CHAPTER XIV 



ANTIBIOTIC SUBSTANCES 



De Bary in 1879 ^ emphasized the significance of the antagonistic 

 relations occurring among the microorganisms. He noted that when 

 two organisms were grown on the same substrate one overcame the 

 other. This phenomenon has been designated as antibiosis. As 

 early as 1897, Duchesne ^ noted that certain Penicillia were capable 

 of inhibiting the growth of various bacteria. In 1913, Vaudremer ^^ 

 demonstrated that Aspergillus fumigatus attenuated cells of Myco- 

 bacterium tuberculosis. The literature on the general field of micro- 

 bial antagonisms has been adequately reviewed by Waksman.^^ 



PENICILLIN 



Seldom has there been such an avid interest shown in a new thera- 

 peutic agent as that displayed in penicillin. The now classic paper of 

 Fleming published in 1929 * on the discovery of a substance which 

 displays antibacterial properties was at first unnoticed and all but 

 forgotten except by a few alert and imaginative workers. Attempts 

 made by Fleming and a few others to interest the medical profession 

 and the microbiologists in carrying out further studies on this anti- 

 bacterial agent met with general apathy or indifference. It was not 

 until the work of Dubos on gramicidin and tyrocidine (tyrothricinfe) 

 awakened the scientific interest in the possibilities of therapeutic 

 agents of microbial origin that the great majority of investigators 

 learned a promising drug of mold origin had been described many 

 years previously. Fleming had, in the course of routine laboratory 

 examination of staphylococcal plates, noted that a contaminating 

 Penicillium had settled to form a colony and that the bacterial colo- 

 nies were being lysed. He also observed that when the mold, which 

 he identified as Penicillium rubrum (later classified as P. notatum 

 Westling), was cultivated in broth it endowed the cultural medium 

 with antibacterial properties. He further determined that the broth 

 filtrate displayed bacteriostatic and bactericidal action only toward 

 certain organisms. Because it seemed to be relatively non-toxic to 

 animals, Fleming suggested that it be used therapeutically in the 

 control of certain bacterial diseases. Clutterbuck, Lovell, and Rai- 



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