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,
BCG vaccine to fall the closer one gets to the equator. A 1994 systematic review found that BCG reduces the risk of getting TB by about 50%. There are differences in effectiveness, depending on region, due to factors such as genetic differences in the populations, changes in environment, exposure to other bacterial infections, and conditions in the lab where the vaccine is grown, including genetic differences between the strains being cultured and the choice of growth medium. A systematic review and meta analysis conducted in 2014 demonstrated that the BCG vaccine reduced infections by 19–27% and reduced progression to active TB by