37. NUCLEIC ACID AND PROTEIN SYNTHESIS 399 



cleic acids involved in protein synthesis, and how does deoxyribonucleic 

 acid exert its ultimate control when it does not participate in the act of 

 synthesis itself? In this section we shall briefly consider the first part of 

 this problem. An able discussion of theoretical aspects of protein synthesis 

 in the light of our newer knowledge has recently been presented by Crick. 6 

 The author and his associates have also presented a brief discussion of these 

 matters. 215 Implicit or explicit in these statements are the following working 

 assumptions: (1) the essential task before us is to understand how the 

 primary structure of protein is determined, i.e., how the amino acids are 

 arranged in a specific sequence. The determination of secondary and ter- 

 tiary structure may be either an active process or a spontaneous result of 

 the order of amino acids. In either case it does not alter the argument since 

 the genetic specificity must reside in the amino acid sequence. (2) We as- 

 sume that the sequence is determined by a template: that some cellular 

 polymer contains information in linear order which may be translated di- 

 rectly into a linear sequence of amino acids. Arguments in favor of template 

 mechanisms have been reviewed recently by Dounce, 216, 217 Spiegelman, 4 

 Dalgliesh, 9 and Crick 6 and will not be presented here. (3) We assume that 

 the template is, in fact, some form of ribonucleic acid and that the linear 

 order of its four bases is somehow directly translatable into the linear order 

 of twenty amino acids in the protein. The mathematical arguments behind 

 the use of four symbols (bases) to code for twenty amino acids have been 

 set forth in detail by Gamow et al., m Brenner, 219 Crick and associates, 6 ' 22 ° 

 and by Delbriick and associates. 221 We are concerned here, not with the 

 manner of coding but with the biological mechanism of information trans- 

 fer, i.e., how the cell makes use of its coded genetic information. (4) We 

 assume that the linear sequence of bases in RNA must be fairly directly 

 related to the linear sequence of bases in DNA — the ultimate repository 

 of the cell's total hereditary constitution. In respect to this latter point, 

 the elegant studies of Benzer 222 and of Jacob 223 have established the linearity 



215 M. B. Hoagland, P. C. Zamecnik, and M. L. Stephenson, in "A Symposium on Mo- 

 lecular Biology" (R. E. Zirkle, ed.), p. 105. Univ. of Chicago Press, Chicago, 111., 

 1959. 



216 A. L. Bounce, Enzymologia 15, 251 (1952). 



217 A. L. Dounce, J. Cellular Comp. Physiol. 47, Suppl. 1, p. 103 (1956). 



218 G. Gamow, A. Rich, and M. Yeas, Advances in Biol, and Med. Phys. 4, 23 (1955). 



219 S. Brenner, Proc. Natl. Acad. Sci. U. S. 43, 687 (1957). 



220 F. H. C. Crick, J. S. Griffith, and L. E. Orgel, Proc. Natl. Acad. Sci. U. S. 43, 416 

 (1957). 



221 S. W. Golomb, L. R. Welch, and M. Delbriick, Kgl. Danske Videnskat. Selskab, 

 Biol. Medd. 23, (9) (1958). 



222 S. Benzer, in "The Chemical Basis of Heredity" (W. D. McElroy and B. Glass, 

 eds.), p. 70. Johns Hopkins Press. Baltimore, 1957. 



223 F. Jacob and E. L. Wollman, in "The Chemical Basis of Heredity" (W. D. McElroy 

 and B. Glass, eds.), p. 468. Johns Hopkins Press, Baltimore, 1957. 



