NUCLEIC ACIDS 149 



be easily detected, and as free phosphoric acid is constantly present in 

 tissue extracts, the decomposition of nucleic acid was generally consid- 

 ered proven, when a free purine base appeared during the digestion of 

 material at the body temperature. 



All of the earlier work upon this subject was confused by unavoid- 

 able sources of error. The physiological decomposition of nucleic acid 

 could not be clearly followed until after the chemistry of the substance 

 had reached a comprehensive stage. Methods of isolating and separating 

 the decomposition products were not known; in fact, the identity of 

 the purine bases themselves was not established until very late. Chemists 

 were limited to one decomposition product, and to one reagent for its de- 

 tection. Putrefaction played an important part that was not taken into 

 account. 



These are a few of the many circumstances that not only put the ear- 

 lier investigators at a great disadvantage, but made their work difficult to 

 understand and in some cases impossible to interpret. It is, therefore, 

 not in derogation of many of these obscure investigations, but in the 

 interest of clearness that we pass immediately to the work of Iwanoff 

 (1903). 



He cultivated various molds (Penicillium glaucum and Aspergillus 

 niger) on thymus nucleic acid, and found that both phosphoric acid and 

 purine bases were produced as the molds grew, although there was not 

 present any ferment that could hydrolyze a protein. Iwanoff naturally 

 concluded that he was dealing with a specific ferment, adapted to the 

 decomposition of nucleic acid, and called it "nuclease." Shortly, follow- 

 ing this work, many researches were reported to show the existence of a 

 similar ferment in animal and plant tissues, so that the wide distribution 

 of nuclease was soon conceded. 



But it was shown later that the physiological decomposition of nucleic 

 acid is a rather complicated matter involving a number of active agents, 

 and that various gland extracts differ markedly from one another in the 

 extent to which they can carry this decomposition. It is certain that the 

 first stage consists in the disruption of the nucleotide linkages with the 

 consequent production of simpler nucleotides, but without setting free 

 either phosphoric acid or purine bases. (Jones (e), 1920.) It would be 

 proper to apply the term nuclease to this ferment, or to abandon the term 

 altogether, since it can have no such meaning as was originally ascribed 

 to it. 



Leaving out of consideration the two pyrimidine nucleotides (of 

 which little is known), the purine nucleotides may undergo enzymatic 

 decomposition in either of two ways, depending on the particular physio- 

 logical agent that they encounter. The purine base may be set free, or the 

 phosphoric acid may be liberated with the production of a nucleoside. 



