BIOSYNTHESIS OF NUCLEIC ACIDS 343 



those of Tichomiroff in 1885' on the increase of purines in developing silk- 

 worm ova and of Kossel in 1886,^ who, although he could find no purines in 

 fresh hens' eggs was able to isolate purines from the nucleoproteins of the 

 chick embryo after several days' incubation. Experiments involving the use 

 of purine-free diets by Socin^ in 1891 with growing mice, and by McCollum® 

 in 1909 with growing rats, demonstrated that in these animals, where nucleic 

 acid synthesis was certainly occurring, no exogenous purines were required. 

 Other experiments by Osborne and Mendel,^ by Benedict,^ and by Ackroyd 

 and Hopkins^ have demonstrated this same fact, although the latter authors 

 erroneously concluded that purines arise from histidine and arginine. A 

 result of the fact that, over the last two decades, purified and fully charac- 

 terized diets have been available for nutritional studies has been the re- 

 peated demonstration that none of the organic constituents of the nucleic 

 acids is necessary in the diet. 



II. The Nature of the Substances Which Can Be 

 Utilized as Polynucleotide Precursors 



Although classical nutritional and balance studies lead to the conclusion 

 that nucleic acids can be synthesized from simple substances, they give no 

 indication as to the materials used or the mechanisms involved in nucleic 

 acid biosynthesis. It was not until isotope tracer techniques became avail- 

 able that nucleic acid precursors could be identified and that pathways of 

 nucleic acid biosynthesis could begin to be described. The earliest experi- 

 ments on nucleic acids in which isotopes were used were those of Hevesy, 

 beginning in 1940,'° in which it was shown that when inorganic phosphate 

 labeled with P'^ -^^g administered to animals it was rapidly incorporated 

 into the nucleic acids. Radioactive phosphorus has proved to be a popular 

 isotope in nucleic acid research and has been particularly useful in the 

 demonstration of biological differences among several nucleic acid fractions 

 based on differences in their renewals. It has also been used as an indicator 

 to demonstrate the effects of various agents upon the processes of nucleic 

 acid synthesis. 



The pioneering experiments of Schoenheimer and his group were extended 

 to the nucleic acids when ammonium citrate labeled with heavy nitrogen 



3 A. Tichomiroff, Z. physiol. Ckem. 9, 518 (1885). 

 ' A. Kossel, Z. physiol. Chem. 10, 248 (1886). 



5 C. A. Socin, Z. physiol. Chem. 15, 93 (1891). 



6 E. V. McCollum, Am. J. Physiol. 25, 120 (1909). 



' T. B. Osborne and L. B. Mendel, Z. physiol. Chem. 80, 307 (1912). 

 8 S. R. Benedict, /. Lab. Clin. Med. 2, 1 (1916-17). 

 s H. Ackroyd and F. G. Hopkins, Biochem. J. 10, 551 (1916). 

 1° G. Hevesy, "Radioactive Indicators." luterscience, New York, 1948. 



