58 Causes of Disease. 



of such a germ-free filtrate (into a suitable animal) evidence of 

 toxic action, especially a specific one, then we must be dealing 

 with a dissolved toxine yielded by the bacteria. The best and 

 simplest example of this is afforded by cultures of tetanus bacilli, 

 the filtrate from which produces typical and characteristic te- 

 tanus symptoms, the dry residue from the evaporation of the 

 filtrate acting in the same manner. 



A second proof that the immediate agent of bacteria is their 

 soluble toxine may be had by artificially removing the latter from 

 the germs. If water be allowed to run for several hours through 

 the residue of bacteria upon the filter they will be washed free 

 of the toxines and can be inoculated in enormous amounts, by 

 the millions, without giving rise to apparent harm (the inert 

 bacterial cells being quickly destroyed by phagocytosis in the ani- 

 mal body). Yet if these harmless bacteria be returned to a nutri- 

 tive medium where they can again multiply, they produce poison 

 anew, this collecting in the substance of the bacteria and in the 

 fluid in such quantities that inoculation of even the smallest 

 quantity, a very few of the bacteria, will produce fatal effects. 



The virulence of toxines is remarkable ; a hundred-thousandth 

 of a cubic centimeter of the filtrate of a tetanus culture is suffi- 

 cent to kill small animals, and a ten-thousandth of a milligram 

 of the dried substance will do the same ; less than one milligram 

 would cause tetanus convulsions in a human being. Such facts 

 prove that some bacteria are provided with toxic agencies of 

 frightfully dangerous power and explain why, when such causes 

 of disease gain entrance into the human or animal body, they 

 prove victorious in their conflict with the animal cells. 



Toxins do not act uniformly upon all animals. Intoxication oc- 

 curs only when they enter into chemical combination, only in 

 bodies whose cells possess substances (receptors) capable of union 

 and having chemical affinity for the toxine. In bodies in which 

 such receptors do not exist the toxine behaves as an indift'erent 

 substance. This explains why certain animals show a natural 

 immunity against certain toxines and why the bacteria producing 

 tlie latter are harmless to these animals, as chickens are insus- 

 ceptible to tetanus toxine. 



There are some germs which produce no toxine separable by 

 filtration as a secretion, but whose toxicity is occasioned by sub- 

 stances enclosed in the body of the microbe and fixed there 

 ( endotoxines). Some of these substances are of albuminous na- 



