VIRUS PROTEINS STANLEY 501 



to the red blood cell, it may be seen that certain viruses such as 

 vaccinia and psittacosis are larger than certain well-recognized 

 organisms such as the pleuro-pneumonia organism. At the lower 

 end of the scale certain viruses such as poliomyelitis and yellow fever 

 viruses are smaller than certain protein molecules. Viruses, there- 

 fore, form an unbroken line with respect to size from the molecules to 

 the organisms, and it is impossible at present to draw a dividing line 

 between the two. Now, let us examine the nature of these agents. I 

 have said that certain viruses have been isolated in the form of high 

 molecular weight proteins, and we know that others have been isolated 

 in the form of heavy materials composed chiefly of protein. The ones 

 so isolated include those of foot-and-mouth disease, the staphylococcus 

 bacteriophage, latent mosaic of potato, tobacco ring spot, severe etch, 

 cucumber mosaic, many strains of tobacco mosaic, the Shope papil- 

 loma, coli-bacteriophage, the Rous fowl sarcoma, vaccinia and psitta- 

 cosis. Many of these have been isolated in such small amounts that 

 it has been impossible to study them adequately, hence it is not known 

 whether or not they really have the ordinary properties of molecules. 

 It is possible that some are not molecules, but molecular aggregates or 

 even small specialized organisms. Methods are now available for the 

 preparation in adequate amounts of most of these entities, hence it is 

 but a question of time until sufficient amounts for complete studies 

 are prepared. However, certain of the virus proteins, notably tobacco 

 mosaic, have been prepared in such large amounts that rather com- 

 plete physical, chemical, biological, and serological studies have been 

 possible. These studies have enabled a rather good yet still incom- 

 plete understanding of the probable nature of this virus protein. 

 This afternoon I should like to discuss certain aspects of these studies 

 which may be of value to us in understanding a bit about the manner 

 in which protoplasm grows. 



Tobacco mosaic virus was first isolated in the form of a high molecu- 

 lar weight crystalline protein early in 1935. The material first isolated 

 was not homogeneous in all respects, but since that time it has been 

 possible to prepare tobacco mosaic virus protein that is homogeneous 

 with respect to its physical, chemical, biological, and serological 

 properties. I should like to dwell upon this last statement regarding 

 the homogeneity of the virus protein only sufficiently to impress upon 



A chart showing the relative sizes of several selected viruses, including bacteriophages, as compared to 

 those of red blood cells, Bacillus prodigiosus, rickettsia, pleuropneumonia organism, and protein mole- 

 cules. The figures for size have been arbitrarily selected from data avoilable in the literature. Par- 

 ticles known to be asymmetric are so indicated and the estimated length and width and the molecular 

 weight in accordance with the asymmetry are given. In other cases where the particles are known or 

 assumed to be spherical, the diameter and the molecular weight based on a sphere of density 1.3 are given. 

 *=evidence regarding shape available. t=large size from filtration and sedimentation of concentrated 

 solutions and small size from diffusion of dilute solutions. (This figure, which is an enlarged and revised 

 version of the one originally accompanying this article, is taken from W. M. Stanley, Recent advances 

 in the study of viruses, in Science in Progress, 1939, Yale University Press, New Haven.) 



