Cowpox is an infectious disease caused by the cowpox virus. After inoculation, vaccination using the cowpox virus became the primary defense against smallpox. Immunity to cowpox is gained when the smallpox vaccine is administered. In 1798 Edward Jenner introduced inoculation with cowpox (smallpox vaccine), a much safer procedure. Four orthopoxviruses cause infection in humans&colon; variola, vaccinia, cowpox, and monkeypox. He noted that inoculation with live cowpox afforded protection against the more dangerous smallpox. Smallpox, cowpox, and other pox viruses belong to this family. Did the vaccine originate in smallpox, horsepox, or cowpox? Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. This work established vaccinia and cowpox as two separate viral species. It was during this time that Jenner revisited the connection between cowpox and smallpox. The classic example is Jenner's use of cowpox to protect against smallpox. Therefore, Jenner was not the first to try cowpox inoculation. At some point, the virus in use was no longer cowpox, but vaccinia. Jenner was the first to prove the effectiveness of vaccination with cowpox using scientific experimentation.