Penicillin: Government: NRRL


Northern Regional Research Laboratory

One government agency that figured significantly in the production effort was the USDA's NRRL. Howard Florey and Norman Heatley initially had met with Ross G. Harrison, the chairman of the NRC, in New Haven shortly after their arrival in the U.S. in June 1941. He referred them to Washington, D.C. to see Charles Thom, the USDA's Bureau of Plant Industry's chief mycologist. Thom introduced the Oxford scientists to Percy Wells, who, although director of the Eastern Regional Research Laboratory, luckily was serving temporarily as director of all four laboratories. Moreover, upon hearing Florey and Heatley's mission of acquiring increased penicillin supplies, he recognized the NRRL's appropriateness. Wells had worked on an earlier government fermentation project-the details of which are discussed below-with several of the NRRL's scientists and knew that they had the potential to assist in penicillin research (Hobby, 87).

Wells contacted Orville E. May, the director of the NRRL, in July 1941. May invited Florey and Heatley to Peoria to meet with him and Robert Coghill, chief of the NRRL's Fermentation Division. The origins of the NRRL can be traced to an amendment to the 1938 Agricultural Adjustment Act, which established four regional research laboratories with the purpose of investigating "…industrial uses for the surplus agricultural commodities," such as corn and wheat at the NRRL (Finlay, 41). Upon U.S. involvement in WWII, however, the regional research laboratories altered their missions to focus on short-term, wartime projects rather than long-range assignments designed to solve the farm economy's imbalances (Finlay, 48). For instance, the revised agendas directed research towards "…the production of new foods, fibers, fuels, medicines, and substitutes for the scores of imported products, [such as Indian jute and rubber,] which were suddenly in short supply" due to the war effort (Finlay, 42). While the NRRL, founded in Peoria, Illinois in late 1940, created new plastics, corks, papers, and fuels, their "…most dramatic and lasting achievement was its role in uncovering an effective commercial process for the production of penicillin" (Finlay, 50).

The Fermentation Division took on the task of overcoming penicillin's growth difficulties, eventually substituting corn steep liquor as a growth medium, developing of higher-yield producing penicillin strains, and improving submerged fermentation techniques. These three accomplishments enhanced the process of penicillin production and made possible the advances that were realized after 1943. In this way, the NRRL is "…where mass production of penicillin first became a reality" (Neushul, 372). [For telegrams between May and Wells, see Hobby, 89-90, notes 4 and 5-taken from Percy Wells, "Some Aspects of the Early History of Penicillin in the United States," J. Wash. Acad. Sci. 65, no. 3 (1975): 96-101 and Northern Regional Research Center, Penicillin Chronology: Science & Education Administration, U.S. Department of Agriculture, compiled by Dean H. Mayberry, NC-173-80, U.S. National Archives, Washington, D.C. (1981).]

May placed mycologist Andrew Moyer in charge of developing a better medium for penicillin. He replaced the Oxford team's brewer's yeast extract, as it was not available in the U.S. in sufficient quantities, with corn steep liquor, a by-product of corn starch manufacture whose efficacy in growing molds he discovered in 1937 (Neushul, 378, 376). Moyer, who had considerable experience in mold fermentation, suggested its use due to its low cost and abundance in Peoria. After adjusting some of the metal and carbohydrate compositions in the medium and substituting glucose with lactose, the new medium resulted in a thirty-fold increase in penicillin yield (Hobby, 99; Neushul, 379). [For information on Moyer's work with corn steep liquor based on his previous experience with mold fermentation, see Neushul, 378, note 20-taken from Andrew J. Moyer to Orville E. May, 24 June 1944, a copy of the letter is found in Moyer's Research in Field of Mold Fermentations and Nutrition (Berkeley: Biology Library, n.d.). For information on the patents filed by Moyer, see Neushul 379-380, notes 22 and 26-taken from a transcript of the NOVA television show: "Rise of a Wonder Drug," appearing on 18 March 1986 (NY: Journal Graphics, 1986). NOVA includes interviews with Coghill and Heatley having to do with corn steep liquor production and Moyer's patent filing. Moyer filed three patent applications on 11 May 1945-granted and listed as "Method for Production of Penicillin," 25 May 1948, No. 2,442,141; 22 June 1948, No. 2,443,989; and 7 July 1949, No. 2,476,107.]

The second accomplishment of the NRRL in overcoming penicillin's growth difficulties was the discovery of more productive strains. Kenneth R. Raper, another NRRL mycologist, "…enlisted the aid of the Army Transport Command in gathering soil samples from all over the world" (Neushul, 381). NRRL scientists then screened the Penicillium strains that they isolated from these soil samples. In fact, the most productive strain that the NRRL discovered was from a moldy cantaloupe that had been found at a Peoria fruit market. It was thus named the "cantaloupe strain," or NRRL 1951, becoming "…the standard from which several more productive strains were subsequently derived" (Neushul, 381). In 1944, scientists at the University of Wisconsin, the University of Minnesota, Stanford University, and the Carnegie Institution's Cold Spring Harbor Laboratory developed these subsequent strains-the penicillin "super strains," such as x-1612 (Neushul, 372). The War Production Board's (WPB) Office of Production Research and Development (OPRD) initiated these research projects in an effort to overcome the "…production 'bottlenecks' which [Albert Elder, the WPB's 'penicillin czar,'] had observed at penicillin production facilities" (Neushul, 388). Specifically, the OPRD allowed the exchange of findings between the project groups and the NRRL; the importance which Elder placed on these projects reveals his support for fermentation.

Lastly, the NRRL addressed penicillin growth problems by seeking an improved means of submerged fermentation. During the 1930s, May, Wells, Moyer, and other scientists conducted research on fermentation at the Bureau of Chemistry and Soil's Color Laboratory in Arlington, Virginia. In May 1935, the group patented a submerged fermentation process in which a mold was grown throughout the medium rather than strictly on the surface of shallow vessels (Neushul, 375). This process was similar to the one they applied to penicillin six years later while working at the NRRL; the group also brought the aluminum fermenters developed by R. Hellbach, the Color Laboratory's instrument maker, to the NRRL to test Penicillium strains under submerged conditions. Until this point, penicillin had been produced via surface culture methods, for the substance was unable to penetrate more than a few millimeters into the medium. Although this process was simpler technically and presented fewer contamination problems, it was not conducive to large-scale production since it required substantial surface area of medium (Raper, 729). The NRRL thus began submerging higher-yield Penicillium strains in rotating drum fermenters and subsequently in larger vat fermenters, increasing production capabilities (Raper, 730). [For pictures of rotating drum fermenters and larger vat fermenters, see images from articles that Erin has scanned into the computer. Neushul, 377 has a picture of a pilot rotary aluminum fermenter installed in 1937 at the USDA's By-Products Laboratory in Ames, Iowa. Hobby, 88 has a picture of the penicillin research team at the NRRL, June 1944, that includes Raper, Coghill, and Moyer.]