How did Pfizer’s deep-tank fermentation revolutionize penicillin production?
Pfizer built deep-tank fermentation out of its own citric acid and gluconic acid work, then applied it to penicillin in a plant that ran 24 hours a day, seven days a week and supplied most of the penicillin that went ashore with Allied forces on D-Day.
The American Chemical Society’s commemorative booklet documents one of the most crucial industrial innovations in medical history. Pfizer’s deep-tank process grew the mold in a submerged aerobic medium in stirred tanks, with control over pH and the sterility of the air, rather than on the surface of shallow pans.
This achievement captures the industrial sprint to mass production. The ACS account shows how engineering innovation was as crucial as scientific discovery in making penicillin available to save lives during World War II.
What the source documents:
- A dramatic production increase: During the fall months after the plant opened, one day’s production of penicillin often exceeded the entire production of 1943
- Round-the-clock operation: The Marcy Avenue plant ran 24 hours a day, seven days a week
- Output beyond the estimate: Pfizer was soon producing five times more penicillin than originally estimated, making it the leading supplier of the drug
- D-Day supply: Most of the penicillin that went ashore with Allied forces on D-Day came from the Marcy Avenue plant in Brooklyn
This American Chemical Society booklet documents the engineering breakthrough that made mass penicillin production possible, demonstrating how industrial innovation can transform scientific discoveries into life-saving treatments at unprecedented scale.
Dr. Kumar’s Take
Pfizer’s deep-tank fermentation story shows me how engineering innovation can be as transformative as scientific discovery. Fleming saw the mold kill bacteria in 1928 and concluded penicillin would never be an important antibiotic, because he could not make enough of it and what he made was unstable. The drug sat as a laboratory curiosity for a decade. The problem was not biology. It was manufacturing.
What impresses me is that Pfizer did not import a solution. Jasper Kane started as James Currie’s 16-year-old lab assistant on the citric acid fermentation problem in 1917, and it was Kane who suggested in 1942 that penicillin should move into the deep tanks that had worked for gluconic acid. Twenty-five years of in-house fermentation experience, on products as unglamorous as citric acid and molasses, is what put the company in a position to answer the question the war was asking. Deep institutional knowledge in one narrow craft turned out to matter more than any obvious cross-industry analogy.
Historical Context
Fleming returned from a long holiday in September 1928 and found a petri dish where a Penicillium contaminant had cleared an area of staphylococcus colonies. He found the mold killed a host of gram-positive bacteria, including those causing scarlet fever, pneumonia, gonorrhea, meningitis, and diphtheria. Because penicillin was hard to cultivate and unstable in the small quantities he could produce, he concluded it would never be important for treating infections.
Howard Florey and a team at Oxford University later demonstrated its life-saving potential, but by then England was at war and mass production was difficult. In 1941 the British government asked the U.S. scientific community for help. Four chemical and pharmaceutical companies responded, Pfizer among them.
Pfizer’s fermentation background ran back decades. James Currie, a food chemist, discovered that citric acid could be fermented from certain strains of the mold Aspergillus niger combined with sugar, and brought the discovery to Pfizer in 1917. Currie and Kane worked the problem with flat pans, then smaller and shallower ones, which raised the yield. Pfizer opened a pilot plant in 1919 and a full plant that began operating in 1926, the year fermentation output surpassed production based on lemons and limes. In 1929 the company produced gluconic acid in stirred deep tanks. In 1936 it began marketing synthetic vitamin C made with submerged fermentation as the first step.
What the Research Shows
The ACS commemorative booklet describes what Pfizer built:
Submerged Fermentation Instead of Surface Culture Kane first used flasks and pans similar to the citric acid technique, and gains in penicillin yield, potency and purity came frustratingly slowly. In 1942 he suggested switching to the deep tanks that had worked for gluconic acid.
Aeration, pH and Sterility Control The gluconic acid process ran in a submerged aerobic medium in stirred deep tanks that controlled for pH and the sterility of the air. Aspergillus niger is aerobic, so getting air into a deep volume of medium without contaminating it was the central engineering problem.
