Penicillin was a brilliant example of an unexpected discovery which required several observations over a period of years. In 1878 Pasteur suggested that one microorganism might prevent the growth of another. In 1897, following in Pasteur’s footsteps and looking for a way to finance his Ph.D. thesis, Ernest Duchesne noted that certain molds kill bacteria. Duchesne had noted that the Arab stable boys at the army hospital kept their saddles in a dark and damp room to encourage mold to grow on them. When he asked why, they told him that the mold helped to heal the saddle sores on the horses. A test conducted on infected guinea pigs demonstrated the curative powers of the mold. He followed up with a series of meticulous experiments, studying the interaction between Escherichia coli and Penicillium glaucum, showing that the latter was able to completely eliminate the former in a culture containing only these two organisms. He went on to demonstrate its effectiveness against typhoid bacilli. Because he was 23 and unknown, the Institut Pasteur did not even acknowledge receipt of his dissertation. Thirty years later, in 1928, Alexander Fleming made his historic observation of old staphylococci culture boxes where molds had time to develop, in particular, a rather common penicillum mold. He called the active principle in mold broth penicillin. Despite publishing his observations, no substantial interest in the findings were aroused. In 1935, a young biochemist, Ernst Chain, joined Professor H. W. Florey at Cambridge University to conduct studies on the toxicity of snake venom. It was during Chain’s investigation of lysozymes that he happened upon Fleming’s forgotten publication. Chain and Florey purified penicillin and described its amazing antibiotic properties in 1940 in The Lancet. Further work led to its final form as the first antibiotic drug.
Acetaminophen (TylenolÒ) owes its discovery to a mistake. Two young doctors, Arnold Cahn and Paul Hepp, in the department of internal medicine at the University of Strassburg (ca. 1880), were investigating the use of naphthalene in the treatment of intestinal worms. Initial results were disappointing, however, one of the patients they treated exhibited a pronounced reduction in fever. Subsequently, it was found that acetanilide had been mistakenly shipped to the laboratory instead of naphthalene. Acetaminophen, a metabolite of acetanilide, was introduced by 1894 and gained widespread use after 1948 when scientists determined it to be safer than acetanilide.
More than one hundred years later, we have not advanced to the Star Trek era wherein drugs are synthesized as needed. We still rely on careful observation, a characteristic of the human mind we can only hope will never leave us.