What improvement made to penicillin during world war ii saved many soldiers’ lives?

Find out what medical development helped World War II soldiers

Learn more about the development of antibiotics and their use in World War II.

Transcript

World War II was a conflict that involved virtually every part of the world from 1939 to 1945.
The war caused an estimated 40 to 50 million deaths, making it the bloodiest conflict in history.
But though World War II was incredibly deadly, it was actually more survivable for soldiers than most wars that came before it.
About 50% of wounded or ill soldiers survived their injuries or illnesses—a stark contrast to the mere 4% survival rate of World War I just a few decades earlier.
Many of the 50% owed their recovery to a new medical discovery that enabled their bodies to fight infection rather than succumb to it: the development of antibiotics.
In 1932 German scientist Gerhard Domagk announced the creation of Prontosil, the first sulfonamide drug.
Sulfonamides are chemical compounds with antibacterial properties. Called “sulfa drugs” and available in powdered and tablet form, soldiers could carry these antibiotics in their medical kits—where they were easily accessible to treat bacterial infections like streptococcal pneumonia, meningitis, and sepsis.
But though sulfa drugs were convenient, they weren’t perfect—and were often accompanied by a whole lot of side effects.
Luckily, research continued on the bacteria-killing properties of penicillin, which had been discovered by Alexander Fleming in 1928.
When isolated into a liquid, penicillin could be injected into the human bloodstream, where it would attack harmful bacteria and leave healthy human cells alone.
By 1941, the more effective drug was available to soldiers in injectable form.

Scaling-up Penicillin Production

Pharmaceutical and chemical companies played an especially important role in solving the problems inherent in scaling up submerged fermentation from a pilot plant to a manufacturing scale. As the scale of production increased, the scientists at Merck, Pfizer, Squibb and other companies faced new engineering challenges. Pfizer's John L. Smith captured the complexity and uncertainty facing these companies during the scale-up process: "The mold is as temperamental as an opera singer, the yields are low, the isolation is difficult, the extraction is murder, the purification invites disaster, and the assay is unsatisfactory."

Because penicillin needs air to grow, aerating the fermentation mixture in deep tanks presented a problem. When corn steep liquor was used as the culture medium, bubbling sterile air through the mixture caused severe foaming. Squibb solved this problem by introducing glyceryl monoricinolate as an anti-foaming agent. Submerged fermentation also required the design of new cooling systems for the vats and new mixing technology to stir the penicillin mash efficiently.

Lilly was particularly successful in making the mold synthesize new types of penicillin by feeding precursors of different structure. Once the fermentation was complete, recovery was also difficult; as much as two-thirds of the penicillin present could be lost during purification because of its instability and heat sensitivity. Extraction was done at low temperatures. Methods of freeze-drying under vacuum eventually gave the best results in purifying the penicillin to a stable, sterile, and usable final form.

The steps of fermentation, recovery and purification and packaging quickly yielded to the cooperative efforts of the chemical scientists and engineers working on pilot production of penicillin. On March 1, 1944, Pfizer opened the first commercial plant for large-scale production of penicillin by submerged culture in Brooklyn, New York.

Meanwhile, clinical studies in the military and civilian sectors were confirming the therapeutic promise of penicillin. The drug was shown to be effective in the treatment of a wide variety of infections, including streptococcal, staphylococcal and gonococcal infections. The United States Army established the value of penicillin in the treatment of surgical and wound infections. Clinical studies also demonstrated its effectiveness against syphilis, and by 1944, it was the primary treatment for this disease in the armed forces of Britain and the United States.

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Penicillin, WWII and Commercial Production

The increasingly obvious value of penicillin in the war effort led the War Production Board (WPB) in 1943 to take responsibility for increased production of the drug. The WPB investigated more than 175 companies before selecting 21 to participate in a penicillin program under the direction of Albert Elder; in addition to Lederle, Merck, Pfizer and Squibb, Abbott Laboratories (which had also been among the major producers of clinical supplies of penicillin to mid-1943) was one of the first companies to begin large-scale production. These firms received top priority on construction materials and other supplies necessary to meet the production goals. The WPB controlled the disposition of all of the penicillin produced.

One of the major goals was to have an adequate supply of the drug on hand for the proposed D-Day invasion of Europe. Feelings of wartime patriotism greatly stimulated work on penicillin in the United Kingdom and the United States. For example, Albert Elder wrote to manufacturers in 1943: "You are urged to impress upon every worker in your plant that penicillin produced today will be saving the life of someone in a few days or curing the disease of someone now incapacitated. Put up slogans in your plant! Place notices in pay envelopes! Create an enthusiasm for the job down to the lowest worker in your plant."

