in deference to authority so truly respectable, has been generally relinquished. This I conceive has been without just reason; for after we have seen, among many others, so strong a case as that recorded by Mr. Edward Withers, Surgeon, of Newbury, Berks, in the fourth volume of the Memoirs of the Medical Society of London (from which I take the following extracts), no one, I think, will again doubt the fact.

"Mr. Richard Langford, a farmer of West Shefford, in this county (Berks), about fifty years of age, when about a month old had the smallpox at a time when three others of the family had the same disease, one of whom, a servant man, died of it. Mr. Langford's countenance was strongly indicative of the malignity of the distemper, his face being so remarkably pitted and seamed as to attract the notice of all who saw him, so that no one could entertain a doubt of his having had that disease in a most inveterate manner." Mr. Withers proceeds to state that Mr. Langford was seized a second time, had a bad confluent smallpox, and died on the twenty-first day from the seizure; and that four of the family, as also a sister of the patient's, to whom the disease was conveyed by her son's visiting his uncle, falling down with the smallpox, fully satisfied the country with regard to the nature of the disease, which nothing short of this would have done; the sister died.

"This case was thought so extraordinary a one as to induce the rector of the parish to record the particulars in the parish register."

It is singular that in most cases of this kind the disease in the first instance has been confluent; so that the extent of the ulceration on the skin (as in the cow-pox) is not the process in nature which affords security to the constitution.

As the subject of the smallpox is so interwoven with that which is the more immediate object of my present concern, it must plead my excuse for so often introducing it. At present it must be considered is a distemper not well understood. The inquiry I have instituted into the nature of the cow-pox will probably promote its more perfect investigation.

The inquiry of Dr. Pearson into the history of the cow-pox having produced so great a number of attestations in favour of my assertion that it proves a protection to the human body from the smallpox, I have not been assiduous in seeking for more; but as some of my friends have been so good as to communicate the following, I shall conclude these observations with their insertion.

Extract of a letter from Mr. Drake, Surgeon, at Stroud, in this county, and late Surgeon to the North Gloucester Regiment of Militia:

"In the spring of the year 1796 I inoculated men, women, and children to the amount of about seventy. Many of the men did not receive the infection, although inoculated at least three times and kept in the same room with those who actually underwent the disease during the whole time occupied by them in passing through it. Being anxious they should, in future, be secure against it, I was very particular in my inquiries to find out whether they ever had previously had it, or at any time been in the neighbourhood of people labouring under it. But, after all, the only satisfactory information I could obtain was that they had had the cow-pox. As I was then ignorant of such a disease affecting the human subject, I flattered myself what they imagined to be the cow-pox was in reality the smallpox in a very slight degree. I mentioned the circumstance in the presence of the officers, at the time expressing my doubts if it were not smallpox, and was not a little surprised when I was told by the Colonel that he had frequently heard you mention the cow-pox as a disease endemial to Gloucestershire, and that if a person were ever affected by it, you supposed him afterwards secure from the smallpox. This excited my curiosity, and when I visited Gloucestershire I was very inquisitive concerning the subject, and from the information I have since received, both from your publication and from conversation with medical men of the greatest accuracy in their observations, I am fully convinced that what the men supposed to be cow-pox was actually so, and I can safely affirm that they effectually resisted the smallpox."

Mr. Fry, Surgeon, at Dursley in this county, favours me with the following communication:

"During the spring of the year 1797 I inoculated fourteen hundred and seventy-five patients, of all ages, from a fortnight old to seventy years; amongst whom there were many who had previously gone through the cow-pox. The exact number I cannot state; but if I say there were nearly thirty, I am certainly within the number. There was not a single instance of the variolous matter producing any constitutional effect on these people, nor any greater degree of local inflammation than it would have done in the arm of a person who had before gone through the smallpox, notwithstanding it was invariably inserted four, five, and sometimes six different times, to satisfy the minds of the patients. In the common course of inoculation previous to the general one scarcely a year passed without my meeting with one or two instances of persons who had gone through the cow-pox, resisting the action of the variolous contagion. I may fairly say that the number of people I have seen inoculated with the smallpox who, at former periods, had gone through the cow-pox, are not less than forty; and in no one instance have I known a patient receive the smallpox, notwithstanding they invariably continued to associate with other inoculated patients during the progress of the disease, and many of them purposely exposed themselves to the contagion of the natural smallpox; whence I am fully convinced that a person who had fairly had the cow-pox is no longer capable of being acted upon by the variolous matter.

