Science history: 90 years ago, a contaminated petri dish changed the world
Alexander Fleming’s first idea for killing bacteria involved snot. His second one was much more successful. Bill Sullivan reports.
Scientists throw away contaminated petri dishes every day. There is probably a frustrated researcher chucking her petri dishes into the bin right now as you read these words, cursing at the contaminant that ruined her experiment.
In those petri dishes are soft beds of agar that bacteria feast upon. Hundreds of bacterial colonies grow on the agar, each one containing millions of bacterial cells. But fungal spores lurk in the air, and if one of them happens to land on the agar, it may grow better than the bacteria. When a mould appears in a researcher’s bacterial dish, it is not a good thing.
Unless you were keeping your eyes peeled for a substance that can kill bacteria.
In the 1920s, a scientist named Alexander Fleming at St. Mary’s Hospital in London, UK, was doing just that. Fleming was growing colonies of Staphylococcus aureus bacteria on his petri dish plates. The species is commonly found on the skin, where it normally lives in peace, but it can turn into a deadly troublemaker if it finds its way into the bloodstream.
One of Fleming’s first discoveries was that snot could kill it. He soon isolated the murderous enzyme (lysozyme), but it proved to be a rather weak assassin with no viable therapeutic potential. Besides, it would have been a marketing nightmare. What would you call it? Snoticide? Boogie bombs?
One fateful autumn day in 1928, Fleming arrived at his laboratory to a pile of petri dishes that needed cleaning. While sorting through them, he noticed a mould growing on one of his culture dishes of S. aureus. He had undoubtedly seen a contaminated dish of bacteria before, but something more caught his eye that day. It turned out to be the discovery of a lifetime – one that has saved an incalculable number of lives.
As Louis Pasteur said, “Chance favours only the prepared mind.” Fleming’s mind was prepared, and he was always on the lookout for things that could kill bacteria. On that contaminated plate of S. aureus, he astutely noted that bacterial colonies grew better if they were farther away from the mould. In fact, no colonies could grow next to the mould.
He figured that the mould was producing a substance that was actively killing any bacteria that dared to come near it. The miserly mould would want to do this so it could have all the nutrients to itself. Fleming named this mystery bacteria-slaying substance “penicillin”, since the mould species was called Penicillium.
He published this extraordinary finding in the British Journal of Experimental Pathology in 1929 and the world … paid absolutely no attention to it at all.
Pathogenic bacteria continued to lead tens of millions of people to early graves through the 1930s. Fleming was no chemist, so he was not in a position to isolate the active ingredient that was killing the bacteria. He needed help. But try as he might, he couldn’t get other scientists interested in the promise of mould as a remedy for bacterial infections.
In hindsight, that seems crazy. But there were practical issues that dampened enthusiasm for his idea.
At the time, fungi were very difficult to grow in bulk, and the strain of Penicillium Fleming promoted produced very little penicillin.
His follow-up studies also suggested that penicillin would not work well in the clinic. Because it was so rare, he was forced to use low doses in his attempts to treat ill patients.
He also applied the “mould juice” topically on the skin instead of injecting it into the bloodstream, which would have been far more effective. These poorly designed experiments led many to the false conclusion that penicillin was an impotent bacterial assassin. You can imagine the sceptics dismissing his work: “First snot, now mould juice? C’mon, Fleming.” Consequently, the discovery laid dormant for over a decade.
In 1939, while leafing through back issues of the British Journal of Experimental Pathology, a chemist at Oxford named Howard Florey decided to revisit Fleming’s ignored penicillin paper. Together with Ernst Boris Chain, this dynamic duo produced a highly purified mould extract and injected it into mice with sepsis. The pair soon published the striking result that their Penicillium extracts cured the mice of this deadly bacterial infection.
Imagine Fleming’s response when he woke up one day to read this report! He was thrilled that someone was making use of his old work and immediately called Florey to arrange a visit to their laboratory. Chain was surprised to hear that he would get to meet Fleming, as he was under the impression that Fleming had passed away.
The trio won the 1945 Nobel Prize in Physiology or Medicine and inspired many microbiologists to search for more bacteria-killing microbes out in the wild.
Before long, our medicine cabinet was filled with additional antibiotics such as erythromycin, tetracycline, streptomycin, and many more. These wonder drugs were being produced naturally by microbes found in the dirt, on rotting foods, and even in the throat of a chicken. Scientists left no stone unturned in their hunt for weapons of microbial destruction.
The story would have a happy ending were it not for two things. In an interview after his Nobel acceptance speech, Fleming gave a very prescient warning about the reckless overuse of antibiotics: "The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism."
Unfortunately, we failed to heed Fleming’s premonition and now face an imminent threat of superbugs: bacterial strains that have evolved resistance to these precious medicines.
Poor Fleming ... ignored twice, but later proven correct on both accounts. Second, virtually no one is in the business of antibiotic discovery any more because it does not generate high profits like medicines for chronic conditions, which patients must take every day for the rest of their lives.
Considered together, Fleming’s near-century old discovery may soon be ineffective and we will return to the “pre-antibiotic” era when a simple scratch from a rosebush could mean death. We need more “prepared minds” in research and in business to keep the antibiotic pipeline strong.
This article was originally published by The Scope and is used with permission. The original can be found here.