Producing Penicillin

Alexander Fleming, a British researcher, observed in 1928 that a blue-green mold that had landed accidentally in a culture of bacteria on his desk produced a substance that killed several disease-causing microbes. He named it penicillin after the mold, Penicillium notatum. During the next 13 years, the British succeeded in converting penicillin into a stable brown powder. In 1941, a few months before Pearl Harbor brought the United States into World War II, they still had not found a way to mass-produce the drug.

In June 1941, two British scientists, Howard Florey and Norman Heatley, came to the United States carrying a small package of brown powder-penicillin. Their mission: to work with Americans to produce the drug in quantity and to keep it out of the hands of the Nazis. From Washington, D.C., they were directed to USDA's Northern Regional Research Laboratory in Peoria, Illinois, where researchers had experienced success in growing molds with a process called deep vat fermentation.

One of the Peoria scientists, Andrew J. Moyer, grew the penicillin in a nutritious medium that included corn steep water, an inexpensive byproduct of the wet corn milling process. He kept adding nutrients to his medium until he had increased penicillin yields by more than 10 times. Moyer's results encouraged four U.S. drug companies to try large-scale penicillin production. The public-private agreement came soon after Pearl Harbor.

But Moyer was dissatisfied with results. He could grow Penicillium notatum on the surface of his medium, but it wouldn't grow in deep vats, where prior experience with other molds had taught him he could increase production substantially.

On the lookout for a more productive strain of Penicillium, a staff member found it on a moldy cantaloupe in a Peoria market. It was Penicillium chrysogenum, and Moyer was finally able to grow it in quantity submerged in deep fermentation vats. The medium was corn steep water and milk sugar. Results were so promising that the U.S. drug industry adopted the medium and the newly found mold and began to increase penicillin production. By the end of 1942, 17 companies were working to increase output still more. Thanks to the combined efforts of the public and private scientists, enough penicillin was available on June 6, 1944, to treat Allied troops wounded on D-day. It was penicillin that helped vanquish the terrible killer of earlier wars, gas gangrene.

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More New Drugs

Selman Waksman at Rutgers University discovered the powerful antibiotic streptomycin in 1943 from among a group of soil microorganisms called actinomycetes. Drug companies soon found more antibiotics--chloromycetin, aureomycin, and terramycin. Researchers in several places, including the ARS lab in Peoria, discovered the antibiotic polymyxin in 1947, and the Peoria lab found a way to increase its production, as it had with penicillin. Waksman, in 1948, discovered neomycin, and in 1950, USDA scientists in Peoria found a new form of streptomycin, produced by a different actinomycete. Today, ARS maintains the world's most complete collection of these valuable microorganisms.

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Search for Cortisone

Shortly after cortisone was found to relieve rheumatoid arthritis in 1948, USDA and the National Institutes of Health conducted a worldwide search for plants containing precursors of the steroid. A precursor is a substance that precedes and is the source of another substance; one important such compound in producing steroids is diosgenin.

Some 6,600 plant species were collected and screened for diosgenin in the 1950's, using analysis techniques developed by Philadelphia lab researchers. Highest yields of the compound were found in a wild Mexican yam. Within a few years, 70 percent of the steroids produced in this country were made from the diosgenin in these tubers.

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Treating Shock in War

A replacement for blood plasma called dextran was first administered intravenously to wounded troops during the Korean War, when plasma was in short supply. Dextran persists in the blood longer than plasma and does not need refrigeration. Developed at the ARS lab in Peoria, dextran proved effective in treating shock and blood loss and is credited with saving thousands of American lives.

Dextran is made by fermenting sugar with a microorganism first found in a bottle of spoiled or "ropy" root beer. Now researchers are producing special dextrans for food processing and industrial applications. These natural carbohydrates could possibly replace costly plant gums as binding agents, emulsifiers, and stabilizers in processed foods. ARS is breeding several strains of the same bacterium used to produce the original dextran to isolate new dextrans.

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Drug from a Yew Tree

The anti-cancer drug taxol was first discovered in the bark and needles of the Pacific yew, an evergreen tree native to the Pacific Northwest. Unfortunately, the yew is a slow-growing tree, and it takes several thousands trees to produce just one pound of the drug.

An ARS biologist and her team in New Orleans eventually found taxol in not one but six different species of Taxus yews. They also were able to employ tissue-culture techniques to grow the taxol-producing cells of the tree in the laboratory. The team's research was patented and licensed by Phyton Inc. of Ithaca, New York (USPN 5,019,504; Docket #1047.87). Additional research on the drug was carried out by Washington State, Colorado State, and Cornell universities and by other institutions.

Subsequently, Bristol-Myers-Squibb began producing taxol, using what the company described as a "semisynthetic" process. The drug passed its clinical trials and has now been approved by the Food and Drug Administration. It is being used to treat ovarian and breast cancer and also appears promising as a treatment for certain forms of lung cancer.

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Updated 7/17/03