RECOGNITION OF ANTIBIOTICS 



17 



bacteriophages in eoml)iiuition with what 

 was then called "mycolysates of staphylo- 

 cocci." These mycolysates were the products 

 of the lytic action of an actinomycete on the 

 pathogen. This actinomycete was identified 

 as Streptothrix alhus and the antibacterial- 

 bacteriolytic complex formed by this or- 

 ganism was named actinomycetin by Welsch 

 in 1937. In a paper published in l!)oO, 

 Gratia said: "We ha\'e used this association 

 of the bacteriophage and of mycolysates of 

 staphylococci in a very great number of 

 cases and we believe that we may say that 

 it is today the most effective treatment of 

 staphylococcal infections. . . ." 



Fleming, working at St. Mary's Hospital 

 of London, had been interested first in the 

 cellular aspect and then in the humoral 

 aspect of immunity. He studied the bac- 

 teriolytic properties of nasal and ocular 

 secretions. In 1922, he gave the name lyso- 

 zyme to a bacteriolytic enzyme al)iuidantly 

 distributed in nature. Lysozyme was later 

 found to be a mucopolysaccharidase which 

 now plays an important role in studies of 

 bacterial biochemistry. In 1929, Fleming 

 pul)lished a paper on the antibacterial ac- 

 tion of a strain of Penicillium. Since the 

 culture filti'ate of the Penicillium was 

 mainly active against gram-positive bac- 

 teria, Fleming considered that it could be 

 used for the making of selective media for 

 the isolation of gram-negative bacteria. He 

 named this active filtrate penicillin. A few 

 more papers were pulilished on this crude 

 substance, but they attracted little atten- 

 tion. In 1982, Clutterbuck, Lovell, and 

 Raistrick published a paper on the metabolic 

 products of the PcnicilHion of Fleming, 

 which was properl^^ identified by Charles 

 Thom as P. notatum. They found a chem- 

 ically defined medium on which it grew and 

 produced the antibacterial substance, which 

 proved to be markedly unstable. Their con- 

 cluding sentence, "The investigation of the 

 isolation and chemical nature of penicillin is 



being continued," was almost the epitaph of 

 Fleming's penicillin ! 



The Discovery of Antibiotics 



The year 1939 was a milestone in the 

 history of the world. The Second World War 

 had started, and as the guns and the bombs 

 began to settle human differences, scientists 

 and physicians were faced with the problem 

 of salvaging what they could of the mangled 

 flesh. 



An impetus was thus gi\'en to the search 

 for antimicrol)ial agents, but this effect was 

 not to be felt immediately in 1939. This date 

 is nevertheless a turning point in the history 

 of chemotherapy. It was about then that the 

 work in Dubos' laboratory at the Rocke- 

 feller Institute yielded tyrothricin, and re- 

 search in the Xew Jersey Agricultural Ex- 

 periment Station yielded actinomycin. It 

 was also at that time that Chain aiul Morey 

 at Oxford I'ni^•ersity carried out their now 

 famous evaluation of penicillin. 



The new study of penicillin showed the 

 great potentialities of this antibiotic as a 

 chemotherapeutic drug. With the war in 

 process, the British investigators needed help 

 to carry out the titanic jjroblem of producing 

 penicillin and elucidating its chemical 

 structure. In 1941, Florey and Heat ley came 

 to the United States. A vast research pro- 

 gram was set up which involved the co- 

 operation of government laboratories, such 

 as the Northern Regional Research Labora- 

 tory in Peoria, of universities, especially the 

 University of Wisconsin, and of many 

 industries. Better media were developed; 

 more acti\'e strains of penicillia were iso- 

 lated; better methods (deep-tank) of culture 

 were introduced on a large scale. Penicillin 

 was found to be therapeutically effective 

 antl could now be produced cheaply. It 

 opened the eyes of the world to a new type 

 of chemotherapeutic agent, of low toxicity 

 and of high activity, against a variety of 

 infectious diseases caused }),v gram-positive 



