34 INFECTION AND RESISTANCE 



these toxins to enzymes, with whicn, as we shall see, they have much 

 in common. The endotoxins on the other hand at least as con- 

 ceived by Pfeiffer, are structural ingredients of the bacterial proto- 

 plasm which are toxic when brought into solution as the cells break 

 up. 



Concerning the accuracy of this conception, however, much doubt 

 has recently arisen, as a result of researches which will be discussed 

 below. 



These two types of poison, moreover, differ from each other not 

 only in mode of origin but in biological characteristics far more 

 fundamental than this. 



The discovery of diphtheria toxin by Roux and Yersin was fol- 

 lowed by diligent investigations into the toxic properties of all 

 known pathogenic bacteria, and it was soon found that a few only 

 of these germs could produce poisons biologically similar to that 

 found in diphtheria cultures. It was in the course of investigations 

 of this kind, indeed, that Pfeiffer, failing to discover an exotoxin in 

 cultures of cholera and other germs, formulated his endotoxin theory. 



The list of true toxin or exotoxin producers, then, is short. 

 Among the more important are, in addition to the diphtheria and 

 tetanus bacilli which have been mentioned above the Bacillus 

 botulinus, 17 the Bacillus pyocyaneus^ and that of symptomatic an- 

 thrax. 19 It has also been claimed that similar toxins are formed by 

 the cholera spirillum (Brau and Denier), 20 by the dysentery bacillus 

 of the Shiga-Kruse type (Kraus and Doerr) 21 and the Bacillus ty- 

 pliosus (Arima). 22 In the cases of the three last-named organisms, 

 however, the secretion of a true exotoxin has not been accepted as a 

 fact by all observers. Indeed, even though such substances may pos- 

 sibly be produced by these bacteria in small amounts it is not likely, 

 in the light of our present knowledge, that they play more than a sec- 

 ondary role in the toxemic manifestations of cholera, dysentery, and 

 typhoid, the important poisons in these cases being those derived 

 from the bacterial cell bodies. 



Similar in essential properties to the true exotoxins also are the 

 erythrocyte poisons (hemotoxins) produced by many bacteria which 

 cause hemolysis of red cells, and the leukocyte-destroying poison 

 (leukocydin) which is a product of the Staphylococcus aureus. 



All of these "true bacterial toxins" or exotoxins, apart from sim- 

 ilarity of origin, as soluble secretions of the living bacteria, possess 

 certain common biological characteristics which sharply differentiate 



17 Kempner. Zeitschr. f. Hyg., Vol. 26, 1897. 



18 Wassermann. Zeitschr. f. Hyg., Vol. 22, 1896. 



19 Grassberger and Schattenfroh. Wien Deuticke, 1904. 



20 Brau and Denier. Ann. de I'Inst. Past., Vol. 20, 1906. 



21 Kraus and Doerr. Wien kl Woch., 42, 1905. 

 22 Arima. Centralbl. f. Bakt., I, Vol. 63, 1912. 



