IV. THE VARIABILITY OF VIRUSES 159 



rate of multiplication of the phage, which can be estimated from the 

 plaque sizes. 



For the variation of phage, however, the multiplication under the 

 altered conditions is not essential. It can be induced, without any 

 multiplication, by a mere addition of such substances as formaldehyde, 

 mercuric chloride, or the antiserum against the phage (68) (69). In 

 these cases the variation would occur in the reduction of the viru- 

 lence, and the altered characters occasionally tended to be transmitted 

 to new viruses produced from the altered virus. If these agents were 

 added in proper quantities just enough to completely inactivate the 

 phage, the antigenic specificity of the latter would be retained unal- 

 tered. The change in the virulence appeared to take place when the 

 inactivation was imcomplete. 



Similar phenomena have been observed with various viruses other 

 than phage. For instance, Salaman (70) found that incubating tobacco 

 roots infected with potato virus Y for a week at various temperatures 

 above 22^ C. produced less virulent forms. By keeping Rous sarcoma 

 tissues for a long time at a temperature below 0^ C, Gheorghiu (71) 

 has succeeded in reducing the virulence of the virus to be unable to 

 kill the fowl, although active enough to produce the tumour. Bjork- 

 man and Horsfall (72) found that a single treatment of influenza 

 virus with lanthanium acetate or with ultraviolet radiation, fol- 

 lowed by subsequent passage in chick embryos, altered the virus in 

 its behaviour towards red blood cells. This altered property of the 

 treated virus persisted through several passages. Miller and Stanley 

 (73) have prepared the phenylureido derivatives of tobacco mosaic and 

 found that although these derivatives produced as many lesions as 

 untreated virus in Nicotiana ghitinosa, they were less infective when 

 treated in Phaseolus vulgaris. 



Thus certain alterations in the structure of virus proteins appear 

 to be accompanied by some change in the virus property, provided 

 alterations are not so extensive as to entirely inactivate the virus. 

 This should only be natural, since the property of a virus should be 

 determined by the structure of the protein and the altered structure 

 in turn should be transferred to the new viruses derived from it as 

 the multiplication of a virus is nothing but the reproduction of the 

 same structure. Newly formed structure of a virus therefore should 

 alwa^'s be inherited together with the altered characters. However, 

 frequently newly formed character would soon be lost with the re- 

 covery of the original one. This is the most important phenomenon 

 arising from the reversibility of protein structure, the detailed ac- 

 counts of which will be given later. 



