Inoculation was a method of minimising the harm done by infection with smallpox. It preceded vaccination - though today popular usage may speak of inoculation and vaccination more or less interchangeably when referring the process of immunisation against disease.

The basic principle of inoculation involved deliberate infection, generally by rubbing material from a smallpox pustule into a scratch on the arm. The recipient would develop smallpox. However, because the infection did not take place by the normal route of infection, a particularly mild form of smallpox developed, which had a far lower mortality rate than catching smallpox in the normal way, and left an immunity to later re-infection. The inoculated subject also usually recovered from the infection with far less facial scarring than occurred with naturally acquired smallpox.

The earliest use of the practice remains unknown. It had occurred in various manners in India and in China for centuries, but documentation exists of its adoption in western Europe. In the early 18th century, Lady Mary Wortley Montagu, whose husband Edward Wortley Montagu served as the English ambassador to the Ottoman Empire from 1716 to 1717, witnessed inoculation in Constantinople. The process impressed her greatly: she had lost a brother to smallpox and bore 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's physician. Sufficient interest arose that Maitland gained permission to test inoculation on six condemned prisoners at Newgate prison, witnessed by a number of notable doctors. The trial succeeded; the prisoners gained their freedom, and in 1722 the Prince of Wales' daughters received inoculations.

The practice of inoculation slowly spread amongst the royal families of Europe, usually followed by the more general adoption amongst the people. J.Z. Holwell described the Ayurvedic system of inoculation against smallpox to the Royal College of Physicians in London in 1767 in a tract called An account of the manner of inoculating for the small pox in the East Indies. He based his account on observations made during his residence in Bengal.

In France considerable opposition arose to the introduction of inoculation: Voltaire, in his Lettres Philosophiques wrote a criticism of his countrymen for having so little regard for the welfare of their children (English translation on-line[1]).

Given the prevalence of smallpox in the 18th century, one could expect almost inevitably to become infected by it sooner or later. The advantages of inoculation seemed so evident that parents would pre-empt the dangerous natural infection by the less risky use of inoculation; but Edward Jenner's introduction of the far safer cowpox in vaccination after 1796 eventually led to the smallpox inoculation falling into disuse.

See also Inoculation effect