160 THE BIOSYNTHESIS OF PROTEINS 



an organism, a foreign substance may combine by chance affinity with 

 those of the y-globuhns which happen to have such a configuration that 

 they form a rather stable complex with the injected substance. Let us 

 assume that the organism reacts by producing more of this diverted 

 y-globulin, the production of specific antibodies will be accounted for. 

 This is essentially Ehrlich's theory reworded in molecular instead of 

 morphological terms. The next question is how the organism is stimulated 

 to produce specifically the y-globulins which happen to combine with the 

 exogeneous substance. Jerne (1955) imagines that the y-globulin-antigen 

 complexes are picked up by competent cells and that they stimulate these 

 cells to copying the particular y-globulin contained in the complex. A very 

 interesting feature of this theory is that it predicts an increasing fitness of 

 the antibody produced in the course of immunization, for the globulins 

 which have the greatest affinity for the antigen will be produced in greater 

 amount and will eventually overwhelm all the others. The assumption that 

 the swallowed y-globulin brings into antibody producing cells the structural 

 information for the synthesis of identical y-globulin molecules is difficult to 

 integrate into the present views on protein synthesis : information is known 

 to flow from the nucleic acids to the proteins, but there is no evidence that 

 proteins can ever transmit the structural information for their own repro- 

 duction to a protein making system. Whatever the value of the hypothetical 

 mechanism proposed by Jerne, the revival of a selection theory of antibody 

 synthesis was very stimulating. Newer hypotheses were soon developed in 

 which the selection was assumed to occur between cell lines rather than 

 between molecules (Burnet, 1959; Lederberg, 1959). These theories also 

 account for several other experimental data which should now be sum- 

 marized briefly. 



When an antigen is injected for the first time into an animal, antibody 

 appears in its blood after a few days ; the titre of antibody then decreases 

 gradually and it may eventually become very low, or undetectable. This is 

 the primary response. If a few weeks or a few months later the animal 

 receives a new injection of the same antigen, it soon produces large amounts 

 of antibody and keeps producing it for a long period. This secondary 

 response indicates that although antibody production ceased, the organism 

 had kept memories of its first contact with the antigen, since it was made 

 more responsive to a second contact. This memory ert'ect should be 

 accounted for. Another puzzling feature of antibody synthesis is that it 

 is caused by foreign substances only, as if the organism was able to distin- 

 guish self from foreign. Moreover, embryos or newly-born animals do not 

 respond to an injection of antigen by producing antibodies; nevertheless 

 the injected substance can change the antibody producing system in such 

 a way that the animal in its adult life will not produce antibodies against 

 the foreign antigen to which it has been exposed during its fetal or early 



