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What causes disease? It seems the most simple of questions one could ask about disease from a public health standpoint. Yet there is nothing simple about it. Consider, for example, what causes the “white plague” of tuberculosis. The typical answer is “mycobacterium tuberculosis,” and this is of course true in some sense. The mycobacterium is a necessary cause of the disease of tuberculosis. But is it also a sufficient cause of the disease? Does every carrier of the mycobacterium develop active tuberculosis? Indeed, does everyone exposed to the mycobacterium become infected?