THE OXIDIZING SUBSTANCE OP THE BLOOD-PLASMA. 139 



favor of Horbaczewski's view have steadily accumulated, while 

 Fischer's position has as steadily gained ground. The prevail- 

 ing view, therefore, is that the alloxuric bases are derived from 

 the nucleins of which the body-cells, and particularly leuco- 

 cytes, are the source, and also from certain articles of food. 

 This constitutes but a subdivision of general metabolism: i.e., 

 that recognized as "nuclein metabolism." 



Again, Horbaczewski, in a series of experiments, observed 

 that splenic pulp, allowed to digest several hours with blood 

 at the body-temperature, gave rise to a marked increase of uric 

 acid and nuclein bases, but that the relative amounts of these 

 products depended entirely upon the degree of oxidation. When 

 simple decomposition prevailed, the nuclein bases were found 

 to predominate, while the more advanced oxidation processes 

 led to the formation of uric acid. That the production of uric 

 acid must be an advanced stage of the processes through which 

 the waste-products are prepared for excretion is thus made 

 probable. This is sustained by the high relative proportion 

 of oxygen higher even than urea: (NH 2 )C0 2 which its 

 formula indicates, and the gradual progression toward this 

 high proportion which the alloxuric bases show: i.e., guanin, 

 C 6 H 5 N 5 0; hypoxanthin, C 5 H 4 N 4 0; xanthin, C 5 H 4 N 4 2 ; and 

 uric acid, C 5 H 4 N 4 3 . Feeding with bodies rich in nucleins, 

 spleen-pulp, thymus, etc., causes a proportionate increase of 

 the most advanced of the alloxuric bodies, uric acid, and in 

 health the greater part of the nitrogen of the nuclein metabo- 

 lism is excreted, not as nuclein bases, but as uric acid. All 

 these facts tend to show that uric acid is not only the normal 

 end-product of nuclein metabolism, but also the most highly oxid- 

 ized of the alloxuric bodies. 



If this conclusion prevails, what is the utility of the oxida- 

 tion of alloxuric bases? This soon appears when their toxicity, 

 as compared to that of uric acid or urea, is realized. Uric 

 acid, notwithstanding the prevailing belief to the contrary, is 

 chemically harmless. It has been fed to animals or injected into 

 their blood in very large doses without giving rise to untoward 

 symptoms. Even its continued administration has failed to 

 bring about the least pathological change in the structures 

 which it is generally thought to assail, as shown experimentally 



