THE LIFE CYCLE 51 



parts may affect the course of metabolism in other parts, and 

 differences in the rate of growth of different parts may produce 

 mechanical effects. Since the action of external factors is variable, 

 both in time and in space, it is impossible for a cell or cell-mass to 

 exist for any considerable length of time under natural conditions 

 without local differences of some sort, temporary or permanent, 

 quantitative or qualitative, appearing in it in consequence of the 

 differential action of external factors. 



Differentiation of some degree and kind is then a necessary and 

 inevitable result of continued existence except where the progressive 

 changes are balanced or compensated in some way, and we must 

 distinguish self-determining, correlative, and external factors in 

 the process. In general, as I have pointed out above, the gradual 

 accumulation and increase in physiological stability of the proto- 

 plasm, either through change in chemical constitution or aggregate 

 condition or both, is self-determined and results from the nature 

 of metabolism and the constitution of protoplasm, while the correl- 

 ative and external factors play a part in determining the character 

 of the structural substratum thus produced. 



The process of differentiation once initiated, each step becomes a 

 factor bringing about further changes. For example, the character 

 of the substances accumulated in a cell seems to depend to a greater 

 or less extent upon the conditions in the cell which affect metabolic 

 rate, such as aggregate condition of protoplasm, enzyme activity, 

 etc. In embryonic, undifferentiated cells, where the internal 

 conditions permit a high metabolic rate, only those substances 

 which form the general metabolic substratum, i.e., protoplasm, 

 remain as constituents of the cell, but as the self-determined meta- 

 bolic rate decreases, other substances begin to appear and remain 

 in the cell. Undifferentiated protoplasm is protoplasm reduced 

 morphologically to its lowest terms. Apparently the metabolic 

 rate in the cell, or the internal conditions on which the metabolic 

 rate depends, are factors in determining the physiological stability of 

 substances. Substances which are either not formed or are broken 

 down and eliminated after formation in cells with a high metabolic 

 rate appear as more or less permanent structural components 

 in cells with a lower rate. As the self-determined metabolic 



