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Phlegming: Perchance a Mould, Diligence, and Chivalry

Vincent G Valentine, MD
University of Texas Medical Branch, Galveston, TX, USA

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During the time of the Great War, a young Scottish physician, serving as a medical officer with the British army, observed many deaths of soldiers from the helpless inability to rid the bacteria hidden within the crevices of their jagged wounds. It was not because he wasn't trying, but rather his attempts at cleansing the wounds with antiseptic chemicals were rarely useful. He began to reason that the best way to render the soldier's wounds germ free would be to inject antiseptic into his blood, but this seemed to be a dangerous proposition. Such an approach was known to be poisonous to both bacteria and people, and he published that antiseptics were killing more soldiers than the infection itself during the War to end all Wars.

After November 11, 1918, he returned to a civilian position at St Mary's Hospital in London as a researcher. He was on a mission to find a substance harmless to humans but deadly to bacteria with a goal to inject a safe antiseptic into patients' bloodstreams. He worked diligently and methodically with failure after failure in his search of such a chemical.

On a hunch, he decided to test the effect of his own nasal secretions on bacteria. He discovered that his own nasal mucus and eventually tears and saliva possessed some bacteria-killing agent that destroyed most cultures of bacteria in Petri dishes. He further discovered that laboratory mice, domestic animals, and every species of fish he caught produced this same substance capable of killing most bacteria. This substance, harmless to humans, he named lysozyme (first line of innate immunity). Photo at right: Sir Alexander Fleming. Photo credit: Science Photo Library

In late summer of 1928, disgruntled after finding that some mould had ruined some of his bacteria cultures, he observed perchance that no germs were growing in a circle around a blob of mould in the culture dish of Staphylococcus aureus. The yellow bacterial colonies had been polluted by green mould. Around the mold, the bacteria lost their healthy golden color and were dissolving into drops of clear fluid. Fleming then swabbed some mould of this culture dish and transferred it to a clean dish. He then cultivated this mould and filtered a liquid he called "mould juice." He later found that this juice killed many deadly bacteria without harming human blood cells. When injected in mice, it did no harm. The mould turned out to be a rare strain of the species, Penicillium notatum.

Next, he launched a quest to determine if all species of mould produced this juice. He cultivated mould from dirt, tainted cheeses, rotten vegetables, and asked his friends, "If any of you chaps have a pair of mouldy old shoes, I'd like to have them." He discovered that none of these different sources of mould produced a significant amount of "mould juice." Then he realized his great fortune of having an airborne mould spore floating into his laboratory through an open window and perchance landing on his culture plates. However, he was much less fortunate when he tested this juice in human volunteers. It did not harm anyone, nor did the juice cure anyone's infection. He noted that this mould juice, penicillin, killed all bacteria in a culture dish, but proved ineffective in human patients. In 1929, he published his disappointing results and abandoned his work with penicillin. Photo at left: Fleming at work. Photo credit: Wikipedia

At Oxford University in 1938, Howard Walter Florey read and studied these earlier works published about Penicillium notatum. Florey and other scientists identified the active ingredient in penicillin and produced large quantities to cure sick mice. During a lull in the violence of World War II, the diligent Scottish physician traveled from London to Oxford to meet Florey and Ernst Boris Chain. It wasn't until 1942 when the Scot learned that Florey's team purified enough penicillin to successfully treat a human patient.

The most noble and notable deed lost and veiled by the knighting of this Scot in 1944 and the jointly awarding of the Nobel Prize in Medicine in 1945 to Sir Alexander Fleming, Ernst Boris Chain, and Sir Howard Walter Florey was when Fleming declined to claim a patent on penicillin. This chivalrous generosity to mankind speedily allowed the mass production of penicillin by every pharmaceutical manufacturer in England and the United States to freely profit and provide the most useful lifesaving drug the world had ever seen.

Disclosure Statement: The author has no conflicts of interest to disclose.