152 PAUL WEISS 



specific attachment, and the rest remaining uninvolved. But to discuss 

 these and other quaHfications in detail, would exceed the scope of this 

 paper. 



Differentiation in Molecular Terms 



We return from this excursion into the molecular realm better 

 equipped to phrase questions about differentiation and growth in tangible 

 form. We can now ask, for instance, whether dift'erentiation really 

 signifies a change in the composition of the molecular population of the 

 cell or merely a change in the distribution of preexisting molecular 

 species. The latter view has been implicit in those embryological and 

 pathological theories which hold that the various cells of a given organ- 

 ism are all composed of essentially the same basic and immutable "proto- 

 plasm," and that their diverse appearances and performances are merely 

 the overt responses to a variety of external situations or "stimuli." A 

 given response display (called "differentiation") is thought to last only 

 as long as the given stimulus situation lasts. Change the latter and the 

 display will change accordingly ("dedifferentiate" and "redifferentiate") 

 in a new direction.^ Yet, when we view the facts from the molecular 

 level, there seems to be no doubt that cytodifferentiation does not leave 

 the chemical composition of "protoplasm" basically unaltered. 



The ubiquitous species of small and simple molecules going in and 

 out of cells remain about the same at all stages except for differences in 

 concentration. Some species of large and complex molecules, including 

 many of the proteins, are also present throughout development (5, 28). 

 All these comprise what we have called above the stock in common to 

 all cells. But in addition to these, differentiation brings with it, or virtu- 

 ally consists of, the continuous elaboration of molecular novelties which 

 have not been present from the beginning. Thus, a liver cell, a nerve cell, 

 a pigment cell, a mucus cell, a thyroid cell, etc., each produces its own 

 chemical specialties. Can this really be taken as evidence that the respec- 

 tive "protoplasms" are chemically different? Might it not be that all 

 mature cells have the synthetic faculty for the whole array of cell 

 products known to the body, and that a given cell is merely prevented 

 by local external conditions from materializing any but the appropriate 

 one ? This contention is contradicted by the experimental evidence quoted 

 above, showing that cells transferred into a different environment 



5 A certain partiality toward such a view can be detected, for example, in the earlier 

 writings of Child, and there have appeared several more modern, if less thoughtful, 

 versions of the same theme. 



