CULTIVATION AND RESISTANCE 961 



has started to multiply. That the growth factors supplied by the cells are relatively 

 specific for different viruses is suggested by Andrewes' (1942) observation that 

 growth of one strain of a given virus may render the tissue culture medium unsuit- 

 able for growth of another strain of the same virus added 24 hours later, though 

 not for a strain of a different virus. This is analogous to experience in the growth 

 of bacteria on lifeless media, and suggests that some substance required for the 

 growth of a particular species is soon exhausted. As Rivers (1932) points out, 

 many viruses in tissue culture exhibit both a species and a cellular specificity. 

 Fowl plague virus multiplies only in the presence of chick embryo skin and brain, 

 not in cultures of fibroblasts ; moreover, avian tissue appears to be essential. 



None of the filtrable viruses has yet been cultivated in the absence of living cells. 

 It is true that Eagles and McClean (1931) and Eagles (1935) state that they have 

 grown vaccinia virus in a cell-free medium, but their results have not so far been 

 confirmed (Maitland et al. 1932, Rivers and Ward 1933). It may indeed be ques- 

 tioned whether such highly parasitic organisms as the viruses appear to be are 

 provided with sufficient enzyme systems to enable them to grow in the absence of 

 the cellular activity of their host. The successful cultivation of the pathogenic 

 viruses on lifeless media may well have to await the reproduction in vitro of the 

 complete ferment mechanism of the living cell. 



Most of the common viruses have now been grown in tissue culture. Another 

 method, which has come into increasing prominence of late years, makes use of 

 the developing hen's egg. It was introduced by Ogston in 1881 for the cultivation 

 of bacteria, and was re-discovered by Woodruff and Goodpasture (1931) fifty 

 years later. Inoculation of the chorio-allantoic membrane is the most generally 

 useful way of appljdng this technique. Some viruses, like vaccinia and psittacosis, 

 produce characteristic lesions or pocks on the membrane ; others, like fowl plague 

 and vesicular stomatitis, kill the embryo before local lesions have had time to 

 develop ; others, like Rift Valley fever and influenza, produce both local membrane 

 lesions and characteristic effects on the embryo ; and others, like poliomyelitis, 

 rabies, and foot-and-mouth disease viruses, fail to grow on the egg membrane 

 at all. Burnet has been particularly fertile in recognizing the potentialities of 

 this method, and readers who are interested in its technical details and general 

 application would do well to consult his monograph (1936). (See also Stevenson 

 and Butler 1939, Burnet and Faris 1942, Dunham and MacNeal 1942.) Inocula- 

 tion into the yolk sac or the amniotic sac, or even directly into the embryo, may 

 be used for certain purposes. 



Resistance. — The filtrable viruses vary considerably in their resistance to 

 nocuous agencies. Generally speaking, they resemble the vegetative bacteria more 

 closely than the spore-bearing organisms ; that is to say they are generally des- 

 troyed by exposure to moist heat at 55-60° C. within half an hour, and succumb 

 to fairly low concentrations of chemical disinfectants. On the whole, they appear 

 to be more resistant than the vegetative bacteria to chemical agencies, but it must 

 be remembered that experiments can never be performed in the complete absence 

 of cellular, or at any rate, of protein material ; their apparently greater resistance 

 may, therefore, be due to the protective action of substances in the medium. 



The effect of desiccation varies, partly with the method employed, and partly 

 with the particular virus in question. The Foot-and-Mouth Disease Research 

 Committee (Report 1927) found that filtered vesicle fluid from the guinea-pig, if 

 dried rapidly on slides at 37° C, was often inactivated immediately ; on the other 



P.B. II 



