On the Origin of Cancer Cells 325 



If the principle Omne granum e grano is valid for the respiring grana, we under- 

 stand why the respiration connected with the grana remains damaged when it has 

 once been damaged; it is for the same reason that properties linked with genes 

 remain damaged when the genes have been damaged. 



Furthermore, the connection of respiration with the grana" also explains a car- 

 cinogenesis that I have not mentioned previously, the carcinogenesis by x-rays. 

 Rajewsky and Pauly have recently shown that the respiration linked with the grana 

 can be destroyed with strong doses of x-rays, while the small part of the respiration 

 that takes place in the fluid protoplasm can be inhibited very little by irradiation. 

 Carcinogenesis by x-rays is obviously nothing eise than a destruction of respiration 

 by elimination of the respiring grana. 



It should also be mentioned here that grana, as Graffi has shown 8 , fluoresce 

 brightly if carcinogenic hydrocarbons are brought into their surroundings, because 

 the grana accumulate the carcinogenic substances. Probably this accumulation is the 

 explanation for the fact that carcinogenic hydrocarbons, although almost insoluble 

 in water, can inhibit respiration and therefore have a carcinogenic effect. 



Increase of Fermentation 



When the respiration of body cells has been irreversibly damaged, Cancer cells by 

 no means immediately result. For Cancer formation there is necessary not only an 

 irreversible damaging of the respiration but also an increase in the fermentation — 

 indeed, such an increase of the fermentation that the failure of respiration is com- 

 pensated for energetically. But how does this increase of fermentation come about? 



The most important fact in this field is that there is no physical or chemical 

 agent with which the fermentation of cells in the body can be increased directly; 

 for increasing fermentation, a long time and many cell divisions are always neces- 

 sary. The temporal course of this increase of fermentation in carcinogenesis has 

 been measured in many interesting works, among which I should like to make 

 special mention of those of Dean Burk 9 . 



Burk first cut out part of the liver of healthy rats and investigated the meta- 

 bolism of the liver cells in the course of the ensuing regeneration, in which, as is 

 well known, the liver grows more rapidly than a rapidly growing tumor. No increase 

 of fermentation was found. Burk then fed rats for 200 days on butter yellow, 

 whereupon liver carcinomas were produced, and he found that the fermentation 

 slowly increased in the course of 200 days toward values characteristic of tumors. 



The mysterious latency period of the production of Cancer is, therefore, noth- 

 ing more than the time in which the fermentation increases after a damaging of the 

 respiration. This time differs in various animals ; it is especially long in man and 

 here often amounts to several decades, as can be determined in the cases in which 

 the time of the respiratory damage is known — for example, in arsenic Cancer and 

 irradiation Cancer. 



The driving force of the increase of fermentation, however, is the energy de- 

 ficiency under which the cells operate after destruction of their respiration, which 

 forces the cells to replace the irretrievably lost respiration energy in some way. They 