"I also inoculated a very considerable number of those who had had a disease which ran through the neighbourhood a few years ago, and was called by the common people the swine-pox, not one of whom received the smallpox. [Footnote: This was that mild variety of the smallpox which I have noticed in the late Treatise on the Cow-Pox (p. 233).]

"There were about half a dozen instances of people who never had either the cow-or swine-pox, yet did not receive the smallpox, the system not being in the least deranged, or the arms inflamed, although they were repeatedly inoculated, and associated with others who were labouring under the disease; one of them was the son of a farrier."

Mr. Tierny, Assistant Surgeon of the South Gloucester Regiment of Militia, has obliged me with the following information:

"That in the summer of the year of 1798 he inoculated a great number of the men belonging to the regiment, and that among them he found eleven who, from having lived in dairies, had gone through the cow-pox. That all of them resisted the smallpox except one, but that on making the most rigid and scrupulous enquiry at the farm in Gloucestershire, where the man said he lived when he had the disease, and among those with whom, at the same time, he declared he had associated, and particularly of a person in the parish, whom he said had dressed his fingers, it most clearly appeared that he aimed at an imposition, and that he never had been affected with the cow-pox." [Footnote: The public cannot be too much upon their guard respecting persons of this description.] Mr. Tierny remarks that the arms of many who were inoculated after having had the cow-pox inflamed very quickly, and that in several a little ichorous fluid was formed.

Mr. Cline, who in July last was so obliging at my request as to try the efficacy of the cow-pox virus, was kind enough to give me a letter on the result of it, from which the following is an extract:

"My DEAR SIR:

"The cow-pox experiment has succeeded admirably. The child sickened on the seventh day, and the fever, which was moderate, subsided on the eleventh. The inflammation arising from the insertion of the virus extended to about four inches in diameter, and then gradually subsided, without having been attended with pain or other inconvenience. There were no eruptions.

"I have since inoculated him with smallpox matter in three places, which were slightly inflamed on the third day, and then subsided.

"Dr. Lister, who was formerly physician to the Smallpox Hospital, attended the child with me, and he is convinced that it is not possible to give him the smallpox. I think the substituting the cow-pox poison for the smallpox promises to be one of the greatest improvements that has ever been made in medicine; and the more I think on the subject, the more I am impressed with its importance.

"With great esteem

"I am, etc., "HENRY CLINE.

"Lincoln's Inn Fields, August 2, 1798."

From communications, with which I have been favoured from Dr. Pearson, who has occasionally reported to me the result of his private practice with the vaccine virus in London, and from Dr. Woodville, who also has favoured me with an account of his more extensive inoculation with the same virus at the Smallpox Hospital, it appears that many of their patients have been affected with eruptions, and that these eruptions have maturated in a manner very similar to the variolous. The matter they made use of was taken in the first instance from a cow belonging to one of the great milk farms in London. Having never seen maturated pustules produced either in my own practice among those who were casually infected by cows, or those to whom the disease had been communicated by inoculation, I was desirous of seeing the effect of the matter generated in London, on subjects living in the country. A thread imbrued in some of this matter was sent to me, and with it two children were inoculated, whose cases I shall transcribe from my notes.

Stephen Jenner, three years and a half old.

3d day: The arm shewed a proper and decisive inflammation.

6th: A vesicle arising.

7th: The pustule of a cherry colour.

8th: Increasing in elevation. A few spots now appear on each arm near the insertion of the inferior tendons of the biceps muscles. They are very small and of a vivid red colour. The pulse natural; tongue of its natural hue; no loss of appetite or any symptom of indisposition.

