1943: Industrial-Scale Penicillin Production (1943)

By 1942, Florey and Chain's Oxford team had proven penicillin's clinical efficacy, but production
remained measured in milligrams—far too little for military or civilian needs during World War II.
A landmark collaboration between British scientists and the American pharmaceutical industry,
coordinated by the US War Production Board, solved this problem through a series of
interconnected technological breakthroughs.

The pivotal technical advance was the shift from surface culture to submerged fermentation in
large stirred-tank bioreactors. Andrew Moyer at the USDA Northern Regional Research Laboratory
(NRRL) in Peoria, Illinois, developed the submerged corn-steep liquor medium that dramatically
increased penicillin yield. His team also identified Penicillium chrysogenum NRRL 1951—isolated
from a mouldy cantaloupe from a Peoria market—as a far more productive strain than Fleming's
original P. notatum.

Pharmaceutical companies including Pfizer, Merck, Squibb, and Lilly invested heavily in scale-up.
Pfizer's engineer John Smith pioneered deep-tank fermentation vessels holding thousands of gallons.
By the spring of 1943, sufficient penicillin was available for military use; by the June 1944
D-Day landings, over 2.3 million doses had been produced to treat battlefield infections. Penicillin
production rose from approximately 21 billion units in 1943 to over 6.8 trillion units in 1945.

This industrial achievement established the modern pharmaceutical fermentation industry and
demonstrated that biotechnology—large-scale microbial production of bioactive molecules—could
be industrialised. The techniques developed for penicillin directly enabled subsequent production
of streptomycin, erythromycin, cephalosporins, and eventually recombinant proteins and biologics.