An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease discovered in some of the Western Counties of England, particularly Gloucestershire, and known by the name of the Cow Pox. [Bound with:] ibid., Further Observations on the Variolae Vaccinae, or Cow Pox. [Bound with:] ibid., A Continuation of Facts and Observations relative to the Variolae Vaccinae or Cow Pox.

London: Sampson Low for the author, 1798, 1799 & 1800.

First edition, exceptionally rare when complete with all three parts, of “one of the great triumphs in the history of medicine” (Garrison-Morton), “the basis of the modern science of immunology” (PMM), which “caused a revolution in medical thought and practice” (LeFanu 1985, p. 28). “Jenner started one of the greatest practical advances in preventive medicine” (PMM). Attempts to use mild strains of the disease to inoculate against smallpox had begun in India, China, and Turkey, and this still-dangerous and unreliable ‘variolation’ was brought to England in 1718. Jenner, a country practitioner in Berkeley, Gloucestershire, became curious about the country wisdom that milkmaids who contracted cowpox, a common and non-fatal infection transferred from cattle, were safe from smallpox. In May 1796 Jenner found a young dairymaid, Sarah Nelmes, who had fresh cowpox lesions on her finger. Using matter from Sarah’s lesions, he inoculated an eight-year-old boy, James Phipps, who then developed a slight fever and a low-grade lesion. On July 1 Jenner inoculated the boy again, this time with smallpox matter. No disease developed. In 1798 he published An Inquiry into the Causes and Effects of the Variolae Vaccinae, an account of 23 successful vaccinations. “Jenner’s discovery of vaccination made possible the immediate control of smallpox and the saving of untold lives … Jenner must be considered the founder of immunology; in vaccination he made the first use of an attenuated virus for immunization. For his coining of the term ‘virus,’ his effort to describe the natural history of the cowpox virus, and his description of anaphylaxis, he must be considered the first pioneer of the modern science of virology … To describe the matter producing cowpox Jenner introduced the term ‘virus’” (DSB). “Jenner used the word virus in the general sense of a disease-producing poison. Its appropriation a hundred years later to a particular class of organisms, which includes the causative agents of smallpox and cow-pox, was due to the currency which Jenner gave to the word in this special connexion” (LeFanu 1951, p. 25). In addition to the landmark discovery of the success of preventive inoculations against smallpox, “in a footnote to Case 4 Jenner describes his accurate observation of the phenomenon afterwards called anaphylaxis [called ‘Allergie’ by von Pirquet in 1906]. It is the first notice of the condition” (LeFanu 1985, p. 31). In Further Observations, Jenner replies to critics, explaining common mistakes (such as the failure to recognise the symptoms of true cowpox, leading to ineffectual inoculations), and considering differences between inoculations in London and in the countryside. A Continuation includes further reports of successful inoculations, and ends with the justifiably ebullient conclusion: “May I not with perfect confidence congratulate my country and society at large in their beholding, in the mild form of the Cow Pox, an antidote that is capable of extirpating from the earth a disease that is every hour devouring its victims; a disease that has ever been considered as the severest scourge of the human race!” The success of Jenner’s work led to the announcement by the World Health Organisation in 1980 that natural smallpox had been eradicated. This copy, together with the Norman copy (Christie’s New York, June 16, 1998, lot 551, $32,200), are the only copies listed by ABPC/RBH in the last century to have all three parts – the last two parts are significantly rarer than the first.

Provenance: Robert Brodhead Honeyman IV (1897-1987), engineer and bibliophile; his sale, Sotheby’s London, 6 November 1979, lot 1757, £11,500 hammer price.

“In the eighteenth century, Small Pox was a dread disease, accounting for about 10% of all deaths. It was especially virulent in infants and children, and when it swept through a village, from 20 to 50% of those infected died as a consequence. Moreover, those who survived were often disfigured from pockmarks, and smallpox led to blindness when it spread to the eyes.

“Around 1720, Lady Mary Wortley Montegue, the wife of the British Ambassador to Turkey, returned to England enthusiastic about Small Pox inoculation, a practice she had learned of in Constantinople. At the time, it was well known that survivors of Small Pox were exempt from the disease during subsequent epidemics. As a consequence, in Asia, protection from Small Pox was commonly attempted by intranasal inhalation of pox material. During a Small Pox epidemic in London in 1721, Lady Montegue had her 4-year-old daughter inoculated with pox material. Subsequently, throughout the eighteenth century, the practice, known as variolation, or simply inoculation, became commonplace throughout the United Kingdom.

