Duggar Develops the First Tetracycline Antibiotic Summary

  • Last updated on November 10, 2022

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.

Summary of Event

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 Lederle Laboratories , where Aureomycin was first isolated by Benjamin Minge Duggar. Aureomycin Antibiotics [kw]Duggar Develops the First Tetracycline Antibiotic (Summer, 1945) [kw]Tetracycline Antibiotic, Duggar Develops the First (Summer, 1945) [kw]Antibiotic, Duggar Develops the First Tetracycline (Summer, 1945) Aureomycin Antibiotics [g]North America;Summer, 1945: Duggar Develops the First Tetracycline Antibiotic[01520] [g]United States;Summer, 1945: Duggar Develops the First Tetracycline Antibiotic[01520] [c]Health and medicine;Summer, 1945: Duggar Develops the First Tetracycline Antibiotic[01520] [c]Science and technology;Summer, 1945: Duggar Develops the First Tetracycline Antibiotic[01520] Duggar, Benjamin Minge Subba Row, Yellapragada Dornbush, Albert Carl

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, Bacteria, drug-resistant[Bacteria, drug resistant] known as atypical bacteria. Among the latter were the rickettsias, chlamydias, and mycoplasmas. Some typical bacteria, including the brucellas, also defied the new drugs. Furthermore, the antibiotics available in the late 1940’s were deficient in another area: Resistant strains of pathogenic microbes were growing ever more numerous. Thus, the fact that many infections were not well controlled, or even affected, by current antibiotics provided a strong incentive to search for more germ fighters.

The discovery of penicillin Penicillin , a mold-derived drug, had sent scientists back to the soil in a quest for natural substances with antibiotic properties; during World War II, this pursuit was taken over by the resource-rich, profit-seeking pharmaceutical industry. By 1945, at least six drug companies had teams of investigators seeking antibiotics. One of them was Lederle Laboratories, a division of American Cyanamid Company. Lederle had specialized in remedies for infectious diseases, and the company’s search for new mold-derived drugs began in 1939.

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 Albrecht, William A. , chair of Missouri’s department of soils. Duggar was pleased to observe that A 377 exhibited antibiotic potential.

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 Streptomyces aureofaciens by Duggar, resisted bacilli signified that it was producing an antibiotic that might have a wider scope of activity than either penicillin or streptomycin. The antibiotic substance extracted from Streptomyces aureofaciens was christened Aureomycin, a name derived from the Latin word aureus (gold) and the Greek mykes (fungus). Both the mold and the antibiotic had a golden hue. Aureomycin was later given the generic name of chlortetracycline.

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.

Significance

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 Rocky Mountain spotted fever , endemic throughout the continental United States and recognized as one of the most severe of all infectious diseases. The tick-transmitted malady killed one out of every five victims. The number of fatalities declined sharply, however, after Aureomycin became available. In its first clinical trials, the drug dramatically restored to health a boy who was in a coma from tick fever. Numerous other diseases caused by atypical bacteria—including typhus, lymphogranuloma venereum (a disabling sexually transmitted disease), trachoma, parrot fever, and mycoplasmal pneumonia—yielded to the new microbe fighter. Aureomycin rapidly became—and remained for several decades—the drug of choice in treating rickettsial, chlamydial, and mycoplasmal infections.

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 Tetracyclines , a family of antibiotics that includes Terramycin, achromycin, and declomycin. Tetracyclines are basically bacteriostatic, meaning they inhibit bacterial growth, and they oppose most of the same microorganisms. They differ mainly in how readily they are absorbed by the body and in how long their effects persist. Many medical experts affirm that next to the penicillin family, the tetracycline group probably represents the most beneficial and least hazardous of the wonder drugs. The tetracyclines are relatively safe antibiotics. Nevertheless, they are capable of causing a variety of reactions, chiefly nausea, vomiting, and diarrhea. In addition, tetracyclines can discolor developing teeth permanently. For this reason, they are contraindicated in the treatment of children and pregnant women.

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. Aureomycin Antibiotics

Further Reading
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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.
  • citation-type="booksimple"

    xlink:type="simple">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

Categories: History Content