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 a 20% incidence of severe scarring), many parents felt that the benefits of inoculation outweighed the risks and so inoculated their children. Two forms of the disease of smallpox were recognised, now known to be due to two strains of the Variola virus. Those contracting "Variola minor" had a greatly reduced risk of death – 1–2% – compared to those contracting "Variola major" with 30% mortality. Infection via inhaled viral particles in droplets spread the infection more widely than the deliberate infection through a small skin wound. The smaller, localised infection is adequate to stimulate the immune system to produce