C. H. WADDINGTON 



and the eye cup has been formed, that this flexibility disappears. The presumptive 

 eye tissue is then said to be fully determined. For most other types of cells there is 

 little evidence that such determination can later be reversed. In the particular case 

 of the eye, however, we have the peculiar phenomenon of Wolffian regeneration of 

 the lens, in which, after removal of the normal lens of a fully developed eye cup, 

 some of the retinal cells lose their differentiation and eventually develop again in 

 another direction to form a lens to replace that which is missing. 



We see that the development of the eye takes place in a series of steps. In each step 

 the developmental capacities of the cells are, in the first place, restricted, so that the 

 later cells are not capable of so many different types of differentiation as the earlier 

 ones; or perhaps, to be more cautious, we should put it that they are not so easily 

 persuaded to undertake so many different types of differentiation as earlier ones 

 are. But the steps are not purely restrictive, since at each successive stage the cells 

 become less dependent on external influences for carrying out a full course of differ- 

 entiation leading to an adult end-product. Finally we may note that even in cells 

 which are at or near their final state of differentiation it may, under some circum- 

 stances, be possible to reverse the course of events and to cause the cells to different- 

 iate again into a different type of end-product. The Wolffian regeneration of the 

 lens is a striking example of this, and it seems probable that similar events occur in 

 the regeneration of other organs in vertebrates. 



We need now to try to form some idea of the physiological processes in the cells 

 which may underlie this type of phenomenon. We must picture some sort of dynamic 

 system which gradually alters in such a way that the types of change open to it 

 become ever more restricted, while at the same time it passes through a series of stages 

 of responsiveness to external influences, the range of external conditions to which 

 it responds becoming less as time proceeds. These are the two phenomena known 

 in embryological terms as 'increasing determination' accompanied by a progressive 

 'restriction of competence'. 



What types of basic elements must be supposed to be involved in this dynamic 

 system ? There is no doubt that one category are the genes in the nucleus. The facts 

 of genetics leave no doubt at all that these play a major role in determining the nature 

 of the processes which will occur during differentiation and thus of the final end- 

 product which will be produced. Again, experimental embryology has shown con- 

 clusively that in many eggs the cytoplasm is not the same in all regions of the egg, 

 but is locally differentiated; and further that these local differences play a part in 

 determining the type of differentiation which will occur in the cells formed out of 

 them. We have to deal, therefore, with a dynamic system involving both nucleus and 

 cytoplasm. Genetics has succeeded in analysing the constitution of the nucleus in 

 considerable detail, but the analysis of the cytoplasm into unequivocally recognizable 

 elements has been more difficult. There are, however, some categories which we may 

 postulate with some confidence. 



In the first place there must be what we may call the raw materials, that is to say, 

 low-molecular-weight substances such as amino-acids, out of which the more com- 

 plex cytoplasmic constituents, such as proteins, as well as the genes themselves, can 

 be synthesized. A second category must be what we may call the final cell consti- 

 tuents. By this I mean the characteristic substances which endow the cell with its 



1 06 