“Variolation held that it was possible to protect against the very high mortality resulting from a natural infection, which usually occurred by the inhalation of a large dose of virus, by the well-controlled inoculation of a smaller dose of the virus into the skin. Physicians became expert in the practice, and set up special inoculation infirmaries to support and care for those who became ill after inoculation. Although it was common for the inoculated to become symptomatic, and some actually succumbed, the mortality rates advertised by the most expert physicians were as low as 1%. As such, variolation became a very lucrative practice for British doctors, especially during epidemics, when the populace was terribly frightened. However, variolation also ensured that the disease would be endemic and never disappear from the communities.

“Edward Jenner was born in 1749 in the UK western county of Gloucestershire. Unfortunately he lost both his mother and father as a young child, and was raised by his older brother. As a consequence of the family’s reduced financial circumstances, he did not attend university at Oxford to be trained for the clergy as was customary for his family, but instead he was apprenticed to a local physician at the age of 13. He proved to be an excellent student, and after 6 years, he was sent to St. Georges Hospital in London, where he was taken in by John Hunter, who was to become one of the world’s most famous surgeons. While he was with Hunter he met and became friends with Joseph Banks, who in 1771 had just returned as the naturalist on Captain Cook’s first around the world voyage. On the recommendation of Hunter, Jenner helped Banks in the arrangement and cataloging of the specimens from the voyage. Banks went on to an illustrious career, and became the President of the Royal Society for more than 40 years. Thus, early in his career, Jenner entered into an exceptional community of scientists and physicians of his generation.

“Toward the end of his training at St. Georges, Hunter offered Jenner a post as his assistant for his teaching and dissecting efforts at the Hospital. However, Jenner declined and returned to his hometown, Berkeley, a small village west of Oxford in dairy country and set up a general practice. There, Jenner spent the next 20 years, administering to the people from the surrounding farmlands. He did find time to pursue his studies in natural history, and submitted his studies on the reproductive habits of the cuckoo to the Royal Society, encouraged by the now Sir Joseph Banks, with whom Jenner was in steady correspondence throughout his life. As a consequence, Jenner was elected as a Fellow of the Royal Society at the age of 39, quite an accomplishment for a ‘simple country doctor.’

“Like the other physicians of his day, Jenner became expert at variolation. In this regard, it is important to appreciate that variolation had become established and practiced for 50 years when Jenner commenced his practice. While administering to his country clientele:

‘I was first excited by observing, that among those whom in the country I was frequently called upon to inoculate, many resisted every effort to give them the Small Pox. These patients I found had undergone a disease they called the Cow Pox, contracted by milking cows affected with a peculiar eruption on their teats. On inquiry, it appeared that this had been known among the dairies immemorial, and a vague opinion prevailed that the Cow Pox was preventative of the Small Pox … This led me to inquire among medical practitioners in the country around me, who all agreed in the sentiment that the Cow Pox was not relied upon as a preventative of the Small Pox’ (Jenner, The Origin of the Vaccine Inoculation. London: D.N. Shury, 1801).

“Although these considerations from the medical establishment temporarily dissuaded Jenner from following his intuition, he persisted in his thoughts, and collected over the years a wealth of experience from variolating people who had previously contracted the Cow Pox.

“After 20 years of general practice, in 1792 Jenner was awarded the MD degree from St. Andrews University, Scotland, upon the recommendation of two of his longtime friends, as well as the payment of a fee, evidently a common practice at the time. Accordingly, now able to advertise himself as a physician and surgeon, MD, FRS, he gave up general practice and became a private consultant. Soon thereafter, Jenner contracted typhus, which led to a long convalescence, and eventually in 1795 his move to Cheltenham, a ‘spa town’ between Berkeley and Oxford, where mineral springs had been discovered. Here, Jenner began to mix with the aristocracy, which migrated there from London to ‘take the waters’ during the summer months (‘The Season’). Also, he now had time to organize and write-up his experiences with variolation of individuals who had a history of a prior illness due to the Cow Pox …

“In 1796, Jenner submitted a manuscript to the Royal Society, which described the case histories of 13 people who had resisted either variolation or natural Small Pox after having a history of Cow Pox. This manuscript also described Jenner’s first vaccination, which will be discussed in detail later. Sir Joseph Banks evidently was not too impressed by the manuscript, as he sent it on to Lord Somerville, President of the Board of Agriculture. Eventually, the manuscript was simply returned without being read to the Royal Society … Rebuffed by the Royal Society, Jenner extended the manuscript with additional case histories, eventually comprising 25 individuals with a history of having had Cow Pox: he tested 24 and found them to resist variolation. Some of these individuals who appeared immune to Small Pox had had a Cow Pox infection several decades previously, thereby suggesting that the Cow Pox ‘immunity’ was very long lasting. Most important, Jenner added a description of at least nine individuals who were injected with Cow Pox, of whom four he variolated and found to resist Small Pox. With this enhanced manuscript, Jenner arranged to have it published in London at his own expense, thereby circumventing the Royal Society … Jenner published his An Inquiry into The Causes and Effects of Variolae Vaccinae, a Disease Discovered in some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of Cow Pox, on June 21st 1798” (Smith).

