Inoculation is the placement of something that will grow or reproduce, and is most commonly used in respect of the introduction of a serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

, vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

, or antigenic
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 substance into the body of a human or animal, especially to produce or boost immunity to a specific disease. It can also be used to refer to the communication of a disease to a living organism by transferring its causative agent into the organism, the implanting of microorganisms or infectious material into a culture medium such as a brewers vat or a petri dish, or the placement of microorganisms or viruses at a site where infection is possible. The verb to inoculate is from Middle English inoculaten, which meant "to graft
Grafting is a horticultural technique whereby tissues from one plant are inserted into those of another so that the two sets of vascular tissues may join together. This vascular joining is called inosculation...

 a scion" (a scion is a plant part to be grafted onto another plant); which in turn is from Latin inoculare, past participle inoculat-.

This article covers variolation, inoculation as a method of purposefully infecting
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

 a person with smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...

 (Variola) in a controlled manner so as to minimise the severity of the infection and also to induce immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...

 against further infection. See vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

 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
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an agent ....

are used more or less interchangeably and popularly refer to the process of artificial induction of immunity
Artificial induction of immunity
Artificial induction of immunity is the artificial induction of immunity to specific diseases - making people immune to disease by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering....

 against various infectious disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

s. The microorganism used in an inoculation is called the inoculant or inoculum.



The Indian historian D.P. Agrawal suggest that the practice originated in India. A religious rite having this effect was attributed to the physician Dhanvantari
Dhanvantari is an Avatar of Vishnu from the Hindu tradition. He appears in the Vedas and Puranas as the physician of the gods , and the god of Ayurvedic medicine...

, founder of the Vedic
Vedic may refer to:* the Vedas, the oldest preserved Indic texts** Vedic Sanskrit, the language of these texts** Vedic period, during which these texts were produced** Vedic pantheon of gods mentioned in Vedas/vedic period...

 tradition, in about 1500 BCE. As with other medical customs, the inoculation was associated with a Hindu goddess. This ancient inoculation procedure featured in the BBC documentary-What the Ancients Did for Us
What the Ancients Did for Us
What the Ancients Did for Us is a 2005 BBC documentary series presented by Adam Hart-Davis that examines the impact of ancient civilizations on modern society.-Production:...

. In the 18th century Dr. J.Z. Holwell wrote the most detailed account for the college of Physicians in London, describing not only inoculation, but also showing that the Indians knew that microbes caused such diseases:

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 (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.

The earliest written record of inoculation is thought to be found in 8th century India
History of India
The history of India begins with evidence of human activity of Homo sapiens as long as 75,000 years ago, or with earlier hominids including Homo erectus from about 500,000 years ago. The Indus Valley Civilization, which spread and flourished in the northwestern part of the Indian subcontinent from...

, when Madhav
Madhav was an 8th century Indian physician who wrote the Nidāna, which soon assumed a position of authority. In the 79 chapters of this book, he lists diseases along with their causes, symptoms, and complications. He also included a special chapter on smallpox .Ayurveda used a system of inoculation...

 wrote the Nidāna, a 79-chapter book which lists diseases along with their causes, symptoms, and complications. According to Donald R. Hopkins (2002), Madhav included a special chapter on smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...

 (masūrikā) and described the method of inoculation to protect against smallpox.


The British historian Joseph Needham
Joseph Needham
Noel Joseph Terence Montgomery Needham, CH, FRS, FBA , also known as Li Yuese , was a British scientist, historian and sinologist known for his scientific research and writing on the history of Chinese science. He was elected a fellow of the Royal Society in 1941, and as a fellow of the British...

 and the American historian Robert Temple
Robert K. G. Temple
Robert K. G. Temple is an American author best known for his controversial book, The Sirius Mystery which presents the idea that the Dogon people preserve the tradition of contact with intelligent extraterrestrial beings from the Sirius star-system...

 write that the practice of inoculation for smallpox began in China during the 10th century. A Song Dynasty
Song Dynasty
The Song Dynasty was a ruling dynasty in China between 960 and 1279; it succeeded the Five Dynasties and Ten Kingdoms Period, and was followed by the Yuan Dynasty. It was the first government in world history to issue banknotes or paper money, and the first Chinese government to establish a...

