I GROWTH AND DEVELOPMENT 713 



chemical differentiation, or indeed, maintenance of the developing organism. A brief 

 general outline of developmental processes is set down for purposes of orientation. 



Development is an integrated complex of activities which are paradoxically meaningful 

 and ill-defined: growth, differentiation and maintenance. Although each term resists 

 precise definition, the superficial meaning of each is clear. Growth ordinarily refers to 

 increase in mass of the organism or of some constituent selected for immediate considera- 

 tion. Differentiation implies progressive embryonic modification, usually in a manner 

 directed toward acquisition of adult form and function. Maintenance is the sum of basic 

 metabolic activities at any instant, construed in such a way that growth and differentiation 

 are excluded. 



The last requirement, exclusion of growth and differentiation from purely maintenance 

 activities, imposes the burden of impossibility on the problem of dissociation of the three 

 fundamental developmental processes, at least at the present time. Schoenheimer (1942), 

 whose work with isotopes of normal body constituents contributed so fruitfully to an 

 understanding of metabolic processes, pointed out: "In general, every regeneration 

 reaction involving an increase in free energy must be coupled with another process." More 

 recent investigations of cellular physiology support and amplify the thesis of related 

 chemical events within the cell. Great strides have been made in the understanding of 

 cytochemistry, cyclic reactions, alternate metabolic pathways, relation of metabolic 

 phenomena to the fine structure of the cell and many other aspects of protoplasmic 

 behavior. Yet this continues to be one of the most active areas of inquiry in the field of 

 biology. The volume and urgency of research in intracellular chemistry and physiology 

 plainly describes the inadequacy of our understanding of the full meaning of maintenance 

 metabolism. Confronted, then, with an incomplete picture of maintenance in adult cells, 

 it would be patently premature to separate definitively the energy and mechanisms of 

 maintenance in embryonic cells from those of growth or differentiation. Dissociability 

 of the three phenomena requires distinction between mechanisms for provision of energy 

 for work designated as growth and for work labeled differentiation. Let us suppose that 

 synthesis of a protein initially, since it is new, is specified as a process of differentiation; 

 repetition of the process, resulting in increase in quantity of the same protein, would then 

 be considered growth. Allocation of energy to the one category or the other would be 

 delicate at best. Continued submolecular modifications, certainly energy-requiring pro- 

 cesses, would, however, be classified as maintenance. Attempts to discriminate between the 

 processes, as reviewed by Needham (1942), have met with only partial and questionable 

 success. When observations are interpreted as evidence for dissociation of growth from 

 differentiation (Spratt, 1948) or maintenance from growth and differentiation (Boell and 

 Poulson, 1939; Moog, 1944; Barth, 1946) the assumption is made that the defective embryo 

 is normal, i.e. that it carries on metabolic activities unprejudiced by induced deficiencies. 

 Such an assumption would appear to be unwarranted, in view of the subsequent fate of 

 the embryos. Boell (1955) marshals rather cogent arguments for caution in interpretation 

 of such experiments. 



Against the background embodied in the foregoing statement rests the decision 

 to refrain from parceling out the several facets of nitrogen metabolism, but rather 

 to apply them to the totality of development, except in those rare instances when 

 the developmental relevance of an observation can be pin-pointed. This aim 

 requires a working interpretation of growth and differentiation. 



Increase in organic mass results from multiplication of, or addition to, protoplasmic 

 components. Let us consider the second item first. Some of the increase may result from 

 the process of osmosis or diffusion through the limiting membrane of the cell ; whether 

 the accumulated substance be water or other diffusible molecule or ion, the cell membrane 

 is selective. Selection and concentration, hence restriction as well, signifies work, and 

 performance of work requires an energy source. Though the selective permeability of the 



Literature p. 744 