As publicity concerning this new "miracle drug" began to reach the public, the demand for penicillin increased. But supplies at first were limited, and priority was given to military use.

Dr. Chester Keefer of Boston, Chairman of the National Research Council's Committee on Chemotherapy, had the unenviable task of rationing supplies of the drug for civilian use. Keefer had to restrict the use of the drug to cases where other methods of treatment had failed. Part of his job was also to collect detailed clinical information about the use of the drug so that a fuller understanding of its potential and limitations could be developed. Not surprisingly, Keefer was besieged with pleas for penicillin. A newspaper account in the New York Herald Tribune for October 17, 1943, stated: "Many laymen - husbands, wives, parents, brothers, sisters, friends - beg Dr. Keefer for penicillin. In every case the petitioner is told to arrange that a full dossier on the patient's condition be sent by the doctor in charge. When this is received, the decision is made on a medical, not an emotional basis."

Fortunately, penicillin production began to increase dramatically by early 1944. Production of the drug in the United States jumped from 21 billion units in 1943, to 1,663 billion units in 1944, to more than 6.8 trillion units in 1945, and manufacturing techniques had changed in scale and sophistication from one-liter flasks with less than 1% yield to 10,000-gallon tanks at 80-90% yield. The American government was eventually able to remove all restrictions on its availability, and as of March 15, 1945, penicillin was distributed through the usual channels and was available to the consumer in his or her corner pharmacy.

By 1949, the annual production of penicillin in the United States was 133,229 billion units, and the price had dropped from twenty dollars per 100,000 units in 1943 to less than ten cents. Most British companies moved over to the deep tank fermentation production of penicillin, pioneered in the United States, after the end of the war to meet civilian needs. In the United Kingdom, penicillin first went on sale to the general public, as a prescription only drug, on June 1, 1946.

In Britain, Chain and Abraham continued to work on the structure of the penicillin molecule, aided by the X-ray crystallographic work of Dorothy Hodgkin, also at Oxford. The unique feature of the structure, which was finally established in 1945, is the four-membered highly labile beta-lactam ring, fused to a thiazolidine ring. In the same year Alexander Fleming, Howard Florey, and Ernst Chain were awarded the Nobel Prize for their penicillin research.

The co-operative efforts of American chemists, chemical engineers, microbiologists, mycologists, government agencies, and chemical and pharmaceutical manufacturers were equal to the challenge posed by Howard Florey and Norman Heatley in 1941. As Florey observed in 1949, "too high a tribute cannot be paid to the enterprise and energy with which the American manufacturing firms tackled the large-scale production of the drug. Had it not been for their efforts there would certainly not have been sufficient penicillin by D-Day in Normandy in 1944 to treat all severe casualties, both British and American."

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Landmark Designation and Acknowledgments

Landmark Designation

The American Chemical Society and Royal Society of Chemistry designated the Discovery and Development of Penicillin an International Historic Chemical Landmark on November 19, 1999, at the Alexander Fleming Laboratory Museum in London, UK. The plaque commemorating the event reads:

In 1928, at St. Mary's Hospital, London, Alexander Fleming discovered penicillin. This discovery led to the introduction of antibiotics that greatly reduced the number of deaths from infection. Howard W. Florey, at the University of Oxford working with Ernst B. Chain, Norman G. Heatley and Edward P. Abraham, successfully took penicillin from the laboratory to the clinic as a medical treatment in 1941. The large-scale development of penicillin was undertaken in the United States of America during the 1939-1945 World War, led by scientists and engineers at the Northern Regional Research Laboratory of the US Department of Agriculture, Abbott Laboratories, Lederle Laboratories, Merck & Co., Inc., Chas. Pfizer & Co. Inc., and E.R. Squibb & Sons. The discovery and development of penicillin was a milestone in twentieth century pharmaceutical chemistry.

Plaques were also given to commemorate the contributions of the U.S. Department of Agriculture National Center for Agricultural Utilization Research and five American pharmaceutical companies including Abbott Laboratories, Lederle Laboratories (now Pfizer, Inc.), Merck & Co., Inc., Chas. Pfizer & Co. Inc. (now Pfizer, Inc.) and E.R. Squibb & Sons (now Bristol-Myers Squibb Company).

Acknowledgments:

Adapted for the internet from "The discovery and development of penicillin 1928-1945," produced by the American Chemical Society and the Royal Society of Chemistry in 1999.

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Cite this Page

American Chemical Society International Historic Chemical Landmarks. Discovery and Development of Penicillin. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html (accessed Month Day, Year).

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