2. Whether the hazard of inoculation be considerably less than that of the

natural smallpox? These questions, thus put forward as of equal moment, did not receive equally full handling. Jurin dismissed the former question in a brief sentence: “Our experience, so far as it goes, has hitherto strongly favoured the affirmative side”--a conditional assent which became an absolute affirmative after a short time. Having thus disposed of the question which has all the scientific or pathological interest, he turned with his whole energy to give a precise arithmetical demonstration of what no one could doubt, namely, that inoculated smallpox was many times less fatal than smallpox in the natural way,--having got the idea of such a comparison from Nettleton as well as a large part of the statistics necessary for it. Jurin’s statement of the questions at issue, and his manner of answering them, became the received mode, so much so that even towards the end of the eighteenth century one finds capable medical men contrasting the almost infinitesimal mortality from inoculation, as then practised, with the high mortality from the natural smallpox, as if that were the question at issue. The permanent impression in favour of inoculation made by Jurin’s arithmetic was shown a generation later, when Dr George Baker pronounced an eulogy upon him in the Harveian Oration before the College of Physicians in 1761[900]. “It was his special glory,” said the orator, to have “confirmed the practice of inoculation by his experiments and his authority.” There was only one experiment, and it was a remarkable one. The Princess of Wales had begged George I. to pardon six Newgate criminals under sentence of death on condition that they would submit to be inoculated. It was assumed that those six had not had smallpox in infancy or childhood, and Sloane, relating the facts in a letter to Ranby some years after, does in fact call them “six condemned criminals who had not had the smallpox[901].” The concurrence of six persons belonging to the criminal classes and about to be hanged together in Newgate, of whom none had already gone through the common infantile trouble of London and other large towns, was singular. They were inoculated, and it was found that they had escaped the death penalty on very easy terms: John Alcock, aged twenty, had most smallpox, but even he had “not more than sixty pustules”; Richard Evans, aged nineteen, had none, but his antecedents were inquired into, and then it was found that he had had smallpox in gaol only six months before. One of the others, a woman named Elizabeth, was chosen for the grand crucial experiment. Sir Hans Sloane and Dr Steigerthal clubbed together to pay her expenses to Hertford where smallpox was then very prevalent; thither Elizabeth went and ministered among the sick; she lay in bed with one in the smallpox, or she lay in bed with various in the smallpox; at all events she exposed herself to contagion and did not catch it, according to certificates from the woman she lodged with and from another person, which certificates were published with much formality and lawyer-like precision[902]. This was the single experiment in which Jurin had any part. What were the chances of her having had smallpox in childhood? What were the chances of her knowing anything about it, or telling the truth about it if she knew? (One of her fellows in the experiment upon the pardoned convicts had smallpox only six months before, but the fact was not discovered until it was wanted.) What were the chances of her taking smallpox at Hertford, supposing that she had hitherto escaped it? These questions do not appear to have been debated[903]. Such was the experiment by which Jurin “confirmed the practice of inoculation.” As for his authority, it was doubtless considerable; but it was more as a follower of the Newtonian mathematics than as a pathologist or physician, and most of all as one of the secretaries of the Royal Society in the last years of Newton’s presidency, that he spoke with authority[904]. His influence, such as it was, availed little. The practice of inoculation fell into total disuse in England after a few years’ trial, so that in 1728 Jurin himself was prepared to see it “exploded.” The principal reason of inoculation having been tried upon decreasing numbers in England after the first year or two, and of its having been dropped absolutely for a time, was the death of some persons of good family, both adults and children--a sacrifice of life which could not but seem gratuitous. Those deaths were not from the fulness of the eruption but from anomalous effects. When inoculation began in London in 1721, it was according to the Greek method of inserting a minute quantity of matter at two or more places. In the case of the Newgate felons, Maitland had reason to do the inoculations over again after three days, being dissatisfied with the appearance of the original punctures. They are admitted to have had a slight disease (the man who had most had only some sixty pustules on his whole body), so that Dr Wagstaffe, who went to see them, said in his letter to Dr Freind: “Upon the whole, Sir, in the cases mentioned, there was nothing like the smallpox, either in symptoms, appearances, advance of the pustules, or the course of the distemper.” Many of the other early cases had likewise a slight eruption; when numbers are given, the pocks are “not more than eleven to eighteen” (as in Maitland’s case of Prince Frederick at Hanover in 1724), or “not above twenty in all upon her” (as in Maitland’s case of a child near Hertford, in 1721). Of the first six charity children inoculated, one had no eruption; of the next five, three had no smallpox from inoculation. The cases that died after inoculation during the first seven years of the practice--seventeen in England and Scotland and two in Dublin, most of them children--owed the fatal result for the most part to some peculiar prostration or lowered vitality, in two cases actually to pyaemia, the eruption being kept back altogether or but feebly thrown out[905]. This was the danger of arbitrarily procuring the smallpox which Dr Schultz remarked upon in 1677, with reference to the Polish practice of “buying” the disease; most, if not all the cases known to him, although they may have had few pocks, yet fell into more serious illness (_gravius reliquis decumbant_). The risk of arbitrarily forcing infection upon a child at a time when it might not be ready for it, or in a position to deal with it in its blood, was afterwards recognized, and was provided against in the long and tedious preparation which the subject for inoculation had to undergo. While those in England who followed Maitland in inoculating