As early as 1780 Jenner learned that the eruptions of the teats of infected cows differed. All were called cowpox and all could be communicated to the hands of the milkers, but only one kind created a resistance to smallpox. He called this type "tru cowpox". Jenner subsequently found that even true cowpox conferred immunity against smallpox only when matter was taken from the cowpox pustules before they were too old (as had been the case with Sutton's smallpox fluid). At that period of time, smallpox was at a low ebb in the Vale of Berkeley and it was some time before he could put his theory to the test.

In 1791 one Mary Barge, who had had cowpox many years previously, was inoculated with smallpox. A pale red inflammation appeared at the inoculation site and spread extensively, but it disappeared within a few days. Jenner noted how remarkable it was that the smallpox virus should produce such inflammation more rapidly than it could produce smallpox itself. He also observed that although cowpox gave immunity to smallpox, it did not confer similar immunity to the cowpox itself.

Breakthrough
The story of the great breakthrough is well known. In May 1796 a farm in Jenner's district was struck with cowpox, and Jenner met a young maid, Sarah Nelmes, who had fresh scars of cowpox on her finger. Sarah was described as a Berkeley milk maid but in fact was from an old highly respected local family, and certainly no peasant.

On May 14, 1796 Jenner obtained consent for a risky experiment from the parents of James Phipps, an eight year old boy with no known history of either cowpox or smallpox. Removing pus from Sarah, Jenner deposited it over scratches he had made on the boy's arms. The boy developed cowpox symptoms a week later, then recovered shortly afterward.

On July 1, 1796, Jenner performed a more daring experiment. He inoculated Phipps, this time with pus from a smallpox patient. James did not develop smallpox, even after repeated inoculations. The protection was complete.

Some of Jenner's medical colleagues awaited the results with excitement while others condemned him for the risk he was taking. James Phipps, however, lived to a ripe old age. Sir Walter Farquhar said to Jenner that if he chose to preseve it a secret he might make one hundred thousand pounds by it, but Jenner was determined to give it to the world, and he was as good as his word.

As early as 1881, Louis Pasteur honored Jenner by christening the process "vaccination", for the vaccinia virus of cowpox.

naturally occurring天花在全世界消灭，但是 in the aftermath of the events of September and October, 2001, there is heightened concern that the variola virus might be used as an agent of bioterrorism. For this reason, the U.S. government is taking precautions for dealing with a smallpox outbreak.