308 INFECTION AND IMMUNITY 



shown by Pfeiffer, appear with extraordinary rapidity, so that in these 

 animals the temperature may show the lethal drop within two hours 

 after inoculation, while control animals which have received the 

 same quantity of cholera germs without the serum may not show a 

 similar lethal drop in temperature for four to five hours. 



An explanation of the results of this experiment is found, probably, 

 in the fact that guinea-pigs are able to withstand a certaia quantity of 

 the iatracellular cholera poison (endotoxin) which may be represented by 

 one loopful of a fresh culture. If the animals are given smaller quantities 

 without the serum, say one-fourth to one-half loopful, the bacteria may 

 increase for a time without producing marked symptoms. Parallel 

 with the increase, however, the phenomenon of germ destruction is 

 going on and characteristic symptoms of intoxication appear at the 

 moment when the number of vibrios destroyed has become so large that 

 it corresponds to more than one loopful of the cholera culture. An 

 animal will thus withstand a culture of any size when mixed with im- 

 mune serum, if the dose does not exceed the limit of intoxication before 

 it is entirely destroyed. On the other hand, when guinea-pigs receive 

 the larger dose of three to five loopfuls, the serum, not being anti- 

 toxic, is not able to counteract the fatal effects of the liberated 

 cholera poisons, but, on the other hand, enormously increases the rate 

 of destruction of the vibrios, and hence intoxication appears earlier 

 in such treated animals than in the controls receiving the organisms 

 alone. 



This classic cholera experiment has been selected because it illus- 

 trates the most extreme limit of the endotoxin point of view, and, further, 

 because the cholera organism, standing at one end of the scale, is the 

 most extreme example of pathogenicity by virtue of its own destruction, 

 while the diphtheria bacillus at the other end, as we have seen, is one 

 of the classic examples of pathogenicity by virtue of secreted toxins. 

 Neither of these organisms is truly invasive or highly parasitic, and both 

 are harmful usually by the action of their poisons alone and acting, as it 

 were, from a base of supply on the periphery of the animal system. Be- 

 tween these two extremes stand all grades of pathogenic and infective 

 germs. 



These two organisms are typical examples of their kind, but there 

 are few organisms which secrete such highly toxic soluble bodies as do 

 diphtheria bacilli, and there are few so susceptible as the cholera organ- 

 ism to disintegration within the animal body; and yet there are many 

 germs which are extremely pathogenic, and in many cases capable of 



