86 R. MAEKHAM 



kinetics (Cartwright et al., 1956). This probably means that one particular 

 action is limiting, rather than that one formaldehyde molecule will inactivate 

 one virus particle. One of the striking observations about the action of 

 formaldehyde was that it was, in part, reversible. Formaldehyde does in 

 fact react reversibly with amino groups or, to be more precise, it reacts with 

 unionized amino groups to give a compound of the type R — ^NH — CH2OH. 

 At pH values below that necessary for the ionization of the amino group, the 

 formaldehyde is liberated, and this is probably the reason for the reactivation 

 observed by Ross and Stanley (1938). Fraenkel-Conrat (1954) who favors 

 the structure R — N=CH2 for the formaldehyde complex, found that the 

 virus ribonucleic acid had 2-7 % of formaldehyde bound, presimiably to 

 the primary amino groupings of adenine, cytosine, and guanine, in a relatively 

 unstable manner, and he suggested that this was the reaction which caused 

 the inactivation. This value indicates that most of the amino groups of the 

 nucleic acid are involved in links with formaldehyde. This substitution has 

 the effect of shifting the absorption maximum of the nucleic acid some 

 3-5 m/x toward the visible region. 



L. The Nucleic Acid of the Tobacco Mosaic Virus 



As has abeady been mentioned, the nucleic acid of the tobacco mosaic 

 virus was first isolated by Bawden and Pirie (1937a) by a number of methods, 

 including the denaturation of the virus protein by means of heat in the 

 presence of salts, by the action of pyridine on the virus, and by the action 

 of strong acetic acid on the virus, an action which has been shown recently 

 to dissolve the protein in a relatively undenatured form. These authors 

 foimd that the main constituents of the virus were protein and nucleic acid, 

 and they made the important observation that the latter, which is of the 

 "yeast" type or, as it is now called, ribonucleic acid, was relatively large 

 compared with yeast nucleic acid, which at the time was prepared by an 

 alkaline treatment which is now known to uivolve extensive degradation 

 of the compomid. 



Some time later Sreenivasaya and Pirie (1938) prepared the nucleic acid 

 by dissolving away the protein in a solution of sodium dodecyl sulfate. 



The structure of the virus nucleic acid was first investigated by Loring 

 (1939), who had an immense amount of virus available for this purpose. 

 He found that it had the purine bases, adenine and guanine, and also the 

 pyrimidines, cytosine and uracil. He also made the interesting obser- 

 vation that the uridylic acid was apparently an isomeric form of that 

 reported in yeast nucleic acid. It is now known, of course, that yeast uridylic 

 acid is a mixture of two isomeric substances, namely, uridine 3'-phosphate and 

 uridine 2'-phosphate, and it is possible that Lormg had isolated these in 

 different proportions from those reported for the yeast nucleic acid derivative^ 



