330 On the Origin of Cancer Cells 



The chemical reactions by which ATP is synthesized in respiration are still un- 

 known, but it can be assumed, according to the existing measurements 21 , that 7 

 moles of ATP can be formed when 1 mole of oxygen is consumed in respiration. 



ATP quotients. If we multiply Oo 2 by 7 and Qm N2 by 1, we obtain the number of 

 cubic millimeters of ATP that 1 milligram of tissue (dry substance) can synthesize 

 per hour (22,400 cubic millimeters = 1 millimole of ATP). We call these quotients 

 <2atp° 2 and <2atp N2 3 according to whether the ATP is formed by respiration or by 

 fermentation, respectively. 



Energy production of Cancer cells and of normal body cells. In Table 1, the Q values 

 of some normal body cells are contrasted with the Q values of our ascites Cancer 

 cells. 



The cancer cells have about as much energy available as the normal body cells, 

 but the ratio of the fermentation energy to the respiration energy is much greater 

 in the cancer cells than it is in the normal cells. 



Uncoupling of respiration. If a young rat embryo is transferred from the amniotic 

 sac to Ringer's Solution, the previously transparent embryo becomes opaque and 

 soon appears coagulated 17 . At the same time, the connection between respiration 

 and phosphorylation is broken; that is, although oxygen is still consumed and 

 carbon dioxide is still developed, the energy of this combustion process is lost for 

 life. If the metabolism quotients had previously been 



Qo 2 = -15 5 Q M °2 = 0,Q M N 2= 25, 

 Qatp°2= 105,Q ATP N 2 = 25 



in the amniotic fluid, afterward, in Ringer's Solution, they are 



Qoo = - 15,<2m°2 = 25,Q M N 2 = 25, 

 Qatp°2 = 0,Qatp n 2 = 25 



Because of uncoupling of respiration and phosphorylation, the energy produc- 

 tion of the embryo has fallen from <2atp° 2 + Qatp N2 = 130, to 25; since the un- 

 coupling is irreversible, the embryo dies in the Ringer's Solution. 



This example will show that the first phase of carcinogenesis, the irreversible 

 damaging of respiration, need not be an actual decrease in the respiration quotient 

 but merely an uncoupling of respiration, with undiminished over-all oxygen con- 

 sumption. Ascites cancer cells, which owe their origin primarily to an uncoupling 

 of respiration, could conceivably have the following metabolism quotients for 

 example: Qo2= 50,Q M °2 = ioo,Q M N 2 = ioo, 



Qatp°2 = 0,Qatp n 2 = 100 



which would mean that, despite great respiration, the usable energy production 

 would be displaced completely toward the side of fermentation. One will now have 

 to search for such cancer cells among the ascites cancer cells. Solid tumors — and 

 especially solid spontaneous tumors — need no longer be subjected to such exami- 

 nations today, of course, since the solid tumors are usually so impure histologically. 



Aerobic fermentation. Aerobic fermentation is a property of all growing cancer cells, 

 but aerobic fermentation without growth is property of damaged body cells — for 



