Variolation The mortality of the severe form of smallpox –
variola major – was very high without vaccination, up to 35% in some outbreaks. A method of
inducing immunity known as inoculation,
insufflation or "
variolation" was practiced before the development of a modern vaccine and likely occurred in Africa and China well before the practice arrived in Europe. It may also have occurred in India, but this is disputed; other investigators contend the ancient
Sanskrit medical texts of India do not describe these techniques. The first clear reference to smallpox inoculation was made by the Chinese author
Wan Quan (1499–1582) in his
Douzhen xinfa (痘疹心法) published in 1549. Inoculation for smallpox does not appear to have been widespread in China until the reign era of the
Longqing Emperor (r. 1567–1572) during the
Ming Dynasty. In China, powdered smallpox scabs were blown up the noses of the healthy. The patients would then develop a mild case of the disease and from then on were immune to it. The technique did have a 0.5–2.0% mortality rate, but that was considerably less than the 20–30% mortality rate of the disease itself. Two reports on the Chinese practice of
inoculation were received by the
Royal Society in London in 1700; one by Dr.
Martin Lister who received a report by an employee of the
East India Company stationed in China and another by
Clopton Havers. According to
Voltaire (1742), the Turks derived their use of inoculation from neighbouring
Circassia. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". Variolation was also practiced throughout the latter half of the 17th century by physicians in
Turkey,
Persia, and Africa. In 1714 and 1716, two reports of the
Ottoman Empire Turkish method of inoculation were made to the
Royal Society in England, by
Emmanuel Timoni, a doctor affiliated with the British Embassy in
Constantinople, and
Giacomo Pylarini. Source material tells us on Lady Mary Wortley Montagu; "When Lady Mary was in the Ottoman Empire, she discovered the local practice of inoculation against smallpox called variolation." In 1718 she had her son, aged five, variolated. He recovered quickly. She returned to London and had her daughter variolated in 1721 by
Charles Maitland, during an epidemic of smallpox. This encouraged the
British royal family to take an interest and a trial of variolation was carried out on prisoners in
Newgate Prison. This was successful and in 1722
Caroline of Ansbach, the Princess of Wales, allowed Maitland to vaccinate her children. The success of these variolations assured the British people that the procedure was safe. This practice was widely criticized at first. However, a limited trial showed six deaths that had occurred out of 244 were variolated (2.5%), while 844 out of 5980 died of natural disease (14%), and the process was widely adopted throughout the colonies. The inoculation technique was documented as having a mortality rate of only one in a thousand. Two years after Kennedy's description appeared, March 1718, Dr.
Charles Maitland successfully inoculated the five-year-old son of the British ambassador to the Turkish court under orders from the ambassador's wife
Lady Mary Wortley Montagu, who four years later introduced the practice to England. An account from letter by Lady
Mary Wortley Montagu to Sarah Chiswell, dated 1 April 1717, from the Turkish Embassy describes this treatment:
Early vaccination performing his first vaccination on
James Phipps, a boy of age 8. 14 May 1796. Painting by Ernest Board (early 20th century). In the early empirical days of vaccination, before
Louis Pasteur's work on establishing the
germ theory and
Joseph Lister's on antisepsis and asepsis, there was considerable cross-infection.
