142 PAUL WEISS 



ments, and (b) in each other's places. This can be done by the techniques 

 of explantation (tissue culture) and of transplantation, respectively. 

 The answer has been unequivocal. 



Cells taken from different tissues of late embryonic or mature organ- 

 isms and transferred into standard extraneous media offering nutrition, 

 protection, and support lose many of their specialized aspects, i.e. criteria 

 by which we used to tell their "differentiation." Spectacular as their dif- 

 ferences may have been during residence in the body, they soon come to 

 look and behave much more alike, in adaptation to the common environ- 

 ment. In the early days of tissue culture this simplification of appearance 

 was actually often interpreted as a sign of "dedifferentiation," in the 

 sense of a return not only to a more primitive but to a veritably pri- 

 mordial state. This was again judgment by appearances with all its 

 pitfalls. Yet later work showed clearly that the explanted cells, in spite 

 of their similar disguise, retain distinguishing features of fundamental 

 nature which they pass on unaltered to their descendant cells for in- 

 definite numbers of generations. As a glance at Plate I will illustrate, 

 Schwann cells and endoneurial connective tissue cells, while assuming 

 both the aspect of common "mesenchym," i.e. spindle shape and amoe- 

 boid activity, can be well distinguished by their sizes, nuclear charac- 

 teristics, staining properties, affiliations, and other criteria revealed only 

 by subtler analysis. 



In other words, the parallel modifications which the cell strains under- 

 go on transfer to tissue culture are merely modulations carried out by 

 variously "differentiated" cells that otherwise preserve their basic dis- 

 tinctions. Their distinctiveness persists even during such further modu- 

 lations in culture as the transformation to the macrophage stage. This 

 transformation has thus far been observed in cultures of various con- 

 nective tissues (25), Schwann cells (see above), and muscle (7). They 

 all can give rise under similar conditions to a highly phagocytic amoeboid 

 cell with hydrated nucleus, dense entoplasm, and a more hyaline ruffled 

 border, i.e. macrophage-like characters. But in doing so they also retain 

 the signs of their descendancy, so that a "macrophage" resulting from 

 the conversion of an endoneurial cell can usually be clearly distinguished 

 from one that has come from a Schwann cell. 



Tissue culture thus does not really abolish character differences 

 established during ontogeny. This conclusion is fully borne out by the 

 critical literature on the subject (4, 40). It is strikingly confirmed by 

 experiments in which cells that had lost their more specialized aspects 

 during intensive proliferation in tissue culture were again given oppor- 



