36 On Respiratory Impairment in Cancer Cells* 

 By Sidney Weinhouse 



Some years ago Otto Warburg 1 enunciated a theory of Cancer which, briefly 

 summarized proposed that Cancer originäres when a nonneoplastic cell adopts an 

 anaerobic metabolism as a means of survival after injury to its respiratory System. 

 According to Warburg, the tumor is initiated by a damaged respiration, which 

 persists as a characteristic feature of the neoplastic condition. In a recent paper, 

 entitled "On the origin of Cancer cells," originally published in German 2 and then 

 translated into English 3 , Warburg reiterates this hypothesis and claims further 

 support for it on the basis of experiments with ascites tumor cells. I recognize the 

 great debt that biochemists owe this illustrious investigator and regret the necessity 

 of taking issue with his basic biochemical premise, namely, that cancer cells have 

 an impaired respiration. 



In a comprehensive review of this subject in 1939, Burk 4 first pointed out the 

 essentially fallacious reasoning behind this hypothesis. More recently, Schmidt 5 

 and I 6 reviewed this topic independently in the light of modern findings and con- 

 cluded similarly that there is no sound experimental basis for the belief that oxi- 

 dative metabolism in tumors is impaired. It is recognized by all, including War- 

 burg, that despite their high glycolysis, oxygen consumption is not quantitavely 

 diminished; by and large, a representative group of tumors absorb oxygen about 

 as rapidly as a comparable group of nonneoplastic tissues (see, for example, Burk's 

 extensive tables 4 ). An early Statement by Warburg, illustrative of his views concer- 

 ning the relationship between the high aerobic and anaerobic glycolysis of tumor 

 cells and their oxygen consumption, is the following <i> pp- i»-"i). 



"We determined the Meyerhof quotient for Carcinoma tissue, lactic acid bac- 

 teria, embryonic tissue and a number of other glycolyzing tissues, and as a rule 

 obtained the same mean values as Meyerhof. As a rule 1 mol. of breathed oxygen^ 

 just as in muscle, causes the disappearance of 1— 2 mol. lactic acid. This result . . _ 



* Republished from Science 124 (1956): 267 by permission. 



Zusatz 1961. Die anaerobe Gärung der Asciteskrebszellen der Maus hat in 

 Serum den mittleren Wert Q.^ 2 = = 70, der Meyerhofquotient der embryonalen 

 Zellen in Serum hat einen Mittelwert von 1,5. Wären die Krebszellen embryonale 

 Zellen, so müßte die Atmung Qo, der Krebszellen den Wert 70/1,5 == 47 haben, 

 während wir im Mittel Qo, == 7 finden. Dies meinen wir, wenn wir sagen, daß die 

 Atmung der Krebszellen zu klein ist, obwohl wir wissen, daß z. B. Bindegewebe 

 eine so niedrige Atmung wie Qo, = 1 hat. Im übrigen ist unser Hauptergebnis, die 

 fakulatative Anaerobiose der Krebszellen im Körper, nicht durch eine ununter- 

 brochene „reiteration" erhalten worden, sondern durch eine ununterbrochene 

 Folge von neuen Methoden und neuen Experimenten. Wer ein auf diese Weise 

 errichtetes Gebäude angreift, riskiert, daß er die Wahrheit angreift, eine wenig 

 adaequate Tätigkeit für einen Wissenschaftler. 



