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Penicillin as a Chemotheraputic Agent.


London, The Lancet Limited, 1940. Royal8vo. Bound in contemporary full black cloth with gilt lettering to spine. In "The Lancet", Vol. 2, 1940. A fine and clean copy. Pp. 226-228. [Entire volume: XX, 830 pp.]. ¶ First printing of this seminal paper within microbiology and medicine. Alexander Flemming had in the 20ies discovered penicillin but it was not until Chain and Florey's groundbreaking research, published in the present paper, that the true remarkable features of penicillin - that it was probably the most effective chemotherapeutic drug known - became know and usable on a practical level. Flemming, Chain and Florey received the Nobel Prize in Medicine in 1945 "for the discovery of penicillin and its curative effect in various infectious diseases".

"He [Flemming] was unsuccessful, however, due to his limited knowledge of chemistry, and the "mold juice" remained of limited use until 1940-41, when Ernst Boris Chain and Howard W. Florey, using Flemming's original culture, successfully prepared a pure and stable penicillin extract and demonstrated its usefulness in treating human bacterial infection. Within three years the United States government, in collaboration with the pharmaceutical industry, was producing penicillin on a large scale, with the result that many thousand lives were saved during World War II." (Grolier, One Hundred Books Famous in Medicine).

"In the late 1930's, Florey and Chain began their investigation of this mold broth filtrate from Penicillium notatum as part of their general interest in systemic antibacterial agents. Fleming had isolated penicillin in 1928. He found it was a promising external antiseptic against some pathogenic bacteria, but its chemical instability (among other reasons) soon led him to abandon penicillin as a therapeutic agent.
By May 1940 Chain had produced enough penicillin for Florey to conduct tests on mice infected with deadly hemolytic streptococci. These early tests yielded very promising results, Chain, in collaboration with Edward Abraham, spent the rest of the year improving the extraction and purification of penicillin for clinical tests, which began early in 1941.
Serious problems with the fermentation production of penicillin led the British and American governments, by early 1944. to coordinate hundreds of scientists for the development of a commercially feasible synthesis of penicillin. Chain and his collaborators at Oxford, however, had shed much light on the chemistry of the drug by this time. By October 1943, they proposed what turned out to be the correct structure of penicillin. They established a fundamental understanding of the chemistry of penicillin. This aided fermentation work on the drug in the 1940's and served as the foundation for the development of semisynthetic penicillins from the mid 1950's on.

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