THE NATURE OF TUMORS 335 



change normal into cancerous tissues. Lastly, certain metazoan parasites, such 

 as Bilharzia (Schistosoma), acting on the urinary bladder, the nematode 

 Spiroptera neoplastica, affecting the fore-stomach of rats and mice, and 

 Taenia crassicollis, causing sarcoma in the liver of rats, may function as 

 cancer-producing agents. 



All these stimulating factors have in common that they initiate and main- 

 tain long-continued growth processes. But hormones are the only natural 

 physiological agents known so far, which in this way induce cancerous proc- 

 esses through their normal function. All others are abnormal agents. Struc- 

 turally estrogenic substances may or may not be related to the carcinogenic 

 polycyclic hydrocarbons. Under the influence of these stimulating factors 

 the growth processes, in the tissues on which they act, become step-by-step 

 more intense, until they end in irreversible cancerous proliferations. Some- 

 where during this preparatory process a state of sensitization of the tissue 

 is reached, so that from this point on, without as yet being cancerous, the 

 tissue will continue in its progression to cancer as a result of normal meta- 

 bolic or mechanical factors and without the further aid of the specific cancer- 

 producing agent. While the various stimuli wdiich initiate these growth proc- 

 esses are important in the analysis of cancerous changes, the growth proc- 

 esses which they all set in motion are probably the most characteristic and 

 the most important factor in the origin of cancer. It has been tentatively 

 suggested by us that during this preparatory growth period, an autokatalytic 

 growth substance is produced or increased in amount step by step and that 

 this effects in the end the irreversible cancerous state. 



(2) Hereditary genetic factors may co-operate with the stimulating fac- 

 tors in inducing cancer. In general, the genetic factors, as far as they relate 

 to the development of cancer, are limited to a specific organ or tissue and 

 the mechanism of the hereditary transmission of cancer in a certain organ 

 may differ from that in another organ. Different tumors are, therefore, in- 

 dependent of one another as far as their genetic determination is concerned. 

 These hereditary factors may be of diverse kinds ; they may consist in in- 

 herited malformations of tissues or in certain diseases which cause abnormal 

 stimulation of tissues in localized areas. In the case of mammary gland 

 carcinoma of the mouse, which is a very common type of cancer in that 

 species, it has been found that, in the main, differences in the hereditary 

 tendency to mammary carcinoma in various strains corresponds to the graded 

 ability of the mammary gland tissue to respond with growth processes to 

 the action of ovarian hormones. These differences in the responsiveness to 

 growth stimuli is the essential factor underlying the hereditary tendency to 

 the development of mammary gland carcinoma, and the same factor is pre- 

 sumably active also in other types of cancer. In addition, a virus-like sub- 

 stance, transmitted to the nursing child with the milk of the mother, but 

 present also in certain organs and in the blood, participate in the production 

 of mammary gland carcinoma. The frequency of mammary gland carcinoma 

 in some strains may be zero and in others 100 per cent; normally it affects, 

 almost exclusively, females, because the hormone, estrogen, which in this 



