CLONAL SELECTION THEORY 



Stimulate it to produce in one way or another more globulin 

 molecules of the cell's characteristic type. The obvious way 

 of achieving this is to postulate that stimulation initiates 

 proliferation as soon as the cell in question is taken into an 

 appropriate tissue niche, spleen, lymph node or subacute 

 inflammatory accumulation. 



The reasons for temporarily or permanently discarding 

 the 'indirect template' hypothesis in favour of this clonal 

 selection approach were cumulative and largely indirect. 



(i) In discussing the biology of malignant disease the 

 importance of clonal phenomena in the expendable 

 cells of the body became increasingly evident (Burnet, 



1957^)- 

 (ii) Interest in the auto-immune complement fixation test 



developed in my laboratory by Gajdusek (1957) led to 

 the tentative conclusion that the ' antibody ' concerned 

 was an adventitious mixture of globulin molecules pro- 

 duced by clones of cells which had undergone some 

 type of somatic mutation. 



(iii) Workers in the field of adaptive enzyme production in 

 bacteria are now unanimous that the pattern of the 

 adaptive enzyme is genetically determined and not 

 a 'transcript' of pattern introduced by substrate or 

 inducer molecule. This destroyed the significance 

 of any analogy between adaptive enzyme production 

 and the indirect template hypothesis of antibody 

 production. 



(iv) Changing views on the life-history of the lymphocyte 

 have made it admissible to postulate that a lymphocyte 

 appropriately stimulated could give rise to a clone of 

 descendant cells. In particular, work from Florey's 

 laboratory (Gowens, 1957) shows that lymphocytes 

 can undergo more than one cycle between tissue and 

 circulation. Simonsen (1957), working with avian 

 material, showed that adult fowl blood contained 

 circulating cells which could settle and proliferate in 



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