122 



THE CELL AND PROTOPLASM 



corresponding to a molecular weight of 

 about 400,000 has been found to possess 

 virus activity; hence it is probable that a 

 certain amount of structure may be neces- 

 sary to support such biological activity. 



At the present time, the solution of the 

 virus problem appears to be in the elucida- 

 tion of the structure which is peculiar to 

 materials carrying virus activity. This 

 problem is more complex than that involved 

 in protein structure as such, for, of the virus 

 materials so far isolated, none has been 

 found to yield only amino acids on hy- 

 drolysis. The simplest appear to be com- 

 posed of protein plus nucleic acid ; the more 

 complex, of protein, nucleic acid, and car- 

 bohydrate ; and the most complex, of ma- 

 terials indistinguishable from those found 

 in bacteria. These results may be inter- 

 preted as indicating that viruses are pro- 

 tein or protein-like in nature; but there is 

 little justification for the tendency to ac- 

 cept the results as demonstrating unequivo- 

 cally that viruses are non-living and are 

 merely ordinary protein molecules similar 

 to egg albumin. Although the physical and 

 chemical properties of the virus nucleopro- 

 teins are similar to those of ordinary pro- 

 teins, the biological properties are quite 

 different; and it is because of the virus 

 activity, which implies the ability to multi- 

 ply and to change or mutate, that it is 

 difficult to conclude that they are ordinary 

 protein molecules. Despite this difficulty, 

 the virus nucleoproteins which have been 

 found to have the chemical and physical 

 properties of molecules will be referred to 

 as molecules. Others may wish to refer to 

 these same particles as organisms or cells, 

 but the question of nomenclature is of sec- 

 ondary importance, as will be indicated 

 later. The virus activity is undoubtedly a 

 consequence of the unique architecture of 

 the materials that have been isolated, but 

 before proceeding with such an assumption 

 it is necessary to ascertain whether or not 

 it can be demonstrated that the virus prep- 

 arations are essentially pure and that the 

 virus activity is a specific property of the 

 major component. This demonstration is 

 dependent upon the correlation of chemi- 



cal and physical properties with activity; 

 hence virus activity and its measurement 

 become all-important and must, therefore, 

 be considered. 



The most characteristic and at the same 

 time the most important property of viruses 

 is their biological activity, their infectious- 

 ness or ability to multiply or reproduce 

 when introduced into certain living cells. 

 It is this property that resulted in the 

 original discovery of viruses, and it is this 

 property, more than any other, that has 

 caused viruses to be regarded as elementary 

 living organisms, for the ability to multiply 

 within an essentially non-specific and vari- 

 able environment has been generally con- 

 sidered to be one of the essential character- 

 istics of living organisms. This property 

 also distinguishes viruses from ordinary 

 protein molecules, such as those of egg 

 albumin and of hemoglobin, or even from 

 the biologically active enzyme proteins, 

 such as pepsin or trypsin, which have the 

 ability of multiplication in that they can 

 cause the autocatalytic conversion of spe- 

 cific precursors to pepsin and trypsin. It 

 may be noted here that if specific inactive 

 virus precursors should be found, the virus 

 reaction would then resemble that of the 

 enzymes, pepsin and trypsin. 



During most of the early work with 

 viruses no attempt was made to measure 

 virus activity quantitatively. The activity 

 determinations were merely qualitative and 

 were made to determine whether or not a 

 given preparation could cause infection. 

 In these tests a number of animals or plants 

 were inoculated, and the appearance of dis- 

 ease symptoms was used as an indication 

 of the presence and transfer of virus. At- 

 tempts to make this method quantitative 

 were successful only to the extent that 

 tenfold differences could be detected. The 

 inability to titrate accurately and to follow 

 the major portion of the virus was a great 

 handicap to the earlier workers. However, 

 as a result of the discovery by Holmes in 

 1929 that tobacco-mosaic virus caused local 

 lesions on the leaves of certain plants about 

 two days after inoculation and that the 

 number of such lesions could be used as an 



