Benjamin Minge Duggar directed the research that led to the discovery, production, and application of Aureomycin (chlortetracycline), the first broad-spectrum antibiotic that was both safe and effective. Aureomycin could be taken by mouth, instead of by injection only, and it was effective in 90 percent of cases.
On July 21, 1948, at a conference arranged by the prestigious New York Academy of Sciences in the Museum of Natural History, the new antibiotic Aureomycin was introduced to the public. It was uncommon for a medical breakthrough to be trumpeted to the world as this drug was. About twenty clinicians were present to broadcast the spectacular results they had achieved with it. Also on hand were several scientists from Lederle Laboratories
Before the auspicious debut of Aureomycin, several antibiotics had become available to health professionals. By far the most efficacious of the new “miracle drugs” was penicillin, successful against 40 percent of bacteria-caused diseases, and streptomycin, effective against 30 percent. These therapeutic agents had given physicians the weapons they needed to conquer the terminal and disabling infections.
Nevertheless, many dangerous infections refused to surrender to either agent, and these now stood out. Several were caused by viruses and by small virus-like bacteria,
The discovery of penicillin
The company’s success in developing a new multipurpose antibiotic owed much to the biochemist Yellapragada Subba Row, who joined Lederle in 1940. As director of research, he supervised Lederle’s chemical, medicinal, and pharmaceutical research. During World War II, Subba Row contributed to the research on penicillin and streptomycin in large quantities. He was also responsible for bringing Duggar to Lederle. Mindful of Duggar’s extensive knowledge of molds, Subba Row invited the former professor of several of Lederle’s scientists to take a position with the company as a consultant in mycological research and production.
Although Duggar’s name did not become familiar outside his field until 1948, his work had been known to botanists for a long time. For several decades, he had been recognized internationally as an authority on molds and fungi. Nevertheless, on reaching the age of seventy, he was forced to retire from teaching. Still quite active physically and mentally, Duggar was not content to live in retirement, especially in the midst of a devastating world war. Hence, in 1944, he accepted Subba Row’s offer to join Lederle.
At first, Duggar’s work at Lederle was concerned with plant sources of antimalarial drugs. He was impressed deeply by the success of penicillin, which had just come into widespread use. He perceived that the surface had only been scratched in the field of antibiotics. He soon initiated an immense soil-screening program. His objective was to discover a superior antibiotic—one that would combat diseases that completely resisted penicillin and other available antibiotics.
Duggar and his colleagues believed that one of the lesser groups of molds, known as actinomycetes, might yield a valuable antibiotic. Actinomycetes occupy an intermediate position between genuine bacteria and fungi. An expert on actinomycetes, Duggar remarked that his fellow mycologists had hitherto treated the microorganisms “with static contempt.”
Because molds are denizens of the soil, Lederle scientists began their project by gathering from all over the country more than six hundred soil samples, which they screened for actinomycete strains that might have microbe-killing potential. The molds were tested by putting them in petri dishes, along with specific microorganisms, and then observing their ability to inhibit the growth of neighboring organisms. The screening was a long, tedious task. Duggar and his team suffered disappointment after disappointment. More than thirty-five hundred strains were scrutinized and rejected. Eventually, the investigators came to a petri dish labeled “A 377,” which contained a golden-colored mold obtained from a soil sample taken from the campus of the University of Missouri. It was one of several samples sent to Duggar in the summer of 1945 by his former colleague, William A. Albrecht
According to procedure, the promising mold was subjected next to a battery of tests to assess the extent of its antimicrobial activity and its degree of toxicity. The safety of the substance was a prime consideration; any antibiotic that was injurious to the patient would have no therapeutic value.
Test-tube experiments were conducted in September, 1945, to gauge the mold’s effectiveness against some fifty pathogenic organisms. Albert Carl Dornbush, from the University of Wisconsin, was in charge of the important in vitro work. The results were astounding. The mold arrested the growth of staphylococci, streptococci, and bacilli. That the mold, later named Streptomyces aureofaciens
Two more years of experiments by Lederle scientists demonstrated that Aureomycin was not toxic to laboratory animals and that it had an effective range of action much greater than anyone had expected. In 1947, the new drug was isolated in a relatively pure and inexpensive form; that same year, it was used for the first time on human patients. Clinicians at several university-affiliated hospitals reported success in controlling numerous infections that had responded poorly or not at all to previously available antimicrobial agents. Furthermore, they observed that Aureomycin produced only a small number of side effects. By mid-1948, the drug was being manufactured at the rate of a pound a day. It was first offered to physicians on a wide basis on December 1, 1948. Aureomycin soon took its place among the most useful of all life-saving drugs.
Antibiotics revolutionized the therapy of infectious diseases in the 1940’s, and Aureomycin brought extraordinary assets to the new age of medicine. One was its versatility. Possessing a much broader application than penicillin or streptomycin, it was effective against 90 percent of bacteria-caused infections. Also, unlike the two formerly premier antibiotics, which were usually administered by needle, Aureomycin was effective when taken by mouth. Consequently, it could be dispensed quickly and painlessly either in the physician’s office or in the patient’s home.
