Alexander Fleming’s discovery of the antibiotic penicillin led to the development of a wonder drug that saved millions of lives.
During the early twentieth century, scientists became increasingly interested in bacteriology, or the study of infectious disease. This field has since come to be called microbiology
Alexander Fleming.
Sir Alexander Fleming began his scientific career in 1901, when he inherited a small legacy that enabled him to enter St. Mary’s Medical School in London. Fleming was a prizewinning student and a superb technician. He qualified as a doctor in 1906 and remained at St. Mary’s as a junior assistant to Sir Almroth Edward Wright, a prominent pathologist and well-known proponent of inoculation. In 1909, Fleming was one of the first to use Paul Ehrlich’s new arsenical compound, Salvarsan,
During World War I, Wright and Fleming joined the Royal Army Medical Corps and conducted wound research at a laboratory in Boulogne. Fleming was in charge of identifying the infecting bacteria by taking swabs from wounds before, during, and after surgery. His results showed that 90 percent of the samples contained Clostridium welchii, the anaerobic bacteria that cause gas gangrene. Although scientists could isolate the bacteria, they were uncertain as to the best method for combating diseases. Antiseptics were a known means for killing bacteria but were not always effective, especially when used in deep wounds. Wright and Fleming showed that white blood cells found in pus discharged from wounds had ingested bacteria. Fleming also demonstrated that contrary to popular opinion, when antiseptics were packed into a wound, bacteria survived in the crevasses. Antiseptics destroyed the body’s own defenses (white blood cells), allowing the remaining bacteria to create serious infection unimpeded. The horrors of bacterial infection during World War I had a lasting impact on Fleming, who decided to focus his postwar research on antibiotic substances. Fleming was convinced that the ideal antiseptic or bacteria-fighting agent should be highly active against microorganisms but harmless to the body’s own white blood cell defenses.
In 1921, Fleming observed the dissolving effect that a sample of his own nasal mucus had on bacteria growing in a petri dish. He isolated the antibiotic component of the mucus and named it “lysozyme.” Further research showed that lysozyme
In September, 1928, Fleming noticed that a mold was growing in a petri dish containing strains of staphylococci and that bacteria surrounding the mold were being destroyed. It is likely that the source of the mold spores was the laboratory below Fleming’s, where mycologist C. J. La Touche was growing molds for research on allergies. Because of his interest in antibiotics, Fleming was conditioned to recognize immediately that an agent capable of dissolving staphylococci could be of great biological significance. He preserved the original culture plate and made a subculture of the mold in a tube of broth. Fleming’s mold was later identified as Penicillium notatum. Further experiments showed that the “mould juice” could be produced by several strains of Penicillium but not by other molds. The substance was nontoxic and did not interfere with the action of white blood cells.
Fleming described his findings in a paper titled “On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. Influenzae,” which appeared in the British Journal of Experimental Pathology in 1929. The unusual title refers to Fleming’s use of penicillin to isolate bacteria that were not vulnerable to penicillin. In his paper, Fleming described the mold extract and listed the sensitive bacteria. Most important, Fleming suggested that penicillin might be used in the treatment of infection. In addition to describing his experiments, Fleming also stated that the name “penicillin” would be used to refer to the mold broth filtrate. This article on penicillin came to be regarded as one of the most important medical papers ever written.
Fleming’s petri dish elicited little interest from colleagues at St. Mary’s, who were familiar with his previous work and assumed that this was an example of lysozyme being produced by a mold. Fleming knew this to be untrue, as lysozyme was incapable of destroying a pathogenic organism such as staphylococcus. Once again, Fleming’s limited ability as a writer and speaker left his audience content to shelve his latest discovery along with lysozyme. Even Ernst Boris Chain, who discovered Fleming’s paper during a literature search in 1936, “thought that Fleming had discovered a sort of mould lysozyme which, in contrast to egg white lysozyme, acted on a wide range of . . . pathogenic bacteria.”
During 1929, Fleming continued to investigate the antibiotic properties of penicillin, collecting data that clearly established the chemotherapeutic potential of penicillin. Fleming was unable to purify and concentrate penicillin adequately, and, hence, did not conduct clinical tests that could prove the effectiveness of the antibiotic in vivo. The significance of Fleming’s discovery was not recognized until 1940, when Baron Florey and Chain discovered the enormous therapeutic power of penicillin.
Fleming’s discovery of penicillin had no immediate impact on twentieth century medicine. By 1931, Fleming had discontinued work on the antibiotic and turned to the study of sulfa drugs. In 1940, Florey and Chain succeeded in concentrating and clinically testing penicillin, after which Fleming’s discovery gained enormous notoriety and he was showered with accolades and honors. In 1943, he was elected to fellowship in the Royal Society; in 1944, he was knighted; and in 1945, he received the Nobel Prize in Physiology or Medicine jointly with Florey and Chain.
