192 THE TOXINS PRODUCED BY BACTERIA 



He found that in such an apparatus toxins — at least two kinds 

 tried — will pass through just as an albumose will. 



On the other hand, certain facts indicate that the exotoxins 

 like the endotoxins are the product of internal metabolism 

 in bacteria. Thus Brieger and Boer, working with bouillon 

 cultures of diphtheria and tetanus, separated, by precipitation 

 with zinc chloride, bodies which show characteristic toxic pro- 

 perties, but which had the reactions neither of peptone, albumose, 

 nor albuminate, and the nature of which is unknown. It has 

 also been found that the bacteria of tubercle, tetanus, diphtheria, 

 and cholera can produce toxins when growing in proteid-free 

 fluids. Further; investigation is here required, for Uschinsky, 

 applying Brieger and Boer's method to a toxin so produced, states 

 that the toxic body is not precipitated by zinc salts, but remains 

 free in the medium. If the toxins are really non-proteid they 

 may, on the one hand, be the final product of a digestive action — 

 extra- or intracellular — or they may be the manifestation of a 

 separate vital activity on the part of the bacteria. On the latter 

 theory the toxicity of the toxic albumoses of Sidney Martin may 

 be due to the precipitation of the true toxins along with these 

 other bodies. From the chemical standpoint this is quite possible. 

 Of the nature of the endotoxins nothing is known. 



When we take into account the extraordinary potency of these 

 poisons (in the case of tetanus the fatal dose of the pure poison 

 for a guinea-pig must often be less than '000001 grm.), we can 

 understand how, altogether apart from their instability, attempts 

 by present chemical methods to isolate them in a pure condition 

 are not likely to be successful, and of their real nature we know 

 nothing. Friedberger and Moreschi have shown that the intra- 

 venous injection in the human subject of a fraction of a loopful 

 of a dead typhoid culture gives rise to toxic symptoms, including 

 marked febrile reaction. Such injections are followed by the 

 appearance of agglutinating and bacteriolytic substances in the 

 serum. These results show that intracellular toxins may be 

 comparable with extracellular toxins so far as concerns the ex- 

 tremely small dose sufficient to produce toxic effects. 



The comparison of the action of bacteria in the tissues in the pro- 

 duction of these toxins to what takes place in the gastric digestion, has 

 raised the question of the possibility of the elaboration by these bacteria 

 of ferments by which the process may be started. Thus Sidney Martin 

 put forward the view that ferments may be produced which we may look 

 on as the primary toxic agents, and which act by digesting surrounding 

 material and producing albumoses — these bodies being, as it were, 

 secondary poisons. Hitherto all attempts at the isolation of bacterial 

 ferments of such a nature have failed. 



