{"id":12468,"date":"2017-06-04T08:07:51","date_gmt":"2017-06-04T08:07:51","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=12468"},"modified":"2017-06-04T08:07:51","modified_gmt":"2017-06-04T08:07:51","slug":"d-day-invasion-bolstered-uw-madison-penicillin-project","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/d-day-invasion-bolstered-uw-madison-penicillin-project\/","title":{"rendered":"D-Day invasion was bolstered by UW\u2013Madison penicillin project"},"content":{"rendered":"
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The D-Day invasion of Normandy was bolstered by millions of doses of a precious new substance: penicillin. On the other side of the Atlantic, researchers at the University of Wisconsin\u2013Madison and other institutions had spent the last three years pursuing advances in penicillin production. NATIONAL ARCHIVES<\/figcaption><\/figure>\n

Seventy-three years ago Tuesday, on June 6, 1944, the D-Day invasion of Normandy was bolstered by millions of doses of a precious new substance: penicillin.<\/p>\n

On the other side of the Atlantic, researchers at the University of Wisconsin\u2013Madison and other institutions had spent the last three years pursuing advances in penicillin production. Though discovered 16 years prior, the world\u2019s first natural antibiotic was expensive and difficult to wring from the mold that makes it. By discovering new strains, isolating more productive mutants, and improving growing methods, UW\u2013Madison biologists helped supply Allied troops with enough penicillin to treat life-threatening infections.<\/p>\n

More than 50 UW\u2013Madison scientists participated in the government-organized program. Descendants of the penicillium mold developed at UW\u2013Madison are still used to produce penicillin around the world today.<\/p>\n

In 1941, two British scientists, Howard Florey and Norman Heatley, came to the United States to enlist government and university researchers in increasing penicillin production. Florey\u2019s team had demonstrated that penicillin could safely treat bacterial infections in animals and humans, but they could barely extract enough of the antibiotic to treat a single patient. In Ken Raper, a bacteriologist at the USDA\u2019s Northern Research Regional Laboratory (NRRL) in Peoria, Illinois, Florey found an able partner.<\/p>\n

Raper, who later joined the faculty at UW\u2013Madison after collaborating with his future colleagues throughout the war, was already an experienced mold biologist. His lab at the NRRL had been perfecting fermentation techniques to extract valuable natural compounds from microbes, an expertise well suited to increasing penicillin production. Raper\u2019s experience collecting many different strains of fungi and the social amoebae dictyostelids helped him recognize that better strains of penicillium mold might be found in nature. At the time, only Alexander Fleming\u2019s original mold was known to produce the antibiotic.<\/p>\n

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Kenneth Rapper working in the laboratory in 1949.<\/figcaption><\/figure>\n

In a nationwide search for more productive strains, the best was found growing on a moldy cantaloupe in a Peoria grocery store \u2014 strain NRRL-1951. Unlike Fleming\u2019s mold, which only grew on the surface of liquid cultures, NRRL-1951 grew well when mixed throughout the culture. This submerged growth allowed much higher concentrations of the mold, and penicillin, to be produced.<\/p>\n

Raper sent NRRL-1951 to collaborators around the country. Researchers at Cold Spring Harbor in New York irradiated the strain with X-rays and sent the resulting mutants to the University of Minnesota, where scientists screened them and forwarded promising candidates on to Wisconsin.<\/p>\n

Oral history: Ken Raper<\/strong><\/p>\n

UW\u2013Madison microbiologist Elizabeth McCoy identified the best new mutant, X-1612, which was grown and tested by biochemists William Peterson and Marvin Johnson. Peterson and Johnson oversaw dozens of scientists who tinkered with the mold\u2019s growing conditions to induce more penicillin production. The researchers tested larger fermentation vessels to take advantage of economies of scale. They improved the sterilization, aeration and mixing of the cultures, while perfecting milk- and corn-based culture broths developed in Peoria.<\/p>\n

