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Alexander Fleming’s 1928 discovery of penicillin is one of medical history’s most famous moments. But the original wonder drug languished in laboratories until a World War II research program that rivaled the Manhattan Project-at times literally-brought it to hospitals and battlefields.

By the summer of 1941, Oxford University researchers led by Howard Florey and Ernst Chain had shown that penicillin could cure people of deadly bacterial infections. But making the drug was difficult: The Oxford group started out growing the antibiotic-producing Penicillium mold in bedpans, and even resorted to collecting penicillin from treated patients’ urine. Still, they amassed enough of the drug to treat only six patients. With bombs falling on Britain, Florey and a collaborator went to the United States for help.

A critical stop on their tour was the Department of Agriculture’s Northern Regional Research Laboratory (NRRL) in Peoria, Ill. Quickly convinced of penicillin’s importance, the NRRL researchers went to work. One of their key developments was submerged or “deep” fermentation, a way of culturing the mold within a liquid medium, rather than floating on top. Within a few years, penicillin producers abandoned the thousands of glass flasks or milk bottles needed each day for surface culture in favor of tank fermenters that held thousands of liters like those at Merck and Co.’s Rahway, N.J., plant shown above.

The NRRL also led the search for better-producing variants of Penicillium. They analyzed molds from cheese factories, kitchens and soil samples collected by Army pilots around the world. The best mold came from a cantaloupe found in a Peoria market. To this day, penicillin manufacturers use descendants of that strain.

The NRRL’s early successes and the federal government’s urging helped convince drug companies that large-scale production of penicillin was possible. Ten days after the Pearl Harbor bombing, several industry heads agreed to combine efforts with the government, the military, academia-and each other. Together, the hundreds of researchers at these organizations overcame numerous technical challenges under conditions of wartime scarcity, at times competing with Manhattan Project labs for equipment.

In 1944 the penicillin program paid off: The manufacturers had made enough of the drug to treat all the Allied wounded in the D-Day invasion of Normandy. The next year, penicillin production exceeded 6.8 trillion units-enough for everybody.

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Tagged: Biomedicine

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