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 "
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 "
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.
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 "
'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.]