William Woodville, one of the early vaccinators and director of the
London Smallpox Hospital is thought to have contaminated the
cowpox matter – the vaccine – with smallpox matter and this essentially produced variolation. Other vaccine material was not reliably derived from cowpox, but from other skin eruptions of cattle. During the earlier days of empirical experimentation in 1758, American Calvinist
Jonathan Edwards died from a smallpox inoculation. Some of the earliest
statistical and
epidemiological studies were performed by
James Jurin in 1727 and
Daniel Bernoulli in 1766. In 1768, Dr
John Fewster reported that variolation induced no reaction in persons who had had cowpox. depicting the early controversy surrounding Jenner's vaccination theory
Edward Jenner was born in
Berkeley, England. As a young child, Jenner was variolated with the other schoolboys through parish funds, but nearly died due to the seriousness of his infection. Fed purgative medicine and going through the bloodletting process, Jenner was put in one of the variolation stables until he recovered. At the age of 13, he was apprenticed to
apothecary Daniel Ludlow and later surgeon George Hardwick in nearby
Sodbury. He observed that people who caught cowpox while working with cattle were known not to catch smallpox. Jenner assumed a causal connection but the idea was not taken up at that time. From 1770 to 1772 Jenner received advanced training in London at St. George's Hospital and as the private pupil of
John Hunter, then returned to set up practice in Berkeley. Jenner sent a paper reporting his observations to the Royal Society in April 1797. It was not submitted formally and there is no mention of it in the Society's records. Jenner had sent the paper informally to
Sir Joseph Banks, the Society's president, who asked
Everard Home for his views. Reviews of his rejected report, published for the first time in 1999, were skeptical and called for further vaccinations. Additional vaccinations were performed and in 1798 Jenner published his work entitled
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 Cow Pox. It was an analysis of 23 cases including several individuals who had resisted natural exposure after previous cowpox. It is not known how many Jenner vaccinated or challenged by inoculation with smallpox virus; e.g. Case 21 included 'several children and adults'. Crucially all of at least four whom Jenner deliberately inoculated with smallpox virus resisted it. These included the first and last patients in a series of arm-to-arm transfers. He concluded that cowpox inoculation was a safe alternative to smallpox inoculation, but rashly claimed that the protective effect was lifelong. This last proved to be incorrect. A further source of confusion was Jenner's belief that fully effective vaccine obtained from cows originated in an equine disease, which he mistakenly referred to as
grease. This was criticised at the time but vaccines derived from horsepox were soon introduced and later contributed to the complicated problem of the origin of
vaccinia virus, the virus in present-day vaccine. The introduction of the vaccine to the New World took place in
Trinity, Newfoundland, in 1798 by
Dr. John Clinch, boyhood friend and medical colleague of Jenner. The first smallpox vaccine in the United States was administered in 1799. The physician
Valentine Seaman gave his children a smallpox vaccination using a serum acquired from Jenner. By 1800, Jenner's work had been published in all the major European languages and had reached
Benjamin Waterhouse in the United States – an indication of rapid spread and deep interest. Despite some concern about the safety of vaccination the mortality using carefully selected vaccine was close to zero, and it was soon in use all over Europe and the United States. took the vaccine to Spanish America in 1804. In 1804 the
Balmis Expedition, an official Spanish mission commanded by
Francisco Javier de Balmis, sailed to spread the vaccine throughout the Spanish Empire, first to the Canary Islands and on to Spanish Central America. While his deputy, José Salvany, took vaccine to the west and east coasts of Spanish South America, Balmis sailed to
Manila in the Philippines and on to
Canton and
Macao on the Chinese coast. He returned to Spain in 1806. The vaccine was not carried in the form of flasks, but in the form of 22 orphaned boys, who were 'carriers' of the live cowpox virus. After arrival, "other Spanish governors and doctors used enslaved girls to move the virus between islands, using lymph fluid harvested from them to inoculate their local populations".
Napoleon was an early proponent of smallpox vaccination and ordered that army recruits be given the vaccine. Additionally a vaccination program was created for the French Army and his
Imperial Guard. In 1811 he had his son,
Napoleon II, vaccinated after his birth. By 1815 about half of French children were vaccinated and by the end of the