“The evidence is set out in 23 case histories. Cases 1-12 are of casually acquired cow-pox which afforded immunity from smallpox; several of these cases include more than one patient. Cases 13-15 are records of immunity after horse-pox. Case 16, with plate 1, is that of Sarah Nelmes, from whom Jenner inoculated case 17 – ‘a boy’ – with cow-pox on May 14, 1796. Case 18 in an inoculation with horse-pox from a man to a boy in March, 1798, illustrated on plate 2. Case 19 records the inoculation of a boy with cow-pox directly from the cow and thence from his arm to another boy (case 20 and plate 3), and from the latter to ‘several children and adults’ (including case 21 with plate 4) and then to several others (cases 22 and 23) during March and April. 1798” (LeFanu 1951, pp. 25-26).

“Several points made by Jenner via these case histories are noteworthy. For example, in Case number four, he describes a woman who had Cow Pox 31 years prior to variolation in 1791. Upon inoculation of Small Pox,

‘an effervescence of a palish red color soon appeared about the parts where the (variolous) matter was inserted, and spread itself rather extensively, but died away in a few days without producing any variolous symptoms. It is remarkable that variolous matter, when the system is disposed to reject it, should excite inflammation on the part to which it is applied more speedily than when it produces the Small Pox … It seems as if a change, which endures through life, had been produced in the action, or disposition to action, in the vessels of the skin.’

“Thus, this is perhaps the first description of an anamnestic immune response!

“In Case six, Jenner states,

‘It is so well known among our Dairy Farmers, that those who have had the Small Pox either escape the Cow Pox, or are disposed to have it slightly. Thus, as soon as the complaint shews itself among the cattle, assistants are procured who have had the Small Pox, and are thus rendered less susceptible of the Cow Pox. Otherwise, the farm could scarcely go forward.’

“Accordingly, Jenner describes the reciprocal protection afforded by Small Pox and Cow Pox infections.

“Jenner’s description of his first successful vaccination (Cases 16 and 17) is especially interesting.

‘Sarah Nelmes, a dairymaid at a farmer’s near this place, was infected with the Cow Pox from her master’s cows in May, 1796. She received the infection on a part of the hand, which had previously in a slight degree been injured by a scratch from a thorn. A large pustulous sore and the usual symptoms accompanying the disease were produced in consequence. The pustule was so expressive of the true character of the Cow Pox, as it commonly appears on the hand, that I have given a representation of it in the annexed plate’ [Plate 1].

‘The more accurately to observe the progress of the infection, I selected a healthy boy, about eight years old, for the purpose of inoculation for the Cow Pox. The matter was taken from a sore on the hand of a dairymaid (Sarah Nelmes), and it was inserted on the 14th of May, 1796, into the arm of the boy by means of two superficial incisions, barely penetrating the cutis, each about half an inch long.

‘On the seventh day he complained of uneasiness in the axilla, and on the ninth he became a little chilly, lost his appetite, and had a slight head-ache. During the whole of this day he was perceptively indisposed, and spent the night with some degree of restlessness, but on the day following he was perfectly well.

‘In order to ascertain whether the boy, after feeling so slight an affection of the system from the Cow-pox virus, was secure from the contagion of the Small Pox, he was inoculated the 1st of July following with variolous matter, immediately taken from a pustule. Several slight punctures and incisions were made on both arms, and the matter was carefully inserted, but no disease followed … Several months afterwards, he was again inoculated with variolous matter, but no sensible effect was produced on the constitution’ …

“Jenner followed-up his original publication with a 1799 Further Observations on the Variolae Vaccinae, in which he detailed how to recognize typical Cow Pox lesions and to discriminate them from other similar pustular lesions that were not Cow Pox. In this regard, it is important to point out that the causes of all microbial infections, particularly pyogenic bacterial infections that could be confused with Cow Pox pustules, were completely unrecognized in 1798, and did not become known until Robert Koch’s description of the bacilli that causes anthrax in 1876, almost 100 years later.

“In 1800 Jenner continued to educate physicians about vaccination with A Continuation of Facts and Observations Relative to the Variolae Vaccinae or Cow Pox, in which he chronicled the successes from his physician friends who he had sent Cow Pox material to propagate and to vaccinate individuals in their own communities. Thus, within the early years after his first publication, word of the innocuous nature of vaccination spread fairly rapidly, also making its way to the European continent and to the US. During these years Jenner focused his practice almost entirely on vaccinating all who came to Cheltenham. Consequently, he slowly depleted his savings as the word spread, because he did not charge for the vaccination, especially of the poor” (Smith).