after the Greek fashion produced for the most part an infinitesimal number of pustules or watery pimples, there were others at a distance from London who inoculated by a method of their own and gave their patients a more real smallpox. The chief of these were Dr Thomas Nettleton of Halifax, and Dr Zabdiel Boylston, of Boston, New England[906]. Nettleton made a long incision through the whole thickness of the skin of one arm and of the opposite leg, and laid therein a small piece of cotton soaked in smallpox matter, which he secured in the wound with a plaister for twenty-four hours. Boylston says: “The Turkey way of scarifying and applying the nutshell &c., I soon left off, and made an incision through the true skin,” the rest also of his procedure being the same as Nettleton’s. And just as those two inoculators devised for themselves a more real method of giving the smallpox by insertion, taking means to ensure the absorption of the matter into the blood, so they procured in many cases, although not in all, an eruption of pustules on the skin which came near to being the same as that of natural smallpox of the average discrete type. In the Boston practice, “the number of the pustules is not alike in all; in some they are very few; in others they amount to an hundred; yea in many they amount unto several hundreds, frequently unto more than what the accounts from the Levant say is usual there[907].” Nettleton’s account, which was printed in the same number of the _Philosophical Transactions_ as that from New England, says of the pustules on the skin at large: “The number was very different: in some not above ten or twenty, most frequently from fifty to two hundred; and some have had more than could well be numbered, but never of the confluent sort.... They commonly come out very round and florid, and many times rose as large as any I have observed of the natural sort, going off with a yellow crust or scab as usual[908].” The smallpox procured by inoculation in these English and American trials was thus a more real form of that disease than at Constantinople; compared with the number of pustules given by Timoni and Pylarini, the Boston and Halifax numbers are multiplied ten times. Nettleton thus expressed his belief that inoculated smallpox saved from the natural disease, at the same time grounding that belief on the reality or substantial nature of the artificial disease: “Some of those who have been inoculated, that are grown up, have afterwards attended others in the smallpox, and it has often happen’d that in families where some children have been inoculated, others have been afterwards seized in the natural way, and they have lain together in the same bed all the time; but we have not yet found that ever any had the distemper twice; neither is there any reason to suppose it possible, there being no difference that can be observed betwixt the natural and artificial sort, but only that in the latter the pustules are fewer in number, and all the rest of the symptoms are in the same proportion more favourable[909].” Nettleton returned to the question of the reality of inoculated smallpox, which is the root of the whole matter, in his second letter, to Jurin[910]: “The question whether the distemper raised by inoculation is really the smallpox is not so much disputed now as it was at first.... There is usually no manner of difference to be observed betwixt the one sort and the other, when the number of pustules is nearly the same; but in both there are almost infinite degrees of the distemper according to the difference of that number. All the variation that can be perceived of the ingrafted smallpox from the natural is, that in the former the pustules are commonly fewer in number, and all the rest of the symptoms are in the same proportion more favourable. They exactly resemble what we call the distinct sort.... It will follow as a corollary, that those who have been inoculated are in no more danger of receiving the distemper again than those who have had it in the ordinary way. And this is also thus far confirmed by experience.” It does not appear that Nettleton based so much upon the subsequent experience as upon the antecedent probability. Thus he says of some cases: “These had the eruptions so imperfect as to leave me a little in doubt, but two of these have since been sufficiently try’d by being constantly with those who had the smallpox, without receiving any infection; which makes me inclined to believe they will always be secure from any danger. As to all the rest, neither I nor anybody else who saw them did in the least question that they had the true smallpox.” Nettleton began his inoculations in and around Halifax during a considerable epidemic of smallpox in the winter of 1721-22, of which the following figures were collected by himself (as well as statistics for Leeds, Bradford, Rochdale and other places): Cases Deaths Halifax 276 43 Part of Halifax parish towards Bradford 297 59 Another part of Halifax parish 268 28 In the town of Halifax the smallpox was of a more favourable type than usual, whereas in Leeds at the same time (792 cases and 189 deaths) it was more than usually mortal. In the country round Halifax there was more smallpox than in the town; but the epidemic in general ceased in the spring of 1722. As the people mostly disliked the idea of inoculation, Nettleton did not urge it upon them, but inoculated only the children of those who favoured it. Down to the 22nd of April, 1722, he had inoculated about forty, with one death; at the date of 16 June, he had done fifteen more, his total to the end of 1722 being 61. In 1723 he did nineteen inoculations, in 1724 none, in 1725 and 1726 about forty (in an epidemic of 230 cases, and 28 deaths in Barstand Ripponden and another part of Halifax parish), and in writing to Hartley of Bury St Edmunds in 1730, he gave his total at that date as 119, from which it appears that he had ceased to inoculate after 1726. His name does not appear again in the controversy, and it is probable that he acquiesced in the tacit verdict against inoculation which Jurin himself, in 1728, seemed to think was imminent. Besides this centre of inoculation in Yorkshire in the midst of epidemic smallpox, the only other of importance in the first trials of the practice was at Boston, New England. The smallpox epidemic there in 1721 was a very severe one. There had been no smallpox in Boston since 1702, so that a large part of the population were susceptible of it. The infection was brought by a ship from Barbados in the middle of April, 1721, and made slow progress at first, according to the following table of deaths from it[911]: _Deaths from Smallpox in Boston._ 1721-1722 May 1 June 8 July 20 