World War II Forums - View Single Post - BLOOD TRANSFUSION AND ANTIBIOTICS etc IN WW2

DocCasualty · #18 (**permalink**) May 15th, 2009, 12:07 PM

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Originally Posted by Kai-Petri

Project MUSE

The fact that Germany failed to produce sufficient penicillin to meet its military requirements is one of the major enigmas of the Second World War. Although Germany lost many scientists through imprisonment and forced or voluntary emigration, those biochemists that remained should have been able to have achieved the large-scale production of penicillin. After all, they had access to Fleming's original papers, and from 1940 the work of Florey and co-workers detailing how penicillin could be purified; in addition, with effort, they should have been able to obtain cultures of Fleming's penicillin-producing mold. There seems then to have been no overriding reason why the Germans and their Axis allies could not have produced large amounts of penicillin from early on in the War. They did produce some penicillin, but never in amounts remotely close to that produced by the Allies who, from D-Day onwards, had an almost limitless supply.

They simply had not discovered and had no access to a good method of mass production of PCN. Given time, I'm sure the Germans would have eventually come up with their own method, but that is the nature of scientific and technological discovery. Despite having a long and glorious tradition in chemistry, medicine and pharmaceuticals, that confers no lock on the ability to always be first.

I'm sure if I spent a little more time I could quote a better source than Wiki but here is the basic history. Penicillin - Wikipedia, the free encyclopedia

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Mass production

The challenge of mass-producing the drug was daunting. On March 14, 1942 the first patient was treated for streptococcal septicemia with U.S.-made penicillin produced by Merck & Co.[12] Half of the total supply produced at the time was used on that one patient. By June 1942 there was just enough U.S. penicillin available to treat ten patients.[13] A moldy cantaloupe in a Peoria, Illinois market in 1943 was found to contain the best and highest-quality penicillin after a worldwide search.[14] The discovery of the cantaloupe, and the results of fermentation research on corn-steep liquid at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the USA to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944. Large-scale production resulted from the development of deep-tank fermentation by chemical engineer Margaret Hutchinson Rousseau.[15]

Penicillin was being mass-produced in 1944

G. Raymond Rettew made a significant contribution to the American war effort by his techniques to produce commercial quantities of penicillin.[16] During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds among Allied forces, saving an estimated 12%–15% of lives.[citation needed] Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug, necessitating frequent dosing. Penicillin is actively secreted, and about 80% of a penicillin dose is cleared from the body within three to four hours of administration. Indeed, during the early penicillin era, the drug was so scarce and so highly valued that it became common to collect the urine from patients being treated, so that the penicillin in the urine could be isolated and reused.[17]
This was not a satisfactory solution, so researchers looked for a way to slow penicillin secretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for secretion, such that the transporter would preferentially secrete the competing molecule and the penicillin would be retained. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are administered together, probenecid competitively inhibits the secretion of penicillin, increasing penicillin's concentration and prolonging its activity. Eventually, the advent of mass-production techniques and semi-synthetic penicillins resolved the supply issues, so this use of probenecid declined.[17] Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins.[18]

Also from About.com: http://www.invent.org/hall_of_fame/107.html

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Andrew J. Moyer
Born Nov 30 1899 - Died Feb 17 1959 </B>

Method for Production of Penicillin
Penicillin
Patent Number(s) 2,442,141; 2,443,989

Inducted 1987

Andrew J. Moyer's discoveries provided the foundation for the industrial production of penicillin.

The potential of using penicillin to treat wounded soldiers was immediately recognized in World War II. However the concept of antibiotics was new, and a practical method for large-scale production was not available. Treatments required from 1-2 million Oxford units of the substance. The urgency of finding a method for mass-producing penicillin led to international cooperation.

In the United States, the task was assigned to Moyer, who found that by culturing the Penicillium mold in a culture broth comprising corn steep liquor and lactose, penicillin yields could be increased many fold. This was the first known use of corn steep liquor for growing microorganisms.

Moyer also discovered that with this improved medium, the fermentation could be conducted with continuous shaking, thereby further enhancing the yields and production rate.

Invention Impact

These discoveries led to industrial penicillin production, which saved thousands of lives during the war.

Moyer's work also provided a model for the development of all other antibiotic fermentations. Corn steep liquor is still used in the commercial fermentation processes for making penicillin and many other antibiotics. Moyer contributed to 10 U.S. patents.

Born in Star City, Indiana, Moyer received his A.B. degree from Wabash College in 1922, studied at the University of Wisconsin from 1922 to 1923, and received a M.S. from North Dakota Agricultural College in 1925. In 1929 he was awarded his Ph.D. in plant pathology from the University of Maryland.

Moyer was employed as a mycologist with the U.S. Department of Agriculture, Bureau of Chemistry and Soils, from 1929 until 1940 then worked as a microbiologist at the USDA Northern Regional Research Laboratory in Peoria, Illinois, until his retirement in 1957.

Also History of Penicillin - Alexander Fleming - John Sheehan - Andrew Moyer

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Dr. Howard Florey

It was not until 1939 that Dr. Howard Florey, a future Nobel Laureate, and three colleagues at Oxford University began intensive research and were able to demonstrate penicillin's ability to kill infectious bacteria. As the war with Germany continued to drain industrial and government resources, the British scientists could not produce the quantities of penicillin needed for clinical trials on humans and turned to the United States for help. They were quickly referred to the Peoria Lab where scientists were already working on fermentation methods to increase the growth rate of fungal cultures. One July 9, 1941, Howard Florey and Norman Heatley, Oxford University Scientists came to the U.S. with a small but valuable package containing a small amount of penicillin to begin work.

