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.

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.

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.

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.  in the most severe forms of disease.

Mozart was infected, as was Abraham Lincoln. 

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.

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. 

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.

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.

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. 

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.

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.

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.

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. 

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.

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.

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.

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.

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

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.

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. 

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.

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.

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.

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.

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. 

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.

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 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.

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

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.