342 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



5. The Question of the Character of the "Active" Derivatives of the Purines 

 and Pyrimidines 387 



a. The Constituents of the Acid-soluble Fractions 388 



b. The Possible Positions of Mono- or Oligonucleotides as Polynucleotide 

 Precursors 390 



VI. Addendum 391 



I. Introduction 



In 1877, Miescher' proposed that in the egg the nucleic acid of the embryo 

 is formed by alteration of the protein viteUin. This was undoubtedly the 

 first published speculation on the mode of biosynthesis of nucleic acids, 

 and, although many theories concerning the origin of these compounds have 

 subsequently been presented, we still cannot adequately describe the proc- 

 esses by which nucleic acids are formed in the living cell. This is partly due 

 to the complex nature of the nucleic acids, and to the incompletely under- 

 stood heterogeneity of the substances. It is also apparent that the PNA 

 and DNA of one species are different from those of other species, that within 

 a single species there is a multiplicity of PNA's differing from tissue to 

 tissue, and that there are within each cell several metabohcally distinct 

 PNA's. Although the concept of a constancy of composition of DNA within 

 a species is prevalent, it has recently been shown that the DNA from a single 

 organ can be separated into at least two fractions. Therefore investigations 

 of the biosynthesis of nucleic acids have involved studies on mixtures of 

 compounds, and it is not impossible that the same pathway of synthesis is 

 not common to all of the nucleic acids. 



1. nonessentiality of nucleic acid constituents in mammalian 



Nutrition 



Because of the universal distribution of nucleic acids and their apparent 

 importance to cellular processes, it is not surprising that organisms are able 

 to accomplish the biosynthesis of nucleic acids from simple and generally 

 available metabolites. Except for a few microorganisms, this is true. Numer- 

 ous investigations have clearly demonstrated that both growing and adult 

 animals are capable of synthesizing nucleic acids and are not dependent 

 upon any external source for the purines, pyrimidines, or sugars of these 

 crucial compounds. In 1874, Miescher pointed out^ that the ability of the 

 migrating salmon to form large amounts of nucleic acid for spermatozoa 

 indirectly indicates the power to synthesize these compounds from other 

 body constituents. The earliest direct experimental demonstrations were 



1 F. Miescher, "Die Histochemischen und Phj'siologischen Arbeiten," p. 108. F. C. 

 W. Vogel, Leipsig, 1897. 



2 F. Miescher, Hoppe-Seyler's Med.-Chem. Unters. 6, 138 (1874). 



