History of Smallpox Vaccination

The only human disease to be eradicated so far

By World Health Organization

Parchment signed at Geneva on 9 December 1979, by the members of the Global Commission for Certification of Smallpox Eradication (1979-09-12) by WHOWorld Health Organization

One of the deadliest diseases known to humans, smallpox remains the only human disease to have been eradicated. Many believe this achievement to be the most significant milestone in global public health.

By Lynn PelhamLIFE Photo Collection

Key components of the worldwide smallpox eradication effort included universal childhood immunization programmes in some countries, mass vaccination in others, and targeted surveillance-containment strategies during the end-game.

16th century Aztec drawing of smallpox victims (1500-12-31)Original Source: Scanned from (2009) Viruses, Plagues, and History: Past, Present and Future, Oxford University Press, USA, p. 60

Over thousands of years, smallpox killed hundreds of millions of people. The rich, the poor, the young, the old. It was a disease that didn’t discriminate, killing at least 1 in 3 people infected, often more in the most severe forms of disease.

St Pancras Smallpox Hospital, London, housed in a tented camp at Finchley. Watercolour by F. Collins, 1881 (1905-02-23) by Wellcome ImagesWorld Health Organization

The symptoms of smallpox were gruesome: high fever, vomiting and mouth sores, followed by fluid-filled lesions on the whole body. Death would come suddenly, often within 2 weeks, and survivors could be left with permanent harms such as blindness and infertility. 

President Abraham Lincoln, Washington D.C. President Abraham Lincoln, Washington D.C. (1865) by Mathew B. BradyThe J. Paul Getty Museum

Mozart was infected, as was Abraham Lincoln. 

Tell-tale pockmarks on the 3,000-year-old mummified head of Egyptian Pharaoh Ramses V testify to the length of time that smallpox has scourged humanity (1969-11-30) by WHOWorld Health Organization

Smallpox was highly infectious, with no known cure. It began as early as 1350 BCE, with cases being found in the study of Egyptian mummies.

Hanging scroll painting of the God of Smallpox 장군상 (將軍像) (Late 19th - early 20th century AD)Royal Ontario Museum

The ancient practice of variolation (named for smallpox, also known as variola or ‘la variole’) was widely used in Asia and some parts of Africa. 

Smallpox illustration (1904-09-15) by Wellcome ImagesWorld Health Organization

This consisted of transferring to healthy people small amounts of material from smallpox sores, resulting in milder forms of illness and much lower mortality than natural infection. Some sources suggest practices of variolation were taking place as early as 200 BCE. 

Written accounts from the mid-1500s describe a form of variolation used in China known as insufflation, where smallpox scabs were dried, ground and blown into the nostril using a pipe.

The arm of William Pead from which several children and adults were inoculated by Wellcome ImagesWorld Health Organization

In India, similar practices were carried out through inoculation, using a lancet or needle to transfer material from smallpox pustules to the skin of healthy children. Accounts from the 18th century suggest this technique dates back hundreds of years. 

Lady Mary Wortley Montagu with her son, Edward Wortley Montagu, and attendants by Jean Baptiste Vanmour (1904-09-12) by Jean Baptiste Vanmour (1671-1737), ArtistWorld Health Organization

Variolation (in the form of inoculation) was introduced in Europe by Lady Mary Wortley Montagu 300 years ago in 1721, after she had observed the practice in the Ottoman Empire, where her husband was stationed as ambassador to Turkey. 

First page of a letter from Cotton Mather on inoculation in Boston (1723-05-21) by Cotton Mather FRS (1663-1728)The Royal Society

Around the same time, it came to public attention in the American colonies. Enslaved West Africans had long practised the technique, and after his slave Onesimus told him about how it worked in 1716, Cotton Mather publicized it and argued for its use in response to a 1721 outbreak of smallpox in Massachusetts.

Jenner Edward 1749-1823LIFE Photo Collection

It wasn’t until May 1796 that the world’s first vaccine was demonstrated, using the same principle as variolation but with a less dangerous viral source, cowpox. Having heard of local beliefs and practices in rural communities that cowpox protected against smallpox, Dr Edward Jenner inoculated 8-year-old James Phipps with matter from a cowpox sore on the hand of Sarah Nelmes, a local milkmaid.

History and pathology of vaccination (1905-03-03) by Internet Archive Book ImagesWorld Health Organization

Phipps reacted to the cowpox matter and felt unwell for several days but made a full recovery. Two months later, in July 1796, Jenner took matter from a human smallpox sore and inoculated Phipps with it to test his resistance. 

Phipps remained in perfect health, the first person to be vaccinated against smallpox. 

Edward Jenner vaccinating patients in the Smallpox and Inoculation Hospital at St. Pancras: the patients develop features of cows. (1904-12-07) by James GillrayWorld Health Organization

Not everyone was on board with Jenner and his vaccine. Rumours circulated at the time that it would turn people into cows. But by 1801, through extensive testing, it was shown to effectively protect against smallpox. 

Vaccination certificate from 1863 (1905-02-05) by Jim GriffinWorld Health Organization

The vaccine was soon in use on other continents, where vaccine continued to be inoculated from arm to arm until vaccination programmes were established. Mandatory smallpox vaccination came into effect in Britain and parts of the United States of America in the 1840s and 1850s, as well as in other parts of the world, leading to the establishment of the smallpox vaccination certificates required for travel.

Sign on a public road in Yorkshire, England, during an outbreak of smallpox in 1953 (1905-05-06) by WHOWorld Health Organization

While some European regions eliminated the disease by 1900, smallpox was still ravaging continents and areas under colonial rule, with over 2 million people dying every year. It took another 50 years to achieve global solidarity in the fight against the disease.

