Genie Control of Development 319 



series of changes is more or less irreversible. The substances involved 

 are mostly active proteins. This general description of development is, 

 of course, the same that we gave before, using the terminology of 

 chemodifferentiation in a hierarchy of determinative steps which 

 distribute specifically different cytoplasmic substrate materials by 

 means of stratification. The additional idea of canalization is new, 

 the assumption that, once a course of chemical differentials has been 

 set, it is carried along under its own steam, though this is only a way 

 of expressing the fact of more or less final determination. 



Waddington assumes that the specific cytoplasmic proteins, by 

 which different cell types are characterized, are built from essentially 

 the same building blocks, that is amino acids. This means that before 

 the diversification starts, the genie material permits either type of 

 synthesis, and therefore a competition for these building blocks, the 

 substrate material, exists. (The application to genetics of the idea of 

 competition for a substrate, at present so popular, goes back to Sewall 

 Wright, 1941; and has been especially emphasized by Stern et at, 

 1943-1946.) Slight changes in the available raw materials may shift 

 the whole system from one path into another. Thus the change in 

 rate of synthesis of any one protein due to a change in the con- 

 centration of one or the other raw materials may cause a large change 

 in the collection of final proteins. The differentiation involving many 

 substances may depend upon a single or a few raw materials. Con- 

 sequently, the fact that some raw materials are used up, altering the 

 concentrations of those remaining, will shift the balance of synthetic 

 rates and even lead to synthesis of new proteins, the beginning of 

 progressive differentiation. The following canalization of differentiation 

 (i.e., irreversible determination) may be due to an autocatalytic ele- 

 ment in these synthetic processes which, by necessity, increase the 

 amount of a single product, and, if more syntheses are involved 

 simultaneously, some compatible ones may increase. Such a system 

 would be difficult to reverse, since this would require the restoration 

 of the original concentrations of raw materials. Waddington (1954) 

 has elaborated the same ideas by putting them into the form of 

 kinetic equations, which may or may not prove helpful (in view of our 

 ignorance of the actual reacting substances ) . 



The difference of this point of view from the more generahzed 

 one of stratification of substrates should now be emphasized. Both 

 theories endeavor to explain how different chemical entities are sorted 

 out into different cells and cell groups in a definite way, and the role 

 the genie material is playing in the process. The stratification hy- 



