organisms might be responsible for the cancerous cell proliferation. We must of course remember that our present knowledge of the factors underlying cancer was only gradually acquired; furthermore that certain experiences concerning animal cancer which we shall discuss later, suggested microorganisms as the direct stimulating agencies while the other factors which we analyzed so far would represent merely indirect causes, making the infection with microorganisms more easy. We know indeed that to a certain extent microorganisms can call forth cell proliferation. Thus the tubercle bacillus may cause a limited growth of connective tissue and as especially Borrel has pointed out the organisms causing smallpox and vaccinia may even produce a slight proliferation of the infected epithelium. But in all those cases the proliferation soon ceases and toxic substances produced by bacteria lead usually soon to the death of a great part of the newly-formed cells.
Based on such considerations many attempts have been made to prove the constant presence of certain parasitic microorganisms in human cancer. Under the microscope it is possible to recognize in cancer cells certain inclusions which are usually absent in normal tissues and a number of investigators claimed such included bodies definitely as protozoa (among others, Thoma, Sjoebring, Leyden, Gaylordand Eisen). Even the life cycle of these protozoa was apparently determined by some of these authors. It could, however, be shown that similar cell inclusions may originate otherwise and did in all probability therefore not represent protozoa. Also bacteria (Doyon), mucor (Schmidt), chytridiaceæ (Behla) and other microorganisms were held responsible. Others (Sanfelice, Leopold) believed yeast-like organisms to be frequently demonstrable in human cancer; they cultivated some yeasts in culture media and by injecting the organisms into animals believed to have reproduced the disease. Careful studies by many investigators, however, could not confirm these interpretations. In the case of yeasts it has for instance been shown that although they occasionally occur in cancers, they are on the whole rare and do not reproduce the disease if injected into animals (Busse, Nichols, Loeb, Moore and Fleisher). They act in the body in a similar manner as inert foreign bodies, and we found a yeast which we isolated from a sarcoma to lead, after intravenous injections, to the death of the animal through occlusion of the kidney tubules, without ever producing cancer.
These persistent claims of the discovery of a microorganism as the cause of cancer which could in no case be substantiated led in the case of many pathologists, especially of those mainly interested in the careful study of the structure of pathological tissues, to a reaction which induced them to deny the possible importance of microorganisms in the causation of cancer; they were inclined to hold on the whole the factors already established as sufficient to explain the origin of cancer. On the
