The world has never before witnessed the colossal spending of time and money for research and technology development as it does in the current scenario. It is the consequence of the instrumental research of the 19th and 20th centuries that eventually paved the way for modern science, which now employs more than half a million scientists worldwide. Let’s recollect about one such accidental discovery that not only helped save millions of lives but also reprogrammed modern medicine. This article takes on the journey from the discovery of penicillin to its industrial production.
In a world without soaps, sanitizers, and disinfectants, the discovery of the first antibiotic by Alexander Fleming in 1928 revolutionized medical science. Unfortunately, even a single cut or abrasion could get infected in those times, leading to several compilations of pneumonia, rheumatic fever, etc., and causing distress to the patients and their physicians.
The causative bacteria, therefore, were consequently studied in much detail and cultured in Petri-plates. As accidents would have it, a moldy growth replaced bacterial colonies on one end of a plate inoculated with Staphylococcus. Flemming hypothesized that the mold, later identified as Penicillium notatum, could inhibit the growth of bacteria. Thus, the fungus produced ‘something’ to prevent bacterial growth, which can be used for treating Staphylococcal infections if identified. Eventually, the unknown compound was identified as penicillin, and fortunately, penicillin could also inhibit other bacterial strains and demonstrated a broad range of activity.
Antibiotic extraction from Penicillium
Despite the discovery, it was a long while before its applications could be implemented. Even though penicillin was discovered in 1928, its applications were not realized until the Second World War. Even though Flemming is credited with penicillin discovery, he could not purify the stable form of the antibiotic from the fungus.
Subsequently, penicillin extraction was then taken up by Florey and Chain in 1939 during the advent of World War 2 with the noble objective of saving lives. Large quantities of culture were produced and harvested to isolate the stable antibiotic for clinical trials. Appropriate fermenters were custom-designed to increase the surface area, which substantially increased the culture density. Penicillin was separated from the large volumes of the cell filtrate by extraction in amyl acetate, followed by water extraction. Additional impurities were removed by the column chromatography technique. The technology was then transferred over to industries for scale-up of the production process.
Penicillin production at an industrial scale
Industrial-scale production of penicillin was achieved by mass-producing fungal cells in large fermentation tanks. Interestingly, even though penicillin was discovered from Penicillium notatum, another species – P. chrysogenum was cultivated for large-scale penicillin production. The latter was an improved strain that yielded higher product concentration and productivity for process economization. The penicillin is extracted into amyl acetate (or butyl acetate) under acidic conditions, followed by treatment with potassium acetate for crystallization. The sterilized penicillin can be used for parenteral administration.
Like every hero needs a villain, every great innovation needs a crisis for its applications. Every country was desperate for antibiotics to treat the injured during the war; therefore, penicillin was produced and patented by two independent groups. Penicillin production set a precedent for process patents instead of products which is significant even now. Fleming, Florey, and Chain’s collective effort helped save millions of lives and continues to do so even after 80 years. The history of antibiotic production from fungus was instrumental in identifying other antibiotics from a range of fungal strains. A repertoire of antibiotics is now known to man, and a major percentage was discovered from fungi. The world has witnessed the reliance on antibiotics time and again, especially during the current widespread of COVID infections. Just imagine if that Petri plate was never contaminated with mold back in 1928.