THE ENZYME NATURE OF ECTOTOXINS 259 



unites with the substance it acts upon, is released as this result 

 is obtained, and freed for further action without noticeable 

 loss of quantity." 



Here there is this very confusion that I have already noted, 

 that, namely, of dwelling only upon the combination of toxin 

 and antitoxin in the one case, and of the action of the enzyme 

 upon the substrate in the other. 1 Only two paragraphs lower 

 down Zinsser calls attention to the incubation period in the action 

 of toxins, pointing out that this is longer when small doses are 

 given, shorter when large doses are administered, but always 

 evident. Thus in the horse he points out that it may be four 

 or five days before the action of tetanotoxin shows itself : in 

 mice, as De Waele points out, animals extremely susceptible 

 to tetanotoxin, a minimal lethal dose gives an incubation period 

 of thirty-six hours ; if 3600 lethal doses be administered this is 

 shortened to twelve hours, and whatever the dose, the interval 

 cannot be shortened below eight or nine hours. Such facts as 

 these cannot be explained as due to the activity of an ordinary 

 mineral or alkaloid poison : ordinary poisons have no incubation 

 period. It is wholly consistent with the action of a proteoclastic 

 enzyme which, present in the blood or becoming absorbed by 

 certain cells, by acting upon some specific proteid substrate, 

 splits off a toxic moiety which, accumulating under the continued 

 action of the enzyme, at length is present in sufficient amount 

 to set up symptoms. The full proof of the enzyme nature 

 of ecto toxins has recently been afforded by Abderhalden, who 

 has demonstrated in vitro the proteoclastic properties of these 

 bacterial toxins. In fact we must conclude that just as the animal 

 body gives off free enzymes along the course of the alimentary 

 canal, whereby foreign proteins of the food-stuffs are split up, 

 and so made capable of absorption, so certain bacteria have a 

 like power of discharging enzymes which can act upon the proteins 

 of the animal economy and prepare them to be assimilated by 

 the bacterial body, and it is in this process of disintegration of 

 the proteins of the organism that the toxic moiety is liberated, 

 thus inducing the symptoms of disease. It is these, and not 

 the so-called ectotoxins, which are the immediate causative 

 factor of these morbid phenomena. 



1 [He passes over, without notice, the phase of disintegrative activity of 

 the toxin.] 



