Gye and Kettle (1922), from a study of the effects of subcutaneous inoculation of silica alone, tubercle bacilli alone and tubercle bacilli with silica, arrived at the conclusion that there is, after the introduction of tubercle bacilli with silica, “a much greater local reaction than with an infection of tubercle bacilli alone and, further, that general dissemination is earlier and more active.” As a result, “a small dose of bacilli becomes a dose of considerable magnitude and, inasmuch as an important factor in determining an infectious process is the number of organisms introduced, a simple explanation is forthcoming of the effect of silica upon such tuberculous lesions as we have described.”