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 to Voltaire (1742), the Turks derived their use of inoculation to neighbouring Circassia. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". The Turkish practice was presented to the Royal Society in 1714 and 1716, when the physicians Emanuel Timoni and Giacomo Pylarini independently sent letters from Constantinople. Variolation is documented in India from the eighteenth century, thanks to the 1767 account by J. Z. Holwell. Holwell's extensive 1767 description included the following, that points to the connection between disease and "multitudes of imperceptible animalculae