PREFACE 



SINCE the classical and tundaiiiental ^voik ot Roiix, Versin, 

 Behring, Kitasato, Bordet, P^liiiich, Theobald Smith, Ro- 

 senaii, and others, it has been generally acknowledged that 

 the discovery ot antigenic and solidjle exotoxins ^vas one ot the 

 most triiittul and imjiortant contriijutions to innnnnology and 

 medicine. The ideas stimidated jjy this ^vork brought about eluci- 

 dation ot inninnerable problems in j^athology and clinical medi- 

 cine and ga\e important residts in specitic treatment and prexen- 

 tion ot certain intectious and contagious diseases. Ever since 1892, 

 numerous in\estigators attempted to develop antitoxic sera tor 

 almost exery known bacterial infectious disease. It xvas, hoxvever, 

 soon learned that the possibility of producing antitoxins was 

 limited only to a small gTOup of diseases because the method of 

 demonstration of toxins failed xvith a large percentage of micro- 

 organisms tested. The investigations xvere then side-tracked by 

 the theories of endotoxins. These theories apparently handicapped 

 the original and finidamental progress for many years to come. 

 Ever since the demonstration ot the phenomenon of bacteriolysis 

 by PfeifTer and his formulation of the endotoxin theory, investi- 

 gators used amazing ingenuity in the development of methods for 

 cell destruction. However, the split products and the laboratory 

 artefacts thus obtained coidd not be reasonably considered as 

 responsible agents in e\olution of infectious diseases because of 

 complete lack of specific pathological effect upon experimental 

 animals. The opposing viexvs have been steadily gaining groinid 

 that some unknoxvn agents as yet may be responsible for systemic 

 intoxications in intectious diseases. 



For some years I employed various experiments in order to 

 determine whether meningococcus, B. tyjjhosus and other micro- 

 organisms produced sid)stances similar to soluble exotoxins. As a 

 working hypothesis, I assumed that the microorganisms in \vhich 

 the demonstration of exotoxins Avas hitherto impossible may pro- 

 duce injuries in animal tissues through a mechanism altogether 

 different from the direct injurious effect exerted by diphtheria, 

 botulinus, tetanus, and other true exotoxins. \Vith this idea in 



