120 Essays in Biochemistry 



are all fundamentally identical, and that the eventual cure for one 

 is the cure for all. It is the immediate experiment which dictates 

 the choice of tumor or tissue. The many types of cancer enumerated, 

 as well as those occurring in humans where experimental access is not 

 as good, differ markedly in their transplantability, their anaplasticity, 

 and their capacity to grow rapidly. Rapid growth alone, however, is 

 neither a necessary nor a sufficient criterion for cancer; many cancers 

 grow very slowly. Many normal tissues, on the other hand, are rela- 

 tively hyperplastic or may become so under non-carcinogenic stimuli.'" 

 Embryonic development too consists of rapid cellular multiplication 

 in good part, at least in early phases. It may be instructive, therefore, 

 to compare the growth of a cancer with that of a frog embryo. The 

 latter is comprised of a closed system containing a reservoir of metabo- 

 lites sufficient for development to proceed to a fairly advanced stage 

 without external nutritional supply. Fertilization stimulates the egg 

 to rapid and orderly cleavage, differentiation, and growth, some phases 

 of which can be studied as discrete processes even though they are not 

 sharply separated in time. Early cleavage is signaled by an increase 

 in oxygen consumption which rises gradually throughout development. 

 The fertilized egg continues to divide without apparent morphological 

 differentiation through the blastula stage, the total mass remain- 

 ing constant, and segmentation producing progressively smaller cells. 

 Each new cell, however, has a nucleus and nuclear apparatus visibly 

 equivalent to the original single-cell nucleus. It might appear to the 

 microscopist that DNA is being made at a prodigious rate, but, in fact, 

 there is no synthesis of DNA at all in this early phase of development. 

 Nor is synthesis necessary, for it has been shown that the unfertilized 

 egg already contains an enormous amount of DNA, many times, indeed, 

 the amount of DNA which could be accommodated in one nucleus. 1 

 This is consistent with the fact that the total purines in the embryo 

 are quite constant in amount in the unfertilized egg, the neurula, 

 blastula, and early gastrula stages through which nuclei have been 

 replicated perhaps 40,000-fold. 2 Early cleavage in the frog embryo, 

 then, entails only the reorientation and redistribution of DNA which 

 was preformed in the ovary during maturation. The embryo does not 

 have to bear the burden of synthesis of DNA until comparatively late 

 in development, that is, until the late gastrula stage when differentia- 

 tion commences. Early cleavage, where no growth or synthesis occurs, 



* It is characteristic of carcinogens that the malignant change persists even 

 after the stimulus is removed. 



