SOMATIC MUTATION 



munologically determined) group is not necessarily very great. 

 Any mutation, whether genetic or somatic, produces its effect 

 on the phenotype only against the background of all the impacts 

 of internal and external environments on the cells in question. 



There is a genetically determined condition of one strain 

 of merino sheep in Australia which shows itself by the ap- 

 pearance of multiple skin carcinomata. The cancers arise, 

 however, only where grass seeds become embedded in the skin. 

 The grass seed here is an essential part of the background 

 against which the phenotypic character — multiple skin cancer 

 development — is called into being. The development of malig- 

 nant disease is, I believe, by far the most important aspect of 

 somatic mutation, but somatic mutation can never occur in 

 vacuo, and its results will always be determined more by the 

 conditions which allow or inhibit selective preferential sur- 

 vival of the clone than by the intrinsic character of the mutation. 



Those are the three conditions under which somatic muta- 

 tion is significant. The converse should also be stressed. 

 When, in a given tissue, one cell in a milUon mutates, the 

 effect is completely insignificant if no survival advantage 

 results. A well-known human genetic anomaly is oligo- 

 phrenia associated with absence of phenyl-pyruvic oxidase. 

 This produces idiocy when fully expressed. If the same 

 mutation occurred, say, in a single liver cell, there would be 

 no conceivable way in which it could be recognized. No 

 matter how drastic were functional changes in a single cell, 

 they could never be recognized if lo^ or lo^ normal cells were 

 also present in the same tissue. 



The decision to include a chapter on proliferative diseases 

 of the lymphoid and reticular tissue was based mainly on 

 grounds of logic and symmetry. There are no significantly 

 new facts or ideas to be described, but the field does seem 

 to be one from which useful suggestions may be drawn 

 bearing on inflammatory and immune responses on the one 

 side and malignant disease on the other. 



In human pathology the conditions that can be included 



167 



