On the Nature of Cancer 121 



is not expensive in energy. Early respiration only adds to the store 

 of high-energy intermediates which are reserved for the endcrgonic 

 syntheses of growth and differentiation. 



Although the dividing embryo has a high respiration rate, the egg 

 can divide just as well under anaerobic conditions. 3 Some high-energy 

 phosphate bonds are split during anaerobiosis indicating that at least 

 a little energy might be required for cleavage, but glycolysis alone 

 is sufficient to meet this moderate demand. No growth or synthesis 

 takes place during the time when glycolysis alone can supply all of 

 the energy needed.* 



The cancer cell, on the other hand, has an inordinate growth obliga- 

 tion w T hich the early dividing embryo does not have. Even so, it lacks 

 not only the reserve of substances which appear to be indispensable 

 for growth and differentiation but also the capacity to make them. 

 The vaunted capacity of cancer cells for anaerobic glycolysis is indeed 

 a drastically insufficient compensation for the inadequacy of their 

 oxidative energy generation mechanisms. So sluggish is the cancer 

 cell aerobically that its only alternative in the face of the excessive 

 demands is to parasitize the host for the necessary energy cycle inter- 

 mediates, and in this way impair the host further, by reduction of the 

 liver catalase, 4 or by damaging the heart, 5 for example. This inertia 

 of the cancer cell was demonstrated in striking fashion by the experi- 

 ments of Busch and Baltrush, 6 in which it was found that tumors are 

 incapable of metabolizing either acetate or pyruvate. It has been 

 shown also that the rate of growth of tumor implants is rigorously 

 limited by vascular supply, 7 a fact which also suggests that cancer 

 growth rates depend on parasitic diversion of oxidatively generated 

 factors. It has been observed clinically also that the most rapidly 

 growing tumors are those in blood-rich areas. 



In tissue culture too it has been noticed that tumor cells will grow 

 only in the vicinity of the surface, whereas normal cells will often 

 grow throughout the medium, a fact which also can be interpreted 

 to mean that innate glycolysis alone, however large, is insufficient for 

 growth, and that the growing tumor cell must use oxygen. The usual 

 tissue-culture practice involves a discontinuous process which results 

 in alternately feasting and starving the cultures, these rigors being 

 only meagerly compensated for by the frequency of transfer to fresh 

 media. The cells in the center of a hanging-drop culture, for example, 

 sooner or later begin to suffer from oxygen deprivation and intoxication 



* High rates of glycolysis are a feature of growing tissues irrespective of malig- 

 nancy, hut no growing tissue can survive long under anaerobic conditions. 



