42 RAPER 



activate the antibiotic penicillin in order to test the sterility of the packaged 

 drug; and streptokinase and streptodornase, products of virulent hemolytic 

 streptococci, are used for the debridement of pus and necrotic tissue in 

 wounds and burns. These enzymes are often used in conjunction with or 

 precedent to antibiotic therapy. 



ANTIBIOTICS 



In no other area of human affairs have microorganisms contributed so 

 importantly as they have in modern medicine. Many diseases which formerly 

 claimed thousands of lives annually are today practically non-existent, and 

 many others are effectively held in check by a new class of therapeutic 

 agents, the antibiotics. Whereas man's awareness of such substances goes 

 back many years, realization of their singular curative properties dates only 

 from 1940. Alexander Fleming had in 1929 reported the production of a 

 powerful antibacterial substance by a chance mold contaminant (fig. 1 ) , and 

 he named the elusive substance penicillin after the generic name of the fun- 

 gus, Penicillium, that produced it. He was aware of its potentialities in medi- 

 cine and actually projected these with amazing prescience (fig. 2), but he 

 was not in position to produce and isolate the substance he had revealed. 

 This was done a decade later by Florey, Chain, Heatley, and their asso- 

 ciates at Oxford University. This story has been so often retold that to repeat 

 it here would be superfluous. Equally pointless would be a recounting of the 

 momentous events that led to the large-scale production of this antibiotic by 

 the end of World War II (see "Decade of Antibiotics in America," Mycologia 

 44:1-59, 1952). 



There are, however, certain aspects of this development which are ger- 

 mane to this presentation. The mold isolated by Fleming was subsequently 

 identified, at the request of Harold Rastrick, by Charles Thom as Penicillium 

 notatum, a cosmopolitan fungus found in soil and on decaying vegetation of 

 many kinds. Experience with other fermentations suggested that strains more 

 productive than the original isolate probably could be found, and Thorn's 

 diagnosis gave decisive direction to such a search. Not unexpectedly, almost 

 all strains of P. notatum and of the closely related species P. chrysogenum 

 were found to produce penicillin, and some of the newer isolates produced 

 substantially more than the Fleming strain, particularly when these were 

 grown submerged in large fermenters with strong aeration and agitation. 

 This method of manufacture proved a tremendous boon to large-scale pro- 

 duction, but in itself it could never have provided the quantities of penicillin 

 required by the emergency. Two other developments contributed equally to 

 the success of the program, namely (1) formulation of the lactose-corn 

 steep-liquor medium by Moyer that has so greatly enhanced penicillin produc- 

 tion, and (2) the development of a long series of increasingly productive 