The Plant Itself In September 1943 Pfizer bought the old Rubel ice plant nearby, which had the refrigeration equipment the process required, and rebuilt it into the world’s first large-scale penicillin factory. It opened on March 1, 1944 with fourteen 7,500-gallon tanks. The Marcy Avenue plant was 95% completed by the end of February 1944.
The Production Sequence Production began with a sterile culture of the mold, propagated first in three-liter flasks, then in 200-gallon seed tanks, then moved to fermenter tanks holding corn steep liquor, milk sugar, salts and minerals. The mold grew for two to four days. Extraction was the trickiest step: the broth held only four parts drug per 10,000 parts broth. The extracted material was purified and bottled in sterile rooms, then passed through a freezing apparatus and a vacuum drier.
A Deliberate Commercial Risk Moving to deep tanks meant curtailing production of other, more profitable products. Pfizer executive John Smith described the odds this way: “The mold is as temperamental as an opera singer, the yields are low, the isolation murder, the purification invites disaster. Think of the risks!” The company took the gamble.
Practical Takeaways
- Depth in one craft beats a borrowed analogy: Pfizer’s own citric acid and gluconic acid fermentation experience, not an outside industry’s methods, produced the penicillin solution
- Engineering innovation is as important as scientific discovery: David Wilson wrote that ignoring the deep fermentation breakthrough is the biggest single failing of the penicillin myth, calling it every bit as vital as the laboratory work
- Continuous operation raised output enormously: With the plant running 24 hours a day, seven days a week, one day’s autumn production often exceeded all of 1943
- Industrial vision requires risk-taking: Pfizer sacrificed more profitable product lines during wartime uncertainty to bet on an unproven process
Related Studies and Research
- Penicillin: The Accidental Discovery That Changed Medicine and Won a War
- National WWII Museum: Penicillin’s Wartime Journey
- ACS Landmark: Fleming Discovery and US Wartime Scale-Up
- USDA Rescue of Penicillin: Peoria’s Industrial Role
FAQs
Where did Pfizer’s deep-tank fermentation actually come from?
From Pfizer’s own fermentation business. The company had been fermenting citric acid since Currie brought the process to it in 1917, and in 1929 it succeeded in producing gluconic acid in a submerged aerobic medium in stirred deep tanks. Kane proposed carrying that method over to penicillin in 1942. Pfizer had earlier tried and failed to use deep tanks for citric acid itself.
What made deep-tank fermentation different from the pan methods?
The mold grew submerged throughout a stirred, aerated medium rather than in flasks and shallow pans. The pan approach was subject to the quality of the mold spores, the purity of the cultures, contamination of the air and the medium, humidity and temperature.
What was the impact on D-Day supply?
Most of the penicillin that went ashore with Allied forces on D-Day came from Pfizer’s Marcy Avenue plant in Brooklyn.
What happened after the war?
In 1946 Pfizer researchers found that penicillin’s normal yellow color indicated impurities, and developed a crystallization method producing white penicillin that was stable at room temperature and potent for years. The company applied its fermentation techniques to streptomycin, developed by Selman Waksman and his staff at Rutgers. In 1949, after testing tens of thousands of soil samples, Pfizer scientists found a Midwest soil micro-organism effective against a wide range of deadly bacteria, yielding Terramycin, the first antibiotic developed exclusively by Pfizer scientists.
Bottom Line
Pfizer’s deep-tank fermentation ranks among the most important industrial innovations in medical history, taking penicillin from laboratory curiosity to mass-produced medicine. The method grew out of the company’s own citric acid and gluconic acid fermentation work under Currie and Kane, and the plant it enabled ran around the clock and supplied most of the penicillin that landed with Allied forces on D-Day. The American Chemical Society designated the development of deep-tank fermentation by Pfizer a National Historic Chemical Landmark in a ceremony in Brooklyn on June 12, 2008.
