Abstract

These investigations were begun in the confessedly slender hope of finding a stimulus, injury, or irritation, which when applied to the mammary gland of the mouse would incite neoplastic proliferation and lead to the development of true tumors. They were undertaken in the belief that the basis offered by heredity for the origin of tumors needed to be supplemented by a stimulus originating independently of heredity, whether supplied by an injury of a mechanical or chemical nature, and with or without the intervention of commonly recognized parasites. They were suggested more directly by an observation1 concerning the latter, viz., that the common mites which infest more or less the skin surface of all adult mice were occasionally present subcutaneously, though dead and often disintegrated, in tumor mice and other old mice, while in young mice they were rare in this location. While other parasites such as lice or bedbugs are occasional and when present plainly evident to the naked eye, mites on the other hand are constant and inseparable commensals of all mice at or soon after the acquirement of a hairy coat, and require at least some magnification for their recognition. To such organisms one might naturally look first for any parasitic agent involved in the causation of tumors in mice. In the present connection, they were regarded only as possible secondary factors such as carriers of a less tangible primary agent, or as the instrument of injuries, however subtle, acting as a stimulus. An extensive and varied exploitation of these common parasites, however, furnished a body of negative data and led to the use of other forms of irritation and trauma, with results of some positive significance. In most of the experiments it was necessary to use mice of mixed or unknown ancestry, since those of the more suitable inbred strains of proper age were not yet available. These miscellaneous mice contained irregularly distributed tumor strains; the controls, which therefore presented some difficulties, are discussed under the few experiments which gave results raising the question of control. Considerable detail has been omitted from the descriptions of experiments resulting negatively or equivocally. Only epithelial mammary tumors, developing after experimental procedure not involving transplantation, or arising spontaneously in the controls, are dealt with; no transplanted tumors were used. Most of the tumors were diagnosed microscopically, and in the exceptions a satisfactory gross examination left little room for error. All the mice used were females, normal unless otherwise stated. The statement of the duration of experiments has usually been condensed into an “average survival,” in days or months, which is obtained by adding together the number of days each mouse survived and dividing the result by the number of mice in the experiment at the beginning.

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