The Effect of Impurities on the Chemotherapeutic Action of Crystalline Penicillin.

The possible significance of impurities in the chemotherapeutic action of penicillin was first suggested by Cornman (1944) and by Lewis (1944), who observed that impure but not pure penicillin possessed a selective lethal action against rat and mouse sarcoma cells. Dunham and Rake in 1945 demonstrated that impure penicillin exerted a definite effect on the motility of Treponema pallidum, whereas crystalline penicillin had no such activity. In 1946 Smith showed that germination and root growth is retarded by impure, and not by crystalline, penicillin and stated that the indole-3-acetic acid and phenylacetic acid present in impure penicillins are responsible for this effect. In a recent communication (Hobby et al., 1946), the comparative efficacy of four forms of purified penicillin and random samples of impure penidillin was described. Qn a unitage basis, (CD9o), the relative chemotherapeutic efficacy of penicillins X, dihydro-F, G, F, and K was on the order of 500,. 143, 100, slightly less than 100, and 60, respectively. The values for penicillin F were obtained with a preparation which contained impurities, the action of which was not known. All of the samples of commercial penicillin tested were three to five times more effective than crystalline penicillin G in protecting mice against experimentally produced hemolytic streptococcal infections. The protective action exerted by these impure penicillins was of the same order regardless of the unitage per milligram, or the value of the Bacillus subtilis, Sk&phylococcu= aureus differential ratio. In a series of experiments carried out simultaneously with those reported in the present paper, Welch, Randall, and Price (1947) have confirmed the fact that impure preparations of penicillin are more effective than crystalline penicillin G, and in addition have demonstrated that the action of crystalline penicillin G may be enhanced by the addition of penicillin impurities.