402 S. GARD AND O, MAAL0E 



Timm et al. (1956) found an initial rapid drop in infectivity followed after 

 varying periods of time by a phase of a reduced rate of inactivation, but 

 largely of a first-order type. They also showed that prefiltration of the 

 material had no effect upon the shape of the inactivation curve, although 

 sometimes a considerable retention of virus was observed. 



A Swedish group (Gard, 1955, 1957; Gard and Lycke, 1957; Lycke et al., 

 1957; Wesslen et al., 1957) has reported observations indicating that the 

 reaction is of an order apparently higher than one, and that it is satisfac- 

 torily described by the equation 



log Voly = « log (1 + U) (1) 



iVo = original activity; y = activity at time t; a and b are parameters), the 

 corresponding reaction velocity equation being 



dy ah 



It was shown that the rate of inactivation was independent of the initial 

 virus concentration (Lycke, 1957), indicatmg that the reaction is basically 

 of the first order. It was further shown that the apparent deviation from the 

 first order could not be explained by a gradual loss of active formaldehyde. 

 Filtration or continuous mechanical homogenization during treatment had 

 no effect upon the course of inactivation (Lycke, 1957). Thus, physical in- 

 homogeneity seemed not to be responsible for the deviation from the first 

 order, nor was any genetically conditioned heterogeneity demonstrable. As 

 the apparently only remauiing possibility, it was assumed that the virus 

 particles gradually acquired resistance to formaldehyde in the course of treat- 

 ment and as a direct result of the action of formaldehyde, the progressive 

 fixation or tanning of the protein coat being responsible for the effect 

 (Gard, 1957, 1958). Haas et al. (1957) have presented a large amount of 

 material that is in excellent agreement with the Swedish observations (Gard 

 and Lycke, 1957). 



Bottiger tt al. (1958) found that the time needed for appearance of cyto- 

 pathogenic effects m tube cultures, as well as in the form of plaques, was 

 increasingly prolonged as the time of formaldehyde treatment was extended.^ 

 This phenomenon was at least partly explained by gradually diminished ad- 

 sorption rates, but in addition a prolongation of the first cycle of virus multi- 

 plication may have played a part. However, once the process had started, it 

 seemed to proceed just as rapidly as after infection with untreated virus. 



Within the Hmits of experimental errors the parameter a of equation (1) 

 seemed to be mdependent of environmental conditions, the effect of which 

 was instead reflected in the numerical value of h. The product ah, representing 

 the initial reaction rate (f = o), would correspond to the rate constant of a 



^ This phenomenon was first described by Schultz el al. (1957). 