August 26 September 101 October 402 November 249 December 31 January 6 ---- Total 844 In the course of the epidemic some 5989 persons were attacked, or more than half the population (10,565). All the rest, save about 750, had been through the smallpox before. Inoculation played a very subordinate part amidst these dreadful scenes of smallpox. Its instigator was the Rev. Dr Cotton Mather, who had been shown by Dr Douglass the numbers of the _Philosophical Transactions_ with Timoni’s and Pylarini’s papers in them. The reverend doctor “surreptitiously” employed Douglass’s rival, Dr Boylston, to begin inoculating, in July, 1721, or a few months after the first trials in London. Boylston inoculated 244, whites and negroes, and admitted the deaths of six of them, probably by inhaled infection[912]. But Douglass says: “The precise number of those who dyed by inoculation in Boston, I am afraid will never be known because of the crowd of the sick and dead whilst inoculation prevailed most, the inoculator and relations inviolably keeping the secret.... Some porters who at that time were employed to carry the dead to their graves say that it was whispered, in sundry houses where the dead were carried from, that the person had been inoculated. I could name some who are suspected, but having only hearsay and conjectural evidence, I forbear to affront the surviving relations. I myself am certain of one more who died ‘after inoculation’ as they express it.” He then gives the case, which was clearly one of the natural contagion of smallpox acquired at the same time as the inoculation. In the Charleston inoculations of 1738, which were also done in the midst of an epidemic, there is little doubt that the fatalities were mostly from natural smallpox which the inoculated infection had failed to anticipate or prevent. The inoculators were often in that dilemma with their fatal cases: either the inoculation had killed the patient or it had been powerless to keep off the contagion; sometimes they confess the former as an untoward accident, at other times they plead the latter, which appears to me to have been the more usual of the two in a time of epidemic smallpox[913]. Douglass, for all his bitterness against his rival Boylston, and his severity against the extravagant assertions and loose reasoning of the first inoculators, was far from denying the merits of inoculation, whether in theory or in practice. “We may confidently pronounce,” he says, “that those who have had a genuine smallpox by inoculation never can have the smallpox again in a natural way, both by reason and experience; but there are some who have had the usual feverish symptoms, a discharge by their incisions, with a few _imperfect_ eruptions, that may be obnoxious to the smallpox,”--of which he gives instances. In like manner Nettleton, in Yorkshire, who took pains to make his smallpox a real thing, and succeeded in doing so as well as any inoculator ever did succeed, was persuaded that inoculated smallpox counted for a natural attack. He admitted only one failure, a case at Halifax which had been inoculated without an eruption ensuing and took smallpox by contagion a month after. Failures in England, in that sense, were fewer than the deaths directly from inoculation. The deaths were freely admitted, but any alleged failure of inoculation to ward off the natural smallpox was challenged, investigated, and denied, so that Mead, writing in 1747, declared that he knew of none. There were, however, a few cases recorded, which appear to be authentic. One of the six charity children inoculated at the instance of the Princess of Wales had taken natural smallpox twelve weeks after. The child of one Degrave, a surgeon, had a similar experience. Another familiar case was the son of a person of distinction, inoculated on 7 May, 1724, by the Rev. Mr Johnson. On the 14th a rash came out, on the 15th there was fever, on the 16th, very little eruption to be seen and the fever gone, and on the 18th he was pronounced “secure.” On that day (18th May), his sister was inoculated in the same place, both children remaining together at the inoculator’s house until the 2nd of June, when the boy went home. For a day or two before the 8th of June the boy was ill, and on the 9th he began to have smallpox in the natural way, of a good sort, the disease keeping its natural course. He was supposed to have caught it from his sister, who was inoculated after his own protection was over, and was “very full of smallpox” until the 27th of May, her brother being with her[914]. Another case of failure, which must have been known to some at the time, was not published until some ten years after, when Deering brought it to light[915]: “I was an eyewitness of the inoculation of a little boy, the child of Dr Craft, who is now a sugar-baker in the Savoy. He was inoculated by one Ahlers under the direction of Dr Steigerthal, the late king’s physician in ordinary; and notwithstanding the great care there was taken in the choice of the pus, had the confluent kind severely; and twelve months after had them naturally, and though a favourable sort, yet was very full.” A boy aged three, the son of Mr Richards, M.P. for Bridport, was inoculated in 1743, and had fifty to sixty pocks which maturated and scabbed. About two years after (“one year ago”) he had smallpox again, the pustules numbering from 200 to 300; when the eruption came out the fever declined and did not return. These facts are given in a letter to Dr Dod from Dr Brodrepp, grandfather of the child, who attended him on both occasions[916]. Such cases were not often heard of. As Mead said, “If such a thing happened once, why do we not see it come to pass oftener?” There was, however, little encouragement for anyone to come forward with adverse evidence; witness the case of an unfortunate Welshman, one Jones, of Oswestry, who had innocently mentioned, in writing to his son in London, that natural smallpox had followed an inoculation done by him, on 9th August, 1723, and was frightened out of his wits by the _apparatus criticus_ which Jurin brought to bear upon him[917]. Another reason why so few failures could be discovered was that the inoculated were not kept long in sight. A child of Dr Timoni, the first writer on inoculation, was inoculated at Constantinople in December, 1717, at the age of six months, and had an average effect, namely ten small _boutons_. She died of smallpox in 1741, at the age of twenty-four. This failure came to light by the vigilance of the celebrated De Haën, of Vienna, an opponent of inoculation, who had been told of it by a Scots physician at Constantinople[918]. A good instance of the same thing came to light long after in the practice of the