Variolation or Inoculation was the method first used to immunize an individual against smallpox (Variola) with material taken from a patient or a recently variolated individual in the hope that a mild but protective infection would result. The procedure was most commonly carried out by inserting/rubbing powdered smallpox scabs or fluid from pustules into superficial scratches made in the skin. The patient would develop pustules identical to those caused by naturally occurring smallpox, usually producing a less severe disease than naturally-acquired smallpox. Eventually, after about two to four weeks, these symptoms would subside, indicating successful recovery and immunity. The method was first used in China and the Middle East before it was introduced into England and North America in the 1720s in the face of some opposition. The method is no longer used today. It was replaced by smallpox vaccine, a safer alternative. This in turn paved the way for the development of the many vaccines now available.
The terminology used to describe the prevention of smallpox can cause confusion. In 18th-century medical terminology inoculation refers to smallpox inoculation. Confusion is caused by writers who interchange variolation and vaccination through either mistranslation or misinterpretation. The term variolation refers solely to inoculation with smallpox virus and is not interchangeable with vaccination. The latter term was first used in 1800 soon after Edward Jenner introduced smallpox vaccine derived from cowpox, an animal disease distinct from smallpox. The term variolation was then used from the 19th century to avoid confusion with vaccination. Most modern writers tend to refer to smallpox inoculation as variolation throughout without regard for chronology, as is used here. Further confusion was caused when in 1891 Louis Pasteur honoured Jenner by widening the terms vaccine/vaccination to refer to the artificial induction of immunity against any infectious disease. Inoculation is used synonymously with injection in connection with the use of vaccines or other biopharmaceuticals, but has other meanings in e.g. laboratory work.
Origins of variolation
The Chinese practiced the oldest documented use of variolation, dating back to the fifteenth century. They implemented a method of "nasal insufflation" administered by blowing powdered smallpox material, usually scabs, up the nostrils. Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China.:60 According to such documentation, mild smallpox cases were selected as donors in order to prevent serious attack. The technique used scabs that had been left to dry out for some time. Fresh scabs were more likely to lead to a full blown infection. Three or four scabs were ground into powder or mixed with a grain of musk and bound in cotton. Infected material was then packed into a pipe and puffed up the patient's nostril. The practice of variolation is believed to have been ritualized by the Chinese. The blowpipe used during the procedure was made of silver. The right nostril was used for boys and the left for girls.:45 Variolated cases were treated as if they were as infectious as those who had acquired the disease naturally. These patients were subsequently kept apart from others until the rash had cleared.
Similar methods were seen through the Middle East and Africa. Two similar methods were described in Sudan during the late eighteenth and early nineteenth centuries. Both had been long established and stemmed from Arabic practices. Tishteree el Jidderi ("buying the smallpox") was a practice seen within the women of Sennar in Central Sudan.:61 A mother of an unprotected child would visit the house of a newly infected child and tie a cotton cloth around the ailing child's arm. She would then haggle with the child's mother over the cost of each pustule. When a bargain was struck, the woman would return home and tie the cloth around her own child's arm. Variations of this practice included bringing gifts to the donor. The second method was known as Dak el Jedri ("hitting the smallpox"),:61 a method similar to that used in Turkey and eventually transported into England during the early sixteenth century. Fluid was collected from a smallpox pustule and rubbed into a cut made into the patient's skin. This practice spread more widely through Africa. It may have also traveled with merchants and pilgrims along the middle eastern caravan routes into Turkey and Greece.:15
Spread into Western Europe
Although variolation had become common practice in China and much of Africa by the seventeenth century, Western European medicine still saw the practice as being nothing more than folklore. It was not be until Italian physician Dr. Emmanuel Timoni of Constantinople promoted the practice that variolation began its spread through Western Europe. After coming across the practice in Constantinople, Timoni wrote a letter describing the method in detail which was later published in the Philosophical Transactions in early 1714.:77 His account would become the first medical account of variolation to appear in Europe. Although the article did not gain widespread notoriety, it caught the attention of two important figures in the variolation movement, Bostonian preacher Cotton Mather and wife of the British Ambassador to the Ottoman Empire, Lady Mary Wortley Montagu.
