32 Introduction 



the metabolic rates of these two lines. In the highly virulent line they found 

 extensive fermentation and limited respiration ; in the line of low virulence, limited 

 fermentation and extensive respiration. Anyone who, until then, may have doubted 

 the significance of the fermentation of tumors, could no longer do so (36). 



3. Cells according to Dulbecco-Vogt 



The fastest technique to prepare large amounts of single cells from body cells 

 that are capable of growth is the method of Dulbecco-Vogt, in which a Suspension 

 of animal tissues is made by addition of a dilute Solution of trypsin. 



We have measured the metabolism of such cell suspensions immediately after 

 preparation and after in vitro growth and have found that the purely aerobic meta- 

 bolism of rabbit kidney cells and of chick embryonic cells changes during growth in 

 vitro into the fermentation metabolism of Cancer cells. In the case of embryonic 

 cells this conversion proceeds with special rapidity. Within one to two cell divi- 

 sions their metabolism changes to the fully developed metabolism of Cancer cells, 

 characterized by extensive anaerobic fermentation, limited respiration, and, conse- 

 quently, extensive aerobic fermentation. 



Since a large part of the inoculum in the Petri dishes grows in the in vitro culture 

 and since the metabolism changed after only a few cell divisions, the theory of 

 carcinogenesis by selection (in which all of us believed for many years) must be 

 definitely and totally abandoned. We interpret this readiness for anaerobiosis by 

 the long anaerobic history of living matter, a history which evidently the genes 

 have not yet forgotten (59, 61, 63, 67, 71, 76).* 



The anaerobic past of living matter may also explain the anaerobic fermentation 

 of embryonic cells. This fermentation was discovered soon after that of the Cancer 

 cells but has no physiological significance, because the extensive respiration of 

 embryonic cells always eliminates any anaerobic fermentation by them in the body. 



The most striking property of this "latent" fermentation is that it is especially 

 strong in early development but then decreases rapidly, for example, to one-fourth 

 of its initial value within a few days. This is the behavior of properties that were 

 necessary in phylogenesis but that later became superfluous. 



X. Effect of X-rays on Cancer cells 



If Cancer cells and embryonic cells are irradiated with x-rays under otherwise equal 

 conditions, and if the decrease in metabolism caused by the rays is measured, the 

 reduction in the metabolism of Cancer cells is found to be greater than in the case 



* 1961 Addition. In the meantime, we have discovered that the metabolism 

 characteristic of Cancer is produced in vitro by a substance present in added calf 

 serum ; this substance can be removed from the calf serum by addition of alumi- 

 num hydroxide. Indeed, embryonic cells may now be grown in vitro, with or 

 without fermentation, depending on whether the serum is treated with aluminum 

 hydroxide or not. 