9th: The inoculated pustule on the arm this evening began to inflame, and gave the child uneasiness; he cried and pointed to the seat of it, and was immediately afterwards affected with febrile symptoms. At the expiration of two hours after the seizure a plaster of ung. hydrarg. fort, was applied, and its effect was very quickly perceptible, for in ten minutes he resumed his usual looks and playfulness. On examining the arm about three hours after the application of the plaster its effects in subduing the inflammation were very manifest.

10th: The spots on the arms have disappeared, but there are three visible in the face.

11th: Two spots on the face are gone; the other barely perceptible.

13th: The pustule delineated in the second plate in the Treatise on the Variolae Vaccinae is a correct representation of that on the child's arm as it appears at this time.

14th: Two fresh spots appear on the face. The pustule on the arm nearly converted into a scab. As long as any fluid remained in it it was limpid.

James Hill, four years old, was inoculated on the same day, and with part of the same matter which infected Stephen Jenner. It did not appear to have taken effect till the fifth day.

7th: A perceptible vesicle: this evening the patient became a little chilly; no pain or tumour discoverable in the axilla.

8th: Perfectly well.

9th: The same.

10th: The vesicle more elevated than I have been accustomed to see it, and assuming more perfectly the variolous character than is common with the cow-pox at this stage.

11th: Surrounded by an inflammatory redness, about the size of a shilling, studded over with minute vesicles. The pustule contained a limpid fluid till the fourteenth day, after which it was incrusted over in the usual manner; but this incrustation or scab being accidentally rubbed off, it was slow in healing.

These children were afterwards fully exposed to the smallpox contagion without effect.

Having been requested by my friend, Mr. Henry Hicks, of Eastington, in this county, to inoculate two of his children, and at the same time some of his servants and the people employed in his manufactory, matter was taken from the arm of this boy for the purpose. The numbers inoculated were eighteen. They all took the infection, and either on the fifth or sixth day a vesicle was perceptible on the punctured part. Some of them began to feel a little unwell on the eighth day, but the greater number on the ninth. Their illness, as in the former cases described, was of short duration, and not sufficient to interrupt, but at very short intervals, the children from their amusements, or the servants and manufacturers from following their ordinary business.

Three of the children whose employment in the manufactory was in some degree laborious had an inflammation on their arms beyond the common boundary about the eleventh or twelfth day, when the feverish symptoms, which before were nearly gone off, again returned, accompanied with increase of axillary tumour. In these cases (clearly perceiving that the symptoms were governed by the state of the arms) I applied on the inoculated pustules, and renewed the application three or four times within an hour, a pledget of lint, previously soaked in aqua lythargyri acetati [Footnote: Goulard's extract of Saturn.] and covered the hot efflorescence surrounding them with cloths dipped in cold water.

The next day I found this simple mode of treatment had succeeded perfectly. The inflammation was nearly gone off, and with it the symptoms which it had produced.

Some of these patients have since been inoculated with variolous matter, without any effect beyond a little inflammation on the part where it was inserted.

Why the arms of those inoculated with the vaccine matter in the country should be more disposed to inflame than those inoculated in London it may be difficult to determine. From comparing my own cases with some transmitted to me by Dr. Pearson and Dr. Woodville, this appears to be the fact; and what strikes me as still more extraordinary with respect to those inoculated in London is the appearance of maturating eruptions, In the two instances only which I have mentioned (the one from the inoculated, the other from the casual, cow-pox) a few red spots appeared, which quickly went off without maturating. The case of the Rev. Mr. Moore's servant may, indeed, seem like a deviation from the common appearances in the country, but the nature of these eruptions was not ascertained beyond their not possessing the property of communicating the disease by their effluvia. Perhaps the difference we perceive may be owing to some variety in the mode of action of the virus upon the skin of those who breathe the air of London and those who live in the country. That the erysipelas assumes a different form in London from what we see it put on in this country is a fact very generally acknowledged. In calling the inflammation that is excited by the cow-pox virus erysipelatous, perhaps I may not be critically exact, but it certainly approaches near to it. Now, as the diseased action going forward in the part infected with the virus may undergo different modifications according to the peculiarities of the constitution on which it is to produce its effect, may it not account for the variation which has been observed?

