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.

Until the early 1800s inoculation referred only to variolation (from the Latin word variola = smallpox), the predecessor to the smallpox vaccine.^[1] The smallpox vaccine, introduced by Edward Jenner in 1796, was called cowpox inoculation or vaccine inoculation (from Latin vacca = cow). Smallpox inoculation continued to be called variolation, whereas cowpox inoculation was called vaccination (from Jenner's term variolae vaccinae = smallpox of the cow). 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.^[2] In nontechnical usage inoculation is now more or less synonymous with protective injections and other methods of immunization.^{[citation needed]}

Inoculation also has a specific meaning for procedures done in vitro (in glass, i.e. not in a living body). 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 (wine making), and the production of antibiotics. For example, blue cheese is made by inoculating it with Penicillium roqueforti mold, and often certain bacteria.^{[3][failed verification]}

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' (and by metaphor, 'bud').^[4] (The term innocuous is unrelated, as it derives from Latin in- 'not' + nocuus 'harmful'.)

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.^{[citation needed]}

In contrast, infection of the skin usually led to a milder, localized infection – but, 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.^[5]

Most Old World diseases of known origin can be traced to Africa and Asia and were introduced to Europe over time. Smallpox originated in Africa or Asia,^[25] plague in Asia,^[26][27] cholera in Asia,^[28][29] influenza in Asia,^[30][31] malaria in Africa and Asia,^[32][33][34] measles from Asian rinderpest,^[35][36][37] tuberculosis in Asia,^[38][39] yellow fever in Africa,^[40] leprosy in Asia,^[41] typhoid in Africa,^[42] syphilis in America and Africa,^[43] herpes in Africa,^[44] zika in Africa.^[45] Thus the necessity of immunity through inoculation did not arise until those diseases were introduced in Europe.

In January 1714 the Philosophical Transactions of the Royal Society published an account of a letter John Woodward had received from Emmanuel Timonius in Istanbul.^[46] Smallpox inoculation was advocated as a proven method of curbing the severity of the disease.^{[citation needed]}

The practice was introduced to England by Lady Mary Wortley Montagu.^[47] Lady Montagu's husband, Edward Wortley Montagu, served as the British ambassador to the Ottoman Empire from 1716 to 1718. She witnessed firsthand the Ottoman use of inoculation in Istanbul,^[48] and was greatly impressed:^[49] 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 on six prisoners due to be hanged in exchange for their freedom, an experiment which was witnessed by a number of notable doctors.^[50] All survived, and in 1722 the Prince of Wales' daughters received inoculations.^[51]

The practice of inoculation slowly spread amongst the royal families of Europe, usually followed by more general adoption amongst the people.^{[citation needed]}

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.^[52] However, Mather had been previously unable to convince local physicians to attempt the procedure.^[53] 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.^[54] 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."^[56]

Likewise, in the United States, the Continental Congress issued a proclamation in 1776 prohibiting Surgeons of the Army from performing inoculations. However, in 1777, George Washington, witnessing the virulent spread of smallpox, and fearing the likelihood of mass transmission of the disease throughout the Continental Army, weighed the risks and overruled this prohibition, conducting smallpox inoculation of all troops. He wrote, "Should the disorder infect the Army in the natural way and rage with its usual virulence, we have more to dread from it than from the sword of the enemy." This was the first mass inoculation of an army, and was successful, with only isolated infections occurring, and no regiments incapacitated by the disease.^[57][58]

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),^[59] many parents felt that the benefits of inoculation outweighed the risks and so inoculated their children.^[60]

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. This ensures the less fatal form of the disease is the one caught, and gives the immune system the best start possible in combating it.^{[citation needed]}

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.^[61] 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.^{[citation needed]}

In 1798, British physician 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 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.^[62]

• Psychological resilience (also known as stress inoculation)