celebrated Dr Rush of Philadelphia. “I lately attended a man in the smallpox,” he wrote to Lettsom, “whom I inoculated six-and-twenty years ago. He showed me a deep and extensive scar upon his arm made by the variolous matter”--without which evidence, and the man’s own reminder, confirmed by his mother’s recollection, Dr Rush would probably have had no reason to believe that this particular one of his inoculations had failed[919]. In the nature of the case, such evidence of failure would seldom be opportune. It would have needed a more dramatic presentation of these cases, and many more of them, to discredit the practice of inoculation. It was, indeed, discredited, so much so that it was not practised at all in England from 1728 until about 1740; but that was owing to the disasters directly resulting from it. No amount of evidence as to the inoculated taking natural smallpox afterwards could have touched the popular imagination like the following paragraphs in the London newspapers in 1725: March 16, died Mrs Eyles, niece of Sir John Eyles, alderman of London, of the smallpox contracted by inoculation. June 17, died of the smallpox contracted by inoculation Arthur Hill, esquire, eldest son of Viscount Hilsborough. August 12, died of the smallpox by inoculation--Hurst, of Salisbury, esquire. Inoculation seemed hardly worth having on these terms, granting all that was alleged of its protective power; so that it fell in England into total disuse[920]. It came on again after a time and had a long career, at first among the richer classes, and at length among the common people, who did not cease to use it for their children until it was made a felony by the Act of 1840. After its first brief success, it was revived about 1739-40, in consequence of highly favourable accounts from Charleston, South Carolina, and from Barbados and St Christopher. This second period of inoculation brings in certain modifications of the practice by which the casualties of the earlier period were avoided. The danger from blood-poisoning, pyaemia, or the like, was surmounted. At the same time the inoculated smallpox ceased to have anything of that reality, or approximation to the natural disease, which Nettleton succeeded for a time in giving to it. Revival of Inoculation in 1740: a New Method. As early as the Boston inoculations of 1721, the matter had now and again been taken, not from a case of the natural smallpox, but from the pustules of a previous inoculation[921]. But at Charleston in 1738 there really began, doubtless in the way of empirical trial, a systematic attenuation of virus, which has had great scientific developments in our time and has come to be considered as of the essence of the inoculation principle. Describing the South Carolina practice, Kilpatrick says[922]: “Some persons were of opinion that _the pock of the inoculated_ would be too mild to convey the disease; or, at least, that it must become effete by a second or third transplantation. Experience manifested the contrary. I have inoculated from those who were infected by the matter taken from others of the inoculated, and found no defect. Mr Mowbray, who inoculated many more than any other practitioner, assured me he had infused matter in the fifth or sixth succession from the natural pock, and observed no difference.... The smallest violation of the surface, if it was stained with blood, was a sufficient entrance for the matter, and the least matter was sufficient.” The last point was a return to the Greek practice, and an abandonment of the more severe method of Nettleton and Boylston. The Charleston smallpox of 1738, imported by slave-ships from Africa, became extensively epidemic and mortal. It had been last in Charleston fourteen or fifteen years before, but only one or two died on that occasion, and hardly more than ten were attacked. But for that small outbreak, it had not been known in the South Carolina port for a generation previous to 1738. The number of victims in that year is not known precisely. As at Boston in 1721, the epidemic dragged through the spring months, and became very extensive and mortal in the hot weather of June and July. It was then that Mowbray began inoculating, most of the Charleston faculty being opposed to it. He was soon followed by Kilpatrick, who had lost one of his children in the epidemic, and was moved thereby to inoculate the other two. No exact account was kept of the inoculations, nor, we may be sure, of the protective effects; some said a thousand were inoculated, Kilpatrick says eight hundred, but the total of four hundred is also given. Eight died after inoculation, six whites and two negresses. One child of ten months died in convulsions on the ninth day after inoculation, with few signs of smallpox; a minister, aged 40, sickened on the third or fourth day, which was too soon for the artificial disease, and was almost certainly the effects of the inhaled virus; two other adult whites died in such circumstances as to make it doubtful whether they died of inoculation or of coexistent natural smallpox; one negress died of confluent smallpox, having treated herself unwisely; while two other children and a negress died after inoculation, of whom no particulars are known. Besides the fatal cases after inoculation, some “had an eruption that might be called a moderate confluence”; but in these cases also it is not clear that infection was not taken in the natural way: as regards one gentlewoman who had confluent smallpox, it was not certain in what manner she received the infection, whilst “Miss Mary Rhett’s eruption did not appear until the 14th day, yet was supposed to be effected by art.” To meet such cases Kilpatrick adopted the doctrine that there was “no precise term for the artificial eruption.” Among those “hardly dealt with” by the disease, supposed to have been given by art, were two ladies who had their eyes permanently injured. “With regard to a second infection of the inoculated _who took_, this was asserted by some who wished for it, but were as soon refuted.” Nineteen in twenty of the inoculated had an exceedingly slight eruption, so slight indeed that they thought the confinement indoors irksome and unnecessary. As to the negroes, who had all been born in Africa (and commonly have smallpox there or in the voyage across), it was not easy, he admits, to find out whether they had had smallpox before or not, the pits on their faces being less obvious than in whites, and the marks of other distempers easily mistaken for them. On the whole Kilpatrick was confident that inoculation in this epidemic had saved many lives; and it was the rumour of its success, together with corresponding reports from the plantations in the West Indies relating