Science & Technology

In the Story of Penicillin, Alexander Fleming Was a Minor Character

Most people know the penicillin origin story: In 1928, Alexander Fleming was growing bacteria in Petri dishes in his lab and noticed that one had started growing mold. That mold had cleared a spot in the bacteria, suggesting that it might have antibacterial properties. Fleming named the mold "penicillin," and it became the world's first antibiotic, curing thousands of previously untreatable infections and spawning a new era of human health. That's the story, anyway. But while the first part is true, the facts get hazy as the story goes on. In fact, Fleming never even tested his mold on living subjects — and it was only after another scientist's rediscovery of his paper nearly 10 years later that penicillin's potential was truly fulfilled.

A Slow Start

Here's the problem with Fleming's discovery: The strain of penicillium mold he found camping out in his bacterial colonies, called Penicillium notatum, was incredibly fussy. Fleming and his assistants at St. Mary's Hospital tried for weeks grow more of the stuff and to isolate pure penicillin from the bacteria-killing fluid that seeped from the mold, but they just ended up with a crude solution to work with.

Still, that was enough to demonstrate his findings, and in 1929, Fleming published a paper entitled "On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. Influenzae." That second phrase is important: Fleming made only a passing reference to penicillin's potential in treating infections; most of his paper focused on its use in isolating a particular penicillin-resistant microbe in lab samples.

Professor Alexander Fleming in his laboratory at St Mary's, Paddington, London.

Aside from its appeal to a handful of bacteriologists, penicillin wasn't worth much in the years to follow. That is, until 1938, when Dr. Howard Florey, the director of Oxford University's school of pathology, came across Fleming's paper while looking through back issues of academic journals. He had long been interested in the methods bacteria and mold use to kill each other, and Fleming's discovery was enticing enough to make him test the mold in his own lab.

Florey and his team, which included a biochemist named Dr. Ernst Chain, were also limited in their ability to produce anything more than crude solutions of the bacteria-fighting mold fluid, but they did what Fleming hadn't: They tested it on mice infected with deadly streptococcus. They gave half of the mice injections of penicillin and left the other half untreated. Only the penicillin-treated mice survived.

But those were mice. You'd need 2,000 liters of this mold culture to produce enough pure penicillin to treat just one person — and even that may not be enough. That was tragically demonstrated in 1940 when Florey and Chain first tried their penicillin on a police constable with a horrific infection. After five days of injections, he began to recover, but the team didn't have enough penicillin to continue treatment and he eventually died. The scientists knew that penicillin would never be very useful unless they came up with a reliable way to produce it in large quantities.

Looking for Something New

Unfortunately, Britain's chemical industry was busy with the war effort, so Florey and his colleague Norman Heatley sought help from the United States, which hadn't yet joined the fray of World War II. They found assistance with the Department of Agriculture, which set them up at a research lab in Peoria, Illinois. Despite quick success using different culturing methods to increase their yield of the drug, it wasn't quite enough, and the scientists soon started searching for a new strain of penicillin that was easier to produce.

They tested the contents of soil samples from all over the world, but the mold that would answer their prayers came from a much simpler source. A bacteriologist named Mary Hunt had been collecting moldy food she found at bakeries and grocery stores, then isolating the mold in the lab. The winner ended up being a Texas cantaloupe that was perfectly ripe, save for a small mold growth at its navel. (Hunt even cut up the cantaloupe for the staff to eat, she later recalled. It was reportedly delicious.) The mold turned out to be the fungus Penicillium chrysogeum, which yielded 200 times the penicillin of Penicillium notatum, which was Fleming's strain. And once the fungus was exposed first to X-rays and later to UV radiation, it eventually increased its production to around 1,000 times that of Penicillium notatum.

Soon, penicillin started to change the world. By the end of the war, American pharmaceutical companies were making 650 billion units of penicillin a month. The death rate from pneumonia dropped from 18 percent during World War I to less than 1 percent during World War II. The military death toll from infected wounds and gonorrhea was greatly reduced. You could even say that penicillin played a significant part in the Allied Powers' victory.

In 1945, the Nobel Prize in Physiology or Medicine was awarded to Alexander Fleming, Howard Florey, and Ernst Chain (Heatley was left out, but later got an honorary doctorate from Oxford for his contributions). So why is it that we only remember Fleming? According to Oxford University, PR had a lot to do with it: Soon after Florey's mouse study demonstrated penicillin's potential, St. Mary's Hospital — which employed Fleming and whose dean happened to be Winston Churchill's personal physician — quickly began publicizing the fact that they'd discovered the drug. It didn't help that Florey himself refused to speak to the press.

Alexander Fleming is still the scientist who discovered penicillin, and for that, he should be celebrated. But Howard Florey, Ernst Chain, Norman Heatley, Mary Hunt, and countless others were responsible for turning it into a reliable, practical drug that made it the greatest medical advance of the 20th century. Very few advances come from only one individual, and this breakthrough was the definition of a team effort.

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Read the whole story in "The Mold in Dr. Florey's Coat: The Story of the Penicillin Miracle" by Eric Lax. We handpick reading recommendations we think you may like. If you choose to make a purchase, Curiosity will get a share of the sale.

Written by Ashley Hamer August 2, 2019

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