Pumping air into deep vats containing corn steep liquor (a non-alcoholic by-product of the wet milling process) and the addition of other key ingredients was shown to produce faster growth and larger amounts of penicillin than the previous surface-growth method. Ironically, after a worldwide search, it was a strain of penicillin from a moldy cantaloupe in a Peoria market that was found and improved to produce the largest amount of penicillin when grown in the deep vat, submerged conditions.
Andrew J. Moyer

By November 26, 1941, Andrew J. Moyer, the lab's expert on the nutrition of molds, had succeeded, with the assistance of Dr. Heatley, in increasing the yields of penicillin 10 times. In 1943, the required clinical trials were performed and penicillin was shown to be the most effective antibacterial agent to date. Penicillin production was quickly scaled up and available in quantity to treat Allied soldiers wounded on D-Day. As production was increased, the price dropped from nearly priceless in 1940, to $20 per dose in July 1943, to $0.55 per dose by 1946.

As a result of their work, two members of the British group were awarded the Nobel Prize. Dr. Andrew J. Moyer from the Peoria Lab was inducted into the Inventors Hall of Fame and both the British and Peoria Laboratories were designated as International Historic Chemical Landmarks.
Andrew J Moyer Patent

On May 25, 1948, Andrew J Moyer was granted a patent for a method of the mass production of penicillin.

And this also http://explorepahistory.com/hmarker.php?markerId=974

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Name: G. Raymond Rettew

Region: Philadelphia and its Countryside/Lehigh Valley

County Location: Chester

Marker Location: Walnut and Chestnut Streets, West Chester

Dedication Date: September 17, 2002

Marker Text
A West Chester chemist, he pioneered the mass production of penicillin, the world's first antibiotic. In 1943, with Wyeth Laboratories, his lab, (a converted auto-repair shop here) made and sent more penicillin to the Armed Forces than any other lab in the world, saving countless lives on the battlefields of World War II.

Behind the Marker

On August 1, 1944, a German 88mm artillery shell detonated near U.S. infantryman Murphy Higginbotham, sending shards of metal through his right leg and shoulder, and into the left side of his back. While Higginbotham recuperated in a hospital a letter arrived from his parents in Texas. Incapacitated and unable to respond, Higginbotham had a friend write about his progress. "I got your letter of September 4th with Murphy's address [at the hospital]. So, I checked up and found where he was located, and left the same afternoon," he wrote. "At first they thought they would have to take his leg off. You see, it was long before they really could treat him, as it should have been, and the doctor said that when he first got there it was such a dirty wound, and had gas gangrene. But, they started treating him with the new ‘wonder drug" penicillin and it brought him around ok."

During World War II, American soldiers had a greater chance of surviving wounds...
Credit: The Franklin D. Roosevelt Library.

Several months later, in an Italian hospital, bacteria ravaged the body of British Army sergeant Len Scott. What began as a minor case of athlete's foot turned into ugly boils that spread out along his legs. Doctors called it "diphtheria of the skin." In several weeks the inflammation spread to his arms and hands. "Medical conferences at the foot of my still-too-small-bed were more frequent. I heard a new word mentioned—penicillin. …Things grew better, sores disappeared."

Before the introduction of penicillin in World War II, wounded soldiers were more likely to die of bacterial infections than from their wounds. With inadequate knowledge of how the body healed itself, doctors often were encouraged by the presence of "laudable pus." Others sought to treat the after effects of infection, like gas gangrene, with hydrochloric acid. Penicillin, however, which halts the division of the bacteria, could treat infection at its source.

The chemotherapeutic attributes of penicillin had first been discovered by Alexander Fleming in 1928. In the 1930s, Oxford scientists Howard Florey and Ernst Boris proved the antibiotic's capabilities when mice infected with lethal amount of bacteria fully recovered after the scientists injected them with pure doses of penicillin developed from a specimen of Fleming's mold. News of Florey and Chain's achievement soon reached a quiet young Pennsylvania scientist, Granville Raymond Rettew. Born in West Chester on April 19, 1903, Rettew had studied chemistry at the University of Delaware and Swarthmore College. While employed by the Charles E. Hines Company in Philadelphia, he had become interested in improving mushroom growth by refining the production of mushroom spawn, a mixture of mycelium root structure and sterilized cereal grain that Hines sold to mushroom growers.

By the fall of 1943, Raymond Rettew's Walnut Street Laboratory in West Chester...
Credit: Courtesy of the Chester County Historical Society, Westchester, Pa.

Convinced that the mushroom cultivators "needed scientific study and help," Rettew founded the Chester County Mushroom Laboratories in West Chester and began systematizing the production of quality, marketable spawn in sophisticated labs that boasted sterile air-conditioned growing rooms and UV lights. A tireless tinkerer, Rettew patented a device for collecting mushroom spawn and collaborated with food packagers to develop new processes for freezing produce.

When not developing better spawn, better insecticides, or better mushrooms, Rettew was in his lab working on his "hobby": the extraction of useful compounds from mushrooms. The United States" entry into the World War II in December 1941 prompted the mycologist to assess "whether or not there was anything which could be of help to the War effort." His hobby, Rettew rightly figured, had potential benefits for American fighting man. Having studied penicillin intermittently since 1928, Rettew knew of Florey and Chain's research. He also knew that by altering the culture, or medium in which the mycelium grew, he could improve the quality of the spawn. He figured the same process would apply to penicillin growth. "This," he wrote in his memoirs, "would be our way of contributing to the War effort."