Inoculation


Inoculation is a set of methods of artificially inducing immunity against various infectious diseases. The practice originated in the East before being imported to the Western world. The terms inoculation, vaccination, and immunization are often used synonymously, but there are some important differences between them.

Terminology

The terms inoculation, vaccination, and immunization are often used synonymously. Until the very early 1800s, inoculation referred only to the practice of variolation, the predecessor to the smallpox vaccine. Edward Jenner introduced the latter in 1798, when it was called cowpox inoculation, or vaccine inoculation. Smallpox inoculation continued to be referred to as variolation, whereas cowpox inoculation was referred to as vaccination. Then, in 1891, Louis Pasteur proposed that the terms vaccine and vaccination should be extended to include the new protective procedures being developed. Immunization refers to the use of all vaccines, but also extends to the use of antitoxin, which contains pre-formed antibodies such as to diphtheria or tetanus exotoxins. Inoculation is now more or less synonymous in nontechnical usage with protective injections and other methods of immunization.
Inoculation also has a specific meaning for procedures done in vitro. These include the transfer of microorganisms into and from laboratory apparatus such as test tubes and petri dishes in research and diagnostic laboratories, and also in commercial applications such as brewing, baking, oenology, and the production of antibiotics. For example, blue cheese is made by inoculating the ripening cheese with specific bacterial molds.

Etymology

The term "inoculation" entered medical English through horticultural usage meaning to graft a bud from one plant into another. It is derived from the Latin in + oculus. Though "innoculation/innoculate" is sometimes seen, this is incorrect, possibly erroneously thought to be related to "innocuous", which is derived from the Latin in + nocuus.

Origins

Inoculation originated as a method for the prevention of smallpox by deliberate introduction of material from smallpox pustules into the skin. This generally produced a less severe infection than naturally acquired smallpox, but still induced immunity to it. This first method for smallpox prevention, smallpox inoculation, is now also known as variolation. Inoculation has ancient origins and the technique was known in India, Africa and China.

China

The earliest hints of the practice of inoculation for smallpox in China come during the 10th century. A Song dynasty chancellor of China, Wang Dan, lost his eldest son to smallpox and sought a means to spare the rest of his family from the disease, so he summoned physicians, wise men, and magicians from all across the empire to convene at the capital in Kaifeng and share ideas on how to cure patients of it until an allegedly divine man from Mount Emei carried out inoculation. However, the sinologist Joseph Needham states that this information comes from the Zhongdou xinfa written in 1808 by Zhu Yiliang, centuries after the alleged events.
The first clear and credible reference to smallpox inoculation in China comes from Wan Quan's Douzhen Xinfa of 1549, which states that some women unexpectedly menstruate during the procedure, yet his text did not give details on techniques of inoculation. Inoculation was first vividly described by Yu Chang in his book Yuyi cao, or Notes on My Judgment, published in 1643. Inoculation was reportedly not widely practiced in China until the reign of the Longqing Emperor during the Ming dynasty, as written by Yu Tianchi in his Shadou Jijie of 1727, which he alleges was based on Wang Zhangren's Douzhen Jinjing Lu of 1579. From these accounts, it is known that the Chinese banned the practice of using smallpox material from patients who actually had the full-blown disease of Variola major ; instead they used proxy material of a cotton plug inserted into the nose of a person who had already been inoculated and had only a few scabs, i.e. Variola minor. This was called "to implant the sprouts", an idea of transplanting the disease which fit their conception of beansprouts in germination. Needham quotes an account from Zhang Yan's Zhongdou Xinshu, or New book on smallpox inoculation, written in 1741 during the Qing dynasty, which shows how the Chinese process had become refined up until that point:
Two reports on the Chinese practice 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. But no action was taken.

Circassia

According to Voltaire, the Turks derived their use of inoculation from neighboring 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". The Turkish practice was presented to the Royal Society in 1714 and 1716, when the physicians Emanuel Timoni and Giacomo Pylarini independently sent letters from Constantinople.

India

The mention of inoculation in the Sact'eya Grantham, an Ayurvedic text, was noted by the French scholar Henri Marie Husson in the journal Dictionaire des sciences médicales. However, the idea that inoculation originated in India has been also taken in account, as few of the ancient Sanskrit medical texts described the process of inoculation. Variolation is documented in India from the eighteenth century, thanks to the 1767 account by the Irish-born surgeon John Zephaniah Holwell. Holwell's extensive 1767 description included the following, that points to the connection between disease and "multitudes of imperceptible animalculae floating in the atmosphere":

They lay it down as a principle, that the immediate cause of the smallpox exists in the mortal part of every human and animal form; that the mediate acting cause, which stirs up the first, and throws it into a state of fermentation, is multitudes of imperceptible animalculae floating in the atmosphere; that these are the cause of all epidemical diseases, but more particularly of the small pox.

Holwell ascribes this account to his Brahman informants. However, such a theory has not yet been discovered in any Sanskrit or vernacular treatise. Holwell's use of the word "animalculae" suggests that he may have been aware of the observations of Antonie van Leeuwenhoek made in about 1683. Other parts of Holwell's account, especially his use of the idea of "immediate" and "mediate" causation, and the concept of "fermentation," suggest that these notions may not necessarily be entirely of Indian origin but may also be influenced by contemporary developments in microbiology.
Several historians have suggested that variolation may be older than the eighteenth century in India, but historical evidence for this assertion is lacking. The widespread rumour since the nineteenth century that vaccination was documented in India before the discoveries of Edward Jenner can all be traced to propaganda tracts written in Sanskrit and the Indian vernaculars by colonial officers, in the pious hope of convincing Indians to accept the newly discovered Jennerian procedure. A landmark anthropological study by Ralph Nicholas described the mid-twentieth century rituals of appeasement to Śītalā, the Indian goddess of smallpox, in Bengal.

