In 1928, Alexander Fleming, a Scottish pathologist working at St Mary’s Hospital in London left for a Suffolk holiday, omitting to tidy his lab before departing. On returning, he made a curious observation. Some of his petri dishes growing Staphylococcus aureus – a type of bacteria that causes wound infections – had been contaminated by a Penicillium mould. As the mould grew, the Staphylococcus died.
Fleming was lucky. The phenomenon is notoriously hard to re-create. Nevertheless, he had intuition. Unlike 19th century scientists with similar observations, Fleming interpreted his results correctly. The mould, he realised, made something that killed the Staphylococcus. It wasn’t just depriving the bacteria of nutrients. Fleming named his substance ‘penicillin’ and did a few experiments to show which bacteria were killed by crude extracts. But he had no idea what penicillin was chemically, nor how to purify it. His boss discouraged further work, so Fleming wrote up his results in a second-tier journal and departed the topic.
A decade later, World War Two spurred research in wound infections, including by Howard Florey’s Oxford group. Florey’s colleague, Ernst Chain, a Jewish refugee from Berlin, stumbled on Fleming’s paper. Between them they re-found Fleming’s substance and extended his work. Norman Heatley, another colleague, discovered how to purify penicillin and rigged a Heath-Robinson apparatus that produced enough to dose mice infected with sepsis-inducing Streptococcus bacteria. Treated mice survived; control mice died.
They gave their drug to a dying cancer patient. It didn’t poison her. That counted as toxicity testing. Next, to a policeman, Albert Alexander, dying of sepsis. Alexander began to improve but the penicillin ran out, despite desperate efforts to recover the drug from his urine and to recycle it into his veins. Alexander died but the potential was clear. Another Alexander – Fleming – resurfaced. Unlike Florey he had political friends and a nose for the media.
Penicillin, never patented, passed to U.S. pharma with the skills and money to scale production. From a rotting melon, they isolated a Penicillium mould that made 1,000 times more antibiotic than Florey’s strain. They mutated it with X-rays, further increasing yield. Next, they learnt to grow the mould in huge fermenters, fed with a maize extract, ‘corn steep liquor‘. This led to a consistent product, penicillin G. By 1943, penicillin G was with the Allied military. At first much was used for gonorrhoea, where cases needed little drug and could immediately return to the battlefront. Wound infections responded too, but needed more drug and took longer.
Florey, Chain and Fleming won the 1945 Nobel Prize for Medicine. Heatley was a shameful omission. Without Heatley’s ramshackle production line, penicillin wouldn’t have got off the ground. Fleming – who’d contributed a lucky observation and a shrewd guess – was a lucky awardee, but relished the limelight and is remembered in the popular mind as the ‘discoverer of penicillin’.