324 ANNUAL REPORT SMITHSONIAN INSTITUTION, 19 45 



growth. They acidified the medium slightly, extracted with ether, 

 and on removal of the ether obtained the antibacterial substance in a 

 crude form and to it restricted the name "penicillin." It was found 

 to be extremely labile. A very definite step had been taken 5 and sul- 

 fonamides were not yet discovered. It remained for H. W. Florey and 

 his collaborators to reveal the outstanding therapeutic properties of 

 penicillin. Florey worked first with lysozyme, another of Fleming's 

 discoveries, and in the search for other antibacterial substances pro- 

 duced by micro-organisms, E. Chain and Florey turned their atten- 

 tion to penicillin. A culture of Fleming's fungus was obtained and 

 the penicillin was extracted with amyl acetate. Shaking out the amyl 

 acetate with a buffer solution and evaporating the buffer solution gave 

 a substance which was at first thought to be pure penicillin because it 

 proved to be so active. The results of the clinical trials published in 

 1940 showed that it possesses unique therapeutic properties which, 

 moreover, because of its nontoxicity, make it of outstanding value in 

 the treatment of war wounds. But the penicillin used in these chemical 

 experiments was only about 1 percent pure. Several workers here 

 and in the United States are engaged on research in purifying penicil- 

 lin ; a crystalline sodium salt has been obtained which is a hundred 

 times more active than the first extractions. It is capable of inhibiting 

 the growth of certain bacteria at a dilution of about 1 : 50,000,000. 

 Penicillin is a complex acid of which the exact structure is not yet 

 known. 



[AVhen the first trials had shown that penicillin was likely to prove 

 of enormous value in the treatment of war wounds, the problem was 

 to obtain the necessary amount. Florey, in the autumn of 1940, urged 

 the United States to take up the production and, whatever the reason 

 for this, it is certain that no such effort as that of American scientists 

 and manufacturers could have been made here at that period. New 

 strains of Penicillium notatum were sought for, new media devised, 

 and additional therapeutic trials were carried out. Production was 

 eventually such that all the needs of the fighting forces could be met. 

 Over 90 percent of the penicillin used during the war was of American 

 origin. Very extensive research on the structure of penicillin has been 

 carried out both here and in the United States, but although more than 

 one kind of penicillin has been mentioned, the complicated chemistry 

 of this remarkable substance still remains to be revealed.] 



Until recently, all the Penicillium notatum used, both in the labora- 

 tory and in large-scale manufacture, was from Fleming's original 



8 "Another point which shows what practical results may be expected from such re- 

 search is that penicillin, a metabolism product of Penicillium notatum, is nonirritant and 

 nontoxic, but has a strong though different antibacterial power." Presidential address 

 to Section K of the British Association, Ann. Rep. British Assoc, 1936, p. 215. 



