14 GENERAL CONCEPTIONS. 



studied. The changes in the protoplasm are twofold: First, in the intimate struc- 

 ture of the protoplasm itself and in the size and disposition of its strands and fila- 

 ments; secondly, in the character of the various substances to be found imbedded 

 in the protoplasm. These two kinds of change are well illustrated, the first, by 

 the nerve-cells; the second, by the gland-cells, for instance, in the pancreas. The 

 student can easily see that the character of the protoplasm in the adult nerve-cell 

 differs profoundly from that of a cell from one of the embryonic germ-layers, hav- 

 ing become visibly much more complex. In the secretory cells of the pancreas the 

 zymogen granules are conspicuous; their distribution, uniform size, and refractile 

 qualities demonstrate, immediately their unlikeness to anything found in the embry- 

 onic cells. These granules are not protoplasm, but particles imbedded in the proto- 

 plasm or, as they may be called, enclosures. 



The Law of Genetic Restriction. Another fundamental idea, which it is most 

 important for the student to grasp, is that differentiation acts as a progressive 

 restriction upon the further development. Each successive stage of differentiation 

 puts a narrower limitation upon the possibility of further advance. 



The range of possible changes at any given time is determined not merely by 

 the nature or kind, but also by the stage or degree of the previous differentiation. 

 The law of genetic restriction governs the entire ontogeny. In order to illustrate 

 it and to emphasize it, it will be profitable to consider a few illustrations from each 

 of the germ-layers. First, then, the ectoderm. This layer early separates into two 

 parts, one to form the nervous system, the second the epidermis; the nervous part 

 thereafter never forms epidermal structures, the epidermal part never forms a medul- 

 lary canal. The central nervous system retains in part a simple epithelial charac- 

 ter (ependyma proper), but most of its walls become nervous tissue; its cells pass 

 from the indifferent stage and become neuroglia cells or young nerve-cells (neuro- 

 blasts). Neuroglia cells never become anything else, and the nerve-cells are always 

 nerve-cells to the end. Next, as to the entoderm. Wherever in it specialization 

 takes place, as in the tonsil, thymus, thyroid, oesophagus, liver, or pancreas, each 

 territory of cells keeps its characteristics and never assumes those of another terri- 

 tory. Finally, as to the mesoderm. It is found very early to include in vertebrate 

 embryos four kinds of cells, of which the most numerous are the undifferentiated 

 cells, the other three kinds being the endothelium -of blood-vessels, red blood-cells, 

 and germ-cells. All of these are precociously specialized; they are few in number, 

 yet they are probably the parents of all the cells which are produced of their kind 

 each throughout life. Passing on to a later stage, we note that when a striated 

 muscle-fiber is produced a striated muscle-fiber it always remains, and it never 

 becomes anything else. 



Two Types of Differentiation. There are two distinct types of cell differentia- 

 tion which I think have not hitherto been clearly recognized or defined. For both 

 types the starting-point is the same the undifferentiated embryonic cell. In one 

 type we find that, as the cells proliferate, a portion of them only undergoes differ- 



