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The Luckiest Mistake in Medicine: The Discovery of Penicillin

Every year, millions of people recover from infections that would once have killed them, and most of them never learn that they owe their lives to an untidy laboratory bench in London. The discovery of penicillin, the world's first true antibiotic, is often described as the single most important medical advance of the twentieth century. What makes the story remarkable is not the brilliance of the plan behind it, but the fact that there was almost no plan at all. Penicillin was found by accident, ignored for more than a decade, and rescued only when a second team of scientists decided that a forgotten paper deserved another look.

In the summer of 1928, a Scottish bacteriologist named Alexander Fleming was working at St Mary's Hospital in London, studying Staphylococcus, a common bacterium responsible for sore throats, boils, and deadly wound infections. Before going away on holiday in August, Fleming stacked a pile of culture dishes on a bench beside an open window rather than sterilising them. The dishes had been left uncovered for several weeks, and spores of a blue-green mold had been carried into the laboratory by the damp air of a cold London summer. When he returned in September, the cultures were spoiled. Any careful researcher would have thrown them into the disinfectant tray at once.

Fleming, however, looked at the ruined plates before discarding them, and he noticed something strange. A clear ring surrounded one patch of mold, and inside that ring the bacteria had completely disappeared. If the colonies around the mold had not been destroyed so cleanly, he would probably have washed the dish out without a second thought. He isolated the mold, identified it as Penicillium notatum, and named the substance it released penicillin. In 1929 he published his results in a British medical journal. If Fleming had tidied his laboratory before his holiday, the first antibiotic would not have been discovered in that decade at all.

Yet the paper changed nothing. Fleming was a talented observer but not a chemist, and penicillin proved extremely unstable and almost impossible to purify in useful amounts. He eventually turned his attention elsewhere. By the time Howard Florey and Ernst Chain began their research at Oxford in 1939, Fleming's article had been published for almost ten years and had been overlooked by nearly every scientist who read it. The two researchers, working with a small team and very limited funding, developed a method of extracting and concentrating the drug. In 1940 they injected eight infected mice; the four that received penicillin survived, while the untreated animals died within hours.

The timing could hardly have been more urgent, because the Second World War had already begun and infected wounds were killing soldiers faster than bullets. If the drug had been produced on an industrial scale even two years earlier, tens of thousands of men who died of septic injuries could have been saved. British laboratories were being bombed, so the work was moved to the United States, where deep-tank fermentation allowed enormous quantities to be brewed. The technique had been refined by American engineers before the Normandy landings of June 1944, and by that time enough penicillin had been stockpiled to treat every wounded Allied soldier. Fleming, Florey, and Chain shared the Nobel Prize in 1945. Fleming was modest about his own role. He often remarked that he would never have become a household name if he had been a more careful man.

The invention transformed medicine permanently. Pneumonia, syphilis, rheumatic fever, and infections after surgery or childbirth changed from likely death sentences into ordinary illnesses, and average life expectancy rose sharply across the developed world. Penicillin also created a new industry, since thousands of related antibiotics were developed from the same basic idea.

That success, however, came with a warning that Fleming gave in his own Nobel lecture: bacteria exposed to small doses can learn to survive them. If his advice about careless prescription had been taken seriously from the beginning, the resistant "superbugs" of today might have appeared far more slowly. The story of penicillin therefore teaches two lessons at once — that accidents can change history, and that no discovery stays miraculous unless it is used with care.