“Following the publication of Jenner’s book the practice of vaccination was adopted and spread with astonishing speed. It was taken up not only by medical practitioners but also by country gentlemen, clergymen, and schoolmasters. Jenner found that lymph taken from smallpox pustules might be dried in a glass tube or quill and kept for as long as three months without losing its effectiveness. The dried vaccine could thus be sent long distances. Jean de Carro, Swiss physician living in Vienna, introduced vaccination on the continent of Europe and was instrumental in sending vaccine virus into Italy, Germany, Poland, and Turkey. In 1801 Lord Elgin, British ambassador at Constantinople, sent vaccine virus received from de Carro overland to Bussora (Basra) on the Persian Gulf, and thence to Bombay. The marquis of Wellesley, governor general of India, actively promoted the distribution of the vaccine and many thousands of people were vaccinated in India during the next few years. In Massachusetts, Benjamin Waterhouse introduced vaccination to America with vaccine received from Jenner. Jenner also sent vaccine to President Jefferson, who vaccinated his family and his neighbors at Monticello” (DSB).

“Not everyone immediately embraced the idea, especially the physicians who had lucrative Small Pox inoculation infirmaries and practices. Thus, as time progressed, the UK became divided into those who ascribed to vaccination and those who were skeptical and thought that only Small Pox inoculation would confer true protection against Small Pox. Thus, when several of Jenner’s Cheltenham acquaintances, who were Members of Parliament, petitioned Parliament to award him a prize for his discovery, there were both supporters as well as dissenters. In 1802 Parliament awarded him £10,000, which in today’s currencies is [about] $700,000. However, an award of £20,000 was defeated by only three votes. This award was crucial for Jenner, in that it allowed him to establish himself in Cheltenham society, and to devote himself to furthering the spread of vaccination all over the world. Then in 1807, after he had been recognized by many foreign governments, Parliament awarded him a second prize, this time of £20,000.

“However, despite the fact that vaccination was recognized as a miracle by most of the world, one that saved many lives, the practice of variolation continued in the UK. This practice ensured that Small Pox circulated continuously and intermittently caused epidemics, leading to death, and disfigurement. Moreover, the one thing that would have made a difference in his homeland, i.e., recognition by the Crown, proved elusive. Evidently, those physicians who made their living from variolation held more sway with the King than those who supported Jenner and vaccination. Not until King George III died in 1820, did the new King George IV appoint Edward Jenner Physician Extraordinary to the King on March 16, 1821. However, he was never made a Knight … He died in 1823, at the age of 74. It was not until 1840 that Parliament outlawed the practice of variolation, making Cow Pox vaccination the official UK policy” (Smith).

I. The three parts were issued together, with continuous pagination, in 1800.Dibner, Heralds of Science 127; Garrison-Morton 5423; Grolier, Medicine 53; Heirs of Hippocrates 677 (“epochal work … the foundation of all subsequent work in immunology and virology”); Grolier/Horblit 56 (“a key development in the realm of preventative medicine”); LeFanu, A Bio-Bibliography of Edward Jenner 1749-1823 (1951), 20; LeFanu, A Bibliography of Edward Jenner (2nd ed., 1985), 23; Norman 1162; PMM 250; Wellcome III, p. 351. II. Heirs of Hippocrates 678; LeFanu 1951, 45; LeFanu 1985, 52; Norman 1168; Wellcome III, p. 351. III. LeFanu 1951, 50; LeFanu 1985, 58; Norman 1169; Wellcome III, p. 351. Saunders, Edward Jenner. The Cheltenham Years 1795-1823. Hanover, NH: University Press of New England, 1982. Smith, ‘Edward Jenner and the Small Pox Vaccine,’ Frontiers in Immunology 2 (2011), Article 21, pp. 5.

Three works bound in one vol., 4to (266 x 210 mm). I. pp. [ii, half-title], [i-iii], iv, [1], 2-75, [1, blank], [1, errata], with four plates engraved by William Skelton (no. 1 from his own drawing and nos. 2-4 from drawings by Edward Pearce), colour-printed in sanguine and enhanced with some hand-colouring, each with original tissue guard present (three plates with artist’s name cropped off or shaved, as is the case with most copies). II. pp. [iv], [1], 2-64 (lacking half-title). III. pp. [1-5], 6-42, including half-title (scattered light foxing). Contemporary half-calf and marbled boards, early rebacking in speckled calf, black morocco gilt spine label (boards scuffed). Housed in Honeyman’s characteristic red morocco gilt slipcase.

Item #4913

Price: $65,000.00