To this it may probably be objected that some of the patients inoculated, and who had pustules in consequence, were newly come from the country; but I conceive that the changes wrought in the human body through the medium of the lungs may be extremely rapid. Yet, after all, further experiments made in London with vaccine virus generated in the country must finally throw a light on what now certainly appears obscure and mysterious.

The principal variation perceptible to me in the action of the vaccine virus generated in London from that produced in the country was its proving more certainly infectious and giving a less disposition in the arm to inflame. There appears also a greater elevation of the pustule above the surrounding skin. In my former cases the pustule produced by the insertion of the virus was more like one of those which are so thickly spread over the body in a bad kind of confluent smallpox. This was more like a pustule of the distinct smallpox, except that I saw no instance of pus being formed in it, the matter remaining limpid till the period of scabbing.

Wishing to see the effects of the disease on an infant newly born, my nephew, Mr. Henry Jenner, at my request, inserted the vaccine virus into the arm of a child about twenty hours old. His report to me is that the child went through the disease without apparent illness, yet that it was found effectually to resist the action of variolous matter with which it was subsequently inoculated.

I have had an opportunity of trying the effects of the cow-pox matter on a boy, who, the day preceding its insertion, sickened with the measles. The eruption of the measles, attended with cough, a little pain in the chest; and the usual symptoms accompanying the disease, appeared on the third day and spread all over him. The disease went through its course without any deviation from its usual habits; and, notwithstanding this, the cow-pox virus excited its common appearances, both on the arm and on the constitution, without any febrile interruption; on the sixth day there was a vesicle.

8th: Pain in the axilla, chilly, and affected with headache.

9th: Nearly well.

12th: The pustule spread to the size of a large split-pea, but without any surrounding efflorescence. It soon afterwards scabbed, and the boy recovered his general health rapidly. But it should be observed that before it scabbed the efflorescence which had suffered a temporary suspension advanced in the usual manner.

Here we see a deflation from the ordinary habits of the smallpox, as it has been observed that the presence of the measles suspends the action of the variolous matter.

The very general investigation that is now taking place, chiefly through inoculation (and I again repeat my earnest hope that it may be conducted with that calmness and moderation which should ever accompany a philosophical research), must soon place the vaccine disease in its just point of view. The result of all my trials with the virus on the human subject has been uniform. In every instance the patient who has felt its influence, has completely lost the susceptibility for the variolous contagion; and as these instances are now become numerous, I conceive that, joined to the observations in the former part of this paper, they sufficiently preclude me from the necessity of entering into controversies with those who have circulated reports adverse to my assertions, on no other evidence than what has been casually collected.



III

A CONTINUATION OF FACTS AND OBSERVATIONS RELATIVE TO THE VARIOUS VACCINES, OR COW-POX. 1800

Since my former publications on the vaccine inoculation I have had the satisfaction of seeing it extend very widely. Not only in this country is the subject pursued with ardour, but from my correspondence with many respectable medical gentlemen on the Continent (among whom are Dr. De Carro, of Vienna, and Dr. Ballhorn, of Hanover) I find it is as warmly adopted abroad, where it has afforded the greatest satisfaction. I have the pleasure, too, of seeing that the feeble efforts of a few individuals to depreciate the new practice are sinking fast into contempt beneath the immense mass of evidence which has arisen up in support of it.

Upwards of six thousand persons have now been inoculated with the virus of cow-pox, and the far greater part of them have since been inoculated with that of smallpox, and exposed to its infection in every rational way that could be devised, without effect.

It was very improbable that the investigation of a disease so analogous to the smallpox should go forward without engaging the attention of the physician of the Smallpox Hospital in London.

Accordingly, Dr. Woodville, who fills that department with so much respectability, took an early opportunity of instituting an inquiry into the nature of the cow-pox. This inquiry was begun in the early part of the present year, and in May, Dr. Woodville published the result, which differs essentially from mine in a point of much importance. It appears that three-fifths of the patients inoculated were affected with eruptions, for the most part so perfectly resembling the smallpox as not to be distinguished from them. On this subject it is necessary that I should make some comments.

