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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


The word "Inoculation" refers to the placement of something to where it will grow or reproduce, and is most commonly used in respect of the introduction of a serum, vaccine, or antigenic substance into the body of a person or animal, especially to produce or boost immunity to a specific disease; but also can be used to refer to the communication of a disease to a living organism by transferring its causative agent into the organism, to implant microorganisms or infectious material into a culture medium such as a brewers vat or a petri dish, to safeguard as if by inoculation, to introduce an idea or attitude into someone's mind, any placement of microorganisms or viruses at a site where infection is possible such as to increase soybeans' nitrogen fixation one can treat soybeans at planting with Rhizobium japonicum inoculant. The verb "to inoculate" is from Middle English "inoculaten", which meant "to graft a scion (a scion is a plant part to be grafted onto another plant); which in turn is from Latin "inoculre" or "inocult-".[1][2]

This article covers variolation, inoculation as a method of purposefully infecting a person with smallpox (Variola) in a controlled manner so as to minimise the severity of the infection and also to induce immunity against further infection. See vaccination for post-variolation methods of safeguarding as if by inoculation by administering weakened or dead pathogens to a healthy person or animal with the intent of conferring immunity against a targeted form of a related disease agent.

Today the terms inoculation, vaccination and immunization are used more or less interchangeably and popularly refer to the process of artificial induction of immunity against various infectious diseases. The microorganism used in an inoculation is called the inoculant or inoculum.


The earliest use of inoculation was from the Chinese. It is recorded that the Chinese inoculated their patients by making them snort the powdered scabs of smallpox victims. Another method of their inoculation was by scratching the powder into their skin.[4],[5]

Some scholars suggest that the practice originated in India.

Dr. J.Z. Holwell writes the most detailed account for the college of Physicians in London in 1767 (An account of the manner of inoculating for the smallpox in the East Indies, by J. Z. Holwell, F.R.S. addressed to the President and Members of the College of Physicians in London) ... Holwell's detailed account, not only describes inoculation, but also shows that the Indians knew that microbes caused such diseases:

They lay it down as a principle, that the immediate (or instant) cause of the smallpox exists in the mortal part of every human and animal form; that the mediate (or second) 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.

Importation to the West

File:Charles Jervas 001.jpg
Mary Wortley Montagu, by Charles Jervas, after 1716.

The practice was introduced to the west by Lady Mary Wortley Montagu (May 26, 1689-August 21, 1762). Lady Montagu's husband, Edward Wortley Montagu, served as the British ambassador to the Ottoman Empire from 1716 to 1717. She witnessed inoculation in Constantinople, and was greatly impressedTemplate:Fix/category[citation needed]: she had lost a brother to smallpox and bore facial scars from the disease herself. In March 1718 she had the embassy surgeon, Charles Maitland, inoculate her five-year-old son. In 1721, after returning to England, she had her four-year-old daughter inoculatedTemplate:Fix/category[citation needed]. 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 hangedTemplate:Fix/category[citation needed], an experiment which was witnessed by a number of notable doctors. The experiment succeeded, and in 1722 the Prince of Wales' daughters received inoculationsTemplate:Fix/category[citation needed].

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. Cotton Mather in Boston had a description of the African practice of inoculation from his slave[3] Onesimus and encouraged its application, with considerable controversy and strife. Fearing the outbreak of an epidemic, the editor of the South Carolina Gazette published a detailed description of the inoculation process in the April 22 issue. In Boston, there was opposition from churchmen regarding the practice who regarded it as "bidding defiance to Heaven itself, even to the will of God", though one historian also notes that "...within a year or two after the first experiment nearly three hundred persons had been inoculated ... in Boston and neighbouring towns, and out of these only six had died; whereas, during the same period, out of nearly six thousand persons who had taken smallpox naturally, and had received only the usual medical treatment, nearly one thousand had died." (from A History Of The Warfare Of Science With Theology In Christendom by Andrew Dickson White.)

Natural experiment in inoculation
around Boston, 1721
  Total Died  % Mortality
Variolated c 300 6 c 2%
Unvariolated c 6000 c 1000 "about 14%"[4]

In France considerable opposition arose to the introduction of inoculation. 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.".[5]

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 (according to Voltaire, there was a 60% incidence of first infection, a 20% mortality rate, and a 20% incidence of severe scarring),[6] many parents felt that the benefits of inoculation outweighted the risks and so inoculated their children.[7]


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 20% 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.

Typical site of inoculation in Europe and the British colonies
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 (Variola minor) into a scratch between the thumb and forefinger. [6] 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.

Supplanted by vaccination

In 1796, Edward Jenner introduced the far safer method of inoculation with the cowpox virus, a non-fatal virus that also induced immunity to smallpox. This led to smallpox inoculation falling into disuse and eventually being banned in England in 1840.

See also


  1. Your Dictionary
  2. Inoculation entry at Gardening section of
  3. Silverman,Kenneth. ‘’The Life and Times of Cotton Mather’’, Harper & Row, New York, 1984. ISBN 0-06-015231-1, p. 339.
  4. Harris DF. "Edward Jenner and Vaccination". Retrieved 2007-03-04. 
  5. Lettres Philosophiques. Voltaire. (English translation on-line [1])
  6. In fact, the mortality rate of the Varoiola Minor form of smallpox then found in Europe was 1-3% as opposed to 30-50% for the Variola Major type found elsewhere; however. blindness, infertility, and severe scarring were common. Figures from "The Search for Immunisation", In Our Time, BBC Radio 4 (2006). [2]
  7. Letter of Lady Montagu reproduced at viewed 18 March 2006

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