b F. M. BURNET AND W. M. STANLEY 



obtain a direct solution. The final step will be to build up a detailed account 

 of the sequence of nucleotides (and any other minor components which may 

 emerge from future work) that build up each tjrpe of macromolecule. At the 

 present time such a program may appear to be out of the question but 

 recent success in elucidating the amino acid sequence of some of the simpler 

 proteins suggests that another decade may well see the publication of what 

 we should now regard as a full chemical description of the protein com- 

 ponent and perhaps also of the nucleic acid of tobacco mosaic virus. 



If insulin has been the protein par excellence for the unraveling of a 

 structure which can serve as a model of other proteins of greater biological 

 significance, so we can feel confident that the logical choice for nucleic acid 

 is the E.NA of tobacco mosaic virus or possibly that of one of the small 

 spherical viruses, such as tomato bushy stunt or turnip yellow mosaic. The 

 current hypothesis that in some way each type of RNA must carry the 

 "information" eventually expressed in the structure of the protein associated 

 with it may be qualified and elaborated, but it is inconceivable that there is 

 no significant relationship between the two types of macromolecule. Tobacco 

 mosaic or some other readily available plant virus has the enormous advant- 

 age of providing a system with, as far as we know, one species each of 

 protem and of RNA in association. The fact that the RNA can induce the 

 formation of additional molecules of its own kind and can in addition induce 

 the formation of a highly specific protein with which the RNA eventually 

 combines offers a direct avenue of study of the synthesis of polynucleotides 

 and polypeptides and of their interrelationships. If the chemical significance 

 of the general association of protein and RNA is ever to be elucidated, here 

 is the least complex system we are likely to find for its study. Investigators 

 at the Virus Laboratory in Berkeley have already launched a long-range 

 program of study of this system. A substantial part of the amino acid sequence 

 of the 164 amino acids comprismg the protein subunit of TMV has already 

 been worked out and comparisons with the amino acid sequence of TMV 

 strains have revealed significant differences (Gish et al., 1958; Ramachandran 

 and Gish, 1958; Niu and Fraenkel-Conrat, 1955; see Knight, Chapter 3 of 

 Volume II). Work on the polynucleotides of TMV and certain of its strains 

 has yielded indications of structural differences (Reddi, 1958). Eventually a 

 point-to-point structural relationship between polynucleotide and the 

 polypeptide it induces may be revealed. 



If, as we beheve, the nucleic acids are the essential carriers of all genetic 

 codes in the smaller viruses, we can adopt an analogy with the old view that 

 the mammalian body is a mere temporary carrier of the potentially eternal 

 "germ plasm." It is the nucleic acid of the virus which must be brought into 

 an appropriate environment where it can replicate its pattern. The rest of 

 the virus is mere machinery to allow this to be accomplished. This at least is 



