THE STRUCTURE OF VIRUSES 



121 



It should be emphasized that viruses were 

 first recognized and have continvied to be 

 recognized only by means of their biologi- 

 cal activity, that is, by the diseases which 

 they cause. They were regarded merely as 

 infectious disease-producing principles, and 

 with the exception of viruses of the ele- 

 mentary body type which are as large as 

 accepted organisms, attempts to isolate a 

 virus in tangible form had resulted in fail- 

 ure ; hence little or nothing was known of 

 their true nature. An element of mystery 

 tended to surround them, and they were 

 regarded variously as invisible forms of 

 ordinary bacteria, as Protozoa, as some new 

 type of invisible living orgaiiism, as en- 

 zymes, as unusual products of cellular 

 metabolism, as toxins, and as different kinds 

 of chemical principles. However, because 

 viruses were known to reproduce and- to 

 mutate, and because of certain other prop- 

 erties, most of the workers in the field con- 

 sidered viruses to be living organisms some- 

 what similar to the bacteria. A new 

 viewpoint became possible in 1935, follow- 

 ing the chemical isolation of a material 

 from mosaic-diseased plants, which ap- 

 peared to be a high-molecular-weight pro- 

 tein and which was distinguished by the 

 fact that it possessed the properties of to- 

 bacco mosaic virus. This material could be 

 crystallized in the form of long, thin 

 needles. When carefully prepared it was 

 found to be homogeneous in the Svedberg 

 centrifuge and in the Tiselius electrophore- 

 sis apparatus. The material first isolated 

 was referred to as a globulin because of its 

 solubility characteristics and because no 

 phosphorus was found in the samples which 

 were first prepared for analysis. Later the 

 material was found to contain about 0.6 per 

 cent phosphorus, and after the isolation of 

 nucleic acid from purified preparations al- 

 most simultaneously by Bawden and Pirie 

 and by Stanley, the view was advanced by 

 the former workers that the material was a 

 nucleoprotein. Subsequent work from both 

 laboratories has substantiated this view^ and 

 the material is now generally accepted as a 

 nucleoprotein, although it should be recog- 

 nized that it differs markedly from the 



ordinary nueleoproteins composed of nucleic 

 acid and protamine or histone. The dis- 

 covery of this material was followed by the 

 isolation (by the same or similar chemical 

 methods or by means of differential centri- 

 fugation) of similar high-molecular- weight 

 nueleoproteins possessing the properties 

 respectively of aucuba mosaic, enation 

 mosaic, tobacco ring spot, latent mosaic of 

 potato, severe etch, Shope rabbit papilloma, 

 bushy stunt of tomato, cucumber mosaics 

 3 and 4, and tobacco-necrosis viruses, and 

 of a staphylococcus bacteriophage. The 

 presence of high-molecular-weight protein 

 material in very active preparations of 

 chicken tumor I, equine encephalitis, and 

 foot-and-mouth-disease viruses has also 

 been demonstrated, although Claude's iso- 

 lation of a fraction from normal chick 

 embryo that is quite similar to the purified 

 chicken tumor I preparation casts some 

 doubt upon the significance of the results 

 in the cases of the first two viruses. The 

 isolation of the different high-molecular- 

 weight nueleoproteins was of importance 

 because at last tangible materials possess- 

 ing quite definite physical and chemical 

 properties were available for study, and 

 thus the possibility was offered of corre- 

 lating virus activity with such properties. 

 Although some of the mystery surrounding 

 viruses was removed by the isolation of the 

 nueleoproteins carrying virus activity, the 

 isolation really represented but a small step 

 towards the solution of the problem of the 

 ultimate nature of viruses. Protein struc- 

 ture may be expressed in many different 

 ways, as in hormones, enzymes, toxins, re- 

 spiratory materials, and perhaps as in 

 chromosomes and as in protoplasm, and, 

 since practically nothing is known about 

 protein structure, the addition of viruses to 

 this diverse group aided but little in the 

 establishment of their true nature. All 

 viruses appear to have a high molecular or 

 particle weight; yet this fact alone cannot 

 be used as a criterion of virus activity, for 

 some of the virus nueleoproteins may be 

 inactivated by appropriate treatment with- 

 out changing their size greatly. However, 

 no entity having a size smaller than that 



