𝐒𝐮𝐧𝐝𝐚𝐲'𝐬 𝐓𝐇𝐎𝐔𝐆𝐇𝐓𝐅𝐔𝐋 𝐏𝐨𝐬𝐭 : 𝐓𝐡𝐞 𝐔𝐧𝐭𝐨𝐥𝐝 𝐒𝐭𝐨𝐫𝐲 𝐨𝐟 𝐏𝐞𝐧𝐢𝐜𝐢𝐥𝐥𝐢𝐧"

 𝐒𝐮𝐧𝐝𝐚𝐲'𝐬 𝐓𝐇𝐎𝐔𝐆𝐇𝐓𝐅𝐔𝐋 𝐏𝐨𝐬𝐭

𝐓𝐡𝐞 𝐔𝐧𝐭𝐨𝐥𝐝 𝐒𝐭𝐨𝐫𝐲 𝐨𝐟 𝐏𝐞𝐧𝐢𝐜𝐢𝐥𝐥𝐢𝐧"

You only hear one part of the story of Penicillin. In 1928, Alexander Fleming returned to his lab after a holiday & found mold in one of his Petri dishes. Surprisingly, the volunteer fungus colony that colonized his experiment killed the Staphylococcus bacterium that got too close. Fleming cultured the mold and speculated that its active agent could have therapeutic applications. He never isolated or identified the antibiotic itself before giving up that line of research the following year.

Ten years later, Ernst Chain proposed that Oxford should explore Fleming’s curious findings. The Australian Howard Florey put together a cross functional team to do so. They succeeded in isolating tiny quantities of pure penicillin in a small-scale process that separated it from the mold and the growth medium. Experiments on lab animals demonstrated that the new material was not toxic and could prevent death in mice injected with deadly bacteria. In 1941, Oxford scientists conducted the first clinical trials on a human patient suffering from severe infection. The penicillin injections were highly effective, but insufficient quantities were available at that early date to save that patient’s life.

Fleming’s strain of mold would grow only on the surface of culture media. This growth mechanism was not suited for industrial scale production. The mold had other priorities besides producing antibiotics. It would only generate penicillin as a defensive measure when its growth cycle is inhibited by stress.

Early researchers did not know that closely related Penicillium mold strains would produce different versions of the penicillin molecule, such as 2-pentenylpenicillin versus benzylpenicillin. These were not interchangeable. Each type was effective only against specific disease bacteria. This variability made it difficult for researchers to predict the optimal dose and course of treatment.

In 1942, an intense effort was launched to research penicillin process technology at various locations, including a USDA lab in Peoria Illinois. Located in the leading region for corn (maize) production and processing, the lab chose a readily available corn byproduct mixed with lactose as the growth media. They screened thousands of mold samples to find ones that produced similar toxins and could grow in aerated fermentation tanks.

By manipulating mold strains, optimizing the growth media, finding the most favorable conditions and scaling up the tank sizes, it was possible to increase production exponentially in just two years. The process yields were found to be highly dependent on temperature, pH, Lysine level, Phosphate level, and oxygen availability. By the war’s end, production was taking place in 130,000 liter tanks at 80 – 90% yield.

Groundbreaking research discoveries often take years of tedious development work to become commercial products.

source : Tim Oberle