Returning from holiday on September 3, , Fleming began to sort through petri dishes containing colonies of Staphylococcus, bacteria that cause boils, sore throats and abscesses. He noticed something unusual on one dish. It was dotted with colonies, save for one area where a blob of mold was growing. The zone immediately around the mold—later identified as a rare strain of Penicillium notatum—was clear, as if the mold had secreted something that inhibited bacterial growth.
Fleming found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus and the diphtheria bacillus.
He then set his assistants, Stuart Craddock and Frederick Ridley, the difficult task of isolating pure penicillin from the mold juice. It proved to be very unstable, and they were only able to prepare solutions of crude material to work with. Fleming published his findings in the British Journal of Experimental Pathology in June , with only a passing reference to penicillin's potential therapeutic benefits. At this stage it looked as if its main application would be in isolating penicillin-insensitive bacteria from penicillin-sensitive bacteria in a mixed culture.
This at least was of practical benefit to bacteriologists, and kept interest in penicillin going. Their work on the purification and chemistry of penicillin began in earnest in , just when wartime conditions were beginning to make research especially difficult.
To carry out a program of animal experiments and clinical trials the team needed to process up to liters a week of mold filtrate. They began growing it in a strange array of culture vessels such as baths, bedpans, milk churns and food tins.
Later, a customized fermentation vessel was designed for ease of removing and, to save space, renewing the broth beneath the surface of the mold. In effect, the Oxford laboratory was being turned into a penicillin factory. Meanwhile, biochemist Norman Heatley extracted penicillin from huge volumes of filtrate coming off the production line by extracting it into amyl acetate and then back into water, using a countercurrent system.
Edward Abraham, another biochemist who was employed to help step up production, then used the newly discovered technique of alumina column chromatography to remove impurities from the penicillin prior to clinical trials.
In , Florey carried out vital experiments, showing that penicillin could protect mice against infection from deadly Streptococci. Then, on February 12, , a year old policeman, Albert Alexander, became the first recipient of the Oxford penicillin.
He had scratched the side of his mouth while pruning roses, and had developed a life-threatening infection with huge abscesses affecting his eyes, face, and lungs. Penicillin was injected and within days he made a remarkable recovery.
But supplies of the drug ran out and he died a few days later. Better results followed with other patients though and soon there were plans to make penicillin available for British troops on the battlefield. War-time conditions made industrial production of penicillin difficult. Substantial amounts of penicillin would be needed for the extensive clinical trials required to confirm the promise of the early results and to provide adequate supplies of the drug for therapeutic use if it did live up to its potential.
Florey recognized that large-scale production of penicillin was probably out of the question in Britain, where the chemical industry was fully absorbed in the war effort.
With the support of the Rockefeller Foundation, Florey and his colleague Norman Heatley traveled to the United States in the summer of to see if they could interest the American pharmaceutical industry in the effort to produce penicillin on a large scale. Yale physiologist John Fulton helped to put his British colleagues in touch with individuals who might be able to assist them in their goal.
This contact proved to be crucial to the success of the project, as the NRRL was a key contributor of innovations that made large-scale production of penicillin possible. It was agreed that Heatley would remain in Peoria to share his expertise with his American colleagues.
Within a few weeks, Andrew Moyer found that he could significantly increase the yield of penicillin by substituting lactose for the sucrose used by the Oxford team in their culture medium. Shortly thereafter, Moyer made the even more important discovery that the addition of corn-steep liquor to the fermentation medium produced a ten-fold increase in yield.
Corn-steep liquor was a by-product of the corn wetmilling process, and the NRRL, in an attempt to find a use for it, tried it in essentially all of its fermentation work. Later, the Peoria laboratory increased the yield of penicillin still further by the addition of penicillin precursors, such as phenylacetic acid, to the fermentation medium.
It was recognized that the Oxford group's method of growing the mold on the surface of a nutrient medium was inefficient, and that growth in submerged culture would be a superior process. In submerged culture fermentation, the mold is grown in large tanks in a constantly agitated and aerated mixture, rather than just on the surface of the medium. Florey's Penicillium culture, however, produced only traces of penicillin when grown in submerged culture.
Under the direction of Kenneth Raper, staff at the NRRL screened various Penicillium strains and found one that produced acceptable yields of penicillin in submerged culture. Soon a global search was underway for better penicillin producing strains, with soil samples being sent to the NRRL from around the world. Ironically, the most productive strain came from a moldy cantaloupe from a Peoria fruit market. Fleming and his wife had a son, Robert, who became a general practitioner.
When she passed away after 34 years of marriage, Fleming had a very difficult time. He lost himself in his work, spending most of his time behind closed doors in the lab. In , Fleming married Dr. Amalia Koutsouri-Vourekas in a Greek church in London. Tan SY, Tatsumara Y. Alexander Fleming — : discoverer of penicillin. Singapore Med J. Alexander Fleming and the Discovery of Penicillin. Highlight and copy the desired format. Data is collected weekly and does not include downloads and attachments.
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Isolation of Penicillin at Oxford University. Penicillin and US Involvement. Public Awareness: The Fleming Myth. Secrecy in Wartime England. Production during World War II. The Netherlands The situation in the Netherlands was different. Figure Figure. Nobel Prize in The author thanks Monica Farley for her helpful review of the manuscript.
Macfarlane G. Alexander Fleming: the man and the myth. Gaynes R. Paul Ehrlich and the magic bullet. In: Germ theory: medical pioneers in infectious diseases. Fleming A. On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B.
Br J Exp Pathol. Penicillin as a chemotherapeutic agent. DOI Google Scholar. Further observations on penicillin. American Chemical Society. International historic chemical landmark. Discovery and development of penicillin [cited Nov 19]. Shama G. Zones of inhibition? In: Laskin, AI. Advances in applied microbiology. New York: Academic Press, Inc. Vol 69, Chap. Even in the early experimentation stages, penicillin had no effect against gram-negative organisms but was effective against gram-positive bacteria.
When I woke up just after dawn on Sept. But I guess that was exactly what I did. Though Fleming stopped studying penicillin in , his research was continued and finished by Howard Flory and Ernst Chain, researchers at University of Oxford who are credited with the development of penicillin for use as a medicine in mice.
Penicillin made a difference during the first half of the 20th century. The first patient was successfully treated for streptococcal septicemia in the United States in However, supply was limited and demand was high in the early days of penicillin. Penicillin helped reduce the number of deaths and amputations of troops during World War II. According to records, there were only million units of penicillin available during the first five months of ; by the time World War II ended, U.
To date, penicillin has become the most widely used antibiotic in the world. Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B.
British Journal of Experimental Pathology. Haven KF.
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