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Smallpox is a virus causing a very contagious and highly deadly disease in humans. Estimates are that it was 20-60% fatal, and many survivors were left blind. Scars from smallpox were nearly universal. As recently as the early 20th century, two million people a year died from smallpox. Inoculation by rubbing fluid from smallpox sores into a scratch on an uninfected person reduced the severity of the disease.
Smallpox victim (Image in the public domain, from CDC)

After first contacts with Europeans, the death of a large part of the native population of the new world was caused by European-transmitted diseases. Smallpox was the chief culprit. On at least one occasion, germ warfare using smallpox infected blankets was used against Native Americans by the British army.

In 1796, Edward Jenner became the first scientist to develop a smallpox vaccine by using cowpox fluid. His theory was too radical for the scientific establishment and he had to pay to privately publish his findings. After independent confirmation, the practice of vaccination against smallpox spread quickly and national laws requiring vaccination began appearing as soon as 1805. The last case of wild smallpox occurred September 11 1977 and the disease is now thought to be extinct in the wild, though cultures are kept by the Centers for Disease Control and Russian authorities.