When I consider that out of the great number of cases of casual inoculation immediately from cows which from time to time presented themselves to my observation, and the many similar instances which have been communicated to me by medical gentlemen in this neighbourhood; when I consider, too, that the matter with which my inoculations were conducted in the years 1797, '98, and '99, was taken from some different cows, and that in no instance any thing like a variolous pustule appeared, I cannot feel disposed to imagine that eruptions, similar to those described by Dr. Woodville, have ever been produced by the pure uncontaminated cow-pock virus; on the contrary, I do suppose that those which the doctor speaks of originated in the action of variolous matter which crept into the constitution with the vaccine. And this I presume happened from the inoculation of a great number of the patients with variolous matter (some on the third, others on the fifth, day) after the vaccine had been applied; and it should be observed that the matter thus propagated became the source of future inoculations in the hands of many medical gentlemen who appeared to have been previously unacquainted with the nature of the cow-pox.

Another circumstance strongly, in my opinion, supporting this supposition is the following: The cow-pox has been known among our dairies time immemorial. If pustules, then, like the variolous, were to follow the communication of it from the cow to the milker, would not such a fact have been known and recorded at our farms? Yet neither our farmers nor the medical people of the neighbourhood have noticed such an occurrence.

A few scattered pimples I have sometimes, though very rarely, seen, the greater part of which have generally disappeared quickly, but some have remained long enough to suppurate at their apex. That local cuticular inflammation, whether springing up spontaneously or arising from the application of acrid substances, such for instance, as cantharides, pix Burgundica, antimonium tartarizatum, etc., will often produce cutaneous affections, not only near the seat of the inflammation, but on some parts of the skin far beyond its boundary, is a well-known fact. It is, doubtless, on this principle that the inoculated cow-pock pustule and its concomitant efflorescence may, in very irritable constitutions, produce this affection. The eruption I allude to has commonly appeared some time in the third week after inoculation. But this appearance is too trivial to excite the least regard.

The change which took place in the general appearance during the progress of the vaccine inoculation at the Smallpox Hospital should likewise be considered.

Although at first it took on so much of the variolous character as to produce pustules in three cases out of five, yet in Dr. Woodville's last report, published in June, he says: "Since the publication of my reports of inoculations for the cow-pox, upwards of three hundred cases have been under my care; and out of this number only thirty-nine had pustules that suppurated; viz., out of the first hundred, nineteen had pustules; out of the second, thirteen; and out of the last hundred and ten, only seven had pustules. Thus it appears that the disease has become considerably milder; which I am inclined to attribute to a greater caution used in the choice of the matter, with which the infection was communicated; for, lately, that which has been employed for this purpose has been taken only from those patients in whom the cow-pox proved very mild and well characterized." [Footnote: In a few weeks after the cow-pox inoculation was introduced at the Smallpox Hospital I was favoured with some virus from this stock. In the first instance it produced a few pustules, which did not maturate; but in the subsequent cases none appeared.—E. J.]

The inference I am induced to draw from these premises is very different. The decline, and, finally, the total extinction nearly, of these pustules, in my opinion, are more fairly attributable to the cow-pox virus, assimilating the variolous, [Footnote: In my first publication on this subject I expressed an opinion that the smallpox and the cow-pox were the same diseases under different modifications. In this opinion Dr. Woodville has concurred The axiom of the immortal Hauter, that two diseased actions cannot take place at the same time in one and the same part, will not be injured by the admission of this theory.] the former probably being the original, the latter the same disease under a peculiar, and at present an inexplicable, modification.

One experiment tending to elucidate the point under discussion I had myself an opportunity of instituting. On the supposition of its being possible that the cow which ranges over the fertile meadows in the vale of Gloucester might generate a virus differing in some respects in its qualities from that produced by the animal artificially pampered for the production of milk for the metropolis, I procured, during my residence there in the spring, some cow pock virus from a cow at one of the London milk- farms. [Footnote: It was taken by Mr. Tanner, then a student at the Veterinary College, from a cow at Mr. Clark's farm at Kentish Town.] It was immediately conveyed into Gloucestershire to Dr. Marshall, who was then extensively engaged in the inoculation of the cow-pox, the general result of which, and of the inoculation in particular with this matter, I shall lay before my reader in the following communication from the doctor:

"DEAR SIR:

