Penicillin

by KENNETH B. RAPER

PENICILLIN was still a laboratory curiosity in the summer of 1941. It might have remained so had it not been for certain fortuitous events and the urgency of developing new drugs during the war. Today the drug is being manufactured in large quantities. It is the drug of choice for the treatment of many infections and diseases, and it aided immeasurably in reducing the number of war casualties. To produce the drug in the quantities needed in war and peace, it was necessary to develop a new industry with buildings and equipment valued at more than 25 million dollars. New outlets for agricultural products were realized in the development of this industry. The production of lactose, or milk sugar, was almost doubled, and a new and important use was found for corn steep liquor, a byproduct of the wet corn milling industry.

Penicillin was discovered in 1928 at St. Mary's Hospital in London by Alexander Fleming. He noted the presence of a contaminating blue-green Penicillium in plate cultures of Staphylococcus and observed that adjacent to this mold the colonies of bacteria were apparently being lysed, or dissolved. The phenomenon was investigated. When grown in pure culture, the mold, which was subsequently identified as Penicillium notatum Westling, was found to produce a substance that inhibited the growth of Staphylococcus and other disease-producing, gram-positive bacteria. Professor Fleming published the results of his investigations in 1929 and to the active substance he applied the name "penicillin," after the generic name of the mold that produced it. He determined that the substance was relatively nontoxic and he pointed out that it might have therapeutic value if it could be produced in quantity.

In the years that followed, penicillin was almost forgotten. It was not until 1940 that real interest in it was revived. Professors Florey, Chain, Heatley, and their collaborators at Oxford University demonstrated that a crude penicillin in the form of a brown powder (now known to have contained only 2 or 3 percent pure penicillin) possessed curative properties when injected into mice previously infected with Staphylococcus and other disease-producing bacteria. A year later they presented clinical data on six patients, who showed a favorable clinical response. The toxicity of the substance was found to be very low.

Because of conditions then prevailing in England, it was not feasible to produce there the amount of penicillin needed for further clinical trials. For that reason, aided by the Rockefeller Foundation, Drs. Florey and Heatley came to the United States. Here they were referred to the National Research Council and to Charles Thom, principal mycologist in the Department of Agriculture in Washington. They were advised to come to the Northern Regional Research Laboratory in Peoria, Ill., where members of the staff of the fermentation division had had experience in mold fermentations and a large collection of molds was maintained. Dr. O. E. May, then director of this laboratory, and Dr. R. D. Coghill, head of the Fermentation Division, realized the tremendous possibilities of the drug, and arrangements were made to begin work on the problem at once.

Research on penicillin at the Peoria laboratory was directed primarily along the following lines : To develop, if possible, a culture medium that would favor the production of a greater amount of penicillin; to investigate the possibility of producing penicillin in submerged culture; and to try to develop strains capable of producing increased yields.