Manufacture Of Smallpox Vaccine, Lederly Labs, Pearl River, Ny (1947-04) by Fritz GoroLIFE Photo Collection

Vaccine research and studies in vaccine delivery were carried out around the world in the search for more resilient and effective vaccines.  

By the 1950s, advances in production techniques meant that heat-stable, freeze-dried smallpox vaccines could be stored without refrigeration.

This map depicted the endemic distribution of smallpox between the years of 1954 – 1957 (1905-05-11) by CDC/ Dr. Donaldson; World Health Organization; Pan American Sanitary BureauWorld Health Organization

Vaccination led to smallpox elimination in western Europe, North America and Japan. In the absence of a large-scale coordinated international programme, the disease persisted in other areas.

The logo certifying the eradication of smallpox in Somalia, and consequently, in the world (1979-10-26) by WHOWorld Health Organization

In 1958, the World Health Assembly called for the global eradication of smallpox – the permanent reduction to zero cases – without risk of reintroduction. 

Members of the Global Commission for the Certification of Smallpox Eradication, Geneva, 9 December 1979 (1979-12-09) by WHO / L. BiancoWorld Health Organization

As the World Health Organization launched the Smallpox Eradication Programme in 1959, WHO Member States enhanced their support and cooperation. Good progress was made in many countries with the support of technical assistance and vaccine provision coordinated by WHO.

The CDC team provided the smallpox vaccine to the local people of Tonga (1905-05-20) by CDC/ Dr. David J. Sencer/ Julie McClure, Atlanta Journal and ConstitutionWorld Health Organization

Efforts were redoubled with the launch of the Intensified Smallpox Eradication Programme in 1967. The Soviet Union provided freeze-dried vaccine, which became the basis for elimination of smallpox from eastern Europe, China and India. 

Participants on this 1967 panel discussing the eradication of smallpox, with some of Nigeria’s Smallpox Eradication Program officials (1905-05-20) by CDC / Dr. Willaim FoegeWorld Health Organization

With renewed political commitment and the contributions of hundreds of thousands of local surveillance officers and health workers, even regions with nascent health systems and tremendous logistical challenges made remarkable progress.

The anti-smallpox procession wends its way through Delhi streets (1905-05-16) by WHO / Tambarahalli S. SatyanWorld Health Organization

Throughout this period WHO played a critical role, with international workers supporting legions of national personnel. Epidemiologists from the Soviet Union and the United States of America worked side by side in the middle of a cold war. 

For example, in 1970, an outbreak in south-west India led to over 1300 cases and 123 deaths. In response, all available national and international health personnel were dispatched on a week-long house-by-house search of the area, vaccinating everyone identified as a contact of a recent case. 

With this strategy they were able to eliminate highly contagious smallpox from the district within weeks.

Smallpox vaccination with the bifurcated needle (1905-05-23) by WHOWorld Health Organization

In higher-risk countries, laboratories began to produce higher-quality freeze-dried vaccines, and mass production of the innovative and easy-to-use bifurcated needle to administer doses contributed to vaccination efforts. 


Thanks to the combined efforts of national health agencies, WHO and scientists around the world, smallpox was eliminated from South America in 1971, Asia in 1975 and Africa in 1977.

Ethiopian poster illustrating the activities of the Smallpox Eradication Programme (1905-05-23) by Gift of Donald A. Henderson, M.D. M.P.H.World Health Organization

The cost of the Intensified Smallpox Eradication Programme was approximately US$300 million, two thirds of which came from endemic countries for their own eradication efforts. British, Canadian, Cuban, French, Soviet, and US vaccines were given freely to WHO and distributed onwards, sometimes with the strategic financial support of Sweden.

Local production of smallpox vaccine in West Africa (1905-05-13) by WHO / Didier HenrioudWorld Health Organization

Also important in the 1970s were vaccine technology transfers allowing countries to become producers of their own freeze-dried vaccine and suppliers within their region. 

Smallpox vaccination with jet injector (1905-05-23) by WHOWorld Health Organization

Through all this, the United States and the Soviet Union worked in rare solidarity. It was an unprecedented demonstration of global unity in the face of a common threat. As a major contributor to the programme, the United States reportedly recoups their investment every 26 days in money not spent on administering further vaccinations and treating new cases. 

"Smallpox is dead!", front cover of the magazine of the World Health Organization, "World Health" (1980-05-01) by Peter DaviesWorld Health Organization

In 1980, WHO declared smallpox officially eradicated

The world and all its people have won freedom from smallpox, which was the most devastating disease sweeping in epidemic form through many countries since earliest times, leaving death, blindness and disfigurement in its wake.

WHO Archives storage facility (2019-02-26) by WHO / Naomi WengerWorld Health Organization

WHO preserves the Archives of the Smallpox Eradication Programme at its headquarters in Switzerland. WHO also maintains a stockpile of vaccines as an emergency reserve in Switzerland and in several other countries.

Bronze statue commemorates the 30th anniversary of the eradication of smallpox (2010-05-19) by WHO / Jess HoffmanWorld Health Organization

A cure was never found for smallpox before eradication, with those infected being treated only by cleaning wounds and lessening pain.

Bronze statue commemorates the smallpox eradication (2010-05-19) by WHO / Jess HoffmanWorld Health Organization

Instead, following the discovery of Dr Jenner’s vaccine, eradication was achieved through prevention, as he himself predicted. Bolstered by efforts united around the world, Jenner’s concept survived to defeat a historic scourge.

After 3000 years of suffering and death from the disease, there hasn’t been a recorded case of smallpox in almost half a century.

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