page_title: History of penicillin
section_title: Manufacturing
hierarchical_section_title: History of penicillin / Isolation and mass production / Manufacturing
caption_attribution_description: A poster attached to a curbside mailbox offering advice to World War II servicemen: Penicillin cures gonorrhea in 4 hours.
context_page_description: The history of penicillin follows a number of observations and discoveries of apparent evidence of antibiotic activity in moulds before the modern isolation of the chemical penicillin in 1928. There are anecdotes about ancient societies using moulds to treat infections, and in the following centuries many people observed the inhibition of bacterial growth by various molds. However, it is unknown if the species involved were Penicillium species or if the antimicrobial substances produced were penicillin.
  The Scottish physician Alexander Fleming was the first to suggest that a Penicillium mould must secrete an antibacterial substance, and the first to concentrate the active substance involved, which he named penicillin, the first modern antibiotic, in 1928. During the next twelve years Fleming grew, distributed and studied the original mold, which was determined to be a rare variant of Penicillium notatum.
  Many later scientists were involved in the stabilization and mass production of penicillin and in the search for more productive strains of Penicillium. Important contributors include Ernst Chain, Howard Florey, Norman Heatley and Edward Abraham.
context_section_description: When production first began, one-liter containers had a yield of less than 1%, but improved to a yield of 80–90% in 10,000 gallon containers. This increase in efficiency happened between 1939 and 1945 as the result of continuous process innovation. Orvill May, the director of the Agricultural Research Service, had Robert Coghill, who was the chief of the fermentation division, use his experience with fermentation to increase the efficiency of extracting penicillin from the mold. Shorty after beginning, Andrew Moyer replaced sucrose with lactose in the growth media, which resulted in an increased yield. An even larger increase occurred when Moyer added corn steep liquor.
  One major issue with the process that scientists faced was the inefficiency of growing the mold on the surface of their nutrient baths, rather than having it submerged. Even though a submerged process of growing the mold would be more efficient, the strain used was not suitable for the conditions it would require. This led NRRL to a search for a strain that had already been adapted to work, and one was found in a moldy cantaloupe acquired from a Peoria farmers' market. To improve upon that strain, researchers subjected it to X-rays to facilitate mutations in its genome and managed to increase production capabilities even more.
  Now that scientists had a mold that grew well submerged and produced an acceptable amount of penicillin, the next challenge was to provide the required air to the mold for it to grow. This was solved using an aerator, but aeration caused severe foaming as a result of the corn steep. The foaming problem was solved by the introduction of an anti-foaming agent known as glyceryl monoricinoleate.
caption: Penicillin ad for World War II servicemen, c. 1944
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