VIRUSES AS MOLECULES 3 



mutants are formed, giving rise to new viruBes which cause slightly different 

 diseases. I'he bright spot on the leaf pictured in figure 1 is the result of 

 a mutant having arisen at that point from tobacco mosaic virus. From this spot 

 a new virus, one which produces a disease characterized by the development of 

 bright yellow mottling, was Isolated. 



Before proceeding further, it would be desirable to formulate a definition 

 of viruses. Viruses seem to be disease-causing agents, resembling somewhat or- 

 dinary bacteria, but differing from most bacteria in at lease two important re- 

 spects; In their absolute dependence upon the living cells of the host for 

 reproduction, and in their small size, usually below, but in a few instances, 

 just at the lower limit of visibility with the microscope. Ko virus has ever 

 been recognized which is not pathogenic, at least under some conditions. This 

 may, of course, be attributed largely to the absence of criteria for their 

 recognition other than pathogencity . Because they were too small to be seen, 

 the true nature of these agents long remained a secret. It was only as re- 

 cently as 1935 that any substantial clue concerning the real nature of these 

 filterable, sutmicroscopic bodies was obtained, for in that year Stanley suc- 

 ceeded in Isolating by chemical means from tobacco plants infected with this 

 same tobacco mosaic a crystalline protein of high molecular weight possessing 

 virus activity. 



We know that the virus material is a protein because, like other proteins, 

 such as egg albumin, it reacts with certain common specific reagents to give 

 the usual color reactions expected of proteins. It can be precipitated by a 

 whole series of reagents known to precipitate proteins. It can be denatured 

 by heat and other means, i.e., it can be changed into a permanently insoluble 

 form by a reaction analogous to that taking place when an egg is boiled. Final- 

 ly, this material derived from mosaic diseased tobacco plants shows some of the 

 characteristic Immunological properties of proteins; that is, it can be used as 

 an antigen and the resultant antibodies will undergo the precipitation reaction 

 with the virus protein. All of these properties of the material leave no doubt 

 that it is a protein. In addition to carbon, nitrogen, hydrogen and oxygen in 

 the usual proportions, this virus protein is made up of 0.2?% sulfur and 0.6> 

 phosphorus. In common with all proteins, the building blocks are amino acids. 

 Thus far, from fifteen to seventeen of the twenty or more common amino acids 

 have been isolated or identified. They are alanine, arginlne, aspartic acid, 

 cysteine, glutamic acid, isoleuclne, leucine, lysine, phenylalanine, proline, 

 serine, threonine, trjrptophane, tyrosine, and valine, and possibly histidine 

 and methionine. In addition to these amino acids, the virus also contains about 

 5;t nucleic acid of the yeast or rlbose type. I'he purines and pyrimidines of 

 this nucleic acid have been isolated or identified. 



This virus protein can be precipitated from solution by adjusting the acid- 

 ity to the isoelectric point or by adding ammonium sulfate to a concentration 

 of 2056, It separates in the form of needle-shaped paracrystals , visible with 

 the microscope. A photo micrograph of crystals of tobacco mosaic virus protein 

 is reproduced in Figure 2. 



