Antibiotics in Action

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    Digging for a Cure

       Rene Dubos
      René Dubos
     
       Selman Waksman
      Selman Waksman

    Penicillin was discovered by Alexander Fleming in 1928 and developed for use as a drug by Howard Florey and Ernst Chain in England in the early 1940s. But the work on penicillin was far from done. Scientists knew it was a powerful drug, but it could only be made in small batches. In both the United States and the United Kingdom, the quest was on to figure out how to mass produce penicillin. This involved the combined efforts of several laboratories and pharmaceutical companies in the United States. Eventually they found the right “recipe” for producing large vats of the penicillin extract during the critical years of World War II.

    This kicked off a search to find other drugs that living things might be producing. So further work on the search for antibiotics was done in the United States by René Dubos at the Rockefeller Institute and Selman Waksman at Rutgers University.

    Waksman maintained a life-long research interest in soil organisms including bacteria, actinomycetes (filamentous bacteria), and fungi. He also actively pursued studies of marine microbes. In 1939, Waksman began an extensive screening of thousands of soil microbes, enlisting the help of some fifty graduate students and other scientists who visited his Rutgers University laboratory. This work took place over several decades. Some of the same techniques that Waksman developed are used in the investigation activities Medicine from Dirt: Isolation of Actinomycetes and Name that Actinomycete: Isolating Soil Organisms.

    From the many antimicrobial agents isolated from soil actinomycetes, only streptomycin (purified by Waksman's student, Albert Shatz, in 1943) proved to be safe for humans. Streptomycin later proved to be a useful in treating tuberculosis. Another antibiotic, actinomycin, was discovered later came and to be used as an anticancer agent.

      Hazen and Brown
      Elizabeth Lee Hazen (left) and
      Rachel Fuller Brown (right).
     

    Two other people important to the research for effective antibiotics were Elizabeth Lee Hazen and Rachel Fuller Brown. Hazen was a microbiologist orignally from Mississippi and Brown was a chemist born and raised in Massachusetts. They both worked in research laboratories of the New York State Department of Health and were interested in Waksman's search for antimicrobial organisms in soil. By 1948, Hazen had identified new antifungal agents among the actinomycetes using Waksman's soil-sample techniques. Brown's task was to isolate the active ingredients from cultures that Hazen had isolated, using solvent extractions. The isolated active ingredient was then returned to Hazen to test against the fungi that seemed to be susceptible to the extract. Nearly all the antifungal agents that were effective in killing test fungi were also highly toxic in animals, unfortunately. But one useful antifungal was found in the actinomycete Streptomyces nouresi. The species name, nouresi, was the Latin form of Nourse, the family name of friends of the two investigators. The Nourse family supplied some soil from their garden, and it was from this dirt that the Streptomyces nouresi organism was eventually extracted. The antifungal agent was named nystatin, for the New York State Public Health Department for which Hazen and Brown worked.

    nystatin A1

    For more information, at other Web sites...

      The Nobel Prize in Physiology or Medicine 1952 — biography and work of Selman Waksman from the Nobel e-Museum.

      Soil Bacteria and Actinomycetes — from the U.S. Bureau of Land Management National Science and Technology Center.

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    Image Credits

      René Dubos: Courtesy National Library of Medicine.

      Selman Waksman: Courtesy National Library of Medicine.

      Elizabeth Lee Hazen and Rachel Fuller Brown: Gift of Rachel Fuller Brown.


    Copyright ©2002 The Chemical Heritage Foundation