The Wonder Drug

Today would have marked the 137th the birthday of influential biologist Sir Alexander Fleming, most notably known for his work with penicillin for which he won the 1945 Nobel prize in Medicine along with colleagues Howard Florey and Ernst Chain.

Fleming’s story highlights the underlying serendipity behind many of the greatest discoveries in science, particularly the improbably incredible series of chance events that delivered Fleming’s discovery and made it opportunely possible. As part of Fleming’s research interests as a Professor of Bacteriology at St. Mary’s Hospital in London in 1928, his work involved growing cultures of staphylococci bacteria on agar in small glass petri dishes. Luckily enough, Fleming had not disposed of the dishes as he went on a month’s summer holiday and upon returning from the holiday, he was sorting his bench of old plates so that they could be washed for reuse when he chanced upon a Staphylococcus plate where a certain bluish-green mould had grown and contaminated it. Astoundingly, in a circular zone all around the mould, no germs were growing and the bacterial colonies were disintegrating. According to Fleming’s records, “the bacterial colonies became transparent and were obviously undergoing lysis”. The mould, Pencillium notatum, had produced a substance which killed the bacteria. Fleming called the substance penicillin.

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Sir Alexander Fleming

The series of events which led to this serendipitous scientific discovery were astonishing. How such mould of incredibly rare variety had accidentally infiltrated the culture is not known. It could have been that the tiny spore of Penicillium got in through the windows or it could have originated from a neighbouring laboratory that was studying moulds from the homes of asthmatic sufferers. In addition, just as Fleming had gone on holiday, London was hit by a cold spell of weather furnishing the ideal growth conditions that had favoured the development of the mould.

Fleming had grown increasingly wary of the significance of his finding, albeit to the relative lack of interest of some of his colleagues. His assistant Ronald Hare recounts “The rest of us, being engaged in researches that seemed far more important than a contaminated culture plate, merely glanced at it, thought that it was no more than another wonder of nature that Fleming seemed to be forever unearthing, and promptly forgot all about it.” Although Fleming was able to demonstrate that a liquid medium of the mould inhibited growth of various kinds of bacterial species, he found himself unable to isolate the substance and interest among his colleagues remained at a low. Research into penicillin went on a hiatus for a number of years.

It wasn’t until the late 1930s that interest had regrown. Howard Florey and Ernst Chain began studying penicillin and further developed fermentation and fractionation methods for the large-scale production of pencillin. They won some support from the British government by promising revolutionary treatments for battlefield injuries. Britain, however, was too busy with war for its industrial capacity to afford the production of penicillin. Undeterred, Florey and Chain sought US collaboration and won a massive grant from the Rockefeller Institute. Florey, Chain, and colleagues were, subsequently, able to uncover pencillin’s therapetuic potential in animal and human studies. Further improvements in production technologies saw the mass production of penicillin from alternative strains such as P. chrysogenum, which produced 25 times more penicillin in medium than Fleming’s original isolate of P. notatum, and its widespread clinical use after World War II.

Fleming may not, indeed, have been the first to discover penicillin. Its effects were previously studied by prominent names in science such as John Sanderson, John Tyndall, and Joseph Lister. But, they all either failed to grasp its significance, failed to pursue their results, or left no notes such that their research was lost. For instance, Tyndall had mistakenly concluded that the antibacterial effect of Penicillium was only due to oxygen deprivation caused by the thick layer of mould. Fleming’s fundamental genius, thus, rests in his foresight to realise that something unusual had happened and to remark: “That’s funny!”. As the statistician Francis Galton once famously said, in science, the credit usually goes to the person who convinces the world and not the person to whom the idea first occurs.

Fleming saw what others had seen before him, but he asked what noone else had asked before him.

“The more intelligent a question you ask of Mother Nature, the more intelligent will be her reply” — Sir Charles Sherrington

“When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.” — Sir Alexander Fleming

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