Chapter V 

 PENICILLIN 



Penicillin was discovered by Professor Alexander Fleming in 1928. He 

 observed that colonies of Staphylococcus surrounding a contaminating blue- 

 green mold failed to grow. Fleming isolated the mold in pure culture; 

 demonstrated its capacity to produce a powerful bacteriostatic substance, 

 which he named "penicillin"; and recommended the use of the substance 

 for obtaining pure cultures of Bacillus influenzae (1929). He noted in 

 additiim that it might have therapeutic value if it could be produced in 

 quantity, for he found it to be highly effective against a number of Gram- 

 positive bacteria when tested in laboratory cultures. In 1932 Clutterbuck, 

 Lovell, and Raistrick published the results of their limited studies on the 

 production of penicillin by Fleming's mold. In this country, Roger Reid 

 (1933, 1934, 1935) confirmed the production of an antibacterial substance 

 by the same mold, but did not isolate the antibiotic or add materially to 

 the information already published by Fleming and Raistrick 's group in 

 England. 



Interest in penicillin was revived in 1940 through the demonstration of 

 its potential therapeutic value by Professor H. W. Florey, E. Chain, and 

 others at Oxford University. The following year the same group published 

 a more detailed account (Abraham, et al.) in which methods of production 

 and assay were described, and in which some clinical trials were reported. 

 Shortly before this the work on penicillin at Oxford had been interrupted 

 due to war conditions, and Professor Florey and Dr. N. G. Heatlej^ had 

 come to the Northern Regional Research Laboratory where work on peni- 

 cillin was initiated in July 1941. Here a broad program of research was 

 undertaken (1) to develop a more productive culture medium, (2) to find 

 molds capable of producing increased yields of penicillin, and (3) to de- 

 velop, if possible, methods for the production of penicillin in submerged 

 culture. 



Early developments in this country have been reported by Coghill (1944), 

 Thorn (1945), and Raper (1947), whereas the story as it unfolded in Eng- 

 land has been told by Fleming (1944), Chain and Florey (1944), and others; 

 it need not be repeated here. Popular accounts have been published by 

 Ratcliff (1945) and Masters (1946). 



Surface Production and the Development of a Suitable Medium 



Early studies at the Northern Laboratory centered around the produc- 

 tion of the antibiotic in surface culture (fig. 24A), the method which had 



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