THE SEAT OF FORMATION OF UREA 683 



The question of the possible origin of urea from ammonium 

 salts could be investigated in two ways, either by perfusing blood 

 containing ammonium salts through various surviving organs, 

 or by eliminating the liver in an otherwise intact animal. Both 

 methods have been used. Schroder perfused blood containing 

 ammonium salts through the surviving kidneys of dogs with negative 

 results. He performed similar experiments, using the lower half 

 of a dog's body, also with negative results. With regard to the 

 other method of experiment, it is manifestly impossible to prove 

 a negative, that no other organ than the liver can produce urea 

 from ammonium salts. But the experiments already referred to 

 of Hahn, Massen, Nencki, and Pawlow on dogs with an Eck's 

 fistula, the analyses of Horodynski, Salaskin, and Zaleski, and 

 Schroder's experiments on nephrectomised dogs, make it extremely 

 unlikely that ammonium salts can be converted into urea else- 

 where than in the liver. 



There still remains the possibility that the other tissues 

 might be able to produce urea from some substance other than 

 ammonium salts or arginin. We have seen that there is evidence 

 that some of the intermediate products of the metabolism of 

 tissue proteids are converted into ammonia previous to their 

 conversion into urea ; but in some cases the evidence of this is 

 slight, and in other cases we have no evidence at all. Further, 

 our knowledge of what are the actual intermediate products of 

 nitrogenous metabolism in the body is meagre, and there is 

 no a priori improbability of there being substances, other than 

 those already considered, which are converted into urea in 

 the tissues. No systematic series of experiments have been 

 carried out in which blood containing mono-amino acid or uric 

 acid, &c., has been circulated through various organs or muscles. 

 We have, therefore, no direct evidence whether tissues other 

 than the liver can or cannot produce urea from anything else 

 than ammonium salts or arginin. Such evidence as we have 

 on this point has been obtained in the following indirect way. 

 If the liver is the sole seat of urea formation it would follow 

 that putting the liver out of the circulation, or removing it, 

 ought theoretically to make the urea completely disappear from 

 the urine. Hahn, Massen, Nencki, and Pawlow carried out 

 experiments to test this point. Their method was to make 

 an Eck's fistula in a dog, and subsequently either to tie the 



