450 CHEMICAL AGENTS 



3. SELECTIVE ACCUMULATION 



We have customarily thought of the inhibiting of an unwanted or- 

 ganism as a problem in selective toxicity, to find materials which are 

 inherently more toxic to one form of life than to others. It has been 

 assumed that the ultimate basis for such a selective action must be the 

 existence of some sensitive protoplasmic reaction in the undesirable 

 organism which does not exist, or is dispensable, in other species. This 

 approach has, of course, had its successes, notably in explaining the 

 chemotherapeutic value of the sulfonamide drugs, but the major effort 

 of modern biology has been to show how similar are all forms of life 

 in fundamental biochemical aspects and thus to render less and less 

 likely the prospect of finding truly selective agents at the protoplasmic 

 level of action. 



It now appears that another selective principle may be equally im- 

 portant: the differential accumulation of a toxicant by the unwanted 

 organism. The term selective accumulation has been used by Yarwood 

 (460) to describe the finding that spores of Uromyces phaseoli accumu- 

 late more sulfur from a fungicidal treatment with the vapor phase 

 than do the leaves of the host plant. That is, we may hope that some 

 materials which are perhaps equally toxic to all organisms may be 

 accumulated selectively by a fungus; the result, of course, is equivalent 

 to selective toxicity and is a form of it, but does not depend on an 

 inherent protoplasmic or enzymatic sensitivity. Selective accumulation 

 does, of course, require that the sensitive organism differ physiologically 

 from the insensitive, but it does not require us to postulate, for ex- 

 ample, that protein synthesis or energy metabolism of the susceptible 

 species differs from that of the resistant. The problem becomes nar- 

 rower and more manageable: by what mechanism does the sensitive 

 organism accumulate, or the insensitive exclude, the toxicant? 



In the previous section, some evidence has been cited that resistant 

 strains of microorganisms owe their resistance to the failure of the 

 toxicant to reach sensitive sites. This is in a sense the reverse of 

 selective accumulation, to be considered provisionally as selective ex- 

 clusion. 



The idea of selective accumulation is not, of course, new; it has 

 been known for some time that the lethal action of heavy metals on 

 bacteria follows upon accumulation of the toxicant by cells in amounts 

 far in excess of their concentration in the external medium (455). It 

 is apparent that fungus spores can similarly remove from the medium 

 very large amounts of many different toxicants. Marsh (273) found 