 (960–1279) chancellor of China
Chancellor of China
The Chancellor , variously translated as Prime Minister, Chancellor of State, Premier or Chief Councillor, was a generic name given to the highest-ranking official in the imperial government in ancient China...

, Wang Dan (957–1017), 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
Kaifeng , known previously by several names , is a prefecture-level city in east-central Henan province, Central China. Nearly 5 million people live in the metropolitan area...

 and share ideas on how to cure patients of it. From Mount Emei
Mount Emei
"峨眉山" redirects here. For the county-level city that Mount Emei is located in, see Emeishan CityMount Emei is a mountain in Sichuan province, China...

 in Sichuan
' , known formerly in the West by its postal map spellings of Szechwan or Szechuan is a province in Southwest China with its capital in Chengdu...

, a Daoist hermit, a nun known as a "numinous old woman" and "holy physician"—who Temple says was associated with the 'school of the ancient immortals' and thus most likely specialized in 'internal alchemy'—introduced the technique of inoculation to the capital. However, the sinologist Joseph Needham
Joseph Needham
Noel Joseph Terence Montgomery Needham, CH, FRS, FBA , also known as Li Yuese , was a British scientist, historian and sinologist known for his scientific research and writing on the history of Chinese science. He was elected a fellow of the Royal Society in 1941, and as a fellow of the British...

 states that this information comes from the Zhongdou xinfa (種痘心法) 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 (1499–1582) Douzhen xinfa (痘疹心法) 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 (寓意草), or Notes on My Judgment, published in 1643. Inoculation was reportedly not widely practised in China until the reign of the Longqing Emperor
Longqing Emperor
The Longqing Emperor was the 12th emperor of the Ming dynasty in China between 1567-1572. His era name means "Great celebration". His name at birth was Zhu Zaihou and he was born during the reign of his father Emperor Jiajing, at the Forbidden City at the Ming Dynasty capital Beijing....

 (r. 1567–1572) during the Ming Dynasty
Ming Dynasty
The Ming Dynasty, also Empire of the Great Ming, was the ruling dynasty of China from 1368 to 1644, following the collapse of the Mongol-led Yuan Dynasty. The Ming, "one of the greatest eras of orderly government and social stability in human history", was the last dynasty in China ruled by ethnic...

 (1368–1644), as written by Yu Tianchi in his Shadou jijie (痧痘集解) of 1727, which he alleges was based on Wang Zhangren's Douzhen jinjing lu (痘疹金鏡錄) 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 (considered too dangerous); 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
Mung bean
The mung bean is the seed of Vigna radiata. It is native to the Indian subcontinent.-Description:They are small, ovoid in shape, and green in color...

 in germination
Germination is the process in which a plant or fungus emerges from a seed or spore, respectively, and begins growth. The most common example of germination is the sprouting of a seedling from a seed of an angiosperm or gymnosperm. However the growth of a sporeling from a spore, for example the...

. Robert Temple quotes an account from Zhang Yan's Zhongdou xinshu (種痘新書), or New book on smallpox inoculation, written in 1741 during the Qing Dynasty
Qing Dynasty
The Qing Dynasty was the last dynasty of China, ruling from 1644 to 1912 with a brief, abortive restoration in 1917. It was preceded by the Ming Dynasty and followed by the Republic of China....

 (1644–1912), 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 people—and 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.

As for other methods used in China, the technique of scratching the skin and putting pox onto the scab seems to have developed later than the first accounts made in China, and possibly came from Central Asia
Central Asia
Central Asia is a core region of the Asian continent from the Caspian Sea in the west, China in the east, Afghanistan in the south, and Russia in the north...

—according to Temple.

Importation to the West

The practice was introduced to the west by Lady Mary Wortley Montagu
Lady Mary Wortley Montagu
The Lady Mary Wortley Montagu was an English aristocrat and writer. Montagu is today chiefly remembered for her letters, particularly her letters from Turkey, as wife to the British ambassador, which have been described by Billie Melman as “the very first example of a secular work by a woman about...

 (May 26, 1689 – August 21, 1762). Lady Montagu's husband, Edward Wortley Montagu, served as the British
Great Britain
Great Britain or Britain is an island situated to the northwest of Continental Europe. It is the ninth largest island in the world, and the largest European island, as well as the largest of the British Isles...

