238 DEFENSE AGAINST NON-ANTIGENIC POISONS 



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

 the serum of animals immunized to morphine will neutralize to some 

 degree the toxic effects of morphine, 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 scarcel}'' 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 alcohoUcs 

 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-habit- 

 uated 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 respiratory 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 



' Concerning immunity against morphine see DuMez, Jour. Amer. Med. Assoc, 

 1919 (72), 1069; full bibliography. He summarizes the evidence as follows: 

 "The only knowledge of a positive nature that we have at present concerning these 

 problems is that the different organs and centers of the body acquire tolerance to 

 morphine and heroine to a different degree and with varied degrees of readiness; 

 that these drugs as such are excreted in the feces in diminishing amounts during 

 the period of acquiring tolerance; and that there is evidently present in the blood 

 serum of tolerant animals (dogs) during periods of abstinence a substance or sub- 

 stances which, when injected into normal animals of the same species, causes the 

 appearance of symptoms identical with the so-called withdrawal phenomena. 

 Whether or not the disappearance of these drugs from the feces is due to their 

 increased destruction in the organism is still an unsettled question. It has not 

 been proved that the destruction of morphine in the organism, if it does take 

 place to an increased degree, is a causative factor in the production of tolerance. 

 It may be only a concomitant phenomenon." 



* Deut. Arch. klin. Med., 1913 (109), 271. 



6 See also Voltz and Dietrich, Hiochciu. Zcit, IDl") (08), 118. J. Hirsch, 

 ibid., 191() (77), 129. 



6 Vtui Dongcn, Arch. g(>s. Physiol., 1915 (lt)2), 54. 



^ So(! Myers, jour. I'harmacol.. 1910 (8), 417. lIowevcM-, Biberfeld finds mor- 

 phine tolerance to be specific (Biocnem. Zcit., 1910 (77), 283). 