Napoleonic Empire smallpox deaths accounted for 1.8% of deaths, as opposed to the 4.8% of deaths it accounted for at the time of the
French Revolution. On March 26, 1806, the
Swiss canton Thurgau became the first state in the world to introduce compulsory smallpox vaccinations, by order of the cantonal councillor
Jakob Christoph Scherb. Half a year later,
Elisa Bonaparte issued a corresponding order for her
Principality of Lucca and Piombino on 25 December 1806. On 26 August 1807, Bavaria introduced a similar measure. Baden followed in 1809, Prussia in 1815, Württemberg in 1818, Sweden in 1816, England in 1867 and the German Empire in 1874 through the Reichs Vaccination Act. In Lutheran Sweden, the Protestant clergy played a pioneering role in voluntary smallpox vaccination as early as 1800. The first vaccination was carried out in Liechtenstein in 1801, and from 1812 it was mandatory to vaccinate. The question of who first tried cowpox inoculation/vaccination cannot be answered with certainty. Most, but still limited, information is available for
Benjamin Jesty,
Peter Plett and
John Fewster. In 1774 Jesty, a farmer of
Yetminster in
Dorset, observing that the two milkmaids living with his family were immune to smallpox, inoculated his family with cowpox to protect them from smallpox. He attracted a certain amount of local criticism and ridicule at the time then interest waned. Attention was later drawn to Jesty, and he was brought to London in 1802 by critics jealous of Jenner's prominence at a time when he was applying to Parliament for financial reward. During 1790–92 Peter Plett, a teacher from
Holstein, reported limited results of cowpox inoculation to the Medical Faculty of the
University of Kiel. However, the Faculty favoured variolation and took no action. John Fewster, a surgeon friend of Jenner's from nearby Thornbury, discussed the possibility of cowpox inoculation at meetings as early as 1765. He may have done some cowpox inoculations in 1796 at about the same time that Jenner vaccinated Phipps. However, Fewster, who had a flourishing variolation practice, may have considered this option but used smallpox instead. He thought vaccination offered no advantage over variolation, but maintained friendly contact with Jenner and certainly made no claim of priority for vaccination when critics attacked Jenner's reputation. It seems clear that the idea of using cowpox instead of smallpox for inoculation was considered, and actually tried in the late 18th century, and not just by the medical profession. Therefore, Jenner was not the first to try cowpox inoculation. However, he was the first to publish his evidence and distribute vaccine freely, provide information on selection of suitable material, and maintain it by arm-to-arm transfer. The authors of the official
World Health Organization (WHO) account
Smallpox and its Eradication assessing Jenner's role wrote: Compulsory infant vaccination was introduced in England by the
Vaccination Act 1853 (
16 & 17 Vict. c. 100). By 1871, parents could be fined for non-compliance, and then imprisoned for non-payment. This allowed exemption on production of a certificate of conscientious objection signed by two magistrates. Such certificates were not always easily obtained and a further act in 1907 allowed exemption by a statutory declaration which could not be refused. Although theoretically still compulsory, the
Vaccination Act 1907 (
7 Edw. 7. c. 31) effectively marked the end of compulsory infant vaccination in England. Those seeking to enforce compulsory vaccination argued that the public good overrode personal freedom, a view supported by the U.S. Supreme Court in
Jacobson v. Massachusetts in 1905, a landmark ruling which set a precedent for cases dealing with personal freedom and the public good.
Louis T. Wright, an African-American
Harvard Medical School graduate (1915), introduced, while serving in the Army during
World War I, intradermal, smallpox vaccination for the soldiers.
Developments in production Until the end of the 19th century, vaccination was performed either directly with vaccine produced on the skin of calves or, particularly in England, with vaccine obtained from the calf but then maintained by arm-to-arm transfer; initially in both cases vaccine could be dried on ivory points for short-term storage or transport but increasing use was made of glass capillary tubes for this purpose towards the end of the century. During this period there were no adequate methods for assessing the safety of the vaccine and there were instances of contaminated vaccine transmitting infections such as erysipelas, tetanus, septicaemia and tuberculosis. Smallpox vaccine was the only vaccine available during this period, and so the determined opposition to it initiated a number of
vaccine controversies that spread to other vaccines and into the 21st century.