"My neighbour, Mr. Hicks, having mentioned your wish to be informed of the progress of the inoculation here for the cow-pox, and he also having taken the trouble to transmit to you my minutes of the cases which have fallen under my care, I hope you will pardon the further trouble I now give you in stating the observations I have made upon the subject. When first informed of it, having two children who had not had the smallpox, I determined to inoculate them for the cow-pox whenever I should be so fortunate as to procure matter proper for the purpose. I was, therefore, particularly happy when I was informed that I could procure matter from some of those whom you had inoculated. In the first instance I had no intention of extending the disease further than my own family, but the very extensive influence which the conviction of its efficacy in resisting the smallpox has had upon the minds of the people in general has rendered that intention nugatory, as you will perceive, by the continuation of my cases enclosed in this letter, [Footnote: Doctor Marshall has detailed these cases with great accuracy, but their publication would now be deemed superfluous.—E.J.] by which it will appear that since the 22d of March I have inoculated an hundred and seven persons; which, considering the retired situation I resided in, is a very great number. There are also other considerations which, besides that of its influence in resisting the smallpox, appear to have had their weight; the peculiar mildness of the disease, the known safety of it, and its not having in any instance prevented the patient from following his ordinary business. In all the cases under my care there have only occurred two or three which required any application, owing to erysipelatous inflammation on the arm, and they immediately yielded to it. In the remainder the constitutional illness has been slight but sufficiently marked, and considerably less than I ever observed in the same number inoculated with the smallpox. In only one or two of the cases have any other eruptions appeared than those around the spot where the matter was inserted, and those near the infected part. Neither does there appear in the cow-pox to be the least exciting cause to any other disease, which in the smallpox has been frequently observed, the constitution remaining in as full health and vigour after the termination of the disease as before the infection. Another important consideration appears to be the impossibility of the disease being communicated except by the actual contact of the matter of the pustule, and consequently the perfect safety of the remaining part of the family, supposing only one or two should wish to be inoculated at the same time.

"Upon the whole, it appears evident to me that the cow-pox is a pleasanter, shorter, and infinitely more safe disease than the inoculated smallpox when conducted in the most careful and approved manner; neither is the local affection of the inoculated part, or the constitutional illness, near so violent. I speak with confidence on the subject, having had an opportunity of observing its effects upon a variety of constitutions, from three months old to sixty years; and to which I have paid particular attention. In the cases alluded to here you will observe that the removal from the original source of the matter had made no alteration or change in the nature or appearance of the disease, and that it may be continued, ad infinitum (I imagine), from one person to another (if care be observed in taking the matter at a proper period) without any necessity of recurring to the original matter of the cow.

"I should be happy if any endeavours of mine could tend further to elucidate the subject, and shall be much gratified is sending you any further observations I may be enabled to make.

"I have the pleasure to subscribe myself, "Dear sir, etc., "JOSEPH H. MARSHALL

"EASTINGTON, GLOUCESTERSHIRE, April 26, 1799."

The gentleman who favoured me with the above account has continued to prosecute his inquiries with unremitting industry, and has communicated the result in another letter, which at his request I lay before the public without abbreviation.

Dr. Marshall's second letter:

"DEAR SIR:

"Since the date of my former letter I have continued to inoculate with the cow-pox virus. Including the cases before enumerated, the number now amounts to four hundred and twenty-three. It would be tedious and useless to detail the progress of the disease in each individual—it is sufficient to observe that I noticed no deviation in any respect from the cases I formerly adduced. The general appearances of the arm exactly corresponded with the account given in your first publication. When they were disposed to become troublesome by erysipelatous inflammation, an application of equal parts of vinegar and water always answered the desired intention. I must not omit to inform you that when the disease had duly acted upon the constitution I have frequently used the vitriolic acid. A portion of a drop applied with the head of a probe or any convenient utensil upon the pustule, suffered to remain about forty seconds, and afterwards washed off with sponge and water, never failed to stop its progress and expedite the formation of a scab.

"I have already subjected two hundred and eleven of my patients to the action of variolous matter, but EVERY ONE RESISTED IT.

