Original Document
Original Document
G. Raymond Rettew on the production of penicillin during World War II

World War II changed our approach to business. First, I encouraged the industry to study the food value of mushrooms so they could be declared an essential food. This was done by working with Carl Fellars, who had a national reputation as a food authority, at Massachusetts State College. Mushrooms were found to have a high vitamin content and good protein value without the fattening carbohydrates. Later, in 1944, The Mushroom Institute of America, which was composed of the Mushroom Growers Association and most of my competitors, presented me with a scroll and a check for $1,000 in gratitude for my "general work which resulted in a benefit to the mushroom industry."

The second reaction to the War was for me to look over my hobby to find whether or not there was anything which could be of help to the War effort. This hobby was the study of chemical substances produced by the fungi. I had been working on the extraction of the enzyme tyrosinase from mushrooms. The extraction was successful but the medical use was questionable. Dr. Harold Raistrick of the University of London did much pioneer work on the chemical composition of the fungi, and my hobby was centered around the study and laboratory tests covering his work. One substance which Raistrick had studied was penicillin, discovered by Alexander Fleming. When I first studied penicillin, I was unaware of its importance; but in 1941,1 read the papers of the Oxford team (Dr. Ernst Boril Chain, Sir Howard W. Florey, etc.). These articles indicated that penicillin held great promise for healing infected wounds. Therefore, the penicillin work was pulled off the shelf and intensive work started on it. This would be our way of contributing to the War effort….

The original work in 1942 was done in my private laboratory over the garage. This proved that the experience of extracting chemical substances from fungi, together with the techniques used for the culture of mushroom spawn, made a good starting point for the study of penicillin. In order to translate this idea into action, certain steps were taken.

First, through my friend Dr. E. B. Lambert of the U.S. Department of Agriculture, who was a member of the National Academy of Sciences, I contacted Dr. Alfred N. Richards, Chairman, Committee on Medical Research of the Office of Scientific Research and Development, located in the National Academy Building in Washington, D.C. The reason I give this location is that in the very same building was the control center of the development of the atomic bomb. No wonder we had trouble getting through the front door! Nevertheless, we convinced Dr. Richards that the Chester County Mushroom Laboratories could contribute to the penicillin program, which the Federal Government had just established as top priority.

The next step was to obtain a contract with an ethical drug company since we had no knowledge of the pharmaceutical field. At Buck Hill, Joe Strode had a golf partner, Alvin G. Brush, about whose business connections he knew nothing. However, one day Strode happened to mention my work on penicillin to him. A luncheon meeting was then set up at Mr. Brush's home for the three of us. I very guilelessly asked for whom he meant absolutely nothing to me at the time although the company had sales of over 60 million dollars). It turned out that Mr. Brush was Chairman of the Board of American Home Products Corporation and he was very definitely interested. He set up a meeting for me with Harry S. Howard, President of American Home Products Corporation; Frank Law, President, and Alfred Barol, Technical Manager, of John Wyeth Brother, Incorporated; and Dr. Paul Gyorgy, a consultant.

John Wyeth and Brother Incorporated was a well-known ethical drug company and a subsidiary of American Home Products Corporation. This group was interested and sent Dr. Gyorgy out to see our facilities. He approved of what he saw.

In the meantime, Joseph W. Strode and I set up a subsidiary corporation to the Chester County Mushroom Laboratories, called Fungus Products, for the express purpose of further study and production of penicillin. An agreement was made between American Home Products Corporation and Fungus Products to cooperate in this study.

During the remaining part of 1942, I worked alone in my own laboratory, mostly at night, experimenting with the cultivation of the Fleming strain of Penicillium notatum, developing an improved culture medium, and proving the adaptability of the 40-ounce culture flask (a kind of shortnecked bottle with four flat sides), and the equipment of the Chester County Mushroom Laboratories. It was then that I started to develop the method for the recovery of penicillin from fermentation broth.

Work up to this time gave very promising results. Truly our knowledge of fungi and the equipment of the Chester County Mushroom Laboratories were an ideal combination for the development of penicillin production. In January 1943, the first technical assistant was added in the person of Charles Heathcote, Jr., who was a graduate of the Philadelphia School of Pharmacy and Science.

During the spring, unique and original methods for the production of penicillin were developed. The use of wetting agents and a centrifuge were found to solve the difficult emulsion problem which was proving to be a major obstacle to all potential producers. To isolate penicillin from the culture medium, amyl acetate (banana oil) was added and the mixture shaken to extract the penicillin. These mixtures, however, readily formed emulsions, which separated very slowly or not at all. Since penicillin was not particularly stable, degradation was often faster than separation of the liquids. By a combination of adding a chemical surface-active agent and speeding up the separation by use of a Sharples centrifuge, as suggested by my good friend and partner, Joe Strode, we were able to overcome these obstacles. It was the solution of this problem that finally made possible our winning the race for mass production of penicillin. Charles Heathcote, Jr., and I were later granted a patent (U.S. 2,562,715) on the method of extraction, using a surface-active agent to break the emulsion. Penicillin production today would not be possible without this method.

