Fleming, Florey, & Chain: The Discovery and Development of Penicillin

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Fleming: The Discovery of Penicillin

Alexander Fleming (born 1881) was a Scottish biologist who published extensively in several fields, including bacteriology, immunology, and chemotherapy. He’s most well-known for the discovery of the first antibiotic—penicillin—but interestingly enough, he had little to do with actually getting the substance mass-produced for human use.

Fleming began his work on antibacterial substances after the First World War, during which he had witnessed countless soldier’s deaths due to septicemia which resulted from infected wound sites.

In 1928, Fleming was in the midst of investigating a genus of bacteria called staphylococci, and it was during September of that year that he made a serendipitous discovery. The story goes that Fleming was somewhat messy in the lab, and had returned from a vacation to find many of his bacteria culture dishes had been contaminated with mold. He later realized that on one of the dishes, the mold colony had a clear zone around it where bacteria could not grow.

Fleming identified the mold as Penicillium, isolated an extract of the unknown agent, and named it penicillin. He spent some time investigating its antibacterial effects and published his findings to surprisingly little fanfare. He subsequently found that cultivating the mold and extracting penicillin was a laborious task, and because of this and his conviction that the agent could not work effectively in the human body, he eventually abandoned his work.

Florey & Chain: Testing and Mass Production

In 1939, Ernst Chain, a biochemist who had fled to Britain from Nazi Germany, came across Alexander Fleming’s published work on penicillin. He was greatly interested, and soon began working on isolating penicillin. Together with lab supervisor Howard Florey, he isolated the antibacterial agent in greater quantity than Fleming had been able to achieve, and then tested the extract by injecting it into two mice which had been infected with a bacterial disease.

The mice recovered, and the two men then tested the penicillin further in a much larger trial run with fifty mice. They subsequently made enough of the substance to use it in two or three people who were dying from bacterial infections. These experiments proved that penicillin would work effectively in humans, but there was a huge stumbling block, in that it was enormously difficult to isolate enough penicillin to treat even one person. With the Second World War underway, the situation was becoming desperate.

Ernst Chain was the driving force behind isolating and testing penicillin, but when it came to manufacturing on a large scale, it was Howard Florey who made more of a contribution, by locating several U.S. companies which were willing to provide resources when U.K. factories were occupied with the war effort.

Mass production of penicillin began, but soon it became clear that the strain of penicillin which Fleming had originally discovered just wasn’t yielding enough of the drug. A hunt for a better source of penicillin ensued, and eventually, in 1943, a lab worker named Mary Hunt provided the goods – a cantaloupe from her own fridge, which was infected with Penicillin chysogeum.

This new mold species produced around 200 times as much penicillin as Fleming’s original discovery, Penicillin notatum. By mutating the species using x-rays, Florey and the U.S. team eventually were able to create a strain of the mold which produced 1,000 times more penicillin as Fleming’s species.

By the end of the war, U.S. companies were making 650 billion units of penicillin every month – staggering in comparison to the 400 units made between January and May 1943.

For their contributions to the discovery and development of penicillin, all three men—Alexander Fleming, Ernst Chain, and Howard Florey—were awarded a Nobel Prize for Medicine in 1945.