36 b On Respiratory Impairment in Cancer Cells* 

 By Otto Warburg 



In 1950 George Klein of the Karolinska Institute, Stockholm, was kind enough 

 to send to Dahlem a strain of mouse ascites Cancer that consists of nearly 100 

 percent Cancer cells, that can be transplanted with 100 percent takes, and that is 

 resistant to the shaking necessary in manometry. 



Only since that time have we been able to determine quantitatively the metab- 

 olism of pure Cancer cells. All our previous experiments 1 had been carried out 

 with solid tumors — that is, with various mixtures of Cancer cells and normal cells. 

 The more Cancer cells a tumor contained, the higher was the fermentation and the 

 lower was the respiration. But no absolute values could be obtained. 



Thus, the year 1950 brought about the transition from the study of the metab- 

 olism of the mixed cells to the study of the metabolism of pure Cancer cells, a very 

 great progress in Cancer research-. Weinhouse 3 is not appreciative of this progress, 

 or of many important discoveries made since 1925 — for example, the nonfermen- 

 tation of the rapidly regenerating liver; the structural difference between energy 

 production by respiration and by fermentation; the genetic autonomy of the 

 respiring grana and the role of grana in the pathology of neoplasms ; and carcino- 

 genesis by respiratory poisons. Most of the comment by Weinhouse might have 

 been written before 1925. 



As expected, the fermentation of the pure Cancer cells was found to be much 

 higher than any previously observed fermentation of Cancer cell mixtures. Indeed, 

 mouse ascites Cancer cells produced anaerobically per hour nearly 30 percent of 

 their dry weight of lactic acid. In comparison with this enormous fermentation, 

 respiration of the pure Cancer cells was, as expected, very low. 



Even more important were the results obtained in 1956 with Earle's in vitro 

 cultures of pure mouse Cancer cells. Such cells were available as two strains of high 

 and low "malignancy," both derived from one and the same single cell. When, in 

 the laboratory of Dean Burk, the respiration and the fermentation of these two 

 strains of different malignancy but the same genetic origin were measured, the 

 result was as follows : the higher the malignancy, the greater the fermentation and 

 the smaller the respiration (2 pp - 313 - 314 ) . The absolute fermentation values for the 

 high-malignancy cells were as high as the values for the mouse ascites Cancer cells. 



These experiments with pure Cancer cells — the ascites cells and Earle's cells of 

 different malignancy — were decisive and conclusive. They correspond, in the 

 problem of relativity, to the observed red displacement in the gravitational field. 



Among normal cells, the nearest equivalent to pure Cancer cells is the chorion 

 in the first days of embryonic development. The chorion grows rapidly. It is histo- 

 logically almost pure. It is so thin that it is not necessary to slice it for measure- 

 ments of metabolism. It is so hardy that it can be shaken many hours in mano- 



Republished from Science 124 (1956): 269 by permission. 



