400 MAHLON B. HOAGLAND 



of information in DNA, and the work of Ingram 224 has shown us that a 

 change in genetic constitution results in corresponding small changes in 

 amino acid sequence. The autonomy of DNA with respect to its ability 

 to induce specific changes in genetic constitution of organisms (i.e., their 

 enzyme content) has been amply and elegantly shown b}' Hershey, 225 by 

 Avery et al. 22 and by Hotchkiss. 23 



Our assumptions are then, that information passes in only one direction 

 in cells: from DNA to RNA to protein; and that the information resides in 

 the linear arrangement of the monomer units of each of these polymers. 

 (Crick has referred to these concepts as the "Central Dogma" and the 

 "Sequence Hypothesis" respectively. 6 ) 



Theoretical contributions to our understanding of chemical mechanisms 

 of protein synthesis, based on modern concepts of energy-transfer mecha- 

 nisms have been made in particular by Lipmann, 78 Chantrenne, 226 * 227 

 Dounce, 217 and Koningsberger. 228 All of these hypotheses in common en- 

 visioned a direct reaction between amino acid and template: either by 

 amino acid acylation or animation of nucleic acid phosphate groups, the 

 positioning of the amino acid being somehow due to noncovalent interac- 

 tion between an amino acid R-group and template surface (cf. also Loft- 

 field 7 ). There was chemical precedent for the reactions suggested but the 

 mechanism by which the amino acids were directed into the proper order 

 remained vague. 



As the result of the discovery of the role of transfer RNA in protein 

 synthesis, the author and his associates suggested 14, 215 that it might react 

 with the ribosomes by hydrogen bonding between its bases and comple- 

 mentary bases on ribosomal RNA, thereby affording a specific mechanism 

 for locating the amino acids. This is depicted schematically in Fig. 7. Such 

 a concept had been arrived at independently by Crick on theoretical 

 grounds. Crick stated : 



"I cannot conceive of any structure (RNA or DNA) acting as a direct template 

 for amino acids, or at least as a specific template. In other words, if one considers the 

 physico-chemical nature of the amino acid side chains we do not find complimentary 

 features on the nucleic acid. Where are the knobby hydrophobic surfaces to distin- 

 guish valine from leucine and isoleucine? Where are the charged groups, in specific 

 positions, to go with the acidic and basic amino acids? It is true that a 'Teller' scheme, 

 in which the amino acids already condensed act effectively as part of the template, 

 might be a little easier, but a study of sequences from this point of view is not en- 

 couraging. 



224 V. M. Ingram, Nature 180, 326 (1957). 



225 A. D. Hershey, Advances in Virus Research 4, 25 (1957). 



226 H. Chantrenne, Biochim. et Biophys. Acta 2, 286 (1948). 



227 H. Chantrenne, Pubbl. staz. zool. Napoli 23, Suppl. 70 (1951). 



228 V. V. Koningsberger, Thesis, University of Utrecht (1955). 



