Inoculation


Inoculation is the act of implanting a pathogen or other microbe or virus into a person or other organism. It is a method of artificially inducing immunity against various infectious diseases. The term "inoculation" is also used more generally to refer to intentionally depositing microbes into any growth medium, as into a Petri dish used to culture the microbe, or into food ingredients for making cultured foods such as yoghurt and fermented beverages such as beer and wine. This article is primarily about the use of inoculation for producing immunity against infection. Inoculation has been used to eradicate smallpox and to markedly reduce other infectious diseases such as polio. Although the terms "inoculation", "vaccination", and "immunization" are often used interchangeably, there are important differences. Inoculation is the act of implanting a pathogen or microbe into a person or other recipient; vaccination is the act of implanting or giving someone a vaccine specifically; and immunization is the development of disease resistance that results from the immune system's response to a vaccine or natural infection.

Terminology

Until the early 1800s inoculation referred only to variolation, the predecessor to the smallpox vaccine. The smallpox vaccine, introduced by Edward Jenner in 1796, was called cowpox inoculation or vaccine inoculation. Smallpox inoculation continued to be called variolation, whereas cowpox inoculation was called vaccination. Louis Pasteur proposed in 1861 to extend the terms vaccine and vaccination to include the new protective procedures being developed. Immunization refers to the use of vaccines as well as the use of antitoxin, which contains pre-formed antibodies such as to diphtheria or tetanus exotoxins. In nontechnical usage inoculation is now more or less synonymous 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 it with Penicillium roqueforti mold, and often certain bacteria.

Etymology

The term inoculate entered medical English through horticultural usage meaning to graft a bud from one plant into another. It derives from Latin in- 'in' + oculus 'eye'.

Origins

Inoculation originated as a method for the prevention of smallpox by deliberate introduction of material from smallpox pustules from one person into the skin of another. The usual route of transmission of smallpox was through the air, invading the mucous membranes of the mouth, nose, or respiratory tract, before migrating throughout the body via the lymphatic system, resulting in an often severe disease.
In contrast, infection of the skin usually led to a milder, localized infectionbut, crucially, still induced immunity to the virus. 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:

Method of storing the material. Wrap the scabs carefully in paper and put them into a small container bottle. Cork it tightly so that the activity is not dissipated. The container must not be exposed to sunlight or warmed beside a fire. It is best to carry it for some time on the person so that the scabs dry naturally and slowly. The container should be marked clearly with the date on which the contents were taken from the patient.
In winter, the material has yang potency within it, so it remains active even after being kept from thirty to forty days. But in summer the yang potency will be lost in approximately twenty days. The best material is that which had not been left too long, for when the yang potency is abundant it will give a 'take' with nine persons out of ten peopleand finally it becomes completely inactive, and will not work at all. In situations where new scabs are rare and the requirement great, it is possible to mix new scabs with the more aged ones, but in this case more of the powder should be blown into the nostril when the inoculation is done.

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.

The Circassian women have, from time immemorial, communicated the small-pox to their children when not above six months old by making an incision in the arm, and by putting into this incision a pustule, taken carefully from the body of another child. This pustule produces the same effect in the arm it is laid in as yeast in a piece of dough; it ferments, and diffuses through the whole mass of blood the qualities with which it is impregnated. The pustules of the child in whom the artificial small-pox has been thus inoculated are employed to communicate the same distemper to others. There is an almost perpetual circulation of it in Circassia; and when unhappily the small-pox has quite left the country, the inhabitants of it are in as great trouble and perplexity as other nations when their harvest has fallen short...

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 Emmanuel Timoni and Giacomo Pylarini independently sent letters from Istanbul.

India

The French scholar Henri Marie Husson once noted in the journal Dictionaire des sciences médicales that inoculation was mentioned in the Ayurvedic text Sact'eya Grantham. However, it is not stated whether this method of inoculation was used specifically for the prevention of smallpox, and the original text of the Sact'eya Grantham has not been found. The idea that inoculation originated in India has also been taken into account, although there is little evidence in ancient Sanskrit medical texts clearly describing the practice. 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. Doctors who performed variolation were known as Tikadars. However, such a theory has not yet been discovered in any Sanskrit or vernacular treatise.
By the 18th century, variolation was widely practiced in India. Several historians have suggested that variolation may be older than the 18th century in India. Oliver Coult in 1731 wrote that it had been "first performed by Dununtary a physician of Champanagar". However these reports have been called into question.
Vaccinations were introduced to India in 1802, when 3-year-old girl in Mumbai received a smallpox vaccine, making her the first person to take a vaccine in India. 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 hope of convincing pious Indians to accept the newly discovered Jennerian procedure and abandon older variolation practices. A landmark anthropological study by Ralph Nicholas described the mid-twentieth century rituals of appeasement to Śītalā, the Indian goddess of smallpox, in Bengal.