398 PRINCIPLES OF EMBRYOLOGY 



of the melanocytes surrounding the graft by a virus- or plasmagene-like 

 particle from the pigmented cells of the transplant. This particle must be 

 capable both of self-duplication and of causing the host cell to produce 

 pigment ; possibly it may be the pigment-forming particle itself, in which 

 case these two actions would amount to the same thing. 



There are two alternative hypotheses to be eliminated before this theory 

 can be accepted. On the one hand, the spreading of dark pigmentation 

 around a graft might be due to the migration of actual pigmentary cells 

 rather than of intra-cellular particles. Such migration certainly occurs in 

 embryonic grafts of pigmentary cells in birds, but Billingham and 

 Medawar argue that it does not account for all the phenomena observed 

 in mammals, if indeed it occurs at all. In particular, it is difficult to recon- 

 cile with the fact that if a graft of, say, black skin from the ear is grafted 

 onto the sole of the foot, and pigmentation spreads around it, this black- 

 ened area will have the characteristics usually found in sole-of-foot epi- 

 dermis and not that of the ear-skin which initiated it. But although this 

 makes it difficult to suppose that the spread of pigmentation is due to the 

 migration of actual ear-skin cells, it suggests the other of the alternatives 

 to the plasmagene hypothesis, namely that we are dealing merely with a 

 serial evocation, in which some substance of low molecular weight diffuses 

 from a dark cell to the neighbouring unpigmented one and sets going 

 within it an already present pigment-producing system. There are, how- 

 ever, phenomena which this possibility cannot easily explain. For instance, 

 if a graft is made of black skin from guinea-pig A onto guinea-pig B, the 

 halo of pigment formed round it retains the immunological specificity of 

 individual A. If another graft of yl's skin is made onto B, it will set up an 

 immunological reaction and as a consequence of this the pigment particles 

 disappear from the zone of pigment spread around the original graft, 

 although the dendritic cells themselves do not seem to be adversely 

 affected. Billingham and Medawar, on these and other grounds, argue 

 that we must be dealing with a particle large and complex enough to 

 carry the immunological specificity of the individual from which it 

 originated, and capable both of spreading from cell to cell of the dendritic 

 system and of identical self-duplication. 



This case is of great interest and theoretical importance, since it is 

 one of the very few examples of an alleged plasmagene in a higher animal 

 which has been thoroughly studied in recent years, and in which there is 

 no question of our being deceived by an extraneous virus. There are 

 several further points to notice about it. First is the rather surprising fact 

 that the 'plasmagene' carries the immunological specificity of the indi- 

 vidual in which it arises, which makes it extremely difficult to transmit 



