W. H. MANWARING 1079 



receptors thus formed are in time cast off by the living cell; and (/.') that these cast- 

 off receptors are the specific antibodies with which we deal. To account for their de- 

 fensive action, Ehrlich assumes: (/) that the cast-off receptors still retain their origi- 

 nal accidental affinities for the specific antigen; and (m) that they unite with this an- 

 tigen in the body fluids, thus preventing its union with the living cells. To explain cer- 

 tain minor phenomena he assumes: (») that the freed or circulating receptors still 

 retain an affinity for their cells of origin ; (0) that receptors are of different types de- 

 pending upon whether or not they require the co-operation of some normal serum 

 component for their full defensive action against the specific antigen; and (/?) that 

 there are differences in the number, avidity, and valence of the same receptors nor- 

 mally present in different cells of the animal body and in corresponding cells of dif- 

 ferent animal species, 



THE EHRLICH HYPOTHESES AS AN EXPLANATION OF KNOWN IMMUNOLOGICAL FACTS 



The hypotheses thus formulated explain and co-ordinate all known immunologi- 

 cal facts. The high susceptibility of certain animal species for a given antigen, for ex- 

 ample, is a logical result of an assumed multiplicity of accidental receptors for this 

 antigen in vital tissues of this species, or of receptors having an assumed unusually 

 high avidity for this antigen. The relative insusceptibility of other animal species is 

 logically explained as a result of an assumed paucity or low avidity of the same re- 

 ceptors in vital tissues, or as a result of an assumed multiplicity or high avidity of 

 these receptors in physiologically inert tissues, thus binding the injected antigen to 

 inert structures, preventing its action on vital parts. 



The development of specific hypersusceptibility would be a logical result of an 

 assumed local multiplication of specific receptors in vital tissues, with little or no libera- 

 tion of these receptors in the body fluids, A subsequent desquamation of the same 

 receptors into the body fluids would change the hypersusceptibility to an immunity. 

 Passive immunization would be a logical result of a sufficiently large number of freed 

 receptors in the body fluids. Passive sensitization would logically follow a small num- 

 ber of freed receptors, most of the transferred receptors becoming attached to the 

 body cells of the recipient, thus increasing its affinity for the antigen. All specific test- 

 tube reactions would be logically explained as a result of direct chemical union be- 

 tween specific antigens and corresponding freed receptors, the details being determined 

 by the number, type, avidity, and valence of these receptors, 



VALIDITY OF THE EHRLICH HYPOTHESES 



My conviction that there is something radically wrong in the major assumption 

 of the Ehrlich theory arose from a consideration of the almost universal failure of 

 therapeutic methods based on these assumptions. According to the Ehrlich theory, 

 for example, any specific antibody that can be caused to appear or to increase in the 

 circulating blood as a result of active immunization is a specific defensive chemical 

 substance and represents the only specific immunological adaptation in the body. It 

 is only necessary to obtain this antibody in sufficiently large quantities to have a val- 

 uable therapeutic agent. Yet in spite of millions of dollars spent in research and in 

 the commercial exploitation of such antibodies, therapeutic sera have been lamenta- 

 bly unsuccessful except in a small group of relatively unimportant diseases. This 



