THE PROBLEMS OF VIROLOGY O 



have been extensively studied but suffer from the disadvantage that the 

 ribonucleic acid present is only about 1 % of the dry weight of the infective 

 particle. In addition, the virus particle is a rather loosely organized entity 

 which appears to contain relatively large amounts of host cell material whose 

 precise relation to the specifically viral components is still not established. 

 There is nothing inconsistent with the view that RNA is the carrier of the 

 genetic qualities of influenza virus but equally there is nothing to exclude 

 the possibility that viral protein may be partly or wholly concerned in pro- 

 viding the patterns to which the new generation of virus particles is built. 



Possibly the most important question for the future development of theo- 

 retical virology is the direction in which research on nucleic acids will develop. 

 The methods by which the proximate constituents, purine and pyrimidine 

 bases and sugars, can be identified and quantitated are well established. 

 Where pure virus has been obtainable these qualitities have been recorded. 

 Perhaps the most interesting findings have been (1) the identification of 

 hydroxymethylcytosine and glucose in the DNA of the T-even bacterio- 

 phages by Wyatt and Cohen (1953); (2) the finding of a significant difference 

 in the bases present in viral RNA from A and B strains of mfluenza virus 

 (Ada and Perry, 1956); and (3) the observation by Reddi (1957) that analysis 

 of RNAase (ribonuclease) digests can demonstrate significant differences in 

 the structure of nucleic acids from different strains of TMV. The next step 

 wall probably be to develop methods analogous to those that have been used 

 in protem chemistry with the ultimate objective of establishing the sequence 

 of bases in the polynucleotide. The technical difficulties are extreme. In the 

 first place it is necessary to estabhsh whether or not the nucleic acid in a 

 virus particle is in the form (a) of a single nucleotide structure (single chain, 

 double helix, or something else) of essentially unique character, (b) of a 

 series of 1, 2, or more types of nucleotide structures, each present in certain 

 constant or variable numbers. In other words, if the nucleic acid could be 

 extracted from a mass of purified virus essentially in the form in which it is 

 present in the mfective particle, how many molecular species would be 

 found? Once means have been found for obtaining each natural molecular 

 species in a pure form, it will obviously be necessary to establish the general 

 pattern of structure. In the case of tobacco mosaic virus, the preliminary 

 evidence favors a single poljoiucleotide chain following the helical pattern 

 of the protein subunits. In the case of a DNA virus, it wiU be necessary to 

 determine whether the Watson-Crick formulation applies and what quali- 

 fications need to be introduced in each specific case. The recent work of 

 Levinthal (1956) and Stent and associates (Stent and Jerne, 1955; Stent et at., 

 1958) with heavily labeled phage represents a current approach in this 

 direction, making use, however, of the biological attributes of DNA to allow 

 chemical deductions, rather than to use chemical and physical methods to 



