170 DIPHTHERIA 



of the tonsils. However, since the healthy carrier plays a large part 

 in the distribution of this disease, more attention to oral hygiene might 

 be of service in this as well as other directions. 



Roux and Yersin discovered diphtheria toxin. Cultures several 

 weeks old were filtered through porcelain. The germ-free filtrate in 

 minute doses kills animals. The toxin has not been obtained in a 

 pure state, and we are still in doubt concerning its chemical composi- 

 tion. It resembles in some respects the ferments. It acts slowly 

 and after a period of incubation; it is active in exceedingly small 

 amounts; it is destroyed by heat, and when repeatedly injected into 

 animals in non- fatal, but increasing, doses, the animal becomes immune 

 by elaborating an antibody. In these respects diphtheria toxin 

 resembles the ferments. It differs from many ferments in the fact 

 that a given amount produces only a certain effect and apparently 

 goes no further. Different strains of the bacillus show wide variations 

 in their toxin production, and the highest toxin producers are not 

 always the most virulent bacilli. What is called diphtheria toxin is an 

 old filtered culture, and the strength of this is determined by ascertain- 

 ing the minimum amount necessary to kill a guinea-pig of from 200 to 

 250 gm. weight within four days. This minimum lethal dose may 

 be as small as 0.0005 c.c., though that usually employed in the pro- 

 duction of antitoxin is much less powerful than this. 



The effect of this toxin on animals has opened a new field of 

 research, has given a new understanding of disease processes and has 

 led to one of the most beneficent discoveries, that of diphtheria anti- 

 toxin. When a fatal dose of this toxin is injected into an animal, 

 there is a period of incubation during which the animal shows no 

 marked departure from the normal. This incubation period varies 

 with the size of the dose, but is never less than about eight hours, even 

 when many times the fatal amount has been used. The significance 

 of this incubation has, in the writer's opinion, been misunderstood. It 

 should not be inferred that nothing happens during this time. The 

 disturbance simply does not rise to the plane of gross clinical observa- 

 tion. The toxin begins to act soon after its introduction. Within an 

 hour or two the temperature begins to rise and proceeds slowly until 

 some hours before death when it begins to fall, and at death it is 

 several degrees below normal. The skin about the point of injection 