Penicillin achieved particular notoriety because of World War II and the demand for an antibiotic that could halt diseases such as gas gangrene, which infected the wounds of numerous soldiers during World War I. With the help of Florey and Chain’s Oxford group, scientists at the U.S. Department of Agriculture’s Northern Regional Research Laboratory developed a highly efficient method for producing penicillin using fermentation. An excellent cornstarch medium was developed for both surface and submerged culture of penicillium molds. After an extended search, scientists also were able to isolate a more productive penicillium strain (Penicillium chrysogenum). By 1945, a strain was developed that produced five hundred times more penicillin than Fleming’s original mold.
During World War II, the U.S. Office of Scientific Research and Development’s Committee on Medical Research conducted large-scale clinical tests of penicillin on 10,838 patients. Their results provided doctors with effective methods and dosages for use of penicillin in treatment of many diseases.
American pharmaceutical companies were galvanized by the development of an efficient production technique and positive clinical tests. Corporations such as Merck, Pfizer, Squibb, and many others built large factories to mass-produce penicillin for use by the U.S. armed forces. The War Production Board increased production by allocating supplies and equipment to twenty-two U.S. chemical companies engaged in the production of the antibiotic. Penicillin prevented many of the horrendous casualties that Fleming witnessed during World War I.
Penicillin is regarded as among the greatest medical discoveries of the twentieth century. Almost every organ in the body is vulnerable to bacteria. Before penicillin, the only antimicrobial drugs available were quinine, arsenic, and sulfa drugs. Of these, only the sulfa drugs were useful for treatment of bacterial infection, but high toxicity precluded their use in many cases. With this limited arsenal, doctors were helpless as thousands died in epidemics caused by bacteria. Diseases such as pneumonia, meningitis, and syphilis are now treated with penicillin all over the world.
Penicillin and other antibiotics also had a broad impact on medicine as major procedures such as heart surgery, organ transplants, and management of severe burns became possible once the threat of bacterial infection was minimized. Fleming’s discovery brought about a revolution in medical treatment by offering an extremely effective solution to the enormous problem of infectious disease.
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Epstein, Samuel, and Beryl Williams. Miracles from Microbes. New Brunswick, N.J.: Rutgers University Press, 1946. Presents the background of the development of several antibiotics, including penicillin and streptomycin. -
Fleming, Alexander. “On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. Influenzae.” British Journal of Experimental Pathology 10 (1929): 226-236. Fleming’s first description of his discovery gives valuable insight into his experimental technique and understanding of the antibiotic potential of penicillin. -
Hare, Ronald. The Birth of Penicillin, and the Disarming of Microbes. London: George Allen & Unwin, 1970. Provides a firsthand description of Fleming’s work by a scientist who worked at St. Mary’s at the time of Fleming’s discovery and was among those who witnessed Fleming’s early work with penicillin. Presents an interesting perspective on penicillin research before 1940. -
Hobby, Gladys L. Penicillin: Meeting the Challenge. New Haven, Conn.: Yale University Press, 1985. Presents a good overall description of the roles played by Fleming, Florey, Chain, and numerous other scientists in the discovery, development, and eventual mass production of penicillin. Includes extensive footnotes. -
Lax, Eric. The Mold in Dr. Florey’s Coat: The Story of the Penicillin Miracle. New York: Henry Holt, 2004. Relates the story of the discovery of penicillin and its development into a useful drug. Sheds light on the personalities of the scientists involved—Florey and Chain as well as Fleming. Includes bibliography and index. -
Ludovici, L. J. Fleming: Discoverer of Penicillin. London: Andrew Dakers, 1952. Contemporary biography of Fleming reflects the fact that he was revered both by the author and by the general public. -
Macfarlane, Gwyn. Alexander Fleming: The Man and the Myth. Cambridge, Mass.: Harvard University Press, 1984. Authoritative biography of Fleming draws on interviews as well as Fleming’s own notes to dispel somewhat the “Fleming myth” that abounds in earlier biographies. -
Mateles, Richard I., ed. Penicillin: A Paradigm for Biotechnology. Chicago: Canadida Corporation, 1998. Volume reprints The History of Penicillin Production, a classic work first published in 1970, along with new chapters that address advances in penicillin research since that time. Also discusses the status of penicillin and its derivatives at the end of the twentieth century. -
Maurois, André. The Life of Alexander Fleming. New York: E. P. Dutton, 1959. Authorized biography of Fleming includes two chapters on his penicillin research. -
Ryan, Frank. The Forgotten Plague: How the Battle Against Tuberculosis Was Won—and Lost. Boston: Little, Brown, 1993. Written for nontechnical readers, a significant portion of this volume discusses the methodology behind the discovery and testing of many major antibiotics. -
Sheehan, John C. The Enchanted Ring: The Untold Story of Penicillin. Cambridge, Mass.: MIT Press, 1982. Definitive history of the discovery, development, and marketing of penicillin, accessible to general readers.
Ehrlich and Metchnikoff Conduct Pioneering Immunity Research
Ehrlich Introduces Salvarsan as a Cure for Syphilis
Schick Introduces a Test for Diphtheria
Tuberculosis Vaccine BCG Is Developed
U.S. Food and Drug Administration Is Established
Florey and Chain Develop Penicillin as an Antibiotic