ADVANCES IN VIRUS RESEARCH—STANLEY 915 
obvious that a sharp line dividing living from nonliving things can- 
not be drawn and this fact serves to add fuel for discussion of the 
age-old question “What is life?” 
Attempts to learn something about the nature of viruses through 
studies on their general properties began with Beijerinck’s work in 
1898 and were continued in different laboratories for over 30 years 
without too much success. Although Beijerinck and Allard made 
important contributions, perhaps the most significant work was that 
of Vinson and Petre during the years from 1927 to 1931 when they 
showed that tobacco mosaic virus could be subjected to several kinds 
of chemical manipulations without loss of virus activity. Never- 
theless, in 1932 the true nature of viruses was a complete mystery. It 
was not known whether they were inorganic, carbohydrate, hydro- 
carbon, lipid, protein, or organismal in nature. It became necessary, 
therefore, to conduct experiments which would yield information of 
a definite nature. Tobacco mosaic virus was selected for these initial 
experiments because it appeared to provide several unusual ad- 
vantages. Large amounts of highly infectious starting material 
were readily available and the virus was known to be unusually 
stable. Furthermore, it was possible to titrate or measure the amount 
of this virus in a preparation with ease and rapidity and with great 
accuracy. During the course of a wide variety of early exploratory 
experiments, it was found that the enzyme pepsin inactivated tobacco 
mosaic virus only under conditions under which pepsin is active as a 
proteolytic agent. It was concluded that tobacco mosaic virus was 
a protein or very closely associated with a protein which could be 
hydrolyzed by pepsin. With this as a lead, efforts were made to 
concentrate and purify tobacco mosaic virus by means of the methods 
previously employed in work with proteins. Soon, by means of a 
combination of procedures involving salting-out, isoelectric precipita- 
tion and adsorption on and elution from an inert material, a crystal- 
line material was obtained which possessed the properties of tobacco 
mosaic virus. This crystalline material was found to be a nucleo- 
protein with rod-shaped molecules or particles about 280 by 15my in size 
and with a molecular weight of about 40,000,000. Early skepticism 
that a virus could exist in the form of a crystallizable nucleoprotein 
has largely disappeared, chiefly because the results of a vast amount 
of experimental work have indicated that the virus activity is a 
specific property of the rod-shaped nucleoprotein. 
Tobacco mosaic virus exists in the form of many strains which 
appear to have arisen by a process similar to that of mutation in 
higher organisms. Several of these strains have been obtained in 
purified form by means of differential centrifugation. Purified prep- 
arations obtained from plants diseased with different strains of 
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