44 RAPER 



induced mutations. To this latter endeavor the writer was privileged to con- 

 tribute, and the end result of researches so initiated and subsequently car- 

 ried forward most effectively by Backus and Stauffer was to increase peni- 

 cillin yields from ca. 80 to 3500 units per milliliter in the decade between 

 1943 and 1953. 



From a purely business point of view this tremendously increased pro- 

 ductivity proved not to be an unmixed blessing, as illustrated by the follow- 

 ing production and valuation (wholesale) figures: Total production of the 

 drug in 1943 amounted to 29 pounds, valued at $3 million ($200 per million 

 units); production in 1945 had risen to 14,000 pounds valued at $70 mil- 

 lion; in 1951, 636,000 pounds were produced valued at $137 million; and in 

 1954, production amounted to 860,000 pounds valued at $63 million ($0.09 to 

 $0.10 per million units). The precipitous decline in the wholesale value of 

 the drug over the past twelve years has placed manufacturers in the awk- 

 ward position of receiving less and less for more and more. Viewed from a 

 more humanitarian point of view, however, it has meant wholly adequate 

 supplies of the drug for all the manifold uses where it has proved beneficial, 

 including the use of very large quantities as feed supplements. Whereas new 

 and improved chemical syntheses tend constantly to supplant the microbial 

 production of certain fermentation products (e.g., acetic acid and ethyl and 

 butyl alcohols), industrial manufacture by such means has never challenged 

 the microbial production of penicillin, although a synthesis of the drug was 

 reported as early as 1945. Its adoption today would be utterly inconceivable. 



The tremendous contributions of penicillin to world health need not be 

 recounted. It is sufficient to say that it was the first of a lengthening list of 

 antibiotic drugs, and even now it is the least toxic of these. It was and is 

 the drug of choice for combating virtually all infections caused by gram- 

 positive bacteria. Yet it is not and never was a cure-all. The pathogenic 

 gram-negative bacteria are relatively insensitive to it; it is ineffective against 

 the rickettsiae and viruses; and with its continued use penicillin-resistant 

 strains have developed among those bacterial pathogens against which it 

 was initially most effective, e.g., the staphylococci and streptococci. Addi- 

 tional wonder drugs were and are urgently needed. There are still no adequate 

 chemotherapeutic agents for the control of virus diseases, and cancer in its 

 many forms still resists all forms of medication. 



Spurred on by the singular therapeutic properties of penicillin and by 

 the success that attended the researches which led to its large-scale manu- 

 facture, investigators in many laboratories embarked upon a vast campaign 

 of discovery. Out of this unprecedented search has come more than a dozen 

 additional antibiotics which together with penicillin have extended man's life 

 expectancy by several years. These newer drugs are of course obtained from 

 different microorganisms, but without exception they are produced by modifi- 



