TOLERATION AND IMMUNITY 163 



which give the serum its bactericidal and antitoxic properties. Alexines 

 and antitoxines are products of the leucocytes, which fight against the 

 bacteria more by means of these substances than by virtue of their 

 phagocytal functions. This way of looking at the matter effects a 

 compromise, that is already widely recognized, between the theories of 

 Metschnikoff and the French school, and the German doctrine of anti- 

 toxines (147). 



Another natural means of defence against bacterial poisons possessed 

 by man and all other organisms is the power of acquiring toleration of 

 poisons. It is indeed only a special case of the ability possessed by all 

 living substance to accustom itself to external influences when these increase 

 slowly and do not exceed a certain degree. It is well known that this 

 power is highly developed in some organisms and is subject to great 

 individual variation. We only need recall the acclimatization of animals, 

 of plants, of the races of mankind, and even of bacteria themselves, living 

 as these do in pure cultures under conditions totally different from those of 

 their native haunts. Instances of habituation are familiar enough ; arsenic- 

 eaters are able in time to endure 0-4 gram of arsenic at once, the fatal dose 

 being ordinarily from 01 to 0-2 gram. Morphinomaniacs accustom them- 

 selves gradually to four times the fatal dose (0-4 gram per os}. 



By very gradual augmentation of the dose white mice have been made 

 immune to ricin (the poison of the castor-oil seeds), so that they were able 

 finally to stand one hundred times the fatal dose without injury (148). 



The body can also accustom itself to the toxines of pathogenic bacteria, 

 and it will be found worth while to review from this standpoint (neglecting 

 for the time being the antitoxine theory) some of the innumerable observa- 

 tions that have been made during the last ten years in the fields of immunity 

 and serum therapeutics. For instance, in order to make a guinea-pig 

 actively immune to diphtheria poison, one proceeds as follows (149). First 

 of all the minimal lethal dose of a virulent filtered bouillon culture is 

 determined ; i. e. the number of cubic centimetres which suffice to kill 

 a guinea-pig when injected subcutaneously. Perhaps 0-3 c.c. per kilo, 

 body- weight is enough ; i. e. for a guinea-pig of 250 grammes about 0-08 c.c. 

 This quantity is naturally not a fixed amount, comparable to a normal 

 solution used for volumetric analysis ; it changes according to the virulence 

 of the bacilli. One then begins by injecting a guinea-pig with a much 

 smaller amount, oooi c.c. for instance, which perhaps causes only temporary 

 sickness. Then the dose is gradually and continually increased until 

 at last an amount far exceeding the fatal dose can be borne without 

 injury. The animal has become immune to the poison. In this way, 

 too, horses are immunized for the preparation of Behring's diphtheria 

 serum. Instead of minute doses of a highly toxic filtrate, larger doses 

 may be employed of a filtrate whose virulence has been weakened either 



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