"The result of my experiments (which were made with every requisite caution) has fully convinced me that the TRUE COW-POX is a safe and infallible preventive from the smallpox; that in no case which has fallen under my observation has it been in any considerable degree troublesome, much less have I seen any thing like danger; for in no instance were the patients prevented from following their ordinary employments.

"In Dr. Woodville's publication on the cow-pox I notice an extraordinary fact. He says that the generality of his patients had pustules. It certainly appears extremely extraordinary that in all my cases there never was but one pustule, which appeared on a patient's elbow on the inoculated arm, and maturated. It appeared exactly like that on the incised part.

"The whole of my observations, founded as it appears on an extensive experience, leads me to these obvious conclusions; that those cases which have been or may be adduced against the preventive powers of the cow-pox could not have been those of the true kind, since it must appear to be absolutely impossible that I should have succeeded in such a number of cases without a single exception if such a preventive power did not exist. I cannot entertain a doubt that the inoculated cow-pox must quickly supersede that of the smallpox. If the many important advantages which must result from the new practice are duly considered, we may reasonably infer that public benefit, the sure test of the real merit of discoveries, will render it generally extensive.

"To you, Sir, as the discoverer of this highly beneficial practice, mankind are under the highest obligations. As a private individual I participate in the general feeling; more particularly as you have afforded me an opportunity of noticing the effects of a singular disease, and of viewing the progress of the most curious experiment that ever was recorded in the history of physiology. "I remain, dear sir, etc., "JOSEPH H. MARSHALL."

"P.S. I should have observed that, of the patients I inoculated and enumerated in my letter, one hundred and twenty-seven were infected with the matter you sent me from the London cow. I discovered no dissimilarity of symptoms in these cases from those which I inoculated from matter procured in this country. No pustules have occurred, except in one or two cases, where a single one appeared on the inoculated arm. No difference was apparent in the local inflammation. There was no suspension of ordinary employment among the labouring people, nor was any medicine required.

"I have frequently inoculated one or two in a family, and the remaining part of it some weeks afterwards. The uninfected have slept with the infected during the whole course of the disease without being affected; so that I am fully convinced that the disease cannot be taken but by actual contact with the matter.

"A curious fact has lately fallen under my observation, on which I leave you to comment.

"I visited a patient with the confluent smallpox and charged a lancet with some of the matter. Two days afterwards I was desired to inoculate a woman and four children with the cow-pox, and I inadvertently took the vaccine matter on the same lancet which was before charged with that of smallpox. In three days I discovered the mistake, and fully expected that my five patients would be infected with smallpox; but I was agreeably surprised to find the disease to be genuine cow-pox, which proceeded without deviating in any particular from my former cases. I afterwards inoculated these patients with variolous matter, but all of them resisted its action.

"I omitted mentioning another great advantage that now occurs to me in the inoculated cow-pox; I mean, the safety with which pregnant women may have the disease communicated to them. I have inoculated a great number of females in that situation, and never observed their cases to differ in any respect from those of my other patients. Indeed, the disease is so mild that it seems as if it might at all times be communicated with the most perfect safety."

I shall here take the opportunity of thanking Dr. Marshall and those other gentlemen who have obligingly presented me with the result of their inoculations; but, as they all agree in the same point as that given in the above communication, namely, the security of the patient from the effects of the smallpox after the cow-pox, their perusal, I presume, would afford us no satisfaction that has not been amply given already. Particular occurrences I shall, of course, detail. Some of my correspondents have mentioned the appearance of smallpox-like eruptions at the commencement of their inoculations; but in these cases the matter was derived from the original stock at the Smallpox Hospital.

I have myself inoculated a very considerable number from the matter produced by Dr. Marshall's patients, originating in the London cow, without observing pustules of any kind, and have dispersed it among others who have used it with a similar effect. From this source Mr. H. Jenner informs me he has inoculated above an hundred patients without observing eruptions. Whether the nature of the virus will undergo any change from being farther removed from its original source in passing successively from one person to another time alone can determine. That which I am now employing has been in use near eight months, and not the least change is perceptible in its mode of action either locally or constitutionally. There is, therefore, every reason to expect that its effects will remain unaltered and that we shall not be under the necessity of seeking fresh supplies from the cow.