684 COLLECTED STUDIES IN IMMUNITY. 



the relapse have undergone a biological alteration, in that they have 

 become serum-fast. 1 The alteration in these parasites is not super- 

 ficial in character. On the contrary it may persist for many months 

 and through repeated passage through normal animals. The re- 

 lapse strain maintains its resistance to the antibodies produced by 

 the original strain, and can thus be positively identified. 



It was necessary to attempt to gain an insight into the 

 nature of this alteration. After varying the experiments in many 

 ways we reached the following conclusion: The original strain is 

 plentifully supplied with a certain uniform type of nutri-receptor, 

 which we may term group A. If the parasites are now killed and 

 dissolved in the mouse's body, group A acts as antigen and gives 

 rise to antibodies having definite relationship to group A. When 

 living parasites are brought into contact with this antibody, either 

 in vitro or in vivo, the antibody is anchored by the parasites. As 

 a result of this occupation of its receptors, the parasites undergo the 

 biological alteration which leads to the relapse strain. The altera- 

 tion consists in the disappearance of the original group A, and its 

 replacement by a new group, B. The following experiment shows 

 that the relapse strain contains a new group. Two mice are infected 

 with the relapse strain, which possesses group B, and are then com- 

 pletely healed. On infecting one mouse with the original strain, 

 the other with the relapse strain, it will be found that infection with 

 the original strain, carrier of group A, is successful, while reinfection 

 with the relapse strain is at first unsuccessful. This shows that the 

 original strain and the relapse strain are not identical, that they 

 must be carriers of two different functional groups. We are dealing, 

 therefore, with a typical case of disappearance of receptors following 

 immunization, arid accompanied by the formation of an entirely new 

 variety of receptor. 



It is probably of little consequence whether this alteration is 

 regarded as a mutation or a variation. The important thing is 

 that it can be artificially produced at will, and that it is hereditary. 

 In view of the great interest attaching to this problem in biology and 

 embryology, we have attempted a further analysis of the phenomenon. 



1 Exactly the same strain can be produced in much simpler fashion, by 

 infecting mice with the original strain, and healing the animals on the second 

 day with a full healing dose. After two or three days they are then again 

 infected with the same strain. After a time parasites will appear in the blood, 

 and these will be found to correspond entirely to those of a relapse strain. 



