Infectious Disease · 1928
Fleming's discovery of penicillin
Before the antibiotics era, bacterial infections killed patients who had survived surgery, childbirth, and war wounds. Streptococcal sepsis, pneumococcal pneumonia, and staphylococcal bacteremia had no reliable treatment beyond supportive care and, in some cases, antiseptic wound management. Alexander Fleming, a bacteriologist at St Mary's Hospital in London, had been interested for years in naturally occurring antibacterial substances. He had previously described lysozyme, an enzyme present in nasal secretions that lysed certain bacteria. The contaminated plate he returned to in September 1928 fit into a line of inquiry he had already been pursuing.
Fleming found a Petri dish he had left before vacation covered with Staphylococcus colonies except for a clear halo surrounding an uninvited Penicillium mold. He identified the mold, confirmed that a diffusible substance in its culture fluid was lethal to a range of gram-positive bacteria, and named the substance penicillin. His 1929 paper in the British Journal of Experimental Pathology documented these findings thoroughly. The problem was concentration: the broth produced only tiny amounts of active material, and Fleming could neither purify it nor maintain potency through successive preparation steps. After several years of effort he largely set the work aside.
The compound spent most of the 1930s in the literature rather than the laboratory. Howard Florey, an Australian-born pharmacologist directing the Sir William Dunn School of Pathology at Oxford, and Ernst Boris Chain, a German-Jewish biochemist who had fled Nazi Germany, took up the purification problem in 1939. Chain reviewed Fleming's paper and recognized that the stability issue might be soluble with modern biochemical techniques. By 1940, Florey and Chain had a partially purified preparation; in a mouse protection experiment that May, eight mice given lethal doses of streptococci were treated with penicillin, and survivors included those treated while controls died.
Human trials began in 1941 under difficult wartime conditions, with material hand-produced in whatever containers Florey's team could repurpose, including bedpans. Early results were striking but complicated by supply; one patient died when the team ran out of drug mid-course. Florey traveled to the United States to secure industrial-scale production, and collaboration between American and British pharmaceutical manufacturers expanded output rapidly. By 1943, sufficient penicillin existed to treat Allied casualties; by 1944, it was reaching civilian patients.
Fleming, Florey, and Chain shared the Nobel Prize in Physiology or Medicine in 1945. Popular accounts of the discovery focused heavily on Fleming's chance observation, which oversimplified a story in which a decade of additional work was required before a patient could be treated. By 1944, infection-related mortality in Allied forces had fallen substantially compared with World War I rates, a reduction that military medicine attributed in large part to penicillin availability.
Key People
- Alexander Fleming — Bacteriologist who observed and named penicillin
- Howard Florey — Pharmacologist who led the Oxford purification and animal trials
- Ernst Boris Chain — Biochemist who isolated and characterized the active compound
Br J Exp Pathol, 1929
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