BCG vaccine bacilli that seemed less virulent, and changed the course of their research to see if repeated subculturing would produce a strain that was attenuated enough to be considered for use as a vaccine. The BCG strain was isolated after subculturing 239 times during 13 years from virulent strain on glycerine potato medium. The research continued throughout World War I until 1919, when the now avirulent bacilli were unable to cause tuberculosis disease in research animals. Calmette and Guerin transferred to the Paris Pasteur Institute in 1919. The BCG vaccine was first used in humans in 1921. Public acceptance was slow,
Inoculation specific immunity to the virus, while requiring more generations of the virus to reach levels of infection likely to kill the patient. The rising immunity terminates the infection. So the twofold effect is to ensure the less fatal form of the disease is the one caught, and to give the immune system the best start possible in combating it. Inoculation in the East was historically performed by blowing smallpox crusts into the nostril. In Britain, Europe and the American Colonies the preferred method was rubbing material from a smallpox pustule from a selected mild case ("Variola minor") into a scratch