Topley, in the Goulstonian lectures, discusses this subject. He says: “The first difficulty with which we were faced in forming any theory of the spread of bacterial infection, which should conform to the known facts of epidemiology, was to find some explanation of the perpetuation of the virus during interepidemic periods. The bacteriologic data which have accumulated, especially during the last twenty years, have shown that the causative agents of specific diseases are to be found in apparently normal persons who give no history of having been in contact with the disease in question, as well as in contact with actual cases of the disease. Moreover, the organisms in question have been shown, in certain cases, to persist for long periods of time in or upon the tissues of their hosts, and we must always remember that the difficulty of bacteriologic technic is likely to lead to a serious under-estimate. Clinical and epidemiologic investigations have yielded confirmatory evidence, and we are thus left with a conception of the virus of a given disease being distributed fairly widely throughout the world as an apparently harmless parasite on the human host, but taking on during epidemic periods a new and sinister role, only to relapse again into comparative quiescence as the epidemic subsides.” He explains the rise of the epidemic wave as follows: “There are at least three possible explanations—an increase in the power of the parasite to produce disease, a decrease in the resistance of the host, and some attraction in the surrounding circumstances which favor the transference of parasites from case to case without any alteration of the pathogenicity of the one or in the resistance of the other. The third of these hypotheses may, I think, be disregarded. That alterations in environment may be the determining cause in initiating an outbreak of bacterial disease is probable enough; but they will almost certainly act through the variations which they bring about in the other two factors. The whole of bacteriologic knowledge is clearly against the occurrence of a considerable epidemic in which the pathogenicity of the parasite and the resistance of the host remain constant. Again, while we may well believe a lowered resistance of a certain number of the host-species to be an important factor in the initiation of the process, yet we cannot believe that it is the whole story. The widespread ravages of many epidemics would seem altogether to preclude such an explanation. We seem forced therefore to the conclusion that an increase in the pathogenicity of the specific parasite is an essential factor in the rise of epidemics, excluding from this category small sporadic outbreaks which may be due to the introduction of a fully virulent parasite by a healthy carrier in some other way.”