On the Origin of Cancer Cells 327 



that adenosine triphosphate can be synthesized in homogeneous Solutions with 

 crystallized fermentation enzymes, whereas so far no one has succeeded in syn- 

 thesizing adenosine triphosphate in homogeneous Solutions with dissolved respi- 

 ratory enzymes, and the structure always goes with oxidative phosphorylation. 



Moreover, it was known for a long time before the advent of crystallized fer- 

 mentation enzymes and oxidative phosphorylation that fermentation — the energy- 

 supplying reaction of the lower organisms — is morphologically inferior to respi- 

 ration. Not even yeast, which is one of the lowest forms of life, can maintain its 

 structure permanently by fermentation alone; it degenerates to bizarre forms. 

 However, as Pasteur showed, it is rejuvenated in a wonderful manner if it comes 

 in contact with oxygen for a short time. "I should not be surprised," Pasteur said 

 in 1876 10 in the description of these experiments, "if there should arise in the mind 

 of an attentive hearer a presentiment about the causes of those great mysteries of 

 life which we conceal under the words youth and age of cells." Today, after 80 

 years, the explanation is as follows : the firmer connection of respiration with struc- 

 ture and the looser connection of fermentation with structure. 



This, therefore, is the physicochemical explanation of the dedifferentiation of 

 Cancer cells. If the structure of yeast cannot be maintained by fermentation alone, 

 one need not wonder that highly differentiated body cells lose their differentiation 

 upon continuous replacement of their respiration with fermentation. 



I would like at this point to draw attention to a consequence of practical impor- 

 tance. When one irradiates a tissue that contains cancer cells as well as normal cells, 

 the respiration of the cancer cells, already too small, will decline further. If the 

 respiration falls below a certain minimum that the cells need unconditionally, 

 despite their increased fermentation, they die; whereas the normal cells, where 

 respitation may be harmed by the same amount, will survive because, with a greater 

 initial respiration, they will still possess a higher residual respiration after irradia- 

 tion. This explains the selective killing action of x-rays on cancer cells. But still 

 further : the descendants of the surviving normal cells may in the course of the 

 latent period compensate the respiration decrease by fermentation increase and, 

 thence, become cancer cells. Thus it happens that radiation which kills cancer cells 

 can also at the same time produce cancer or that urethane, which kills cancer cells, 

 can also at the same time produce cancer. Both events take place from harming res- 

 piration : the killing, by harming an already harmed respiration ; the carcinogenesis 

 by the harming of a not yet harmed respiration. 



Maintenance Energy 



When dedifferentiation of the body cells has occurred and cancer cells have thereby 

 developed, there appears a phenomenon to which our attention has been called by 

 the special living conditions of the ascites cancer cells. In extensively progressed 

 ascites cancer of the mouse, the abdominal cavity contains so many cancer cells 

 that the latter cannot utilize their füll capacity to respire and ferment because of 

 the lack of oxygen and sugar. Nevertheless, the cancer cells remain alive in the 

 abdominal cavity, as the result of transplantation proves. 