the valuable lives of negroes saved, that gave a fresh impulse to the practice in England. In 1743 Kilpatrick came to London, where he republished his Charleston essay, with an historical appendix, and soon got into the leading practice as an inoculator, having proceeded to the degree of M.D. and changed the spelling of his name to Kirkpatrick. Woodville says “he was esteemed the most scientific inoculator in London.” During the eleven years from his setting up in practice there until the publication of his _Analysis of Inoculation_ (1754), he had almost certainly been applying the arm-to-arm method which he learned from Mowbray in Charleston, having briefly indicated it in his first essay and avowed it more explicitly in his second. The establishment of Kirkpatrick in London, to practise the Charleston method of inoculation, corresponds, as nearly as one can trace it, with the revival of the practice in the south of England, to the extent of some two thousand cases in the counties of Kent, Surrey, Sussex, Hampshire and Dorset. We have a glimpse of that practice in the essay on inoculation published in 1749 by Dr Frewen, of Rye in Sussex[923], a physician of considerable learning (of the school of Boerhaave), whose theories of the effects of inoculation are reflected in Kirkpatrick’s _Analysis_ of 1754. In 350 cases, Frewen had only one fatality, the death of a child, aged four, from worm fever on the eighth day of a discrete eruption. He still used the incision on the arm, but less deep than Nettleton’s, keeping the pledget of lint, moistened with matter, bound upon it for twenty-four hours; also he encouraged the rendering from the incision for some weeks, giving the same reason as before, that “Nature by means of a continual drain is greatly aided in her attempts to throw off the matter of the disease.” In his general account of the effects of inoculation, we seem to be reading of as real symptoms and as many pocks as Nettleton described--the eruption, always of the simple distinct kind, beginning on the 9th day, all out in three or four days after, the pocks filling and turning yellow for the next four or five days, then scabbing and falling, leaving temporary shallow marks. But it is clear that he had other results than these from trying new ways of procuring matter. “Experience,” he says, “has convinced me that it is in reality of no consequence from what kind of smallpox it [the matter] is procured.” If taken from the natural smallpox, it should be taken from ripe pustules: “yet I have sometimes applied it sooner, while only a limpid water.” Oftentimes it happened that an inoculation produced too “slight” pustules to furnish matter for the succeeding operations. The question then arose whether the matter rendering from the incisions on the arms in these cases was merely common pus or whether it had the property of “variolosity.” This abstract quality, as it were the essence or quiddity of the pustular exanthem, was assumed to be present if the pus of the rendering incision could be made to raise a pustule on another arm, and if the person so infected could stand exposure to natural smallpox with impunity. One person so inoculated did have an attack of smallpox by contagion, so that Frewen concluded that the matter used for his protection had “run off all its variolosity.” But others inoculated with the same, “in whom the symptoms were remarkably light, and in some few no pustules at all,” were equally exposed to contagion without catching it, so that they were “judged to be secure from ever taking the smallpox again.” Frewen’s general conclusion, if it be not very logical, is at least modest: “However, it may be worth the attention to reflect seriously whether it be not highly probable, from the success attending the numbers I have been concerned for, that inoculation has been often times a security against taking the most dangerous kinds of the natural smallpox.” Whether Frewen got the ideas of these novelties of method from Kirkpatrick’s first account of the South Carolina practice, or struck them out for himself, it is clear that Kirkpatrick, in his next essay of 1754, has adopted variolosity as an abstract doctrine to surmount certain difficulties in the concrete reason. Many of his inoculated cases had only a few bastard pustules of smallpox, some had none. Was their disease smallpox? Did it warrant their future security? “As many of the inoculated have very few pustules, and they are sometimes disposed to scab and wither away with very little suppuration, it might be of service to discover that the matter from the incisions would infect. But it would be certainly satisfactory to find it would where there was no eruption from inoculation, as its variolosity would greatly warrant the future security of the person it was taken from. That it is variolous is now evinced by the fact that it infected others to the like slight degree[924].” The movement towards attenuating the virus used for inoculation was general in Europe. One of the mild methods, invented by Tronchin, of Amsterdam and afterwards of Paris, was to raise a small blister on the arm and to pass through the fluid a thread moistened with smallpox matter. This became one of the most common continental methods and was in use until the beginning of the 19th century. Kirkpatrick, who went to see the practice of Tronchin, found the method by blister to produce as slight effects in the way of eruption as he describes for his own method: “I attended and infected five poor children:--three, about seven years old, by incision; and two, about five years old, by vesication. Of the first three, one, a girl, had a pretty moderate but very kindly sprinkling; the two boys very few. The two by blisters, a boy and a girl, had rather less,--the boy Dudin, a very fair delicate little child, not having above three or four, all which had not matter enough to infect one patient[925].” Everywhere after the middle of the eighteenth century inoculation was coming into fashion again. In France it was lauded by the _philosophes_, while it was scouted by the medical faculty. La Condamine, a mathematician who had acquired fame by his journey to the Amazon to measure the three first degrees of the meridian, became interested in the subject by hearing from a credulous Carmelite missionary at Para how he had saved half of his Indian converts by inoculation after the other half had been destroyed by the natural smallpox. The mathematical philosopher on his return became an enthusiast for inoculation, and twice harangued the Académie des Sciences thereon. “The practice of inoculation,” he said, “was improved during the time of its disgrace.” What this improvement consisted in he also explained: “Neither the eruption is essential to the natural nor the pustules to the artificial smallpox: and perhaps art will one day come to effect what one hopes for and what Boerhaave and Lobb have even tried--I mean a change in the external form of this malady without any increase of its danger[926].” The Suttonian Inoculation. Daniel Sutton, though an empiric, has given his name to the slight and safe method of inoculation which had been used in England for a good many years before his advent. So completely was his name joined to the practice of smallpox inoculation in its later period that in a Bill before Parliament in 1808 it is called “the Suttonian inoculation,” to distinguish it from cowpox inoculation. The idea of attenuating the virus used for inoculation, and of making the effects minimal, was not his. It had been reached empirically years before by Mowbray, of Charleston, in 1738, who carried inoculation from arm to arm to the fifth remove, by Frewen, of Rye, in 1749, who was satisfied with an abstract “variolosity” of the incisions, in cases where there was no eruption at all or only a few pustules that did not fill, by Kirkpatrick, “the most scientific inoculator in London,” who endorsed the doctrine of variolosity, by La Condamine, and most of all by Gatti of Paris. Gatti used the unripe matter from a previous inoculation and inserted a most minute quantity of it at a very small puncture; and, to make sure that no general eruption should follow, he used the cooling regimen in various ways, including the prolonged immersion of the hands in cold water. Thus he promised his clients “the benefits of inoculation without its risks.” But Gatti’s career of prosperity was cut short by a series of conspicuous failures of his artificial smallpox to prevent the natural or real disease when it was epidemic. One of his patients, the Duchess de Boufflers, a great lady whose _salon_ was frequented by the _philosophes_ and _beaux esprits_, fell into the natural smallpox two years and a half after her inoculation[927]. So many others in Paris had the same disappointment that a discussion arose in the Faculty of Medicine, the result of which was that the Parliament of Paris prohibited the practice of inoculation, for various reasons, within the limits of the capital. Gatti’s friend and correspondent in London was Dr Maty, who, “though born in Holland might be considered a Frenchman, but he was fixed in London by the practice of physic and an office in the British Museum[928].” Having conducted the foreign correspondence of the Royal Society, he became in 1765 its secretary in ordinary, and about the same time Principal Librarian of the British Museum. His interest in inoculation, which was shown by his translating La Condamine’s first discourse on that subject in 1755, led him in 1765 to suggest to Gatti that he should write an essay for publication in England, “both to reclaim the thinking part of Paris, and to vindicate his own operations from the contemptuous treatment of his antagonists.” The essay was written in due course, and Maty brought it out in English[929]. Gatti’s own experiments and those which had previously been made in England by the most experienced inoculators had satisfied him of the truth of what he had long suspected, namely, that the operation could be made “still more harmless, though not less efficacious” (p. 29). There would be hardly any fever, certainly a very slight eruption and perhaps none at all (p. 68), It had, indeed, been questioned whether a patient who had but very few pustules, or only one, has had the smallpox as truly as one who has been very full, and whether he is equally safe from catching it. He answers in the affirmative, according to the doctrine of variolosity: “No reason can be alleged, why we should have the smallpox but once, that will not equally hold good for one as for ten thousand pustules” (p. 69). Some, however, will not believe that one pustule is as good as ten thousand, “notwithstanding the obviousness of this truth.” If one were absolutely bent upon giving a certain number of pustules, he would advise to inoculate according to his method (insertion with a needle) at twenty, thirty, or fifty places: “then you would be sure of one pustule at least at each puncture, and, probably, of many more in other parts.” He would do this, however, only to humour prejudice, and with a feeling that he was doing the patient “more harm than was necessary.” He was seriously satisfied of the “sufficiency of a single pustule,” and believed that every wise man should run the venture of it and “embrace the method here laid down.” There was no theoretical objection to this method, but there was the practical one, that it might be _too_ slight in its effects. Patients could hardly rest satisfied with so little to show for smallpox; and inoculators themselves found that they might have all their work to do over again. An eminent Irish physician wrote in 1765 to Dr Andrew, of Exeter, that crude matter from a previous inoculation was “less communicative of the disorder and more apt to disappoint us” than matter from a natural smallpox eruption taken “five or six days before the maturation of it[930].” It was also the experience of Salmade, of Paris, in 1798, that serous matter, taken from arm to arm through a long succession of cases, was apt to go off altogether, or to be “weakened to the point of nullity,” whereby it disappointed the operator[931]. Reid, of Chelsea Hospital, was said to have carried the succession to thirty removes from the natural smallpox. Bromfeild knew for certain of matter being used at the sixteenth remove. So long as the operation held at all, and had not to be repeated, Dr Andrew believed that effects which “no one would have taken for the smallpox,” were “sufficient security against any future infection[932].” Heberden, indeed, has recorded a case adverse to that view; but one case is not enough, even if it had been in as eminent a person as Madame de Boufflers[933]. Daniel Sutton, who gave his name to the slighter kind of smallpox inoculation, was not a regular practitioner. His father, a doctor of medicine in Suffolk, was a specialist inoculator, as others of the regular profession here and there were becoming, and had operated upon 2514 patients from 1757 to 1767. In 1763 Daniel began business on his own account at Ingatestone in Essex, where patients from all parts were boarded and subjected to his regimen, as at a water-cure. In 1764 he made 2000 guineas, and in 1765 £6300. In the three years 1764-66 he inoculated 13,792 persons, and his assistants some 6000 more--without a single death. Sutton kept his method at first a secret, and for that reason was looked at askance by eminent