The Off-Key Bard
History

This Day in History — Alexander Fleming Discovers Penicillin

On this day in 1928

On September 3, 1928, Fleming returned from holiday to find a contaminated dish — and instead of throwing it away, asked why the bacteria around the mold had dissolved.

The Off-Key Bard looks across a cluttered laboratory bench at something most scientists would have thrown away: a contaminated Petri dish.

"Some discoveries begin with a carefully designed experiment. This one began when someone noticed that a mistake was doing something interesting."

On September 3, 1928 — the date traditionally assigned to the discovery, based on Fleming's later account of returning to his lab that morning — Scottish bacteriologist Alexander Fleming came back to his laboratory at St. Mary's Hospital in London after a summer holiday in Scotland. Before leaving, he had stacked several Petri dishes of Staphylococcus aureus cultures on his workbench and left them uncovered.

One of them had been contaminated by a mold. This was not unusual. Contaminated cultures were a routine laboratory nuisance. Fleming's usual response, like any working scientist's, would have been to discard the ruined plate.

Instead he looked more closely. Around the mold — later identified as Penicillium notatum, though Fleming initially misidentified it as Penicillium rubrum — the surrounding staphylococcal colonies had dissolved into transparency. A clear halo of dead bacteria encircled the fungus. Whatever the mold was releasing into the agar, it was killing or lysing the bacteria in its immediate environment.

Fleming called it "mold juice." He spent the following weeks growing more of it, confirming the effect was real and consistent. He found the substance killed not just staphylococci but streptococcus, meningococcus, the diphtheria bacillus, and a range of other dangerous pathogens. He named it penicillin after the genus of the mold. He published his findings in the British Journal of Experimental Pathology in June 1929.

The mold spore that had contaminated the dish most likely drifted up from the mycology laboratory of Charles La Touche, which was one floor below Fleming's lab.

A Decade of Near-Miss

Fleming's 1929 paper attracted relatively little attention. The substance was difficult to isolate and unstable; he could not produce it in a concentrated, purified form suitable for medical use. For roughly a decade, penicillin remained primarily a laboratory curiosity — an interesting observation in search of a chemist who could make it clinically useful.

That chemist arrived in the form of a team. Around 1938, Howard Florey and Ernst Boris Chain at the University of Oxford revisited Fleming's work. With Norman Heatley providing crucial extraction and purification methods, the Oxford team developed techniques for processing what they still called "mold juice" into something approaching clinical-grade penicillin. The scale was absurdly small. Processing gallons of the fragile mold culture yielded only milligrams of purified drug. In the early stages, Heatley and colleagues cultured the mold in whatever shallow vessels they could commandeer — pie dishes, milk bottles, and, famously, hundreds of ceramic hospital bedpans pressed into service as fermentation vessels.

The Cantaloupe That Changed the War

Even the Oxford team's purified penicillin was nowhere near sufficient for large-scale use. The original Penicillium notatum strain produced vanishingly small amounts of the drug. Scaling production to wartime needs required something different.

In 1941, Florey and Heatley flew to the United States and began working with the USDA Northern Regional Research Laboratory in Peoria, Illinois. The team ran a systematic search for mold strains that would yield more penicillin under the large-scale deep-tank fermentation conditions that pharmaceutical manufacturers could actually use. In the summer of 1943, a laboratory assistant brought in a rotten cantaloupe from a local Peoria market, covered in what she described as a "pretty, golden mold." The mold was Penicillium chrysogenum. It produced approximately 200 times more penicillin than Fleming's original Penicillium notatum strain, and it thrived in the submerged fermentation conditions needed for industrial production.

The identity of the person who brought the cantaloupe has since become disputed. She was long credited as Mary Hunt — "Moldy Mary" in laboratory lore. A USDA Tellus investigation found evidence suggesting the cantaloupe may actually have been brought in by Mary Lou Finley Roberson. The mold itself is not in question. Neither is its importance.

By 1944, penicillin was available in substantial quantities for Allied troops. The drug was there for the D-Day landings. Infections that had routinely killed soldiers from wounds that should have been survivable suddenly were not. After the war, civilian availability expanded rapidly. The American Chemical Society estimates penicillin has saved approximately 500 million lives.

The Warning Nobody Wanted to Hear

Fleming, Florey, and Chain shared the 1945 Nobel Prize in Physiology or Medicine. In his Nobel lecture, Fleming issued a warning as clear as it was uncomfortable: if bacteria were exposed to penicillin in concentrations too low to kill them, the resistant organisms would survive, multiply, and pass their resistance on. He had already observed this in his laboratory. He could see exactly where it led.

Decades of antibiotic overuse and misuse have made antibiotic resistance one of the defining medical crises of the 21st century. As of 2019, antimicrobial resistance was directly responsible for an estimated 1.27 million deaths per year worldwide. The man who discovered penicillin predicted this problem precisely and publicly in 1945 — in the same speech where he accepted the prize for saving hundreds of millions of lives.

"A speck of mold, a culture spoiled,
Yet something strange within it boiled.
Where others might have cleared the plate,
A curious eye discovered fate."

History reminds us: science isn't always about getting the result you expected. Sometimes the experiment fails — and the scientist who asks why discovers something that changes the world. And sometimes that same scientist, at the height of his triumph, tells you exactly how to avoid squandering it.

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