A famous story with soft edges
The usual telling goes like this: a scientist returns from vacation, notices that mold has killed bacteria on a dish, and invents the first antibiotic. The core is true, but the popular version leaves out most of the people and most of the work. It also contains details that historians treat as uncertain. This page is a history of who contributed what, not guidance on any treatment.
London, 1928
Alexander Fleming was a bacteriologist at St Mary’s Hospital in London. He had a track record of interest in natural antibacterial substances. Wound infections were a serious problem in his time, and surgeons had long tried to limit them through antiseptic surgery. In 1921 he had found lysozyme, an enzyme in tears and other body fluids that dissolves some bacteria, and that earlier work probably prepared him to notice something unusual.
In September 1928 he looked at culture plates of staphylococcus bacteria that had been left aside. On one of them a mold had grown, and around the mold the bacterial colonies appeared transparent or dissolved. Fleming recognized that something produced by the mold was acting against the bacteria. The mold was identified as a species of Penicillium, and he called the active material penicillin.
Several details of the event are disputed.
- The exact timing. Fleming’s later recollections, and the accounts of colleagues, differ on when the plate was contaminated and what the weather was like. Some modern writers suggest a particular sequence of temperatures was needed for the effect to appear, but this is a reconstruction.
- Where the mold came from. It has been suggested that spores drifted in from a laboratory on a floor below, where mold work was done, but this is not firmly established.
- Fleming’s reaction. Later narratives of an immediate flash of insight probably simplify what was a gradual realization.
What Fleming did next
Fleming grew the mold in broth and showed that the liquid from it prevented the growth of several kinds of bacteria. He noted that it did not seem to harm white blood cells in his tests, and he reported his findings in 1929 in the British Journal of Experimental Pathology. He suggested it might be useful as an antiseptic for surfaces and for selecting between kinds of bacteria in the laboratory.
He had difficulty, however, making a stable, concentrated preparation. The substance broke down easily, and he was not a chemist. Chemists at other British laboratories worked on it for a time without success. The research stalled through the 1930s, though Fleming kept the mold alive and occasionally referred to it. Whether he ever seriously tested it as an injected drug is itself debated. He did, apparently, try it on a few surface infections, with mixed results.
Oxford, 1939 to 1941
The turning point was at the Sir William Dunn School of Pathology in Oxford. Howard Florey, an Australian pathologist who led the school, had assembled a team that included Ernst Chain, a biochemist who had left Germany in 1933, and Norman Heatley, a biochemist with a talent for improvised laboratory equipment. Edward Abraham and others helped with the chemistry.
Starting in about 1939 they set out to study antibacterial substances in nature, and Fleming’s paper led them to penicillin. They found methods to extract and concentrate it, and Heatley devised ways to grow large amounts of mold and to move the active material from one liquid to another. In 1940, they gave the substance to mice infected with streptococcus. In the experiment, those given penicillin survived while untreated mice did not.
In 1941 the first trials in people were done on a small number of patients. Supplies were very limited, and in one well-known case a patient improved at first but the material ran out, and he later died. The team recovered penicillin from patients’ urine for re-use. The result, in spite of the shortage, was convincing enough to justify pressing on. Like the insulin discovery of the early 1920s, it shows how a laboratory finding becomes a usable drug only after teams solve purification. The step from this laboratory success to large supplies is the subject of the account of wartime production.
Credit
In 1945 the Nobel Prize in Physiology or Medicine went jointly to Fleming, Florey and Chain. Heatley and Abraham did not receive it, and some historians think Heatley’s part in particular was undervalued. Several broad views are common.
- Fleming is credited with the observation and the name, and with drawing attention to the mold.
- Florey’s team is credited with turning an observation into a usable drug, which required purification, animal testing and the first clinical work.
- Earlier researchers had reported that molds could inhibit bacteria, and a few recorded observations before Fleming are cited in the literature. Whether they should count as “discoverers” is a matter of definition.
So “Fleming discovered penicillin” is true in one sense, and incomplete in another. A fairer summary is that penicillin was observed in London, understood and made into a medicine in Oxford, and scaled up in the United States and Britain.
A note on the lesson
Fleming himself warned in his Nobel lecture that using too little of the drug could encourage resistant bacteria. That awareness has been part of antibiotic history from the start.