Rachel Fuller Brown - Discovering Fungal Antibiotic

Discovering Fungal Antibiotic

However, the antibacterial and antifungal work that she is best known for did not begin until 1948. During this year, Brown embarked on a project with Elizabeth Lee Hazen, a leading authority on fungus and bacteria related research. The project would eventually bring the two scientists national recognition for discovering an antibiotic to fight fungal infections.

Penicillin had been discovered in 1928, and in the years that followed, antibiotics were increasingly used to fight bacterial illness. However, one side effect was that these antibiotics allowed for a rapid growth of fungus, which could lead to sore mouths or upset stomachs. Other fungal diseases without cures including infections attacking the central nervous system, athlete’s foot, and ring worms were also a major problem during this time. However, fungal diseases were not well understood at this time, and there were no antifungal medications safe for human use. At this time, people knew of microorganisms called actinomycetes that lived in soil and were known to produce antibiotics, some of which killed fungus. However, these antibiotics also proved fatal in tests involving lab mice and thus could not be put into production.

The successful partnership between Hazen in New York City and Brown in Albany was due in part to the efficiency of the United States Postal Service in the 1940s. In her New York City laboratory, Hazen cultured organisms found in soil samples and tested their ability to fight against two fungi: Cryptococcus neoformans, a fungus responsible for the chronic disease cryptococcosis, which affects lungs, skin, and other body parts like the central nervous system, and Candida albicans, which causes candidiasis, which can be minor in some cases (e.g. a vaginal yeast infection), or a serious infection in patients treated with broad-spectrum antibiotics. If she found such promising antifungal activity in a particular culture, she would mail it to Brown in a mason jar.

At her end, Brown isolated the active agent in the culture, or the ingredient in the soil sample that could potentially be used to cure these fungal diseases. This was before the days of high-performance liquid chromatography and other separation techniques and required meticulous labor as well as a great deal of patience and paintstaking attention to detail. After isolating the active ingredient, Brown would return the sample to Hazen in New York, where it was retested against the two fungi. If effective, the toxicity was then evaluated in animals.

Nearly all the agents that killed the test fungi also turned out to be highly toxic to animals, signifying that they could not be safely used for human treatment. Interestingly enough, of the hundreds of soil samples sent to Hazen and Brown from around the world, the one culture that was effective against fungi and not fatal to animals was originally found in the soil near a barn of two of Hazen’s friends, the Walter B. Nourses. The microorganism discovered in the soil was later named Streptomyces norsei in their honor. Brown’s chemical testing showed that the microorganism in this particular soil sample produced two antifungal substances called Fractions N and AN. Fraction N was fatal on tests with animals, just like the other substances that Hazen tested. However, Fraction AN proved safe in tests on live animals and was effective not only against the initial two fungi, but fourteen others as well. Brown then purified this second antibiotic into small white crystals. The two scientists first named the drug fungicidin, but upon discovery that the name was already in use, changed it to “Nystatin” in honor of the New York State Division of Laboratories and Research.