754 6. AESENICALS 



and arsenical withdrawal are not exactly comparable. It is impossible to 

 answer such questions with the information we have but they must be 

 considered in the formulation of experimental programs and theories of 

 mechanism. The difficulty of establishing a mechanism in organisms whose 

 metabolism is poorly understood, and in which the motility and mitotic 

 processes are almost completely unknown, cannot be overestimated. 



EFFECTS ON BACTERIA, FUNGI, YEASTS, AND VIRUSES 



Since 1860 it has been known that arsenite inhibits putrefaction, and by 

 1900 it was realized that some bacteria are sensitive and some are not; 

 e. g., streptococci and the cholera and typhoid bacilli are killed by rela- 

 tively low concentrations, whereas staphylococci, Escherichia coli, and 

 Proteus species grow fairly well in higher concentrations. E. coli will actually 

 grow in 75 vaM arsenite, according to early work. Yeasts and fungi are 

 relatively resistant to arsenite; it may require 20 mM to kill yeast cells, 

 although this depends on the density of the cell suspension, and Penicillium 

 brevicaule grows in 15 raM arsenite, while various other molds have long 

 been known to be capable of growing in Fowler's solution. We shall see 

 later that many fungi have the ability to metabolize arsenicals readily. 



Bacteria 



Only a very small amount of work has been done on the antibacterial 

 activity of the arsenicals, inasmuch as attention has been directed mainly 

 at the protozoa. We can find, for example, that arsenite inhibits the growth 

 of Thiohacillus thiooxidans at 0.1 raM, without altering sulfur oxidation 

 or respiration (Vogler et al., 1942), that 10 mM arsenite completely inhib- 

 its the growth of Bacillus suhtilis, although there is no effect on the germi- 

 nation of spores (Hachisuka et al., 1955), that more than 2 mM arsenite 

 is required to abolish the growth of Proteus vulgaris (Kandler et al., 1956), 

 and similar isolated bits of data, but in no case has a thorough or compar- 

 ative study been made, and only in isolated instances have the organic 

 arsenicals been used. The only really interesting results were published by 

 Albert et al. (1944), who reasoned that if the mercurials inhibit bacteria 

 by acting on SH groups, as Fildes had postulated, arsenicals should also 

 be bacteriostatic; they were surprised to find no references to such work 

 on the organic arsenicals earlier than 1942, when Hirsch (1942) demonstrated 

 inhibition of E. coli with atoxyl (which is probably unrelated to SH groups 

 since the action is antagonized by p-aminobenzoate), and Osgood (1942) 

 reported that neoarsphenamine can inhibit the growlh of Streptococcus 

 viridans in bone marrow culture after many hours. Albert and his co- 

 workers determined the concentrations which just inhibit growth (see 



