294 THE BIOCHEMISTRY OF B VITAMINS 



made the observation that raw egg white has a toxic effect when incor- 

 porated into the diet, and in 1927 Boas 161 observed the presence in certain 

 foods of an organic substance that would protect against this effect. As 

 the result of extended subsequent researches Eakin et al. found that the 

 symptoms of egg-white toxicity were due to the presence in egg white of 

 a protein, avidin, 162 ' 164 which is able to bind biotin in a firm complex which 

 is not readily broken by the usual digestive processes. An enzyme is 

 present in the blood, however, which can break the combination. Subse- 

 quently, the feeding of raw egg white has become a standard procedure 

 in producing the symptoms of biotin deficiency in a wide variety of 

 animals. 165 



It has recently been suggested that the retardation of sexual develop- 

 ment in chickens, which occurs on diets containing otherwise optimal 

 amounts of vitamins and minerals, but large amounts of whole milk 

 powder, may be due to a similar avidin-like effect. 166 



Inhibition of B Vitamin Activity by Competitive Action. For three 

 centuries preceding the discovery that nicotinic acid deficiency was in- 

 volved in the etiology of pellagra, it was realized that the affliction was 

 associated with the use of corn as a major portion of the diet, and it was 

 suggested from time to time that pellagra was due to some toxic agent 

 in the corn. This theory completely disappeared for a time when it was 

 shown that pellagra primarily indicates a nicotinic acid deficiency. It 

 was soon realized, however, that in consideration of the amounts of 

 nicotinic acid and tryptophan present in various corn diets, there remained 

 far too high an incidence of pellagra. Thus on the rice diets of India, 

 which provided about 5 rag of nicotinic acid per day, pellagra was rare, 

 while it was endemic in Moldavia, where the staple corn diets provided 

 15 mg per day. 72 Similar paradoxes were encountered broadly in the 

 United States. 167 It thus appears that corn does, in fact, contain a pella- 

 gragenic factor. 



"Woolley 168 has suggested that the toxic action may be due to some 

 structural analogue of nicotinic acid, or its associated metabolites, which 

 competes with the nutrilite for some enzyme (Chap. VI D), thus prevent- 

 ing the full nicotinic acid activity. A one hundred thousandfold concentra- 

 tion of the factor was achieved, using mice as assay animals, and the toxic 

 effect was found to be reversed by nicotinamide. Since it was reported 

 that 3-indoleacetic acid produced a corn-like pellagragenic action in rats, 

 and this substance is known to be present in corn in considerable amounts, 

 heteroauxin was believed to be the toxic agent. 169 Subsequent experiments, 

 however, have indicated this to be untrue, and the chemical nature of 

 the pellagragenic agent in corn, if it exists, remains as yet unknown. 170-172 



Subsequent to the study of thiaminase, it was found that a wide variety 



