396 S. GARD AND O. MAAL0E 



was used as a test plant. Problems of this nature assume particular importance 

 in production and testing of "killed" virus vaccines, and further examples 

 will be mentioned in the following sections. 



Apparently, therefore, a virus particle can be considered as truly inacti- 

 vated only if its reproductive capacity is definitely and irreversibly destroyed 

 through a chemical alteration of its nucleic acid. A chemical agent, in order 

 to produce such effects, must first penetrate the non-nucleic acid protective 

 cover, or destroy and remove it. Apart from enzymes, to which the protein 

 is most probably impermeable, no chemical agents could be expected to be 

 suSiciently specific to react only with the nucleic acid. It is, thus, to be 

 expected that inactivation by chemical means will involve not only the 

 nucleic acid but, to an even greater extent, the non-nucleic acid components 

 of the virus. Obviously, the mechanisms of chemical inactivation cannot be 

 fully understood unless the structure of the virus and the various functions 

 of its integral parts are known. Needless to say, our present knowledge is too 

 fragmentary to permit a really rational approach to this problem. It is im- 

 portant, however, to keep the various possibilities in mind. Experimental 

 data on inactivation, when carefully analyzed and correctly interpreted, are 

 likely to add to our knowledge of the nature of viruses and their mode of 

 action. 



In the present situation it may be helpful, as a first approximation, to 

 compare the structure of the virus particle to that of a bacterial cell. In both 

 cases the vital interior is enveloped in a fairly resistant membrane, function- 

 ing more or less as a mechanical and chemical sieve. The capacity of a 

 chemical agent to cause inactivation will, thus, depend, not only upon its 

 reactivity toward the nucleic acid, but also upon its molecular size, charge, 

 and chemical affinity to the "membrane." The kinetics of inactivation will be 

 shaped by the balance of these various factors. For instance, a first-order 

 type of reaction (when the chemical agent is present in excess) should be 

 expected under two conditions only: either (a) when mainly surface reactions, 

 involving a specific receptor mechanism, are responsible for the loss of in- 

 fectivity, or (b) when no interaction between the agent and the surface 

 structures takes place. All reactions with the latter will — in one way or 

 another — disturb the rate-determining difiiision through the membrane. 

 Thus, it should be expected, at very low concentrations of the chemical, that 

 the diffusion pressure would remain insignificant until the surface was 

 "saturated." In other words, as in the case of disinfectants versus bacteria, 

 the chemical agent would have to exceed a critical concentration level in 

 order to produce a measurable inactivation. Furthermore, any reaction taking 

 place in the membrane must be expected to affect its permeability, causing a 

 continuous change in the rate of diffusion. A "fixation" (in the histological 

 sense) of the protein cover would be associated with a gradual slowdown of 