Meanwhile, UW\u2013Madison botanists John Stauffer and Myron Backus took McCoy\u2019s strain and exposed it to ultraviolet light to create more mutations in the mold. Eventually, they isolated Q-176, the most productive penicillium strain of the wartime program.<\/p>\n

\u201cAnd when they got this one breakthrough, it doubled the production in a month,\u201d recalls former UW\u2013Madison Professor of Biochemistry Robert Burris, who was part of the penicillin project, in an oral history<\/a> from university archives. \u201cYou could do it by submerged fermentation, you could do it on cheap media, and the extraction process was worked out by that time so you could get reasonably clean material at a low price and it just was a real boon in the treatment of a variety of diseases and infections.\u201d<\/p>\n

Oral history: Robert Burris<\/strong><\/p>\n

According to Raper\u2019s accounts of the work, the descendants of Q-176 are still used to produce the drug today.<\/p>\n

\u201cWhen the English came over here \u2026 it was figured out that they were getting about four units per milliliter of penicillin,\u201d says Raper in an archived oral history of his work<\/a>. \u201cBy Christmas of that year in Peoria \u2014 when we started in July \u2014 we were getting about 40. This mold came off the cantaloupe in its native state produced about 100. By making selections from it we had 250. The X-ray mutant produced 500 and the ultraviolet mutant that they had here in Wisconsin produced 900 so the thing was going up like this, you see. There was great excitement.\u201d<\/p>\n

Marcin Filutowicz<\/a>, a professor of bacteriology at UW\u2013Madison who uses Raper\u2019s dictyostelid collection<\/a> to search for new antimicrobials, says the story of wartime penicillin research was well-known in his native Poland after the war.<\/p>\n

\u201cProduction of penicillin was the first major step in the development of industrial microbiology,\u201d says Filutowicz. \u201cThis was the first instance of the paradigm that scientists can use their basic understanding of a beneficial organism to improve the metabolic output of compounds that provide social benefits and have commercial value.\u201d<\/p>\n

\u201cAntibiotics have saved millions of lives since the discovery of penicillin,\u201d says Filutowicz.<\/p>\n

The strains of penicillium mold produced at UW\u2013Madison were not patented, but were given freely to private industry to grow as much as possible for the war effort. Improved techniques were shared widely. By the end of the war, the cost of 100,000 units of penicillin \u2014 just a fraction of a single dose \u2014 dropped from $20 (about $500 today) to three cents. Whereas Florey struggled to extract enough penicillin to treat a single patient in 1941, before the war was over production was high enough to allow civilian use of the drug.<\/p>\n

The antibiotic era that this scientific collaboration among departments, institutions and nations launched continues at UW\u2013Madison to this day, with researchers scouring the world\u2019s insects and marine environments<\/a> for new compounds while other teams<\/a> try to discover new ways<\/a> to combat infectious microbes. The legacy of these historic and ongoing efforts are the countless lives saved by these drugs.<\/p>\n

\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Seventy-three years ago Tuesday, on June 6, 1944, the D-Day invasion of Normandy was bolstered by millions of doses of a precious new substance: penicillin. On the other side of the Atlantic, researchers at the University of Wisconsin\u2013Madison and other institutions had spent the last three years pursuing advances in penicillin production. Though discovered 16 […]<\/p>\n","protected":false},"author":6,"featured_media":12470,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[17],"tags":[],"class_list":["post-12468","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",1024,1024,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1-150x150.jpeg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1-300x300.jpeg",300,300,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1-768x768.jpeg",750,750,true],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",750,750,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",1024,1024,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",1024,1024,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",800,800,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",570,570,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",600,600,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",600,600,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",490,490,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",360,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",65,65,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",640,640,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",96,96,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2017\/06\/Raper-cropped-1024x1024-1.jpeg",150,150,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/12468","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=12468"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/12468\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/12470"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=12468"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=12468"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=12468"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}