1 1 14 CHEMOTHERAPY OF BACTERL\L DISEASES 



tive tubercle bacillus. While Churchman originally believed that the bacteriostatic 

 activity of gentian violet closely followed the gram reaction, i.e., was effective against 

 gram positive organisms but not against B. coli and other gram negative bacilli, he 

 has more recently discovered that the process is not so specific, since he found in a 

 culture of the colon bacillus two different strains, one which was restrained by gen- 

 tian violet and one which was not; Churchman has designated this as "microbic dis- 

 sociation," and the discovery indicates how involved and complicated is this subject 

 of the selective activity of the dyes. 



Furthermore, dyes belonging to the same series may show opposite effects. For 

 example, acidic and basic fuchsins also belong to the triphenylmethane dyes, but yet, 

 as shown by Churchman, these restrain and kill gram negative organisms like B. coli, 

 B. pyocyaneus, etc., designated as "reverse selective activity," whereas gentian violet 

 kills the gram positives like B. diphtheriae, B. anthracis, the staphylococci, strepto- 

 cocci, etc. In other words, such closely related dyes as basic triphenylmethanes 

 (magenta) differ in bacteriostatic power from acidic triphenylmethanes (the sulpho- 

 nated compound, acid fuchsin), since the former is more active than the latter. The 

 subject is of importance in relation to the chemotherapy of bacterial infections, since 

 knowledge already gained indicates that when a dye is to be used for the treatment 

 of a localized infection it should be selected on the basis of greatest bacteriostatic and 

 bactericidal activity in pus for the particular kind of organism present, at least to the 

 extent of selecting gentian violet for gram positive and acid fuchsin or acrifiavin for 

 gram negative bacteria. Furthermore, if new compounds of the dyes are to be 

 synthesized, like compounds with mercury, copper, silver, etc., the selection of the 

 dye should be influenced according to the particular group of organisms for which the 

 compound is intended in order that the bactericidal activity of the compound may be 

 enhanced by the intrinsic bactericidal activity of the dye. 



CHEMISTRY OF THE ANILIN DYES IN RELATION TO CHEMOTHERAPY 



Unfortunately, but little may be written at the present time upon this very im- 

 portant subject of the relation of chemical constitution of the anilin dyes to their 

 bacteriostatic and bactericidal activities. Experts in the dyeing industries have 

 worked out certain laws governing the dyeing of fabrics in relation to chemical con- 

 stitution of both dye and fabric, but our information in relation to the bacteria is very 

 meager. It is practically certain, however, as shown by Churchman and others, that 

 staining or dyeing of living bacterial cells does not necessarily kill them, and that the 

 bactericidal portion of a dye may be indeed a colorless portion, these observations 

 indicating that the relation between chemical constitution and disinfection is much 

 more complicated than between chemical constitution and mere protoplasmic 

 staining. 



But some information has been gained in this important subject. Browning and 

 Gilmour, for example, working with the triamidotriphenylmethane group of dyes, 

 observed that the unsubstituted triphenylmethane compound (pararosanilin) has 

 only a comparatively weak bactericidal action. The substitution of alkyl grou})s in the 

 amido-side-chains (hexamethyl- and hexaethyl-violet) leads to the most active bac- 

 tericidal substances known for staphylococcus, as originally shown by Dreyer, 