Ethiopia

Early travellers to Ethiopia report that variolation was practiced by the Amhara and Tigray peoples. The first European to report this was Nathaniel Pearce, who noted in 1831 that it was performed by a debtera who would collect "a quantity of matter" from a person with the most sores from smallpox, then "cuts a small cross with a razor in the arm" of his subject and puts "a little of the matter" into the cut which was afterwards bound up with a bandage. Subsequent visitors who described this practice included the British traveller William Cornwallis Harris and Dr. Petit of the French scientific mission of 1839–1841.

West Africa

The knowledge of inoculating oneself against smallpox seems to have been known to West Africans, more specifically the Akan people. A slave named Onesimus explained the inoculation procedure to Cotton Mather during the 18th century; he reported to have acquired the knowledge from Africa.

Importation to the West

In January 1714 the Philosophical Transactions of the Royal Society published an account of a letter John Woodward had received from Emmanuel Timonius in Constantinople. Smallpox inoculation was advocated as a proven method of curbing the severity of the disease.
The practice was introduced to England by Lady Mary Wortley Montagu. Lady Montagu's husband, Edward Wortley Montagu, served as the British ambassador to the Ottoman Empire from 1716 to 1718. She witnessed firsthand the Turkish use of inoculation in Istanbul, and was greatly impressed: she had lost a brother to smallpox and bore facial scars from the disease herself. When a smallpox epidemic threatened England in 1721, she called on her physician, Charles Maitland, to inoculate her daughter. She invited friends to see her daughter, including Sir Hans Sloane, the King's physician. Sufficient interest arose that Maitland gained permission to test inoculation at Newgate Prison in exchange for their freedom on six prisoners due to be hanged, an experiment which was witnessed by a number of notable doctors. All survived, and in 1722 the Prince of Wales' daughters received inoculations.
The practice of inoculation slowly spread amongst the royal families of Europe, usually followed by more general adoption amongst the people.
The practice is documented in America as early as 1721, when Zabdiel Boylston, at the urging of Cotton Mather, successfully inoculated two slaves and his own son. Mather, a prominent Boston minister, had heard a description of the African practice of inoculation from Onesimus, an enslaved man in his household, in 1706 and later from Timoni's report to the Royal Society., However, Mather had been previously unable to convince local physicians to attempt the procedure. Following this initial success, Boylston began performing inoculations throughout Boston, despite much controversy and at least one attempt upon his life. The effectiveness of the procedure was proven when, of the nearly three hundred people Boylston inoculated during the outbreak, only six died, whereas the mortality rate among those who contracted the disease naturally was one in six. Boylston traveled to London in 1724. There he published his results and was elected to the Royal Society in 1726.
In France, considerable opposition arose to the introduction of inoculation, and it was banned by the Parlement. Voltaire, in his Lettres Philosophiques, wrote a criticism of his countrymen for being opposed to inoculation and having so little regard for the welfare of their children, concluding that "had inoculation been practised in France it would have saved the lives of thousands."
Inoculation grew in popularity in Europe through the 18th century. Given the high prevalence and often severe consequences of smallpox in Europe in the 18th century, many parents felt that the benefits of inoculation outweighed the risks and so inoculated their children.

Mechanism

Two forms of the disease of smallpox were recognised, now known to be due to two strains of the Variola virus. Those contracting Variola minor had a greatly reduced risk of death – 1–2% – compared to those contracting Variola major with 30% mortality. Infection via inhaled viral particles in droplets spread the infection more widely than the deliberate infection through a small skin wound. The smaller, localised infection is adequate to stimulate the immune system to produce specific immunity to the virus, while requiring more generations of the virus to reach levels of infection likely to kill the patient. The rising immunity terminates the infection. So the twofold effect is to ensure the less fatal form of the disease is the one caught, and to give the immune system the best start possible in combating it.
Inoculation in the East was historically performed by blowing smallpox crusts into the nostril. In Britain, Europe and the American Colonies the preferred method was rubbing material from a smallpox pustule from a selected mild case into a scratch between the thumb and forefinger. This would generally be performed when an individual was in normal good health, and thus at peak resistance. The recipient would develop smallpox; however, due to being introduced through the skin rather than the lungs, and possibly because of the inoculated individual's preexisting state of good health, the small inoculum, and the single point of initial infection, the resulting case of smallpox was generally milder than the naturally occurring form, produced far less facial scarring, and had a far lower mortality rate. As with survivors of the natural disease, the inoculated individual was subsequently immune to re-infection.

Obsolescence

In 1798, the English surgeon/scientist Edward Jenner published the results of his experiments and thus introduced the far superior and safer method of inoculation with cowpox virus, a mild infection that also induced immunity to smallpox. Jenner was not the first person to inoculate with cowpox nor the first to realize that infection with cowpox gave immunity to smallpox. However, he was the first to publish evidence that it was effective and to provide advice on its production. His efforts led to smallpox inoculation falling into disuse and eventually being banned in England in 1840.