PROLIFERATIVE DISEASES 



In Australia recently there has been much interest in what 

 are known as fleece mosaics in sheep (Fraser and Short, 

 1958). Certain short- woolled sheep are found to produce 

 areas of long loosely crimped wool over sharply delimited 

 areas of skin. The evidence from the extent of the skin in- 

 volved in the thirty or forty sheep which have been studied 

 suggests strongly that the condition results from a mutation 

 occurring in one of the early divisions of the fertilized ovum. 

 One sheep in which approximately 50 % of the skin area was 

 involved presumably developed from an embryo in which the 

 mutation occurred in one of the cells from the first segmenta- 

 tion division. Three others with 20 to 25 % involvement 

 might have sprung from embryos in which the mutation 

 occurred one cell generation later. 



(ii) Somatic mutation produces a change in a cell by 

 which its descendants respond to some environmental 

 stimulus by active proliferation which gives them a survival 

 advantage over unmutated cells of the same stock. 



The preceding chapters were concerned with the implica- 

 tions of this approach at the immunological level. It was 

 assumed!that when, by differentiation or mutation, a mesen- 

 chymal cell developed patterns with a complementary rela- 

 tionship to an antigenic determinant, contact with that 

 determinant under the right conditions caused selective 

 proliferation of cells of that clone. At the present time no 

 other physiological system is known for which a process of 

 this type can be postulated. 



(iii) Somatic mutation results in a change by which a cell 

 and its descendants are released from one or more of the 

 controls that maintained its type in normal spatial and 

 numerical relation with the rest of the body. 



This could equally well be expressed by saying that the 

 mutation confers an intrinsic proliferative advantage on the 

 mutant clone under the conditions existing in the body. Such 

 changes are those that initiate progress of a cell line on the 

 road to malignancy. The difference from the second (im- 



166 