Lady Mary Wortley Montagu
No stranger to smallpox, Lady Mary had lost her brother to the devastating disease. Soon afterwards she also contracted smallpox. Although she survived she was left with severe facial scarring. While in Turkey she came across the process of variolation as it was practiced amongst the people of Constantinople. She first mentioned variolation in the famous letter to her friend, Sarah Chiswell, in April 1717.:55 in which she enthusiastically recounted the process, which in Constantinople was most commonly administered by experienced elderly women. In 1718, she had the practice conducted on her five-year-old son, Edward Montagu. The procedure was supervised by the embassy doctor Charles Maitland. On her return to England she had her four-year-old daughter inoculated in the presence of physicians of the royal court in 1721.:90 Both variolations proved successful. Later on that year Maitland conducted an experimental inoculation of six prisoners within the 
Despite opposition, variolation established itself as a mainstream medical treatment across England. Part of its success was founded on statistical observation which confirmed that variolation was a safer alternative to contracting smallpox naturally, strengthened by the assumption that it protected against the disease for life. The major faults of variolation lay within its simplicity. Doctors sought to monopolize the simple treatment by convincing the public that the procedure could only be done by a trained professional. The procedure was now preceded by a severe bloodletting, in which the patient was bled often to faintness in order to 'purify' the blood and prevent fever. Doctors also began to favor deep incisions, which also discouraged amateurs.:18
The Suttonian Method
Thomas Nettleton (1683-1748) was a precursor of the Suttons around 1722.
The main forerunners of the English variolation movement were the Suttons, a family of physicians who would revolutionize the practice of variolation. The patriarch Robert Sutton was a surgeon from Suffolk who began experimenting with the practice of variolation. In 1757 the procedure failed on one of his sons.:20 He sought a new method in which the procedure would become as mild as possible. By 1762 he began advertising "A New Method of Inoculating for Small-Pox." Sutton kept his method a secret and only passed it down to his three sons. The mystique and effectiveness behind this new method helped to promote their business which soon became wildly successful. They established a network of variolation houses and clinics and offered franchises to other variolators for a share of the profits and on the condition that the secret would not be revealed. By 1770, the Suttons had treated over 300,000 satisfied customers.:94 Daniel, the eldest of the Sutton sons, eventually revealed the family secret in his book The Inoculator published in 1796.:22 The success of their method lay in a shallow scratch, careful selection of only mildly-affected donors, and no bleeding or extreme purging. Although the renown of the Suttons gradually faded after this revelation, the family's lasting impression would remain for generations.
Other prominent English variolators included Thomas Dimsdale who published accounts of his method in 1769 and 1781; William Woodville appointed Director of the London Smallpox and Inoculation Hospital in 1791, who published a history of variolation in 1796; and John Haygarth who published an ambitious plan to exterminate smallpox in 1783.
In 1738 variolation was added to the second edition of Chambers' Cyclopædia, which in its time was an authority of knowledge for the literary class. Later in 1754, variolation received the sanction of the Royal College of Physicians.:47 All of this made England the international center of variolation, attracting visitors from all over the world to explore this new method of prevention. The nation also acted as a magnet for those who sought to introduce the benefits of variolation to their own countries. A remarkable example of this is the introduction of variolation into Russia. Thomas Dimsdale, a prominent banker, politician, and physician, was invited to visit St Petersburg to variolate Catherine the Great. In 1769, he variolated Catherine, her son 14 year old Grand Duke Paul, and over 140 prominent members of the Court. The results were successful. Dimsdale was created a baron of the Russian Empire, awarded £10,000, with £2000 for expenses and an annuity of £500. His son, who accompanied him was also rewarded. In case Dimsdale's variolations had ended badly, Catherine had arranged a relay of horses to carry them safely out of the country.
France was the last European country to embrace variolation. It was not until an outbreak of smallpox in Paris in 1752 nearly killed the heir to the French throne that the public embraced the practice after seeing the prince variolated.:102 Similarly in Japan, Chinese merchant Li Jen-Shan proposed the method of traditional Chinese intranasal variolation after a severe smallpox outbreak in Nagasaki in 1744. This led Japanese physician Ogata Shunsaku (ja) to variolate children using a human smallpox vaccination method during an outbreak in Chikuzen Province from 1789 to 1790.:95 There were no deaths among the children, and they all appeared to be protected.By the end of the eighteenth century, variolation had gained widespread global respect and was thought to be one of the greatest medical successes of its time. It had become the subject of serious medical study, leading physicians like John Haygarth from Chester, England, to explore its application on a larger scale. In 1793 he published A Sketch of a Plan to Exterminate the Small-Pox from Great Britain. This relied on rules summarised by Donald Hopkins;:77
Systematic inoculation throughout the country, isolation of patients, decontamination of potentially contaminated fomites, supervised inspectors responsible for specific districts, rewards for observation of rules for isolation by poor persons, fines for transgression of those rules, inspection of vessels at ports, and prayers every Sunday.Its implementation at the time was impractical for logistical reasons and the risk that variolation would spread smallpox. However with suitable modifications, such as the substitution of vaccination for variolation, it was remarkably similar to the strategy adopted during the puritan minister Cotton Mather learned of the technique from his North African slave Onesimus.:45 Further research into the matter revealed to Mather that several other slaves had too been variolated. In 1714, he came across Timoni's article in Philosophical Transactions in which he described methods of variolation found in Turkey. Mather was able to implement this new method in 1721 when Boston suffered a smallpox outbreak, although others such as William Douglas strongly opposed the idea.
