Penicillin: Breakthrough to the Era of Antibiotics
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Weinberger realized the potential of and additional crosses are made each this specialty fruit and was responsive year. There is reason to expect a com- to the industry need for reliably tested plete replacement of present varieties. freestone varieties. A sequence of sim- Weinberger's interest in improving ilar varieties over a period as long as Japanese-type plums led to a resump- for peaches is envisioned. tion of breeding for new varieties. An As was true with peaches, main crop earlier, very productive, cooperative apricot varieties were static for many program between the USDA and the years. As a consequence, the varieties, California Agricultural Experiment mostly of European origin, became Station at Davis had developed *Bur- less well suited to changing market mosa,' 'Redheart,' 'Nubiana,' 'La- demands. Commercial drying of fruit roda,' and several other varieties which became less prevalent, and the need became important to the industry. for larger fruit and for resistance to Using these and other varieties as pit burning—browning of flesh adja- parents, Weinberger produced over cent to the pit—became more im- 17,000 hybrids and now is testing portant as more fruit was shipped fresh many promising selections. One was or canned. named 'Frontier' in 1967. It com- Weinberger realized the need for bines the high quality of the leading greater resistance to pit burning, im- red-fleshed variety with much better proved firmness, and larger size in exterior color, thus increasing its mar- varieties similar to the major varieties. ket appeal. 'Friar', an amber-fleshed In 1963, 'Gastleton' was introduced and black-skinned variety, was in- by USD A because it fulfilled these troduced in March of 1968. Other objectives. The other selections which selections are undergoing rigorous plot promise to complement this variety and commercial testing. Weinberger are in various stages of testing. Over is growing some 3,200 plum seedlings 2,100 seedlings have not yet fruited. which have not yet fruited. Penicillin: Breakthrough to the Era of Antibiotics FRANK H. STODOLA To many, scientific research don in 1928. This discovery was a is an impersonal and forbidding pur- highly improbable event and involved suit. This notion is something of a two elements of luck. The right kind of myth, perhaps never more so than for mold spore had to come in contact penicillin. Its story abounds in drama with the right kind of disease germ and and human interest. thereby produce an unusual eflect. Forty years have now passed since And this eflect had to be observed by Alexander Fleming was led by a "curi- someone who knew its meaning, ous concatenation of circumstances" Fleming was such a man: A highly to the discovery of this astonishing sub- trained and acute observer who had stance at St. Mary's Hospital in Lon- devoted his whole career as a medical 339 bacteriologist to the search for nontoxic 1930, he sent a subculture of Fleming's agents for the treatment of disease. It mold to the U.S. Department of Agri- would be hard to find a better example culture's Bureau of Plant Industry at of fortune favoring the prepared mind. Beltsville, Md., to be examined by Not only did Fleming make the Charles Thom, a world authority on original observation on penicillin—he fungi, including the Penicillia. The sensed the importance of his discovery. result of this first visit of the penicillin He preserved the mold; and he care- organism to America is recorded in fully described its behayior in a paper Thom's notebook as follows : entitled "On the Antibacterial Action 5112 H. Raistrick of Cultures of Pénicillium." Beautiful Rec'd 5-14-30 in its simplicity, this paper was to 5112.1 P. rubrum (?) isolated by Fleming. become one of the classics of medical British collection No. 3127. Culture on literature. It was the opening gun in Dox-glucose agar Apr.25.30 the victorious battle against the in- = P. notatum fectious diseases. It ushered in the Era Thom's assignment of the mold to of Antibiotics and altered the whole the correct species (P. notatum) was course of modern medicine. invaluable. It identified the culture In his paper, Fleming wrote "A with a cosmopolitan series of molds certain type of pénicillium produces and, later, gave direction to the search in culture a very powerful antibacterial for more productive strains. substance. The action is very Valuable contributions were made marked on the pyogenic cocci and the by the Raistrick group to the produc- diphtheria group of bacilli. Pen- tion and chemistry of penicillin. Un- icillin is nontoxic to animals in enor- fortunately, the work was not con- mous doses and is nonirritant." He tinued beyond 1932 because of the suggested, "It may be an efficient anti- accidental death of the Mycologist septic for application to, or injection Charles and the