H. WADDINGTON 



from the beginning preserve their character unchanged, but rather as if we are dealing 

 with a series of reactions during which the state of the system continuously changes 

 until the final condition is gradually built up. We are already faced with the difficulty 

 of accounting for this progressive series of changes in a system one of whose major 

 components consists of genes, which we believe to retain their identity throughout. 

 The difficulty is only made the greater if we have to suppose that the major factors in 

 the cytoplasm also retain their identity. 



As a third argument, one may point to the fact that the localization of different 

 organs within the developing body may often be altered by factors which operate 

 after the segregation of plasmagenes in the egg cytoplasm must have been completed. 

 For instance, one might be tempted to attribute the localization of the organs in a 

 developing Drosophila to the segregation of organ-forming substances or plasmagenes 

 in the eggs, which are known to belong to the mosaic type; yet an environmental 

 treatment applied many hours after fertilization can cause an extra mesothorax to 

 develop instead of the normal metathorax (Gloor, 1947). Even as late as the third 

 larval instar environmental treatments (temperature shocks) applied to flies homo- 

 zygous for aristapedia can change the proportion of the antennal bud which de- 

 velops into a leg-like organ or into an arista (Vogt, 1946). The mere fact that a gene, 

 like aristapedia, can cause a mass of tissue which should normally develop into an 

 antenna to develop into a leg instead, shows that, even if we try to attribute the 

 major processes of differentiation to plasmagene-like bodies, these bodies cannot be 

 autonomous in their properties but must be highly susceptible to modifications 

 caused by interaction with genes. 



It appears, therefore, that the postulation of true plasmagenes as organ-forming 

 substances in the cytoplasm of the egg does not materially simplify the theoretical 

 task of accounting for the phenomena of differentiation. That does not necessarily 

 mean, of course, that such bodies do not or cannot exist ; we should have to take 

 account of them if there was unequivocal evidence for the existence in the eggs of 

 multi-cellular animals of cytoplasmic factors which had genetic continuity inde- 

 pendently of the nucleus. As yet I know of no compelling evidence to this effect. 

 Indeed, attempts to assess the autonomy of cytoplasmic factors in the egg over against 

 the nucleus have been few and far between. The brilliant studies of Baltzer and his 

 pupils (cf. Baltzer, 1950) with hybrid merogons in amphibia are perhaps the most 

 promising. So far as I know, the facts there can all be accounted for in terms of a 

 mere persistence of cytoplasmic character, without the need to postulate that the 

 cytoplasmic factors can reproduce while retaining their specific nature. One may 

 conclude, I think, that there is hardly any evidence that plasmagenes with complete 

 autonomous genetic continuity exist in metozoan eggs, and that it seems most im- 

 probable that the major phenomena of differentiation can be attributed to them. 

 The same conclusion applies even more forcibly to the plasmagenes of category 

 (3), namely microscopically visible cytoplasmic particles with genetic continuity. 

 These certainly occur in certain special cases, as for instance in ciliates, but in general 

 the histological evidence makes it clear that differentiation does not consist to any 

 major extent of the mere sorting out of the already existing particles in the egg cyto- 

 plasm. Such particles probably play an important part in development, but not by 

 the mere retention of their original characteristics. 



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