physicians. He used pills and powders, which were found, by the analysis of Ruston, to be a preparation of antimony and mercury, the drugs supposed to be antidotes to natural smallpox, or the means of preventing its pustular eruption. But the essence of his method was found to be, in Chandler’s words, “the taking of the infective humour in a crude state [from a previous inoculation] before it has been, if I may allow the expression, variolated by the succeeding fever[934],” or, in Dimsdale’s words, “inoculating with _recent_ fluid matter,” or in Sir George Baker’s words, “with the moisture taken from the arm before the eruption of the smallpox, nay, within four days after the operation has been performed[935].” Sutton made it known that the effects of this method were exceedingly mild--no keeping of bed, no trouble at all: “if any patient has twenty or thirty pustules, he is said to have the smallpox very heavy.” Being put on his trial at Chelmsford for spreading abroad the contagious particles of smallpox by the number of his inoculations, his defence was to have been (if the bill had not been thrown out by the grand jury), that he “never brought into Chelmsford a patient who was capable of infecting a bystander.” The mildness of his artificial smallpox was acknowledged with satisfaction by some, with dissatisfaction by others. Dr Giles Watts, an inoculator in Kent, says it was “a most extraordinary improvement. The art of inoculation is enabled to reduce the distemper to almost as low a degree as we could wish.... There is now an opportunity of seeing what a very small number of the multitude of persons of all ages, habits and constitutions, who have been inoculated in these parts, have been ill after it.” Comparing it with the method which he had practised before, he says that he never knew ten or twelve inoculated together “in the old way” but one or more had the distemper in a pretty severe manner; on the other hand, he had inoculated four of his children in the new way and all of them together had not so many as eighty pustules. He adds that sometimes the inoculated had not even a single pustule (besides the one at the point of insertion) or at other times not more than two or three[936]. The Suttonian practice was objected to by Bromfeild in an essay dedicated to Queen Charlotte. Tracing it to Gatti, whose manifesto had been published in England two years before, he said that it was mere credulity “to have given credit to a man who should assert, that he would give them a disease which should not produce one single symptom that could characterize it from their usual state of health.... Inoculation, though hitherto a great blessing to our island, will in a very short time be brought into disgrace,” if it were assumed “that health and security from the disease can be equally obtained by reducing the patients so low as only to produce five to fifteen pimples[937].” Bromfeild was not openly supported except by Dr Langton, of Salisbury, who contended that “the matter communicated is not the smallpox, because numbers have been inoculated a second, third and fourth time, that therefore it is no security against a future infection.” He cites Gatti’s case of the Duchess de Boufflers, and declares, as to the English inoculations, that not above one in ten have so many variolous symptoms as may be remarked in her case. “The old method of inoculating,” he says, “was to take the infection from a good subject where the pustules were well maturated, whereby the operation was sure of succeeding; but the present practice is to take the matter from the incision the fourth day after the incision is made [this was Sutton’s avowed practice]. By this means you have a contagious caustic water instead of laudable pus, and a slight ferment in the lymph is raised, producing a few watery blotches in the place of a perfect extrusion of the variolous matter[938].” There was no difference of opinion as to the exact purport and upshot of the new method; it was to reduce the eruption to the lowest point or to a vanishing point. Nothing can be more emphatic than Gatti’s profession of belief that a single pustule, at the place of insertion, was as effectual as ten thousand; and it is not only likely, on the face of it, that such a mitigation as Reid’s to the thirtieth remove from natural smallpox, would produce merely the local pustule, but it is clear that Gatti saw no way of ensuring more by his method, supposing he were to gratify the prejudices of the laity in favour of more, than by puncturing the skin at twenty, thirty, or fifty separate points. It is not to be supposed, however, that the minimum result was obtained in all cases, or that all inoculators were equally adroit in procuring it; even Sutton had to admit that some of his thirteen thousand patients had more pustules on the skin than he desired. Perhaps the most exact record of the number of pustules produced in a comparative trial of various methods is that of Sir William Watson at the Foundling Hospital in 1768[939]. Of 74 children inoculated in October and November, twelve had no eruption at all, but yet were held to have been protected by the operation. The remaining sixty-two had a very small average of pustules in addition to the local pustules, which average, small as it was, came mostly from two or three severer cases (e.g. one with 440 pustules, one with 260, and one with near 200), the most having three or four or a dozen or perhaps two dozen (e.g. three had only 7 pustules among them, or, in another batch of ten done with crude or ichorous matter, “the most that any boy had was 25, the least 4, the most that any girl had was 6, the least 3,” or, in another batch of ten, also with crude lymph, two had no eruption, seven had 35 pustules among them, and one had 30). Of the amount of smallpox upon the whole sixty-two cases which had some eruption Watson says: “Physicians daily see in one limb only of an adult person labouring under the coherent, not to say confluent smallpox, a greater quantity of variolous matter than was found in all these persons put together.” Watson’s sole measure of “success” in inoculating was the slightness of the effect produced; and as he found that crude or watery matter from the punctured spot of a previous inoculation had the least effect, he decided to use that kind of matter always in future at the Foundling Hospital. On the other hand, Mudge, of Plymouth, raised a different issue and put it to the test of experiment on a large scale. Did crude matter infect the constitution? Did it make the patient insusceptible of the effects of a second inoculation with purulent matter? The experiment came out thus: At Plympton, in Devonshire, in the year 1776, thirty persons