On the Origin of Cancer Cells 323 



hour, and fermentation of 60 cubic millimeters of lactic acid produced per milli- 

 gram, per hour. This, converted to energy equivalents, means that the Cancer cells 

 can obtain approximately the same amount of energy from fermentation as from 

 respiration, whereas the normal body cells obtain much more energy from res- 

 piration than from fermentation. For example, the liver and kidney of an adult 

 animal obtain about 100 times as much energy from respiration as from fermen- 

 tation. 



I shall not consider aerobic fermentation, which is a result of the interaction of 

 respiration and fermentation, because aerobic fermentation is too labile and too 

 dependent on external conditions. Of importance for the considerations that follow 

 are only the two stable independent metabolic processes, respiration and anaerobic 

 fermentation — respiration, which is measured by the oxygen consumption of cells 

 that are saturated with oxygen, and fermentation, which is measured by the forma- 

 tion of lactic acid in the absence of oxygen. 



Injuring of Respiration 



Since the respiration of all Cancer cells is damaged, our first question is, How can 

 the respiration of body cells be injured ? Of this damage to respiration, it can be 

 said at the outset that it must be irreversible, since the respiration of cancer cells 

 never returns to normal. Second, the injury to respiration must not be so great 

 that the cells are killed, for then no cancer cells could result. If respiration is dam- 

 aged when it forms too little adenosine triphosphate, it may be either that the oxygen 

 consumption has been decreased or that, with undiminished oxygen consumption, 

 the coupling between respiration and the formation of adenosine triphosphate has 

 been broken, as was first pointed out by Feodor Lynen 2 . 



One method for the destruction of the respiration of body cells is removal of 

 oxygen. If, for example, embryonal tissue is exposed to an oxygen deficiency for 

 some hours and then is placed in oxygen again, 50 percent or more of the respiration 

 is usually destroyed. The cause of this destruction of respiration is lack of energy. 

 As a matter of fact, the cells need their respiratory energy to preserve their struc- 

 ture, and if respiration is inhibited, both structure and respiration disappear. 



Another method for destroying respiration is to use respiratory poisons. From 

 the Standpoint of energy, this method comes to the same result as the first method. 

 No matter whether oxygen is withdrawn from the cell or whether the oxygen is 

 prevented from reacting by a poison, the result is the same in both cases — namely, 

 impairment of respiration from lack of energy. 



I may mention a few respiratory poisons. A strong, specific respiratory poison is 

 arsenious acid, which, as every clinician knows, may produce cancer. Hydrogen 

 sulfide and many of its derivatives are also strong, specific respiratory poisons. We 

 know today that certain hydrogen sulfide derivatives, thiourea and thioacetamide, 

 with which citrus fruit Juices have been preserved in recent times, induce cancer 

 of the liver and gall bladder in rats. 



Urethane is a nonspecific respiratory poison. It inhibits respiration as a chem- 

 ically indifferent narcotic, since it displaces metabolites from cell structures. In 



