It is unknown how many people died of smallpox in the 3,000 years it has likely infected humans, but it has been estimated in the 20th century alone to have killed more than 300 million people. How do you fight something that terrible and seemingly unstoppable? In hindsight, the answer seems pretty straightforward: Start with a basic knowledge of the principles of immunity.

Smallpox constituted one of the worst of viral plagues experienced by humanity, and it was indeed a terrible disease for many who contracted it. After an incubation period of 7-19 days, those infected experienced an initial fever accompanied by body aches for another 2-4 days. Sores began to form in the mouth, then spread to the face, extremities, and the whole body within 4 days, and filled with liquid and pus. In people that survived this viral onslaught, their sores began to crust over, forming scabs that could result in scarring for life. It is unknown how many people died of smallpox in the 3,000 years it has likely infected humans, but it has been estimated in the 20th century alone to have killed more than 300 million people.

How do you fight something that terrible and seemingly unstoppable? In hindsight, the answer seems pretty straightforward: Start with a basic knowledge of the principles of immunity. For centuries, people understood that individuals who acquired many diseases become immune to getting them again, but what they didn’t understand is that immunity could be induced in order to protect individuals who never had the disease.

This began to change, possibly in the 16th century, when the technique of variolation, derived from the Latin name for the virus, Variola (meaning “spotted”), began to be adopted in the west (its origin is unknown). With variolation, scabs of smallpox sufferers were ground up and dried, then exposed to naive (i.e. never infected) individuals by rubbing on the skin or by small circular needle perforations on the back of the hand, or in some cases, sniffed into the nose or on cotton placed into one nostril.

Those that received the inoculation mostly experienced a mild form of disease, with a transient fever and a small number of pustules at the site of inoculation, and upon recovery were ‘forever free from fear of contagion’, as Boston minister Cotton Mather wrote around 1714, after being convinced by his African slave, who had been variolated. The procedure was not without risks; variolated individuals were still contagious, and it was estimated that 1-3 out of one hundred died from a more severe form of the disease due to the inoculation. However, this was a substantial improvement over the maximum 30% mortality of natural infection, and the procedure gained acceptance and was employed in England by the early 18th century.

Yet variolation was still treated with suspicion and hostility in much of the rest of Europe, as mentioned by Voltaire in his Philosophical Letters, published in 1734:

It is inadvertently affirmed in the Christian countries of Europe that the English are fools and madmen. Fools, because they give their children the small-pox to prevent their catching it; and madmen, because they wantonly communicate a certain and dreadful distemper to their children, merely to prevent an uncertain evil. The English, on the other side, call the rest of the Europeans cowardly and unnatural. Cowardly, because they are afraid of putting their children to a little pain; unnatural, because they expose them to die one time or other of the small-pox.

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