departure of the into, areas infected with penicillin- Bacteriologist Lovell. Although tem- sensitive microbes." porarily discouraged by this setback, Everything of importance is in these Fleming did not lose faith in penicillin. few sentences! Yet, who would have In lectures and publications, he con- guessed what a profound effect this tinued to point out its virtues and modest account was to have upon its possibilities. human welfare. The scene next shifts from London Knowing that chemical studies on to the Sir William Dunn School of penicillin were next in order, Fleming Pathology at the University of Oxford. was pleased when Harold Raistrick of There Howard Fiorey, a medical man the London School of Hygiene and who had extensive experience with the Tropical Medicine undertook the iso- antibacterial enzyme lysozyme dis- lation of penicillin. Being a careful and covered by Fleming in 1922, joined experienced worker on the chemistry forces in 1939 with Biochemist Ernest of mold products, Raistrick took the Chain, Organic Chemist E. P. Abra- necessary first step in such work by ham, and Bacteriologist Norman Heat- establishing with certainty the identity ley in a new and determined attack on of the penicillin organism. On April 29, the penicillin problems. Aided by a $5,000 grant from the Rockefeller Foundation, they succeeded by late FRANK H. STODOLA hos been in charge of the 1940 in taming the previously intracta- Pioneering Laboratory for Microbiological Chemis- ble penicillin by converting it into a try at the Northern Utilization Research and stable, dry powder. Development Division, Agricultural Research So effective was this purified ma- Service, Peoria, III,, since 1957. He worked for Ja years before that in the Fermentation Division, terial in the treatment of some human whose members received the Lasker Award in 2946 infections that by early 1941 Fiorey for penicillin research. and his associates were convinced that 340 if penicillin could be made available molds, had succeeded, with the help in quantity, its use in the treatment of of Heatley, in increasing the Oxford war wounds would result in a marked yields tenfold by the use of corn steep physical and psychological advantage liquor, a byproduct of corn starch over the enemy. Unfortunately, it was manufacture. not possible at that time for the al- On December 17, this highly en- ready overburdened British chemical couraging result was disclosed by and drug manufacturers to undertake Robert D. Coghill, head of the Fer- large-scale production of penicillin, mentation Division at NRRL, to rep- so in July 1941 Florey and Heatley resentatives of four companies (Merck, came to this country to take advantage Squibb, Pfizer, and Lederle) at a meet- of the more favorable conditions and ing called in New York by A. N. the American knack for mass produc- Richards, a friend of Florey's, chair- tion. They were not to be disappointed. man of the Committee on Medical Their first stop was at New Haven, Research of the Office of Scientific Conn., where Florey's children had Research and Development. This meet- been staying at the home of J. F. ing established a vital link between Fulton during the bombing of London. government research at NRRL and There, R. G. Harrison, chairman of the chemical and pharmaceutical firms the National Research Council, ad- capable of large-scale production and vised the English visitors to see Thom. led to a fruitful collaboration that was He promptly recommended the newly to continue throughout the war. established Northern Regional Re- The simplest and quickest way of search Laboratory (NRRL) at Peoria, producing penicillin in quantity in 111., where USD A investiga tojs were 1941 was by the "surface" method, in already familiar with industrial fer- which the mold grows as a mat on the mentation processes and where a large top of a nutrient solution. Pilot plant collection of molds was maintained. production of penicillin by this process The following telegram on July 9 from was slow at first because of contamina- P. A. Wells, acting head of the Bureau tion and isolation problems. By March of Agricultural Chemistry and Engi- 1942, only enough penicillin was neering, to O. E. May, director of the available in the United States for the laboratory, was to set in motion a treatment of one case. series of events of utmost importance Prospects were vastly improved, to the war effort. however, when K. B. Raper, a former "Thom has introduced Heatley and collaborator of Thom, found a superior Florey of Oxford. Here to investigate strain of P. notatum-chrysogenum at pilot scale production of bacteriostatic NRRL, which doubled the yield of material from Fleming's pénicillium penicillin, raising it to 150 units per in connection with medical defense milliliter of nutrient solution com- plans. Can you arrange for shallow pared to the two units of the Oxford pan setup to establish laboratory re- group.