RADIATION AND VIRUSES 337 



Sect. 3-2). Protection against both agents is generally afforded by the 

 same substances. 



2-1 b. Direct Effect. The inactivation of viruses b}' the indirect effect 

 of ionizing radiations is mediated by chemicals produced in the medium. 

 Its rate is affected by the temperature and by the distribution of dose in 

 time, as e.xpected from considerations of chemical kinetics. Because of 

 its occurrence some questions have been raised as to the very existence of a 

 direct effect exerted by the primary absorption of radiation energy within 

 the physical domain of the virus particles. Yet such a direct effect is 

 certainly present, and its analysis is possibly more revealing than that of 

 the indirect effects, as far as the mechanism of biological effect of radia- 

 tions is concerned. A direct effect of ionizing radiations is defined as a 

 "nonprotectable" effect, i.e., an effect that cannot be eliminated by alter- 

 ations of the medium. If the concentration of protective substances in 

 the medium is increased beyond a certain level or if the virus is irradiated 

 in the dry state, inactivation will proceed at a minimum rate, which 

 cannot be further reduced (Luria and Exner, 1941 ; Lea, 1946). This 

 residual inactivation is a function of only the total radiation dose and is 

 not modified by changes in oxygen tension (Hewitt and Read, 1950), in 

 temperature (Watson, 1950), or in the intensity of the radiation beam 

 (Wollman et al., 1940; Lea, 1946), thus exhibiting all the characteristics of 

 photochemical reactions. The distinction between direct and indirect 

 effects has recently been emphasized, at least in the case of bacteriophage, 

 by the finding that the biological properties of phage particles inactivated 

 by X rays in the presence of an excess of protective substances differ in 

 many respects from those of particles inactivated by various types of 

 indirect effects (Watson, 1952; see Sect. 3-2).^ 



The direct effect of ionizing radiation on viruses has been analyzed 

 repeatedly in relation to the mechanism of radiation action not only on 

 viruses but on genetic units and cells in general (Lea, 1946). In all well- 

 investigated cases, inactivation of viruses proceeds according to Eq. (9-1). 

 This indicates that one radiation "hit" inactivates a virus particle, i.e., a 

 particle is inactivated by one successful act of absorption, without sum- 

 mation of individual effects. 



Thus virus inactivation is a good test for further analysis based on the 

 hit theory, and it has been employed widely in testing the validity of the 



'Experiments by A. H. Doermann in 1951 (unpubli.shed) show that addition of 

 cysteine or BAL to a suppo.sedly completely protecting medium such as nutrient broth 

 can reduce the rate of bacteriophage inactivation by X rays by as much as a factor of 

 2. This important discovery, if confirmed, might force a revision of the definition of 

 direct effect. More likely, it may be an indication that the direct efTect, although 

 direct in a geometric sense, i.e., exerted through acts of radiation absorption within the 

 virus particle, is in part mediated through water tiound around or within the virus in 

 a way that permits agents such as cysteine or BAL to interact with the oxidizing 

 products of water decomposition. 



