244 DEFEX^E- AOAIX^T XOXAyTWnXW POISOXS 



notliiiig to explain the acquirement of tolerance to morphine, alcohol, 

 arsenic, and other similar poisons. A few observers have claimed that 

 the serum of animals innnunized to morphine will neutralize to some 

 degree the toxic effects of mor])hine, but these results have not been 

 generally substantiated. Others have claimed that increased oxida- 

 tive powers are developed under the stimulation of the poison which 

 permits of its more rapid destruction, especially in the liver, but the 

 experimental support of this hypothesis is slight. Still another idea 

 is that, at least in the case of morphine, decomposition products are 

 produced, and accumulate in the body, that neutralize physiologically 

 to some extent the morphine itself; this hypothesis can scarcely be 

 applied to arsenic and alcohol tolerance.-^ It has been found that 

 in animals habituated to morphine there is an increased power to de- 

 stroy morphine, but, nevertheless, the blood of such animals still con- 

 tains quantities of morphine toxic for normal animals, so there must 

 be a certain refractoriness or cellular immunity in addition (Riib- 

 samen). Schweisheimer ^^ has shown that when chronic alcoholics 

 and total abstainers are given equal quantities of alcohol, the alcohol 

 content of the blood reaches a higher level, and persists for a longer 

 time at a high level, in the abstainers. Apparently the alcohol- 

 halntuated organism can destroy alcohol more readily, presumably 

 through more rapid oxidation.^" However, other factors are involved 

 in alcohol tolerance, for with equal quantities of alcohol in the blood 

 the abstainers show a more marked intoxication than the habitual 

 drinker. So, too, in morphine tolerance any general resistance through 

 augmented oxidation seems inadequate in view of the specific increase 

 in the tolerance of the respirator^' center observed in this condition.^*" 

 Also we find that tolerance to one drug may be accompanied by toler- 

 ance to other drugs exerting similar physiological action. ^"^ 



It is possible, also, that the cell constituents with which the poisons 

 ordinarily combine are produced in increased amounts under the 

 stimulus of the poison, just as they are in the case of immunization 

 with toxins, with the difference that the combining substances are 

 not thrown off into the blood. For example, it has been claimed that 

 arsenic is ordinarily combined and held in the liver by a nucl(M)])r()- 

 tein, and the suggestion has been made that in arsenic habiturs this 

 nucleoprotein is increased in amount. Again, saponin seems to act 

 upon the cholesterol of the red corpuscles, and Robert observed in- 



3 Concernin}? immunity ajiainst moi-iiliiiio soo Faust, Arcli. oxp. Tatli. u. I'liarm.. 

 1000 (44), 217; Cloctta, ihid., lOO;^ (r)0). 4;"):^; Kiilisauu'ii. ihiiL. l!tOS ( .V.l) . -IIT ; 

 Alliiiiicsc, Arcli. ital. bio]., 1010 (5.3), 430 ; Lan<j;<'r ( licroiii tohMaiUH' i . IliorluMn. 

 Zclt.. 1012 (4.5). 221: Valoiiti. Arcli. exp. Patli., 1014 (75). 4:!7. 



■■iaDout. Arch, kliii. :\Icil.. 101:? (100). 271 



3b Soo also Villi/, and Dictricli, I'.iocJu'ui. Zcit.. 1015 ((iS), US. .1. Ilirsrh. 

 ibid., 1010 (77), 120. 



3<-Van Doiifrcn. Arcli. {Xos. Physiol., 1015 (1()2), 54. 



3d ScKi flyers. Jour. Pharmacol., lOlfi (8), 417. TTowpvor. Bilicrfcld tiiul^^ mor- 

 phine tolerance to he specilic ( Biochem. Zoit., 101(5 (77), 2S;l ) . 



