C. H. WADDINGTON 



simulate a mutation of the virus. If the extracts came to contain free ammonia they 

 would transform the gastrula ectoderm not into neural tissue but into derivatives 

 of the axial mesoderm. More recently Lederberg (1952) has drawn attention to the 

 same source of possible error. Thus to be justified in using such experiments to 

 postulate the existence of a plasmagene, one needs evidence not only that the charac- 

 ter can be transmitted by cell-free extracts but that the effective factor in the extracts 

 is of the right order of complexity. 



From the point of view of their possible importance in differentiation, plasmagenes 

 may be considered under the following headings : 



(1) Exogenous 



Many viruses, such as those producing disease, are clearly not essential con- 

 stituents of the animal or plant and are introduced into the cell from outside. There is 

 considerable variation in the ease with which this introduction can take place. 

 Some of the bodies which were originally thought of as true plasmagenes should 

 perhaps be regarded as essentially exogenous factors for which infection is rather 

 difficult. This probably applies to the kappa particles in Paramecium (Sonneborn 

 1 951) and to the so-called genoid which confers CO a sensitivity on Drosophila 

 (L'Heritier, 1948). One of the most important characteristics of plasmagenes of this 

 kind is that they cannot be manufactured anew by the genes of the cell and thus if a 

 cell is once free of them they will not appear again until introduced from outside. 

 Apart from this fundamental fact, the relations between the exogenous plasmagene 

 and the genotype of the cell may vary over a wide range. In some cases complete 

 resistance to the exogenous particle may be controlled by a single nuclear gene. 

 Thus in variety 4 of Paramecium, the kappa particle cannot persist in the cell unless 

 that contains one or two doses of the nuclear gene K\ the recessive form kk is com- 

 pletely resistant and cannot support the growth of the particles if they are introduced. 

 In other cases, such as the Drosophila genoid and many viruses, there is as yet little 

 evidence of nuclear control of susceptibility or resistance. On general grounds, 

 however, it is probable that there is always some variation in this respect and this 

 will probably be under the control of numerous nuclear genes, each of small effect. 



Again, the physiological result of infection with the exogenous particle in some 

 cases clearly depends on the nuclear constitution of the individual involved. The 

 classical example is the virus-like particle in the King Edward race of potatoes, which 

 has little effect in that stock but which, when transferred to other races of potato by 

 grafting, produces the symptoms of a severe virus disease (Salaman and Le Pelley, 

 1930). In other cases such variation is less in evidence, but it seems likely that 

 careful search would always reveal some degree of variability of this kind. 



( 2 ) True plasmagenes 



One can pass by more or less insensible gradations from cases in which infection 

 is easy and the infecting particle obviously not an essential component of the organ- 

 ism, to the other end of the range at which infection cannot be definitely demon- 

 strated to occur, and the plasmagenes appear to be normal constituents of the 

 organism. Particles coming at the latter end of the range may be considered as true 

 plasmagenes. Most of the cases known are from the plant world (reviewed in Caspari, 



108 



