626 Xlir. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



products of the breakdown themselves may act as stimulants. Since 

 iron and globin are utilized for hemoglobin synthesis (cf. Sections 

 3.2.1. and 3.2.3.), there is good reason to believe that they accelerate 

 hemopoiesis. With regard to the breakdown products of the pros- 

 thetic group, however, the evidence can only be considered suggestive. 

 In a large number of papers {212,7U,1787M93,2867,2868,2870,2871, 

 3015,3179) Verzar and his school have claimed that bilirubin acts 

 as a hemopoietic hormone. This claim is based partly on increases 

 in erythrocyte numbers caused by small amounts of bilirubin fed 

 by mouth (1-2 mg. in rats, 3-5 mg. in rabbits, 5 mg. in dogs, 50 mg. 

 in men) and partly on parallel increases of serum bilirubin and hemo- 

 globin after ascent to high altitudes. The latter, confirmed by 

 Talbot and Dill {2732), can hardly be considered sufficient evidence, 

 since the increases of bilirubin as well as that of hemoglobin may be 

 caused by contraction of the spleen (Drouet, 63 J4.). In the experiments 

 in which bilirubin was ingested, the erythrocyte numbers varied 

 greatly, and it is doubtful whether a statistical analysis would show 

 the increase by bilirubin ingestion to be significant. It is also diffi- 

 cult to understand how ingestion of amounts of bilirubin much smaller 

 than those normally excreted with the bile could increase hemo- 

 poiesis. Larger amounts of bilirubin had the opposite effect {3179). 

 Finally most workers have come to the conclusion that bilirubin is 

 not absorbed from the intestine. Patek and Minot {2118) noted a 

 second reticulocyte response when large doses of bilirubin (of doubtful 

 purity) were fed in iron therapy. More convincing are the experi- 

 ments of Bomford {312), who measured hemoglobin formation in 

 anemic dogs by the technique of Whipple, and injected large doses of 

 bilirubin (50 mg.) intravenously. He observed an increase in the 

 rate of hemoglobin formation and a prolonged reticulocyte response 

 following the administration of bilirubin. This occurred only when 

 iron was also given by mouth or subcutaneously; Bomford considers 

 the hypothesis that bilirubin acts as a hemopoietic hormone as 

 attractive, but so far unproved. 



Conversely, Boycott and Oakley {323) have claimed that blood 

 transfusion causes an active process of red cell destruction, and 

 Robertson {2285) found that by repeated blood transfusions animals 

 could be trained to destroy injected erythrocytes more rapidly. It 

 is doubtful, however, whether these results cannot be explained 

 partly on the basis of decreased resistance of blood subjected to 



