Baron Florey and Ernst Boris Chain concentrated and clinically tested penicillin, the first successful and widely used antibiotic drug.
During the early twentieth century, scientists were aware of antibacterial substances but did not know how to make full use of them in the treatment of diseases. Sir Alexander Fleming discovered penicillin in 1928, but he was unable to duplicate his laboratory results of its antibiotic properties in clinical tests. As a result, he did not recognize the medical potential of penicillin.
Between 1935 and 1940, penicillin was purified, concentrated, and clinically tested by pathologist Baron Florey, biochemist Ernst Boris Chain, and members of their Oxford research group. Their achievement has since been regarded as one of the greatest medical discoveries of the twentieth century. Florey was a professor at Oxford University in charge of the Sir William Dunn School of Pathology. Chain had worked for two years at Cambridge University in the laboratory of Frederick Hopkins, an eminent chemist and discoverer of vitamins. Hopkins recommended Chain to Florey, who was searching for a candidate to lead a new biochemical unit in the Dunn School of Pathology.
In 1938, Florey and Chain formed a research group to investigate the phenomenon of antibiosis, or the antagonistic association between different forms of life. The union of Florey’s medical knowledge and Chain’s biochemical expertise proved to be an ideal combination for exploring the antibiosis potential of penicillin. Florey and Chain began their investigation with a literature search in which Chain came across Fleming’s work and added penicillin to their list of potential antibiotics.
Their first task was to isolate pure penicillin from a crude liquid extract. A culture of Fleming’s original Penicillium notatum was maintained at Oxford and was used by the Oxford group for penicillin production. Extracting large quantities of penicillin from the medium was a painstaking task, as the solution contained only one part of the antibiotic in ten million. When enough of the raw juice was collected, the Oxford group focused on eliminating impurities and concentrating the penicillin. The concentrated liquid was then freeze-dried, leaving a soluble brown powder.
In May, 1940, Florey’s clinical tests of the crude penicillin proved its value as an antibiotic. Following extensive controlled experiments with mice, the Oxford group concluded that they had discovered an antibiotic that was nontoxic and far more effective against pathogenic bacteria than any of the known sulfa drugs. Furthermore, penicillin was not inactivated after injection into the bloodstream but was excreted unchanged in the urine. Continued tests showed that penicillin did not interfere with white blood cells and had no adverse effect on living cells. Bacteria susceptible to the antibiotic included those responsible for gas gangrene, pneumonia, meningitis, diphtheria, and gonorrhea. American researchers later proved that penicillin was also effective against syphilis
In January, 1941, Florey injected a volunteer with penicillin and found that there were no side effects to treatment with the antibiotic. In February, the group began treatment of Albert Alexander, a forty-three-year-old policeman with a serious staphylococci and streptococci infection that was resisting massive doses of sulfa drugs. Alexander had been hospitalized for two months after an infection in the corner of his mouth had spread to his face, shoulder, and lungs. After receiving an injection of 200 milligrams of penicillin, Alexander showed remarkable progress, and for the next ten days his condition improved. Unfortunately, the Oxford production facility was unable to generate enough penicillin to overcome Alexander’s advanced infection completely, and he died on March 15.
A later case involving a fourteen-year-old boy with staphylococcal septicemia and osteomyelitis had a more spectacular result: The patient made a complete recovery in two months. In all the early clinical treatments, patients showed vast improvement, and most recovered completely from infections that resisted all other treatment.
Penicillin is among the greatest medical discoveries of the twentieth century. Florey and Chain’s chemical and clinical research brought about a revolution in the treatment of infectious disease. 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 their high toxicity often limited their use. With this small arsenal, doctors were helpless to treat thousands of patients with bacterial infections.
The work of Florey and Chain achieved particular attention because of World War II and the need for treatments of such scourges as gas gangrene, which had infected the wounds of numerous World War I soldiers. 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. After an extended search, scientists were also able to isolate a more productive penicillin strain, Penicillium chrysogenum. By 1945, a strain was developed that produced five hundred times more penicillin than Fleming’s original mold had.
Penicillin, the first of the “wonder drugs,” remains one of the most powerful antibiotics in existence. Diseases such as pneumonia, meningitis, and syphilis are still treated with penicillin. Penicillin and other antibiotics also had a broad impact on other fields of medicine, as major operations such as heart surgery, organ transplants, and management of severe burns became possible once the threat of bacterial infection was minimized.
An antibiotic destroys a bacterium by causing its cell walls to deteriorate; water then enters the bacterium unchecked until it bursts.
Florey and Chain received numerous awards for their achievement, the greatest of which was the 1945 Nobel Prize in Physiology or Medicine, which they shared with Fleming for his original discovery.
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Bickel, Lennard. Florey: The Man Who Made Penicillin. Carlton South, Vic.: Melbourne University Press, 1995. Relates how the brilliant and ambitious Florey pursued the testing and production of penicillin. Places the work of Florey and Chain in the context of their times. -
Clark, Ronald W. The Life of Ernst Chain: Penicillin and Beyond. New York: St. Martin’s Press, 1985. Biography provides a complete examination of Chain’s career, including four chapters on his penicillin work. Draws on Chain’s papers, which are housed at the Contemporary Medical Archives Center of the Welcome Institute for the History of Medicine in London. -
Hare, Ronald. The Birth of Penicillin, and the Disarming of Microbes. London: George Allen & Unwin, 1970. Excellent firsthand description of Alexander Fleming’s early work with penicillin by an author who was among those who witnessed that work. A brief but very informative account of Fleming’s work that provides the reader with a perspective on the state of penicillin research before Florey and Chain. -
Hobby, Gladys L. Penicillin: Meeting the Challenge. New Haven, Conn.: Yale University Press, 1985. One of the best overall descriptions available of the roles played by Fleming, Florey, Chain, and numerous other scientists in the discovery, development, and eventual mass production of penicillin. Benefits from the author’s extensive personal work with penicillin as a scientist employed by the Pfizer Corporation. 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. Includes bibliography and index. -
Macfarlane, Gwyn. Howard Florey: The Making of a Great Scientist. Oxford, England: Oxford University Press, 1979. Excellent biography of Florey blends both personal and archival data. The author worked at Oxford and was an acquaintance of Florey’s for twenty years. Makes extensive use of the Florey archives at the Royal Society. -
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. -
Williams, Trevor I. Howard Florey: Penicillin and After. New York: Oxford University Press, 1985. A well-documented examination of Florey’s entire scientific career, including both penicillin and his postwar work.
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