PENICILLIN 



91 



production of penicillin upon bran, employing techniques similar to that 

 used for the production of diastatic enzyme preparations with Aspergilhis 

 oryzae. Before penicillin as a drug became generally available, several 

 investigators (Hobson, 1944; Alston, 1944; and Dunayer et al, 1944) studied 

 the production of "crude penicillin," usually by growing the mold on sterile 

 gauze saturated with a suitable culture solution and subsequently applying 

 such gauze preparations directly to surface wounds. By this method, 

 patients for whom penicillin would otherwise have been unavailable were 



Fig. 24. Laboratory methods of producing penicillin. A, Surface or still culture 

 of Penicillium notatum, NRRL 1249. B21, in a wide bottom Fernbach flask (2.8 liters). 

 B, Submerged or deep culture of P. chrysogenum, NRRL 1951. B25, in a 300 ml. Erlen- 

 meyer flask. 



treated with the drug. Carpenter, et al. (1945) produced such preparations 

 in considerable numbers for use in the Hawaiian Islands and by the Navy 

 in the South Pacific area (see also Agmar, 1945; and Larsen, 1945). Cer- 

 tain dangers inherent in this practice in the absence of rigorous asepsis, 

 were pointed out by Raper and Coghill (1943). 



Submerged Production 



Of the various methods proposed, the production of penicillin in sub- 

 merged culture was early realized to be the most important (fig. 24B), and 

 particular attention was given to the development of tliis type of fermenta- 



