1928: Discovery of Penicillin (1928)

In September 1928, Alexander Fleming returned to his laboratory at St Mary's Hospital, London, after
a summer holiday to find that a Petri dish of Staphylococcus aureus cultures had been contaminated
by a mould, Penicillium notatum, which had apparently blown in through an open window. Fleming
observed a clear zone of inhibition surrounding the mould colony—bacteria within this halo had been
lysed. He investigated the phenomenon systematically, demonstrating that a filtrate of the mould
broth, which he named "penicillin," inhibited a wide range of gram-positive bacteria in vitro,
including Streptococcus, Staphylococcus, and Clostridium.

Fleming's 1929 paper in the British Journal of Experimental Pathology described penicillin's
bactericidal activity, remarkable non-toxicity to leucocytes and experimental animals, and potential
for use in isolating penicillin-resistant organisms. However, Fleming was unable to isolate a stable
active substance and did not pursue clinical development, leaving penicillin effectively dormant for
over a decade.

The therapeutic potential of penicillin was only realised between 1938 and 1941, when Howard Florey
and Ernst Chain at Oxford used newly developed freeze-drying and solvent extraction techniques to
isolate and purify penicillin G. Their landmark 1941 clinical trial—treating a policeman with severe
staphylococcal septicaemia—demonstrated dramatic efficacy, though insufficient supplies led to
tragedy when the supply was exhausted before cure was complete. Large-scale fermentation methods,
developed jointly by British and American teams from 1942 onwards, made widespread clinical use
possible.

The 1945 Nobel Prize in Physiology or Medicine was awarded jointly to Fleming, Florey, and Chain.
Penicillin's success launched the antibiotic era, transformed infectious disease mortality, and
inaugurated the pharmaceutical industry's sustained interest in natural product drug discovery.