4q6 MOLECULAR MECHANISMS OF DIFFERENTIATION 5 



is not an end in itself and has no more significance for the understanding of differ- 

 entiation than a descriptive account of the change of any other morphological or 

 physiological property. Ultimately, explanatory value can be attributed to these 

 chemical measurements only insofar as they contribute directly to the interpre- 

 tation of developmental phenomena, not in terms of temporal or spatial correla- 

 tions, but in terms of a chain of concrete molecular interactions which eventually 

 produces the classically described changes in form and function. This requirement 

 would seem to be met most directly by an attempt to define the changes in the 

 protein forming apparatus itself of the developing cell and its control by cellular 

 and extracellular chemical factors. That the analysis of embryonic development 

 is beginning to turn to this problem is borne out by the contents of the two volumes, 

 Butler, Ed. (1955) and Rudnick, Ed. (1954) of the Symposia of the Society of 

 Growth and in particular of the article by Ebert (1954b) contained in the latter. 



The merit of a presentation in which differentiation is regarded as a problem of 

 protein formation ultimately stands or falls with the understanding of the cellular 

 and molecular mechanisms of protein synthesis. Only a few years ago the problem 

 of protein synthesis seemed so untractable that it precluded such an interpretation. 

 This situation has changed rapidly. Recent explorations of some phases of protein 

 formation in the fully difTerentiated cell have advanced so significantly that it 

 would seem highly desirable to follow some of these leads in differentiating tissues'. 

 With only a little optimism one could actually ask whether an investigation of the 

 embryonic cell with its presumably diversified types of protein formation may 

 provide exceptionally favorable material for a comparative study of the problems 

 of protein synthesis. 



In discussing the data on differentiation as a problem of protein formation, the 

 available material was organized in the following way. To a large extent the 

 properties of the protein forming system (PFS) have been inferred from measure- 

 ments not pertaining directly to the constituents of the PFS. One of the first, and 

 still widely used, methods of obtaining information about the activity of the PFS 

 consists of measuring the utilization of protein precursors. Therefore, we will be 

 concerned first with a summary of recent data on utilization of amino acids and 

 other protein precursors in embryos. As the next step in the elucidation of the 

 PFS, attempts to identify the actual molecular composition of this system will be 

 considered. A comparison of such work, carried out with differentiated and em- 

 bryonic cells, thus forms the second section of this chapter. 



The relationship of embryonic diflferentiation to protein biosynthesis is dealt 

 with in a discussion of the control of the PFS. These problems will be considered 

 in section iii. 



1 The rapid progress in this field is documented in the sections on "Amino Acid Activation 

 and Protein Synthesis" and "Protein Synthesis: Microsomes, RNA, and Templates" in 

 Federation Proc, 17, 1958, and in several Symposia (in particular, the Symposium and 

 numerous papers presented at the Fourth International Congress of Biochemistry of Morphogenesis, 

 Vol. 6, 1959). Pertinent also in the present context is the Symposium on ''Chemical Basis of 

 Development'', (W. D. McElroy and H. B. Glass, Johns Hopkins Press, 1958), The 

 "Symposium on Amino Acid Activadon", Proc. Natl. Acad. Sci., U.S., 44 (1958) 667, and the 

 article, "Antigens and Antibodies as Cell Phenotypes", by Schultz (1959). 