An ambassador is the highest ranking diplomat who represents a nation and is usually accredited to a foreign sovereign or government, or to an international organization....

 to the Ottoman Empire
Ottoman Empire
The Ottoman EmpireIt was usually referred to as the "Ottoman Empire", the "Turkish Empire", the "Ottoman Caliphate" or more commonly "Turkey" by its contemporaries...

 from 1716 to 1717. She witnessed inoculation being practiced by physicians
Islamic medicine
In the history of medicine, Islamic medicine, Arabic medicine or Arabian medicine refers to medicine developed in the Islamic Golden Age, and written in Arabic, the lingua franca of Islamic civilization....

 in Istanbul
Istanbul , historically known as Byzantium and Constantinople , is the largest city of Turkey. Istanbul metropolitan province had 13.26 million people living in it as of December, 2010, which is 18% of Turkey's population and the 3rd largest metropolitan area in Europe after London and...

, and was greatly impressed: 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 inoculated. She invited friends to see her daughter, including Sir Hans Sloane, the King
George I of Great Britain
George I was King of Great Britain and Ireland from 1 August 1714 until his death, and ruler of the Duchy and Electorate of Brunswick-Lüneburg in the Holy Roman Empire from 1698....

's physician. Sufficient interest arose that Maitland gained permission to test inoculation at Newgate prison
Newgate Prison
Newgate Prison was a prison in London, at the corner of Newgate Street and Old Bailey just inside the City of London. It was originally located at the site of a gate in the Roman London Wall. The gate/prison was rebuilt in the 12th century, and demolished in 1777...

 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'
George II of Great Britain
George II was King of Great Britain and Ireland, Duke of Brunswick-Lüneburg and Archtreasurer and Prince-elector of the Holy Roman Empire from 11 June 1727 until his death.George was the last British monarch born outside Great Britain. He was born and brought up in Northern Germany...

 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
Zabdiel Boylston
Zabdiel Boylston, FRS was a physician in the Boston area. He apprenticed with his father, an English surgeon named Thomas Boylston. He also studied under the Boston physician Dr...

, at the urging of Cotton Mather
Cotton Mather
Cotton Mather, FRS was a socially and politically influential New England Puritan minister, prolific author and pamphleteer; he is often remembered for his role in the Salem witch trials...

, successfully inoculated two slaves and his own son. Mather, a prominent Boston
Boston is the capital of and largest city in Massachusetts, and is one of the oldest cities in the United States. The largest city in New England, Boston is regarded as the unofficial "Capital of New England" for its economic and cultural impact on the entire New England region. The city proper had...

 minister, had heard a description of the African practice of inoculation from his Sudanese slave, Onesimus
Onesimus (disambiguation)
Onesimus, bishop of Byzantium .Onesimus may also refer to:* Onesimus, the Sudanese slave of Boston Puritan Cotton Mather...

, in 1706, but 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.
Natural experiment in inoculation
around Boston, 1721
  Total Died % Mortality
Variolated c 300 6 c 2%
Unvariolated c 6000 c 1000 "about 14%"

In France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...

, considerable opposition arose to the introduction of inoculation. Voltaire
François-Marie Arouet , better known by the pen name Voltaire , was a French Enlightenment writer, historian and philosopher famous for his wit and for his advocacy of civil liberties, including freedom of religion, free trade and separation of church and state...

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


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 (Variola minor) 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
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

. As with survivors of the natural disease, the inoculated individual was subsequently immune to re-infection.

Supplanted by vaccination

In 1796, The Englishman Edward Jenner
Edward Jenner
Edward Anthony Jenner was an English scientist who studied his natural surroundings in Berkeley, Gloucestershire...

 invented and introduced the far superior and safer method of inoculation with the cowpox
Cowpox is a skin disease caused by a virus known as the Cowpox virus. The pox is related to the vaccinia virus and got its name from the distribution of the disease when dairymaids touched the udders of infected cows. The ailment manifests itself in the form of red blisters and is transmitted by...

 virus, a non-fatal virus that also induced immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...

 to smallpox. This led to smallpox inoculation falling into disuse and eventually being banned in England in 1840.

External links

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