BACTERIAL POISONS 87 



rence of symptoms. Here again snake poisons form an exception 

 since local manifestations may appear within an extremely short 

 period after the injection of the venom or as the result of a snake 

 bite. However, in the case of all other toxins there is a definite 

 lapse of time between the entrance of the poison and the first symp- 

 toms, local or general. This interval is longer when small doses are 

 given shorter when the doses are large but is never entirely elim- 

 inated even when many times the fatal dose is given. 



In the case of tetanus poison, for instance, injections into a horse 

 may riot cause symptoms for as long as four or five days. In mice, 

 animals that are extremely susceptible, the incubation time may be 

 shortened from 36 to 12 hours if we inject 3,600 lethal doses, but, 

 in any case, whatever the dose, this interval cannot be shortened 

 below 8 or 9 hours. 25 Many attempts have been made to explain 

 this. Ehrlich, as we shall see, assumes that the action of a poison 

 depends upon two occurrences: one, the union of the poison with 

 the vulnerable cell, the other the gradual injury of the cell by the 

 toxic atom groups in the poison molecule. The time necessary for 

 the institution of this process, he believes, explains the interval. 

 Richet has suggested that the toxin itself may not be potent until 

 acted upon by the body of the recipient and transformed into a 

 potent form. His views are more directly related to the phenom- 

 enon of anaphylaxis and are discussed in another section. De Waele 

 has recently advanced a theory which implies that the incubation 

 time represents the period necessary for the gradual concentration 

 of the poisons in the vulnerable tissues, a process which depends 

 either upon chemical affinities or solubility of the toxins in the cell 

 lipoids. A little at a time would then be absorbed by the vulnerable 

 cells as they come in contact with the poison, through the circulation, 

 and the symptoms would not appear until a definite intracellular 

 concentration had been attained. His views are so closely bound up 

 with the theories on the selective action of the toxins upon individual 

 tissues and organs that they will be rendered clear as we proceed 

 with a discussion of the latter. 



The majority of pathogenic bacteria do not, as we have seen, pro- 

 duce true toxins or exotoxins. Cultures of cholera spirilla, plague 

 bacilli, and of many other bacteria do not yield toxic filtrates until 

 the cultures have been allowed to stand for prolonged periods during 

 which extraction and possibly autolysis have occurred. In these 

 cases, moreover, definite toxic properties can be demonstrated in the 

 dead cell bodies or in extracts prepared by various methods. In no 

 case, however, is the injection of these "endotoxins" followed by the 

 production of antitoxins. It was very natural to suppose that in 

 micro-organisms of this class the toxic principle might be present in 

 the form of a preformed intracellular poison which could be ex- 

 25 De Waele. Zeitschr. f. 7mm., Vol. 4, 1910. 



