PRODrCTlOX OF ANTIHIOTIC'S 



233 



I!) 12) tVoin a culture of :ui organism l)elieved 

 to l)t> a uocarclia (proacMinomycos) but now 

 recognized as a strrptoniyces. Its antil)ac- 

 terial and other biological properties wore 

 later established by Florey ct al. (1945) and 

 by !Marston and Florey. 



Streptomijcin 



The experience gained in the study oi' the 

 formation and isolation of streptothrichi 

 from culture's of actinomycetes proved to be 

 highly important in planning a search for 

 other antibiotic agents that would possess 

 similar or e\'en more desirable biological and 

 chemical properties, such as a broad anti- 

 biotic spectrum and a lesser toxicit}^ to the 

 animal body. After further extensive studies 

 of many actinomycetes representing a great 

 variety of species and varieties, two cultures 

 were found to yield an important antibiotic. 

 These cultures were isolated from the soil 

 and from the throat of a chicken. They both 

 belonged to a species described in 1916 as 

 Actinomijces griseus, the first representative 

 of which was isolated by Waksman and Cur- 

 tis in 1916 from the soil. The generic name 

 of the organism was changed by Waksman 

 and Henrici in 1943 from Actinomyces to 

 Streptomyces. To honor this new generic 

 name, the new antibiotic was designated as 

 streptomycin. 



As previously noted, the two cultures of 

 the streptomycin-producing organism were 

 fu'st isolated in September 1943. Because of 

 the similarity of the new antibiotic to strep- 

 tothricin, both in isolation procedures and in 

 its antibiotic spectrum, rapid progress was 

 made in the development of suitable methods 

 for the growth of the organism *S'. griseus, for 

 the isolation of streptomycin, and for the 

 evaluation of its antimicrobial properties. In 

 January 1944, four months after S. griseus 

 was isolated, the isolation of streptomycin 

 was announced by Schatz, Bugie, and Waks- 

 man. 



Special iiiclhods wcic soon developed for 

 \hv isolation of other streptomycin-produc- 

 ing cultures, as well as for obtaining more 

 potent strains from the mother culture, by 

 using media containing varying concentra- 

 tions of streptomycin (Waksman, Bugie, and 

 Schatz; Waksman, Reilly, and Schatz), 

 Streptomycin was the first antibiotic pro- 

 duced by actinomycetes that took a promi- 

 nent place in the treatment of mnnerous in- 

 fectious diseases in man, animals, and plants. 

 It also proved to be the first drug effective 

 against the Great White Plague of man, tu- 

 berculosis, as first shown by Schatz and 

 Waksman (1944). 



The activity of streptomycin upon bac- 

 terial infections in experimental animals was 

 first established by Jones et al. (1944), and 

 in experimental tuberculosis by Feldman 

 and Hinshaw (1944), and later by Youmans 

 and McCarter (1945), and Smith and Mc- 

 Closkey (1945). The effectiveness of strepto- 

 mycin in clinical tuberculosis was first es- 

 tablished by Hinshaw and Feldman (1946), 

 followed by Cooke et al. (1946), who treated 

 the first case of tubercular meningitis with 

 streptomycin, and soon by numerous others 

 (Keefer et al.). 



Streptomycin w^as soon isolated in crys- 

 talline form (Carter et al., 1945; Peck et al., 

 1945) and its chemical nature determined. 

 In standardizing streptomycin (Waksman, 

 1945), it was found that 1 unit of the anti- 

 biotic, as determined by its activity upon a 

 standard strain of E. coli, under standard 

 conditions of culture, was equivalent to 1 /xg 

 of the pure base. 



Gottlieb and Anderson have shown that 

 the production of streptomycin by *S'. griseus 

 is dependent on many factors. Among these 

 are the constitution of the medium, hydro- 

 gen-ion concentration, temperature, oxygen 

 supply, and agitation of the medium. The 

 process of antibiotic formation followed the 

 same general pattern in all the media. No 



