1951: the first effective antifungal medicine

The antibiotic era began with drugs against bacteria, and fungi stayed out of its reach for a long time. Substances that kill fungi are usually toxic to human cells as well, because both are eukaryotes with a similar cell architecture. The breakthrough came in the early 1950s, from a laboratory of the New York State Department of Health.

In 1951 Elizabeth Lee Hazen and Rachel Fuller Brown published in the Proceedings of the Society for Experimental Biology and Medicine a paper titled "Fungicidin, an Antibiotic Produced by a Soil Actinomycete". In it they described an antibiotic produced by an actinomycete isolated from soil. The substance halted the growth of pathogenic fungi at concentrations that did not destroy the patient's tissues — and that was precisely the difference that had been missing.

The name fungicidin did not last. The compound entered medicine as nystatin, and it was under that name that the two researchers described it in 1960 in the Annals of the New York Academy of Sciences. Its mechanism turned out to rest on binding ergosterol, a sterol present in fungal cell membranes and absent from human ones. That chemical difference still underpins most antifungal drugs.

Nystatin remains in use more than seventy years after it was described, mainly against candidiasis of the mucous membranes and the skin. The story of its discovery is often told with colourful details, not all of which can now be checked at source. The two papers by the discoverers themselves are enough for the essential point: the first effective antifungal medicine came out of soil, and two women working in a public health laboratory found it.

What the first fungicidin paper demonstrated

Hazen and Brown recovered two antibiotics with different properties from a soil actinomycete culture. The compound released into the medium resembled actidione; the intracellular substance they called fungicidin had the broader antifungal spectrum. They described it as both fungistatic and fungicidal, with no apparent antibacterial action, and reported that horse blood or serum did not reduce its activity. For crude fungicidin administered intraperitoneally to mice, the approximate LD50 was between 20 and 26 mg/kg; toxicity was considerably lower after subcutaneous injection. In mouse models, the preparation showed therapeutic value against experimentally induced histoplasmosis and cryptococcosis.

Fungicidin was later renamed nystatin. One biological correction matters: its producer, Streptomyces noursei, is an actinomycete bacterium, not a fungus. This milestone concerns an antifungal medicine obtained from a bacterial microorganism, and should not be illustrated or described as a mould-derived discovery.