Rediscovery of Penicillin by a Basic Scientific Approach
المؤلف:
Ola Sköld, M.D., Ph.D
المصدر:
Antibiotics and Antibiotic Resistance
الجزء والصفحة:
p13-14
2025-07-08
360
In 1940, Australian-born Howard Florey, a professor of pathology, German-born Ernst Chain, a biochemist, and British-born Norman Heatley, a biochemist, all three at Oxford, England, began scientific studies on penicillin. Fleming had shown that penicillin interfered with the bacterial cell wall, and the three men wanted to investigate agents that had the ability to dissolve the murein of the cell wall in parallel with the enzyme lysozyme, the mechanism of action of which Florey had just studied. Chain first thought of penicillin as an enzyme, but very soon during purification, it emerged as a small molecule. After further purification the therapeutic possibilities could be discerned. It is interesting to note that it was purely a scientific interest in bacterial cell wall degradation that led the three scientists to take up study of the phenomenon discovered by Fleming. The realization of therapeutic possibilities led to what has been called the most important pharmaceutical experiment ever carried out. It began on Saturday morning, May 25, 1940, in Oxford when Howard Florey injected eight laboratory mice intraperitoneally, each with 108 cells of S. pyogenes. One hour later, four of the eight mice were injected subcutaneously with 10 mg of a brown powder dissolved in water. At half past three on Sunday morning, all four of the mice injected with the brown powder solution were healthy and agile, whereas the other four were dead. The brown powder was penicillin, but only 0.1%ofitwas actually penicillin; 99.9% constituted impurities.
The experiment indicated that penicillin could be developed into an important medicine, and Florey and Chain, in collaboration with Norman Heatley, tried to solve the biggest problem at the time: to grow P. notatum insufficient volume to be able to purify penicillin from the growth medium in medically usable quantities. Heatley was the co-worker who devised a purification method and also the method needed to assay penicillin activity. The resources of Oxford were limited because of World War II, but with help from the American pharmaceutical industry, pro duction was begun. The penicillin produced quickly performed as a dramatically efficient remedy against bacterial infections. It immediately provided great relief in the treatment of infected war wounds ,and very soon it found its way into clinical medicine in general. Alexander Fleming, Howard Florey, and Ernst Chain were awarded the Nobel Prize in Physiology or Medicine in 1945. Today, penicillin is produced in copious amounts all over the world using industrial procedures that are so efficient that the final product is pure enough for direct use in pharmaceutical products. The large global production of penicillin today has led to it being regarded as a commodity on the scale of coffee and tea. Organic chemists have succeeded in the total synthesis of penicillin, but industrial production today takes place in large tanks where penicillin-producing mold cells are grown. The original P. notatum has been replaced by Penicillium chrysogenum,which is a more efficient producer.
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