were inoculated with crude or watery matter from the arm of a woman who had been inoculated five days before, and ten persons were at the same time inoculated with purulent matter from the pustules of a case of natural smallpox. The thirty done with crude matter had each “a large prominent pustule” at the place of puncture, “but not one of them had any eruptive fever or subsequent eruption on any part of the body.” Matter taken from their local pustules produced exactly the same result in the next remove, namely, a local pustule, but no eruptive fever nor eruptive pustules. The thirty were inoculated again, this time with purulent matter (five from natural smallpox, twenty-five from inoculated smallpox), and all of them had, besides the local pustule, an eruptive fever and an eruption “in the usual way of inoculated patients.” The ten who were originally inoculated with purulent matter had that result at first[940]. In the subsequent history of inoculation it would appear that the method known by the name of Sutton, of using crude or watery matter from a previous inoculated case, was the one commonly preferred. But it was not always preferred. One of the medical neighbours of the afterwards celebrated Dr Jenner took matter from the pustules and kept it in a phial; his patients inoculated therewith had somewhat active effects, even “sometimes eruptions.” But “many of them unfortunately fell victims to the contagion of smallpox, as if they had never been under the influence of this artificial disease,” so that Jenner, who had probably not heard of Mudge’s experiment, was confirmed in his preference for the crude matter (before the eruptive fever) from a previous inoculation. It was of great importance, he said, to attend to that point, as it would “prevent much subsequent mischief and confusion[941].” Of course there were many more chances of getting matter from natural smallpox than from inoculated; but it would appear that in the former also it was taken in the ichorous or unripe stage of the eruption, according to the practice of Sutton, and despite the experimental proof that Mudge gave of its merely superficial or formal effects. Mudge’s experiment was on a large scale, and designed to test a general or scientific issue. The testing experiment usually made was merely for the sake of the particular case; the patient was inoculated a second time, shortly after the first, with the same matter as before, or a third time, or even a fourth time. Whatever the significance of this for the doctrine of inoculation in general (as in the issue raised by Mudge), the individual was both reassured and fortified so far as concerned his own safety. The experiment of the former generation that was usually cited was that of the Hon. John Yorke. On his leaving the university at the age of one and twenty it was thought prudent that he should be inoculated for smallpox before entering on the great world. He was inoculated by serjeant surgeon Hawkins, and had the local suppuration, some fever, but little or no eruption. The inoculator was satisfied, but not so the youth: he insisted upon a second inoculation, which had no effect. This was considered a leading case. When the Suttonian method came in, and the absence of eruption (barring a few pimples or bastard pustules) became the usual thing, the occasions for a second inoculation became more common, owing to the prejudice, as Gatti said, of the laity in favour of something tangible although not excessive[942]. Dimsdale inoculated many of his patients a second time, and produced the local pustule again, as at first. Of the 74 foundlings in Watson’s experiment of Oct.-Nov. 1767, there were twelve who had no eruption, of whom four were re-inoculated with no better result or with no result. Of the whole twelve he says: “Although they had no eruption, I consider them as having in all probability gone through the disease, as the punctures of almost all of them were inflamed and turgid many days.” It was so unusual for a second inoculation, in a doubtful case, to produce more than the first, that Kite, of Gravesend, communicated to the Medical Society of London two cases where that had happened, as being “anomalous.” He had never before been able to communicate the smallpox, on a second attempt, “to any patient whose arm had inflamed, and who had even a much less degree of fever” than Case 1, who had only the local pustule and “on the eighth day was quite well:” and he cites Dimsdale to the same effect[943]. Perhaps enough has been said to illustrate the subtle casuistry that had gradually arisen out of the old problem of procuring the smallpox by artifice. I make one more citation, from a Hampshire inoculator in 1786, to show how fine were the distinctions, depending, one might suppose, upon the subjective state of the practitioner, drawn between effective and non-effective inoculation: “The incisions sometimes have a partial inflammation for a few days, which then vanishes without producing any illness; in this case the patient is certainly still liable to infection; but I believe it very rarely happens that there is any matter, or even ichor, in the present slight manner they are made, without producing the smallpox.... I have constantly remarked that when the punctured part inflames properly, and is attended with an efflorescence, rather inclining to a crimson colour, for some distance round the same, about the eleventh or twelfth day from the inoculation, although the patient should have very little illness and no eruption, yet that he is secure from all future infection[944].” Extent of Inoculation in Britain to the end of the 18th Century. From 1721 to 1727 the inoculations in all England were known with considerable accuracy to have been 857; in 1728 they declined to 37; and for the next ten or twelve years they were of no account. The southern counties led the revival in the fifth decade of the century, so that before long some two thousand had been inoculated in Surrey, Kent, Sussex and Hampshire. Frewen, however, who could point to 350 cases done by himself in Sussex previous to 1749, says that it “gained but little credit among the common sort of people, who began to dispute about the lawfulness of propagating diseases, and whether or no the smallpox produced by inoculation would be a certain security against taking it by infection,” etc. In London, after the revival under Kirkpatrick’s influence in 1743, inoculation became a lucrative branch of surgical practice, and was done by the heads of the profession--Ranby, Hawkins, Middleton and others, and almost exclusively among the well-to-do. In 1747 Ranby had inoculated 827 without losing one; in 1754 his total, still without a death, had reached