456 ANNUAL KErORT SMITHSONIAN INSTITUTION, 1937 



According to Marshall and Davis (1914) and Fearon (1926) urea is 

 present in all organs and tissues of the body. In the blood and 

 lymph its concentration is usually between 0.02 and 0.03 percent. 

 The common occurrence of urea in the tissues and the harmlessness of 

 it made it another interesting substance for experimental study. 

 Through the interest and cooperation of a number of physicians and 

 surgeons a weak solution (1 percent) of urea in water was given 

 preliminary clinical tests. This concentration was later changed to 

 2 percent. The same types of chronic discharging wounds were 

 treated as with allantoin. 



After a number of a])])lications it became apparent that, like allan- 

 toin, urea possesses remarkable healing characteristics. The odor of 

 the wounds was decreased, they became cleaner, and healing pro- 

 ceeded promptly. In order that the urea treatment might be given 

 more extensive tests, the number of our medical cooperators was 

 considerably increased. The treatment was applied by them to a 

 great variety of chronic nonhealing conditions, and the beneficial 

 results appeared to be somewhat similar to those obtained >vith 

 allantoin. 



Beyond the fact that allantoin and urea have healing qualities 

 apparently shnilar in their action, it has not been showTi that the effect 

 of allantoin is due to the hydrolysis of its side chain to form urea. 

 That conception merely initiated an investigation on urea. Allantoin 

 may bring about its cflects through a different set of reactions. 



One of the reactions of allantoin, however, is its hydration by an 

 enzyme called allantoinasc. This enzyme was discovered and named 

 by Fosse and Brunei (1929) in the soybean and later found in a variety 

 of plant and animal tissues, including some insects. Allantoinasc 

 reacts upon allantoin by the addition of 1 molecule of water to form 

 allantoic acid, as follows: 



NH— Cn-Nn— CO-NRi NHr-CO— NH— en— NH— CO— NIIi 



OC 



I 



+niO= coon 



Allantoin 



NH- C O Allantoic acid 



Strangely enough, whereas allantoin has one side chain NH — CO — NIT2 

 allantoic acid has two. Allantoinasc is not known to occur in 

 mammalian tissues. 



The usual conception as to the occurrence of urea in the animal 

 body appears to be that it is a waste product only and an efficient 

 means of elmiinating excess nitrogen. Owing to this deeply rooted 

 belief, it has been, and still is, difficult for intellectual and scientific 

 persons to grasp the fact that urea is not merely a waste product. 

 The peasantry of Europe and similar classes throughout the world 

 have for ages availed themselves of the healing properties of urine, 

 and are today still using urine on wounds for that purpose. Fre- 