Most important, Aureomycin proved to be remarkably effective against certain infections that had failed to respond to either penicillin or streptomycin. One of these illnesses was Rocky Mountain spotted fever
The golden antibiotic, moreover, became the preferred antimicrobial agent in combating several diseases caused by typical bacteria. For example, it was used extensively in infections of the urinary tract because it often was effective against a broader spectrum of pathogens than streptomycin, and resistant microorganisms did not develop so quickly.
Duggar had predicted that Aureomycin would be a boon to farmers and poultry raisers. Indeed, the antibiotic has been used widely as a feed supplement to stimulate the growth of livestock. Some authorities, however, question the practice, because it breeds resistant bacteria that could pose a public health problem eventually. Furthermore, prolonged low exposure to an antibiotic can sensitize individuals, making them unable to take the drug later to treat infection.
Aureomycin enjoys the distinction of being the first of the tetracyclines
Since 1948, Aureomycin and other tetracyclines have been widely—and often inappropriately—used to treat a wide range of diseases. This unrestricted application caused many pathogenic microorganisms, particularly streptococcus strains, to become resistant. As a result, tetracyclines are no longer the antibiotics of choice for treating most common respiratory or urinary tract infections.
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Cowen, David L., and Alvin B. Segelman, eds. Antibiotics in Historical Perspective. Rahway, N.J.: Merck, 1981. A lavishly illustrated volume that traces the history of substances with antimicrobial activity from ancient Sumer and Egypt to the 1970’s. Streptomycin—which the Merck Pharmaceutical Company helped develop—and penicillin receive prime attention. One chapter is devoted to Aureomycin and another to tetracyclines. Bibliographies. -
Dowling, Harry F. Fighting Infection: Conquests of the Twentieth Century. Cambridge, Mass.: Harvard University Press, 1977. Written by a former medical practitioner who participated in the early clinical trials of Aureomycin. A well-organized, fully documented, indexed history of infectious diseases and their treatment, beginning with early immunization efforts and culminating in the discovery and widespread application of sophisticated germ fighters. An excellent study. -
Interagency Task Force on Antimicrobial Resistance. A Public Health Action Plan to Combat Antimicrobial Resistance. Washington, D.C.: U.S. Department of Health and Human Services, 2001. Available at http://www.cdc.gov/drugresistance/actionplan/aractionplan.pdf. A government report on the resistance of microorganisms to antibiotics, a major, worldwide health concern. -
Lappé, Marc. Germs That Won’t Die: Medical Consequences of the Misuse of Antibiotics. Garden City, N.Y.: Anchor Press, 1982. Written by a pathologist and public health official, this book presents a history of the evolution of antibiotics and laments the problems caused by their widespread application. Lappé argues that the excessive and indiscriminate prescription of these drugs by physicians and their use in animal feeds have contributed to the emergence of resistant bacteria. Glossary, chapter bibliographies, and index. -
Lightman, Alan P. The Discoveries. New York: Pantheon Books, 2005. Lightman, a physicist and novelist, explores some of the most important discoveries in the sciences of the twentieth century, including the discovery of antibiotics. The book also provides primary source material, a bibliography, and an index. -
Mahoney, Tom. The Merchants of Life. New York: Harper & Brothers, 1959. A laudatory descriptive account of the U.S. pharmaceutical industry. Tells the story of eighteen leading companies, including Lederle. Presents an abundance of factual information, especially about their founders and their notable drugs. Index, no bibliography. -
Nicolaou, K. C., and Christopher N. C. Boddy. “Behind Enemy Lines.” Scientific American, May 21, 2001, 54-60. Examines in nontechnical language how microbes are fast becoming resistant to antibiotics. Discusses the history of antibiotics and provides a breakdown of how microbes resist antibiotics. -
Reinfeld, Fred. Miracle Drugs and the New Age of Medicine. Rev. ed. New York: Sterling, 1962. Brief and interesting pictorial panorama of modern medical discoveries, beginning with Louis Pasteur’s germ theory of disease in the nineteenth century to the antibiotics, vaccines, and synthetic drugs of the mid-twentieth century. Appropriate for young readers. Profusely illustrated, index, no bibliography. -
Sneader, Walter. Drug Discovery: A History. Hoboken, N.J.: Wiley, 2005. More than a compilation of drugs, this work provides an interesting narrative of the origins, development, and history of drugs with especially significant social and medical import. Includes discussion of antibiotics. -
Walker, J. C. “Benjamin Minge Duggar.” In Biographical Memoirs. Vol. 32. New York: Columbia University Press, 1958. Until a full-length biography of Duggar becomes available, readers will have to resort to vignettes, and this is one of the best. Includes a list of articles and books written or coauthored by Duggar. -
Williams, J. H., ed. Aureomycin: A New Antibiotic. New York: New York Academy of Sciences, 1948. A highly technical collection of sixteen reports written by Lederle scientists and other researchers who participated in the development and testing of Aureomycin. The highly technical nature of the reports will probably limit their appeal to specialists.
Waksman Discovers the Antibiotic Streptomycin
First Broad-Spectrum Antibiotic Is Discovered
Salk Develops a Polio Vaccine
Isaacs and Lindenmann Discover Interferons
Sabin Develops the Oral Polio Vaccine
World Health Organization Intensifies Its Campaign to Eradicate Smallpox
Scientists Debate the Addition of Antibiotics to Animal Feed
German Measles Vaccine Is Developed