52 R. MARKHAM 



One of the main reasons why the nucleic acids were not recognized as giant 

 molecules was that their relative instability was not appreciated; another 

 was that the methods for characterizing large molecules had not been suffi- 

 ciently developed. 



It was not until the late 1930's that, largely owing to the insistence of 

 cytologists, the biochemists realized that someting was wrong with their 

 ideas about nucleic acids, and this was reinforced later by the discovery of 

 the biological activity of a nucleic acid (this time of the "animal" or deoxy- 

 ribose type) derived from certain strains of pneumococcus by Avery et al. 

 in 1944. Shortly after this methods for investigating nucleic acids were more 

 or less revolutionized by the application of chromatographic techniques. It 

 has smce become very obvious that the nucleic acids are a group of exceed- 

 ingly complex molecules, which are usually partially degraded during their 

 isolation and examination, that their general chemical composition is readily 

 amenable to analysis, and, unfortunately, that their detailed structure 

 presents considerable difficulty in its elucidation. Of all nucleic acids, how- 

 ever, those associated with the plant viruses look the most promising for 

 investigation. Indeed, as will be discussed later, there is some indication 

 that the tobacco mosaic virus may contain one unique chain of nucleotides. 

 If this does prove to be so there is a possibility that quite a lot of information 

 about the general structure of the nucleic acid might be obtained. Unfortun- 

 ately its size is such that the hope of determining fine details of .structure is 

 slight. 



The nucleic acids, like the proteins, contain a structural part, and a part 

 which confers their specificity. The backbone of the nucleic acids is a chain 

 of sugar residues, either consisting of ribose or deoxyribose, joined by an 

 equivalent number of phosphoric acid residues, and forming a linear polymer, 

 which may, of course, be coiled or folded because it is flexible about the 

 phosphate linkages. The latter join C5 of one sugar to C3 of the next one by 

 ester bonds to the primary and secondary alcoholic groups of the sugar 

 which are in these positions. 



The biological specificity of the nucleic acid is conferred by the presence 

 of a number of kinds, usually four, of different nitrogenous heterocyclic 

 compoimds, which are present in most, if not all, cases as iV-glycosides. 

 The arrangement and nature of the nitrogenous compounds, or bases, as 

 they are commonly called, is thought to confer the specificity on the molecule, 

 although the mechanism is as yet obscure. It will be noted that four sub- 

 stituents are more than are necessary for conveying information. In fact 

 the molecule is not by any means an economical repository of information, 

 and the presence of at least four substituents may weU be occasioned by the 

 mechanisms by which the nucleic acid is synthesized. It is also possible that, 

 in ribonucleic acid at least, the compound fulfils a dual purpose. 



