It is likely that the last half of the 20th century may someday be termed the 'Age of Antibiotics'. From humble beginnings as contaminants in a microbiology lab, antibiotics became a big business, helped win World War II, and changed society after the war. The story of penicillin is a nice piece of history. It begins with Alexander Fleming [local] discovering the antibacterial properties of a fungal laboratory contaminant in 1928. Ten years later, Howard Florey and Ernst Chain picked up the observation and began to carry out serious studies

The major obstacle was producing enough of the bioactive compound, penicillin, for human trials. The first test [local] was on a policeman with septasemia, but they ran out of penicillin and the patient died. Clearly, antibiotics were powerful medicines, but how could the English scientists produce enough from their fungi? Unless production could be increased, penicillin would not have any practical impact on medicine.

From England, the focus shifted to Peoria Illinois and the USDA Northern Regional Research Lab during WWII.

"In the summer of 1941 the two British researchers came to the United States to enlist aid in improving yields of penicillin, which from surface cultures at that time were about two Oxford units per mL. Not receiving an enthusiastic welcome from the pharmaceutical firms, they turned to the National Academy of Sciences, which sent them to Dr. Thom. Thom suggested the new laboratory at Peoria as having the requisite flexibility and expertise in fermentation technology and the willingness to start studies on penicillin production immediately."

"At Peoria and across the country the search was on for ways to improve the medium for penicillin production, to produce penicillin in submerged cultures, and to develop more productive strains of the mold. Since only Fleming's strain of P. notatum was known at that time to produce penicillin, and it produced it only in surface culture, Raper's laboratory concentrated on finding more productive strains."

"This work on penicillin was an unusually successful example of cooperative research. Though the NRRL played the leading role, there was a remarkable sharing of information among industrial laboratories, laboratories at Cold Spring Harbor, the University of Wisconsin, the University of Minnesota, and elsewhere. A newsletter distributed the latest information, and the collaborating laboratories met all three of their goals. Before D-Day, the Allies had an adequate supply of penicillin on hand to treat their casualties."

"Growing the Fleming strain in surface culture was very cumbersome, but the strain did not produce penicillin in submerged culture. When NRRL strain 832 (from the Peoria culture collection) was shown to produce some penicillin in submerged culture, a wider search was sparked to find a more effective organism. Cultures from many laboratories were tested in Peoria. But the best strain, NRRL 1951, came from a moldy cantaloupe brought to the laboratory by a Peoria housewife in July 1943."

"In subsequent years the press perpetuated many stories-mostly apocryphal-about "Moldy Mary," but it is fact that the housewife's strain of Penicillium chrysogenum immediately proved equal to the best surface strains and was superior in submerged culture to NRRL 832, the strain generally adopted in industry. An even better subculture, NRRL 1951-B25, produced around 250 as compared with the earlier 2 units per ml. and was immediately put to industrial use. Before the war ended, X-radiation at the Carnegie Institution in Cold Spring Harbor and testing at the Universities of Minnesota and Wisconsin had given rise to strains producing 1,000 units per mL. in submerged culture, allowing for a drop in price from twenty dollars to three cents (wholesale) per 100,000 units. The pharmaceutical industry later took over efforts to raise yields and brought them to their present levels of some 50,000 units per mL."

Quoted from Web site [local].

The discovery of penicillin was rewarded with a Nobel Prize in 1945, but there has followed much controversy [local] about the relative contributions of Fleming, Florey and Chain. Following World War II, the penicillin structure was modified and many derivatives were utilized as antibiotics.