336 On Respiratory Impairment in Cancer Cells 



proves that the influence of the respiration on the cleavage metabolism in the car- 

 cinoma-cell is normal . . . Although in the tumor every oxygen molecule breathed 

 is just as effective as in muscle — the Meyerhof quotient is equal in the two cases — 

 yet the respiration does not cause the glycolysis to disappear. The respiration of the 

 Carcinoma tissue is too small in comparison with its glycolytic power." 



Thus, according to Warburg, the Meyerhof quotient (a quantitative expression 

 of the Pasteur effect) is normal in Carcinoma, and oxygen consumption is also not 

 quantitatively diminished; but respiration is disturbed, because glycolysis persists 

 in oxygen. As I pointed out earlier (6 > p- 276 >, I believe it would be more accurate 

 to State that anaerobic glycolysis is so high in tumors that a normal respiration and a 

 normal Pasteur effect are incapable of eliminating it. 



Although Warburg still states categorically that ". . . the respiration of all Can- 

 cer cells is damaged . . ." ( 3 > p- 309 ), he has given no clearer justification now for 

 this view than he did 26 years ago. In Table l 3 , he shows that whereas liver, kid- 

 ney, and embryo have <2o- 2 's of — 15, the ascites tumor has a Qo 2 of — 7. On these 

 grounds he concludes that the tumor cannot utilize sufficient oxygen for its needs 

 and thus requires fermentative energy. On the assumption that each mole of lactic 

 acid formed from glucose yields 1 mole of ATP, and each mole of oxygen con- 

 sumed gives rise to 7 moles of ATP, he calculates that the tumor obtains more than 

 half of its potential phosphate bond energy by glycolysis, whereas the three non- 

 cancer tissues obtain theirs mainly by respiration. Accepting these results at their face 

 value, it is still necessary to ask why some normal tissues manage to survive with- 

 out glycolysis with Qo-Ss of — 3 to — 6; also, why some tumors glycolyze highly 

 with QoSs as high as — 10 to — 20 (*■. pp- 438 — 441 >? It is also pertinent to ask why 

 certain nonneoplastic tissues, with moderate to high oxygen uptakes — for example, 

 brain, retina, kidney medulla, and intestinal mucosa — glycolyze as highly as many 

 tumors 7 ? It is evident that all tumors produce large amounts of lactic acid, but so do 

 many noncancer tissues ; and just as noncancer tissues display a wide diversity in 

 oxygen uptake, so do tumors. 



Although it is unintentional, I am sure, Table l 3 gives misleading impressions 

 that the respiratory and glycolytic activities are constant and characteristic for a 

 single tissue, and that all tissues produce essentially the same amounts of phosphate 

 bond energy. Actually, tissue even from a single organ will vary considerably in 

 Qo> from one animal to another. In our experience, rat liver slices display Qoz's 

 ranging from — 6 to — 12 (usually about — 7), and rat kidney cortex from — 15 to 

 — 25. Biochemists are confronted with a wide variety of tissues of the most diverse 

 respiratory behavior. Our present State of knowledge does not allow any cate- 

 gorical Statements about what represents a proper respiratory activity for main- 

 tenance of either a normal or a Cancer cell; nor can we State what is an optimal 

 enzyme activity for a particular cell function. 



Perhaps the most damaging evidence against the Warburg hypothesis has been 

 obtained in isotope tracer studies ( 6 > pp 303ff) # The results of such studies leave no 

 doubt of the ability of miscellaneous tumors to convert glucose (and fatty acids) 

 to carbon dioxide at rates similar in magnitude to that of nonneoplastic tissues 5 ' 6 . 

 It is difficult to imagine a type of respiratory disturbance not involving either a 