Next it was necessary to build a penicillin recovery unit at the Laboratories. At this time Wyeth was paying the costs of production while we were supplying the building and equipment. We went ahead and built a recovery building for which i located a portable refrigerator room large enough to hold a Sharples centrifuge and four 100-gallon glass-lined tanks. This was the first time that a Sharples centrifuge, together with complete refrigeration, had been used.

I went to Washington to the War Production Board to get permission to buy pumps and other equipment but was turned down, for they had not yet learned of the importance of penicillin. Soon, however, they were told of its urgency by the Office of Scientific Research and Development. Two months later, the War Production Board sent representatives to encourage us to move faster. "Why were we using water buckets instead of pumps?" they asked. What could we say?

Then the Office of Scientific Research and Development sent a representative, Dr. Robert D. Coghill, who thought he was surely on a wild goose chase. What could mushrooms possibly have to do with penicillin? Nevertheless, he soon learned that equipment for large-scale production of fungus cultures, together with knowledge of chemical production by fungi, was ideal for production of penicillin, and he became our friend and supporter. Dr. Coghill was later the liaison between industry and the Office of Scientific Research and Development. Our contacts developed into a warm, personal friendship that was to continue past the War years.
We knew that the deep culture method would be the ultimate production process, but to get penicillin faster we adopted the surface culture method using the 40-ounce milk bottle and our spawn making equipment including large double-ended sterilizers, sterile inoculating rooms, and air-conditioned growing rooms. We were ahead in the development of a quick method for production of penicillin. Information concerning our methods was transferred through Dr. Coghill and the Office of Scientific Research and Development to those in industry, who were also participants in the penicillin crash program.

Pilot lots were run in the large-scale equipment at the Chester County Mushroom Laboratories using the new recovery facilities. I have not dwelt on the many difficulties that had to be overcome in the pilot plant development of penicillin production. Contamination during fermentation, instability of penicillin during extraction, and repeated assays to evaluate each modification of a process resulted in seemingly slow progress in view of the war emergency.

Soon it was obvious that more growing space was needed, and, for the first time, American Home Products Corporation put up the money to double the space at the Laboratories. There was a regular "barn raising" and the expansion was completed in one month.

Because its value as an antibiotic had been proved, penicillin received much publicity during this time, and the Government gave development and production top priority. Our spawn business, which was one of the largest in the world, was literally pushed out the back door, and all of our facilities were turned over to American Home Products Corporation for penicillin production.
The penicillin produced at that time was very impure and had not been crystallized. Hence a concentrated solution was produced, which was shipped under refrigeration to the Reichel Laboratories at Kimberton, Pennsylvania, a producer of dried blood plasma and a subsidiary of American Home Products Corporation. Here the penicillin was freeze-dried and packaged; for this reason, the first penicillin came out under the label of Reichel Laboratories.

By the end of June 1943, the very first penicillin was delivered to the United States Government, which at this time controlled all distribution with Dr. Chester Keefer in charge. Over 90 per cent of all penicillin went to the Armed Services.

By now our facilities were not large enough. From Walter Penrose we rented The Pennsylvania Garage, which was a large building in the center of West Chester on Walnut Street, across the street from the Philadelphia Electric Company steam plant. In 90 days this building was revamped into a penicillin plant capable of producing 32,000 surface cultures a day, together with the equipment for recovering the penicillin.

In order to expedite materials needed for penicillin production, the Armed Services sent a group of four, whose only mission was to maintain highest priority for our penicillin production. American Home Products Corporation sent Sherry Waldron to teach us corporation business methods and to set up an office for us in the Green Tree Building. By November 1943, we started production at the so-called Walnut Street Laboratory. Thus with the combined facilities, we were able to produce most of the world's supply o f penicillin that first year.

Processing 32,000 surface cultures a day meant expert teamwork by many.

In 1943, the purity was about 12 percent, but the toxicity of both penicillin and impurities was very low. Although 100,000 units, enough for one injection, sold for twenty dollars at that time, by 1945 the cost had been reduced to as little as sixty cents per 100,000 units."

The penicillin produced during this early period was extremely important. I think that each of us engaged in the manufacture of penicillin was impelled by one deep-seated motive-namely, to make the drug available to as many as possible in order to save lives and relieve suffering. The war helped speed up production much faster because the economic factor was relatively unimportant.

West Chester supplied a marvelous team of very dedicated people, both men and women, who worked around the clock and who must still be proud of their efforts. While other pharmaceutical firms were still casting about for ways to build large plants and to perfect the ultimate method of deep tank fermentation, West Chester played the vital role in the breakthrough of mass production of penicillin by surface culture when it was most urgently needed. West Chester has forever earned a permanent place for itself in the pioneering history of the production of penicillin.

Credit: From G. Raymond Rettew, A Quiet Man from West Chester. West Chester, PA: The Chester County Historical Society, 1974.
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