478 A. TSrciTA AM) II. IHAKNKKL-CUNHAT 



themselves with these hi()k)gic:il agents which apijarently were difficult to 

 s(>parate from cellular niateriah 



This situation changed when, in 1935, Stanley announced that he had 

 isolated the tobacco mosaic virus in i)ure and ciystalline form. The term 

 virus then acquired a rlistinctive meaning in physicochemical terms. 

 Soon several otiicr plant viruses were isolated and crystallized, and all 

 were proven to consist of RNA and protein (Bawden and Pirie, 1937; 

 Stanley, 1938). Greater difficulties were encountered in the isolation of 

 animal viruses, but several of them have also been obtained in crj'stal- 

 line form (Schaffer and Schwerdt, 1955). These, as well as the bacterial 

 viruses, proved to contain either RNA or DNA. Through these develop- 

 ments viruses became the subject of intensive physical and chemical, as 

 well as biological, research. With the application of new techniques for 

 the study of macromolecules, such as electron microscopy, X-ray or light 

 scattering, and ultracentrifugation, the structure of many viruses came 

 to be well understood. 



The general pattern emerged that most of the simjile viruses, consist- 

 ing only of RNA and protein, were either of approximately spherical 

 dimensions, or rod-shaped. In all viruses, the nucleic acid was covered 

 by the protein. The amount of protein per jiarticle varied greatly, but 

 the amount of RNA was approximately constant: 1-2 million "molecular 

 weight" per virus particle ranging fi-oni about 5 million for the turnip 

 yellows mosaic virus to 100 million for the influenza virus (Frisch- 

 Niggemeyer, 1956). 



In recent years it has become evident and generally accepted that 

 in the case of many of the simpler viruses the RNA is by itself infec- 

 tious even though of low efficiency (Fraenkel-Conrat, 1956; Gierer and 

 Schramm, 1956). Furthermore, it has been clearly established that the 

 RNA carries the entire genetic information required for virus production. 

 Indications have been obtained that intracellular release of the nucleic 

 acid is one of the first events ujion virus inf(H'tion with the RNA viruses, 

 as was so well demonstrated to be the case with the bacteriophages 

 (Hershey and Chase, 1952). Thus, virus particles are now generally 

 regarded as representing relatively small-molecular genetic nucleic acids 

 wrapped for transport in specifically designed and genetically determined 

 protein overcoats of greater or lesser functional sophistication. In the 

 simple RNA viruses, the role of the protein may be solely structural, but 

 even here evolution has produced some surprising results. Thus, the 

 complete protein coat may represent not only an adequate protective 

 covering for the RNA, but may also give the jiarticle properties of 

 thermal stability and enzyme resistance which are remarkable, consider- 

 ing it.^ predominant protein nature. 



