Before penicillin, the closest thing to a wonder drug that existed was Salvarsan, developed by the German immunologist Paul Ehrlich in 1910, but Salvarsan was effective against only a few things, principally syphilis, and had a lot of drawbacks. For a start, it was made from arsenic, so was toxic, and treatment consisted in injecting roughly a pint of solution into the patient’s arm once a week for fifty weeks or more. If it wasn’t administered exactly right, fluid could seep into muscle, causing painful and sometimes serious side effects, including the need for amputation. Doctors who could administer it safely became celebrated. Ironically, one of the most highly regarded was Alexander Fleming.
The story of Fleming’s accidental discovery of penicillin has been told many times, but hardly any two versions are quite the same. The first thorough account of the discovery was not published until 1944, a decade and a half after the events it describes, by which time details were already blurring, but as best as can be said, the story seems to be this: In 1928, while Alexander Fleming was away on a holiday from his job as a medical researcher at St. Mary’s Hospital in London, some spores of mold from the genus Penicillium drifted into his lab and landed on a petri dish that he had left unattended. Thanks to a sequence of chance events—that Fleming hadn’t cleaned up his petri dishes before departing on holiday, that the weather was unusually cool that summer (and thus good for spores), that Fleming remained away long enough for the slow-growing mold to act—he returned to find that the bacterial growth in the petri dish had been conspicuously inhibited.
It is often written that the type of fungus that landed on his dish was a rare one, making the discovery practically miraculous, but this appears to have been a journalistic invention. The mold was in fact Penicillium notatum (now called Penicillium chrysogenum), which is very common in London, so it was hardly momentous that a few spores should drift into his lab and settle on his agar. It has also become a commonplace that Fleming failed to exploit his discovery and that years passed before others finally converted his findings into a useful medicine. That is, at the very least, an ungenerous interpretation. First, Fleming deserves credit for perceiving the significance of the mold; a less alert scientist might simply have tossed the whole lot out. Moreover, he dutifully reported his discovery, and even noted the antibiotic implications of it, in a respected journal. He also made some effort to turn the discovery into a usable medicine, but it was a technically tricky proposition—as others would later discover—and he had more pressing research interests to pursue, so he didn’t stick with it. It is often overlooked that Fleming was a distinguished and busy scientist already. He had in 1923 discovered lysozyme, an antimicrobial enzyme found in saliva, mucus, and tears as part of the body’s first line of defense against invading pathogens, and was still preoccupied with exploring its properties. He was hardly foolish or slapdash, as is sometimes implied.
In the early 1930s, researchers in Germany produced a group of antibacterial drugs known as sulfonamides, but they didn’t always work well and often had serious side affects. At Oxford, a team of biochemists led by the Australian-born Howard Florey began searching for a more effective alternative and in the process rediscovered Fleming’s penicillin paper. The principal investigator at Oxford was an eccentric German émigré named Ernst Chain, who bore an uncanny resemblance to Albert Einstein (right down to the bushy mustache) but had a far more challenging disposition. Chain had grown up in a wealthy Jewish family in Berlin but had decamped to England with the rise of Adolf Hitler. Chain was gifted in many fields and considered a career as a concert pianist before settling on science. But he was also a difficult man. He had a volatile temperament and slightly paranoid instincts, though it seems fair to say that if there was ever a time when a Jew might be excused paranoia it was the 1930s. He was an unlikely candidate to make any discoveries because he had a pathological fear of being poisoned in a lab. Despite his dread, he persevered and found to his astonishment that penicillin not only killed pathogens in mice but had no evident side effects. It appeared to be the perfect drug: one that could devastate its target without wreaking collateral damage. The problem, as Fleming had seen, was that it was very hard to produce penicillin in clinically useful quantities. Under Florey’s command, Oxford gave over a significant amount of resources and research space to growing mold and patiently extracting from it tiny amounts of penicillin.
By early 1941, they had just enough to trial the drug on a policeman named Albert Alexander, who was a tragically ideal demonstration of how vulnerable humans were to infections before antibiotics. While pruning roses in his garden, Alexander had scratched his face on a thorn. The scratch had grown infected and spread. Alexander had lost an eye and now was delirious and close to death. The effect of penicillin was miraculous. Within two days, he was sitting up and looking almost back to normal. But supplies quickly ran short. In desperation the scientists filtered and reinjected all they could from Alexander’s urine, but after four days the supplies were exhausted. Poor Alexander relapsed and died.
With Britain preoccupied by World War II and the United States not yet in it, the quest to produce bulk penicillin moved to a U.S. government research facility in Peoria, Illinois. Scientists and other interested parties all over the Allied world were secretly asked to send in soil and mold samples. Hundreds responded, but nothing they sent proved promising. Then, two years after testing had begun, a lab assistant in Peoria named Mary Hunt brought in a cantaloupe from a local grocery store. It had a “pretty golden mold” growing on it, she recalled later. That mold proved to be two hundred times more potent than anything previously tested. The name and location of the store where Mary Hunt shopped are now forgotten, and the historic cantaloupe itself was not preserved: after the mold was scraped off, it was cut into pieces and eaten by the staff. But the mold lived on. Every bit of penicillin made since that day is descended from that single random cantaloupe.
Within a year, American pharmaceutical companies were producing 100 billion units of penicillin a month. The British discoverers found to their chagrin that the production methods had been patented by the Americans and that they were now required to pay royalties to make use of their own discovery.
Alexander Fleming didn’t become famous as the father of penicillin until the closing days of the war, some twenty years after his serendipitous discovery, but then he became very famous indeed. He received 189 honors of all types from around the world, and even had a crater on the moon named for him. In 1945, he shared the Nobel Prize in Physiology or Medicine with Ernst Chain and Howard Florey. Florey and Chain never enjoyed the popular acclaim they deserved, partly because they were much less gregarious than Fleming and partly because his story of accidental discovery made better copy than their story of dogged application. Chain, despite sharing the Nobel Prize, became convinced that Florey had not given him sufficient credit, and their friendship, such as it was, dissolved.
As early as 1945, in his Nobel acceptance speech, Fleming warned that microbes could easily evolve resistance to antibiotics if they were carelessly used. Seldom has a Nobel speech been more prescient.