714 NITROGEN METABOLISM AND GROWTH 9 



cell membrane is a well known phenomenon whose analysis has resulted in a new concept 

 of membrane physiology, namely active transport [cf. Symposium of Society for Experi- 

 mental Biol., No. VIII, Active Transport and Secretion 1954) the problem with respect 

 to embryonic development is more complex. Flexner and Flexner (1948, 1949) have shown 

 that the apparent capacities of membranes of liver cells and of brain cells in the guinea 

 pig change sharply at 42 days gestation age. The change may be due to structural modi- 

 fication of the membrane, though this is unlikely since their criteria include Cr concen- 

 tration and Na"^ concentration; it would appear that more probably the alteration of 

 membrane selectivity is the result of acquisition of new mechanisms within the cells for 

 altering concentration of the measured substances and energy necessary for doing it. 

 Concentration of metabolites within the confines of a cell may be interpreted not only as evi- 

 dence for modified membrane activity but also as the antecedent of further developmental 

 phenomena, such as diflferential increase in enzyme activity. Adaptive enzyme formation is 

 well established in microorganisms, though controversial in details (Spiegelman, 1948) ; but 

 Gordon and Roder (1953) have supplied evidence for a similar phenomenon in develop- 

 ment of the chick. They speculate that "it is not inconceivable that the known variations 

 in the substrates on metabolites of the embryo, both qualitative and quantitative, are 

 fundamental to and the cause of the variations in enzyme activity." Their viewpoint is 

 supported by Jones, Featherstone and Bonting (1956) who demonstrated in vitro a 

 stabilizing effect of added acetylcholine upon cholinesterase. It would hardly seem to be 

 coincidence that, concomitant with acquisition of greater selectivity by liver and brain 

 cells (Flexner and Flexner, 1948, 1949) is the appearance of new functional activities of 

 these organs. It is too soon to generalize the applicability of the premise, but such "selec- 

 tive" growth should be given consideration as a means of promoting new activities in 

 embryonic cells. 



In addition to this aspect of cellular growth and its possible consequences, 

 increase in organic mass requires the synthesis of complex molecules. Of special 

 interest is the synthesis of structural proteins and enzymes. These problems will 

 be considered in some detail below. 



In passing, we must make note of the fact, however, that in metazoan animals 

 the variety of processes of cellular growth is increased by cell division. Cell 

 division is a mechanism for growth in metazoan animals (perhaps the result of 

 growth in unicelhilar animals). Two exceptions will be noted. The earliest 

 divisions of the egg, encompassing the period of cleavage, do not ordinarily restilt 

 in a significant increase in total mass; cell division, in addition to providing for 

 increase in mass in later development, provides also the basis for structural and 

 functional diversity. Duplication of all parts of a cell, then, in later development 

 is not always precise; or alternatively, if precise, requires during the intermitotic 

 period of a cell alteration of its substance, and hence that of its progeny. The 

 mechanisms responsible for perpetuation of identical protoplasmic components 

 are those of growth ; the mechanisms responsible for diversification are those of 

 differentiation. 



Differentiation asserts itself at the molecular and cellular level, but the con- 

 sequences are more elaborate. The peculiar aptitudes conferred upon cells by 

 their intrinsic qualities manifest themselves in a variety of ways (Weiss, 1953a): 

 migration, response to influence of their neighbors, secretory abilities, capacity 

 to multiply and in the many specialized functions recognizable in adult tissues. 



In summary, development consists of the epigenetic elaboration of the potential 

 of the egg through mitosis, accretion, synthesis, differentiation, differential growth 

 and migration of cells or cell aggregates. We shall be primarily concerned with 



