814 



SCIENCE. 



[N.S. Vol. XVI. No. 412. 



as affording a complete explanation of the 

 toxic phenomena of this class of infections 

 are so obvious that naturally efforts have 

 been made to learn whether bacteria which 

 produce no strong soluble toxins in our 

 ordinary culture media may not do so on 

 other media of special composition or in a 

 demonstrable way within the living body. 

 Work in these two directions has not been 

 altogether barren, as shown by results of 

 experiments made by Hueppe, Cartwright 

 Wood, Marmorek, and others along the 

 former lines, and by Metchnikoff, Roux 

 and Salimbeni along the latter, but it can- 

 not be said that these experiments have 

 led to any generally accepted solution of 

 the main difficulties. Some are therefore 

 inclined to lay the chief emphasis upon dis- 

 ordered cellular metabolism, but this is 

 only a restatement of the question. Every- 

 body recognizes abnormal metabolism as an 

 essential condition in infections. The 

 very point needing explanation is how the 

 bacteria derange metabolism. 



I wish here to advance a hypothesis which 

 seems competent to explain the source, the 

 mode of production and the nature of 

 certain bacterial toxins. It would appear 

 to be a natural inference from the receptor 

 theory of Ehrlich and the recent M'ork on 

 cytotoxins. The following considerations 

 will, I hope, make clear the essential points. 



As I have already stated, we know that 

 the injection of foreign eeUs, such as 

 pathogenic bacteria, red blood corpuscles, 

 spermatozoa, epithelium, into the tissues of 

 a living animal leads to the formation of 

 poisons, called cytotoxins, acting specific- 

 ally upon these cells; that the substances 

 which stimulate the cells of the host to 

 produce one constituent of this class of 

 toxins consist of certain atom complexes 

 derived from the injected cells; that cer- 

 tain cells of the host thus stimulated gen- 

 erate and discharge one component of the 



toxin, called the intermediary body, which, 

 although by itself not poisonous, becomes 

 the medium of intoxication through union, 

 on the one hand, with a preexisteut toxo- 

 phore substance, called the complement, 

 and, on the other hand, with the foreign 

 cell which started the reaction. 



Such is the response on the part of the 

 host to the entrance of the foreign cells; 

 but how about a possible response of a like 

 nature on the part of the invading cells to- 

 ward the host resulting in the production 

 of special cytotoxins, of analogous consti- 

 tution, injurious to the host? This latter 

 response, being of a vital nature, can take 

 place only when the invading cells are liv- 

 ing, as in the case of bacteria and other 

 pai-asites. 



I see no reason why suitable substances 

 derived from the host may not stimulate 

 parasitic organisms, through a physio- 

 logical mechanism similar to that operative 

 in the development of cytolytic immunity, 

 to the production of intermediary bodies 

 which, if provided with the requisite affi- 

 nities, have the power to link complements 

 to cellular constituents of the host, and 

 thereby to poison the latter. Expressed in 

 terms of Ehrlich 's side-chain theory, cer- 

 tain substances of the host of cellular 

 origin, assimilable by the parasites through 

 the possession of haptophore groups with 

 the proper affinities, become anchored to 

 receptors of the parasitic cell, which, if 

 not too much damaged, is thereby stimu- 

 lated to the over-production of like recep- 

 tors ; these excessive receptors of the 

 parasite, if cast off into the fluids or the 

 cells of the host, there constitute inter- 

 mediary bodies or amboceptors with special 

 affinities for those cellular constituents or 

 derivatives of the host which led to their 

 production, and for others which possess 

 in whole or in part identical receptors. 

 Provided the host is supplied also with the 

 appropriate complements, there result cyto- 



