Penicillin: the First Antibiotic
المؤلف:
Ola Sköld, M.D., Ph.D
المصدر:
Antibiotics and Antibiotic Resistance
الجزء والصفحة:
p9-12
2025-07-08
370
Penicillin was the first antibiotic in the strict sense of the word: that is, an antibacterial agent produced in a living organism. The original observation was made by Alexander Fleming at the bacteriological laboratory of Saint Mary’s Hospital in London. In his research, Fleming was interested in staphylococci, particularly in the color and form of staphylococcal colonies on an agar plate. He had a hypothesis, which could never be verified, that there was a connection between the appearance of staphylococcal colonies and their pathogenicity .Among his staphylococcal plates ,on one occasion, Fleming observed a plate with a large patch of mold growing on it (Fig. 1). The staphylococcal colonies on the same plate seemed to maintain a distance from the mold, not growing in its vicinity.
Fig1. The discovery of penicillin. A replica of the original plate of Alexander Fleming showing a patch of Penicillium mold and Staphylococcus colonies seeming to avoid the mold patch.
This phenomenon caught Fleming’s attention, and one of the many biographies about him (Gwyn Macfarlane, Alexander Fleming, The Man and the Myth, The Hogarth Press, London,1984) describes how on a sunny September morning in 1928 on the lawn outside the laboratory, he showed the plate to two fellow bacteriologists. None of the three could explain the phenomenon on the plate or at all imagine that at that moment they had a tryst with destiny. The interpretation of this phenomenon would open the way for the greatest triumph of scientific medicine: the control of bacterial infections with selectively acting drugs. The full impact of the observation was finally appreciated, and the original agar plate, showing antagonism between two microorganisms via a soluble agent, is now in the British Museum in London. The diffusible agent inhibiting bacterial growth on the plate in the vicinity of the mold was named penicillin by Fleming, and together with its many derivatives, it would eventually become dominant among antibiotics in the treatment of bacterial disease.
There is another whim of destiny in the penicillin story. By its mechanism of action , penicillin cannot act on resting nondividing bacterial cells—only on growing bacteria. This circumstance, together with the property of mold to grow much more slowly than staphylococci, led to the conclusion that penicillin could not have been discovered in the manner described. If the agar plate was already polluted with mold cells when Fleming streaked it with the staphylococci he was interested in, they would have grown out to be insusceptible to penincillin long before the mold had grown out enough to produce penicillin. The mold could also not have grown out to form a colony before inoculation with bacteria, since no microbiologist would use a contaminated agar plate. This microbiological mystery seems to be explained by a fantastic sequence of coincident circumstances. Fleming seems to have inoculated the agar plate at the end of the month of July and then left for summer holiday in Scotland, forgetting that the plate was on the bench and thus not placed in the 37◦Cincubator. The weather records for London from 1928 show that the first week of August that year was unusually cold, followed by hot summer weather. Mold cells grow faster than bacteria at low temperatures, which means that a mold colony could have formed during the cold spell, while the staphylococci caught up in the following warm period, then to meet with the penicillin produced and diffused out from the mold, forming the famous zone. This could be looked at as an example of serendipity, a scientist finding something quite significant without having looked for it (Fig. 2).
Fig2. Sir Alexander Fleming celebrated by students at the University of Edinburgh.
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