RECOGNITION OF ANTIBIOTICS 



i;^ 



designated later by him as "penicillin," and 

 demonstrated its effectiveness in the treat- 

 ment of human diseases. Thus was cul- 

 minated the historical background of the 

 most useful of the antibiotics. With hind- 

 sight we can say that, as was true of the 

 sulfa drugs, penicillin could have been dis- 

 covered sooner. 



2. An even older antibiotic, pyocyanase, 

 offers another illustration. This antibiotic 

 was extensively studied for nearly half a 

 century. It failed, however, tf) achieve 

 practical use because it was a, highly com- 

 plex and somewhat toxic compound. Had 

 another organism producing a more de- 

 sirable substance been used, the field of 

 antibiotics might have been opened much 

 earlier. 



3. The production of antibacterial sub- 

 stances by aerobic spore-forming bacteria 

 has been known for many years. It was in- 

 vestigated hi detail by Xicolle in 11)07, by 

 Pringsheim in 1920, and by Much and 

 Sartorius in 1924-192."), to name only a few. 

 All this work failed to receix'c the attention 

 it deserved. It took some years before this 

 problem was taken up again in a more 

 systematic manner by Dubos (1939), who 

 successfully isolated in 1938 a group of 

 active substances known as tyrothricin, 

 thus opening the field of the antil)acterial 

 antibiotics. 



4. The l''rench clinician N'audremer re- 

 ported in 1913 that the mold Aspergillus 

 fiimigatus exerts a marked antitubercular 

 effect. The extracts of this mokl were used 

 in the treatment of 200 tubercular patients 

 with varying degrees of success. Had the 

 potentialities of such a method of treat- 

 ment been more clearly visualized, screening 

 methods might have been established, the 

 study of chemotherapy of tuberculosis 

 might have been initiated, and perhaps the 

 problem might have been solved much 

 earlier; the world would not have had to 

 wait nearly three decades longer before 



streptomycin was isolated and its anti- 

 tubercular properties were established. 



o. Lieske (1921) in Germany, Krassilni- 

 kov and Koreniako (1939) and Kriss (1940) 

 hi Russia, Gratia and Dath (1924) in 

 Belgium, and Rosenthal (1925) in France, 

 among others, recognized that cultures of 

 the various actinomycetes possess marked 

 antibacterial properties. The agents studied 

 by these investigators were often bacterio- 

 lytic. The concept of a nonlytic antibiotic 

 was not very clear. Gratia and his collab- 

 orators were able not only to experiment on 

 animals with the therapeutic powers of 

 preparations obtained from an actinomycete 

 (Streptothnx albus), but even to treat with 

 success human patients suffering from 

 staphylococcal infections. The methods were 

 ciuasi-immunological. The lytic properties of 

 the actinomycetes have been associated with 

 the phages of d'Herelle and with the lyso- 

 zyme of Fleming, and to this day the litera- 

 ture on the actinomycetic agent of Gratia, 

 later named aclinomucetin by Welsch (1937, 

 1942), tends to be rather confusing. 



(). Whereas most of the above observa- 

 tions were largely concerned with the anti- 

 bacterial properties of actinomycetes, 

 Aliillcr (1908) and, more recently, Alex- 

 opoulos and Herrick (1942) demonstrated 

 that as many as 38.8 per cent of such cultures 

 were also effective against fungi. 



The opening of the field of the antibiotics 

 of actinomycetes was delayed until 1940, 

 when actinomycin, a substance simpler than 

 actinomycetin, was isolated in our labora- 

 tories. Here again, a lack of foresight on our 

 part should be noted. We understood the 

 concept of antiliiosis, but we did not foresee 

 the potentialities of actinomycin as an anti- 

 tumor agent. This discovery had to wait for 

 the investigations of Stock (1950), Hack- 

 mann (1952), and numerous others. 



Despite this fumbling, antibiotics be- 

 came a part of our li\-es, following the route 

 that we now will trace. 