The main arguments against variolation were on religious grounds. Because religion was never far from any aspect of life in eighteenth century Boston, several wondered how this new method would coincide with religious teachings. The simplest debate argued that variolation was ungodly because it was not mentioned specifically in the Bible. Inoculation was also a direct affront to God's innate right to determine who was to die and how and when death would occur. Several believed smallpox outbreaks were well-merited punishments for the sins of those who contracted the disease. Those who were empirically-minded saw the notion of using the products of such a deadly disease to prevent said disease as being an insult to logic.:142
Despite these persistent arguments, Mather also gained several supporters. Among this group of followers was surgeon Zabdiel Boylston who urged Mather to further promote the procedure. With the support of Mather, Boylston went on to successfully variolate 300 patients with only six of them dying. By contrast, 1,000 of the 6,000 people who acquired smallpox naturally died during the same period. Boylston traveled to London in 1724. There he published his results and was elected to the Royal Society in 1726.:144
From Boston, the practice spread throughout the colonies. In 1775, Continental Army be variolated. By the end of the American Revolutionary War, variolation had gained widespread acceptance in the larger cities and towns of the United States.:47
Transition into vaccination
The success of variolation led many, including medical professionals, to overlook its drawbacks. Variolation was practiced on the assumption that it protected against smallpox for life and was unlikely to kill. Both these assumptions eventually proved to be false. In some cases, even natural smallpox failed to protect one from a second attack. These cases were a result of a lapse of immune "memory" while others may have been misdiagnosed (experts often confused smallpox with chickenpox). Variolation also required a level of skill and attention to detail which some physicians lacked. Many physicians failed to take note of local redness and discharge to assure the variolation had taken, resulting in inadequate treatment. However, it was its great risk to others that led to the end of the practice. The collateral smallpox cases spread by variolated subjects began to outweigh the benefits of the procedure.
From the 1760s a number of individuals, including John Fewster, Peter Plett, Benjamin Jesty and particularly Edward Jenner were interested in the use of material from cowpox, an animal infection, to protect against smallpox. In 1796 Jenner vaccinated James Phipps, did more vaccinations in 1798 and was the first to publish evidence that cowpox protected against smallpox, was safer than variolation, and that his vaccine could be maintained by arm to arm transfer. The use of variolation soon began to decline as smallpox vaccine became widely used and its benefits appreciated. Various countries made variolation illegal, starting with Russia in 1805.:246 Variolation served as a natural precursor to the discovery of vaccination. The major differences between the two were that in vaccination, material from cowpox, an animal disease was used but particularly that it was safe to those vaccinated and was not transmitted to their contacts. Vaccination offered the public a less harmful method of preventing smallpox. Vaccination would revolutionize the control of smallpox leading to it eventual eradication. The extension of the principle of vaccination by Pasteur and his successors would lead to the development of vaccines for diseases such as diphtheria, measles, mumps, rubella and influeza and make the eradication of infectious diseases particularly poliomyelitis a realistic prospect.
The end of variolation
Although variolation eventually declined or was banned in some countries, it was still practiced in others. "Buying the smallpox" was still practiced in Sudan until the late nineteenth century.:159 However, variolation survived longer elsewhere. During the :683–5 Passage of time and information about the survival of smallpox virus make it extremely unlikely that any infectious samples have survived,:1173–7
Although variolation has ceased, it has influenced the concept of other traditional practices, such as "Pox Parties" in which children are intentionally exposed to diseases like chickenpox and measles and rubella in order to gain solid natural immunity. Although strongly discouraged by public health officials, the practice persists.:73
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