Sydney Arthur Monckton Copeman, an English Government bacteriologist interested in smallpox vaccine, investigated the effects on the bacteria in it of various treatments, including
glycerine. Glycerine was sometimes used simply as a
diluent by some continental vaccine producers. However, Copeman found that vaccine suspended in 50% chemically pure glycerine and stored under controlled conditions contained very few "extraneous" bacteria and produced satisfactory vaccinations. He later reported that glycerine killed the causative organisms of erysipelas and tuberculosis when they were added to the vaccine in "considerable quantity", and that his method was widely used on the continent. Vaccine produced by Copeman's method was the only type issued free to public vaccinators by the British Government Vaccine Establishment from 1899. At the same time the
Vaccination Act 1898 (
61 & 62 Vict. c. 49) banned arm-to-arm vaccination, thus preventing transmission of syphilis by this vaccine. However, private practitioners had to purchase vaccine from commercial producers. Although proper use of glycerine reduced bacterial contamination considerably, the crude starting material, scraped from the skin of infected calves, was always heavily contaminated and no vaccine was totally free from bacteria. A survey of vaccines in 1900 found wide variations in bacterial contamination. Vaccine issued by the Government Vaccine Establishment contained 5,000 bacteria per gram, while commercial vaccines contained up to 100,000 per gram. The level of bacterial contamination remained unregulated until the
Therapeutic Substances Act 1925 (
15 & 16 Geo. 5. c. 60) set an upper limit of 5,000 per gram, and rejected any batch of vaccine found to contain the causative organisms of erysipelas or wound infections. Collier added 0.5%
phenol to the vaccine to reduce the number of bacterial contaminants but the key stage was to add 5%
peptone to the liquid vaccine before it was dispensed into ampoules. This protected the virus during the freeze drying process. After drying, the ampoules were sealed under nitrogen. Like other vaccines, once reconstituted it became ineffective after 1–2 days at ambient temperatures. However, the dried vaccine was 100% effective when reconstituted after 6 months storage at allowing it to be transported to, and stored in, remote tropical areas. Collier's method was increasingly used and, with minor modifications, became the standard for vaccine production adopted by the WHO Smallpox Eradication Unit when it initiated its global smallpox eradication campaign in 1967, at which time 23 of 59 manufacturers were using the Lister strain. Smallpox vaccine was inoculated by scratches into the superficial layers of the skin, with a wide variety of instruments used to achieve this. They ranged from simple needles to multi-pointed and multi-bladed spring-operated instruments specifically designed for the purpose. A major contribution to smallpox vaccination was made in the 1960s by
Benjamin Rubin, an American microbiologist working for
Wyeth Laboratories. Based on initial tests with textile needles with the eyes cut off transversely half-way he developed the
bifurcated needle. This was a sharpened two-prong fork designed to hold one dose of reconstituted freeze-dried vaccine by capillarity. Easy to use with minimum training, cheap to produce ($5 per 1000), using one quarter as much vaccine as other methods, and repeatedly re-usable after flame sterilization, it was used globally in the WHO Smallpox Eradication Campaign from 1968.
Eradication of smallpox Smallpox was eradicated by a massive international search for outbreaks, backed up with a vaccination program, starting in 1967. It was organised and co-ordinated by a
World Health Organization (WHO) unit, set up and headed by
Donald Henderson. The last case in the Americas occurred in 1971 (Brazil), south-east Asia (Indonesia) in 1972, and on the Indian subcontinent in 1975 (Bangladesh). After two years of intensive searches, what proved to be the last endemic case anywhere in the world occurred in Somalia, in October 1977. Long-term eradication efforts were constantly being delayed because of the distinct political and cultural views different countries had. In the following decades, smallpox became more difficult to ignore, requiring more attention than ever before. In the 1970s, the chief of the WHO SEP (Smallpox Eradication Program), W.A. Henderson, wanted to lead the action and form campaigns that would help eradicate smallpox. His team's efforts worked out to help eradicate smallpox as more health programs formed and countries finally arrived to a mutual agreement on how to handle smallpox in effective ways.
Anti-terrorism preparation Among more than 270,000 US military service members vaccinated with smallpox vaccine between December 2002, and March 2003, eighteen cases of probable
myopericarditis were reported (all in first-time vaccinees who received the NYCBOH strain of vaccinia virus), an incidence of 7.8 per 100,000 during the 30 days they were observed. All cases were in young, otherwise healthy adult white men and all survived. In 2002, the United States government started
a program to vaccinate 500,000 volunteer health care professionals throughout the country. Recipients were healthcare workers who would be first-line responders in the event of a bioterrorist attack. Many healthcare workers refused or did not pursue vaccination, worried about vaccine side effects, compensation and liability. Most did not see an immediate need for the vaccine. Some healthcare systems refused to participate, worried about becoming a destination for smallpox patients in the event of an epidemic. Fewer than 40,000 actually received the vaccine. On 21 April 2022,
Public Services and Procurement Canada published a notice of tender seeking to stockpile 500,000 doses of smallpox vaccine in order to protect against a potential accidental or intentional release of the eradicated virus. On 6 May, the contract was awarded to
Bavarian Nordic for their Imvamune vaccine. These were deployed by the
Public Health Agency of Canada for targeted vaccination in response to the
2022 mpox outbreak. == Origin ==