110 SITE OF ANTITOXIN FORMATION 



derived mainly from the red blood-corpuscles. This view, 

 however, seems very difficult to believe when we consider that 

 these substances are devoid of protoplasm and nuclei, and do not 

 present any of those appearances indicative of active metabolism 

 or secretion which we should expect in the case of a cell perform- 

 ing so profound a physiological function, as the production of an 

 antitoxin. 



Nor is there any evidence, except in the one doubtful case of 

 the action of brain substance on tetanus antitoxin, of the presence 

 of substances like antibodies in the normal tissues and organs, in 

 spite of the fact that they must contain receptors which would 

 neutralize the toxins to which they are tested. Thus Calmette 

 did not find that emulsions of brain possessed any neutralizing 

 action on snake venom, although that substance certainly acts on 

 the central nervous system, and there are many similar researches 

 on the actions of other emulsions of organs on other toxins, all 

 with negative results. We may quote, for example, those of Blum, 

 who submitted various organs of the horse liver, spleen, etc., all 

 of which are certainly acted on by diphtheria toxin, since they 

 show definite morphological lesions in acute cases of fatal intoxi- 

 cation to prolonged autolysis, and found nothing in the nature of 

 an antitoxin for diphtheria or snake venom in the resulting 

 material. In one case that of autolyzed lymphatic glands of the 

 calf he found a substance which reacted like tetanus antitoxin. 



On the whole, therefore, it would seem that there is no good 

 evidence for the theory that the cells which are acutely and 

 powerfully poisoned by means of toxin are those from which the 

 antitoxin is derived. It is certain, however, that this substance 

 must be formed from cells which are reached and affected in some 

 way by the toxin. The cells which especially require discussion 

 are those of the connective tissues and the leucocytes. 



Attention is drawn especially to the connective tissues from the 

 fact that the most powerful production of antitoxin is usually 

 elicited by a subcutaneous injection of toxin ; intraperitoneal 

 injection is in general less potent, and intravenous injection less 

 still, and may not be followed by any production of antitoxin 

 at all. The same law holds, and even more strongly, in the 

 production of the other antibodies, although some exceptions 

 occur. 



Now in some cases it is true that these toxins have a local 

 pathogenic action on the tissues into which they are injected, but 



