REGULATION 159 



hoped that the interesting works quoted above will be extended and that 

 the primary structure of a large part of the antibody molecule will be un- 

 ravelled. This does not appear beyond the reach of experimentation, for 

 the large antibody molecule can be split into fragments some of which 

 contain the specific groups which react with the antigen (Porter 1950b, 

 1958). Knowledge of the primary structure of these fragments would be of 

 fundamental importance. It would provide not only a test for the direct 

 template hypothesis but also an essential foundation of any coherent theory 

 of immunological response. 



According to the direct template hypothesis, antibody can be produced 

 only as long as the antigen is present. It is a fact that immunity can last 

 for several years after the last injection of antigen ; unfortunately it is very 

 difficult to find out experimentally whether the antigen does persist for 

 years in antibody producing cells and it is impossible as well to prove that 

 it does not persist, for in a template process a few molecules per active cell 

 might be sufficient to ensure continued antibody production. 



A theory, which derives from the preceding one but avoids the require- 

 ment for the persistence of the antigen, was proposed by Burnet and 

 Fenner (1949). Here the antigen is assumed to modify the agents of globu- 

 lin synthesis permanently and in such a way that they will produce a new 

 globulin, the antibody, even when the antigen has been eliminated. This 

 is the indirect antigen-template theory. The permanent modification is 

 assumed to concern a piece of the protein making machine which is respon- 

 sible for the specificity of the synthesis. For instance, a modification of the 

 DNA of the antibody producing cell has been suggested as an obvious 

 possibility (Schweet and Owen, 1957). 



Recently, the old natural selection theory of Ehrlich was revived in a 

 new form by Jerne (1955). Ehrlich's theory has been abandoned because 

 many workers found it incredible that antibodies specific for strange artifi- 

 cial organic groups could pre-exist in the organism. But this opinion was 

 based on the more or less implicit assumption that each antigen evokes an 

 antibody which is different from any other globulin and which is perfectly 

 adapted to the antigen. Actually, the response is not as perfect and the 

 specificity of the reaction not so absolute. Many proteins are bad antigens, 

 not all chemical groups have antigenic properties, and all the animals do 

 not react equally well to an individual antigen. In response to an antigen, 

 an animal often produces a heterogeneous group of antibodies (Talmadge, 

 1957; Lapresle, 1959). Cross reactions occasionally occur between 'un- 

 related' antigens (Dixon and Maurer, 1955). The blood of a non-immunized 

 animal often contains proteins which manifest a great affinity for certain 

 foreign substances (Jerne, 1956). It is conceivable therefore that an animal 

 produces a broad but finite assortment of y-globulins able to form com- 

 plexes with many various kinds of chemical groups. When introduced into 



