Observations on the Protective Action of Normal Serum. 297 
ten days is required, and it was apparent that the occurrence of this 
particular lesion in protected animals was simply dependent on the survival 
of the animal. In rabbits, which are less susceptible to experimental 
B. diphtheriae infection and resist larger doses than guinea-pigs, it has 
been noted that sub-lethal doses may produce similar marked local lesions 
apart from any serum protection. 
Discussion. 
These observations represent a further contribution to the study of 
non-specific immunisation by parenteral injection of normal serum. 
While it is possible that in the case of horse serum a natural antitoxin 
may contribute to the protection noted, and it is of importance that the 
active substance in the serum corresponds to antibodies in thermostability, 
the action of the serum in bringing about some other antagonistic effect 
must be considered. This effect apparently does not depend on the trans- 
ference of bactericidal complement or a natural bactericidal antibody ; 
the serum is protective against infection apart from intoxication ; thus the 
organisms are absent from the local lesion. It might be claimed, however, 
that the antitoxic factor contributes to the elimination of the bacteria by 
rendering them more susceptible to phagocytosis through neutralisation 
of their toxin. It is to be noted also that normal serum is not antitoxic as 
regards the local toxic effects, whereas diphtheria antitoxin protects animals 
against local as well as general effects. The fact that the parenteral in- 
jection of the serum of one guinea-pig into another exerts a " delaying " 
effect in diphtheria infections and even complete protection, though this 
species has little natural immunity to B. diphtheriae and no natural anti- 
toxin can be demonstrated in the serum, clearly indicates that some 
mechanism other than that of a natural antitoxin or other antisubstance 
transferred with the serum plays the important part in increasing the 
resistance of the animal. 
These experiments are therefore of interest in their bearing on the general 
question of " non-specific immunity," and provide a further illustration of 
how the resistance of the tissues to a particular organism may be enhanced 
by the parenteral injection of normal serum. The results, however, clearly 
exclude the possibility that normal horse serum could be as effective a 
therapeutic agent as a potent diphtheria antitoxin. 
Conclusions. 
1. In guinea-pigs experimentally infected with B. diphtheriae, normal 
serum (horse, ox, sheep, cat, human), injected subcutaneously at the same 
time as the inoculation, exerts a definite protective action. 
