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Elizabeth Hazen experiments her way to success at age 66
The year was 1944. World War II raged abroad, while in New York City 59-year-old Elizabeth Hazen focused on fungus. A microbiologist for the state Department of Public Health, she regularly spent a full day at the department’s East 25th Street offices in Manhattan, then journeyed north to put in hours of nighttime research at its West 168th Street laboratory. There she identified new types of microscopic fungus, with a goal of creating new disease-fighting tools at a time when no fungicidal antibiotics existed.
Hazen brought three decades of experience to the task. She had been studying bacteriology since before World War I, including a wartime stint at army laboratories, a master’s and a doctorate from Columbia University, clinical work at a West Virginia hospital lab when she as in her 30s, and clinical and teaching positions at Columbia’s hospital and medical school when she was in her 40s. Now, in her late 50s, she expanded her studies to include fungi. As the war dragged toward an end, Hazen established standards defining the most efficient ways to identify disease-causing fungi.
As part of that project, she assembled a collection of microscopic fungi for use in teaching and research, hunting down new types of fungus in any soil samples she got her hands on. To make the collection as complete as possible, when she traveled she would dig dirt samples and bring them back to the lab. As one colleague recalled, Hazen “treasured every positive specimen, slide or culture, carefully preserving it … to take to her own laboratory, thus bringing mycological manna as well as gospel to her disciples and associates at the Division of Laboratories and Research.”
Although she had no formal training in mycology, Hazen soon developed a reputation as a fungus expert. She taught medical students about fungus, received out-of-state requests for help in identifying fungus, and mailed samples from her fungus collection to other labs.
Then she began to see a further goal for her research. Perhaps she could accomplish something like what bacteriologist Alexander Fleming had stumbled upon in 1928 at St. Mary’s Hospital in London. He had noticed that a blue-green mold had contaminated a petri dish and was blocking the spread of Staphylococcus bacteria that he was growing there. Intrigued, he discovered that the mold produced a bacteria-killing substance that he called penicillin. By the late 1930s its medical potential as an antibiotic was clear, but no one knew how to produce it in bulk. After the war began, an international research effort, based far from combat in Peoria, Ill., developed high-volume production methods that allowed penicillin to be used to treat the wounded on D-Day.
New Jersey bacteriologist Selman Waksman followed in Fleming’s footsteps, seeking potential antibiotics produced by bacteria in soil. In 1943, by analyzing soil samples he and his student Albert Schatz discovered streptomycin, the first antibiotic that was effective against tuberculosis. Hazen thought bacteria in soil might also produce chemicals that killed fungus, so in 1945 she set out to find them. She teamed up with Schatz in a 1948 research paper on the search for anti-fungal medicines and with colleague Albrecht Weber in screening a new round of soil samples for fungicides. But she found her most valuable partner 150 miles up the Hudson River in Albany, N.Y.
She needed a chemist who could  isolate and identify the active compounds in microorganisms that Hazen spotted, so she went to Albany to seek help from Gilbert Dalldorf, the new division head. He took her to the lab of Rachel Brown, 50, a talented, patient organic chemist with more than two decades of laboratory experience and a master’s and doctorate from the University of Chicago. Dalldorf would allow her to partner with Hazen as long as Brown continued to do her other work.
As a biographer explained, “Dalldorf was not a harsh taskmaster, but he believed strongly that a researcher should have other jobs to do – jobs that might be routine, but provide a useful service. From his own experience he knew that in the course of doing research there were often obstacles that seemed to stop forward movement; if the researcher had other things to do, contributions could be made there while the investigator waited for fresh inspiration. The researcher with nothing else to do could easily become frustrated and fail to find a way around the impasse.”
Over the coming months, the two women worked together, 150 miles apart. They kept their experimental samples in glass Mason jars, which they carefully wrapped, then mailed back and forth between Manhattan and Albany.
Hazen tested hundreds of soil samples to see whether bacteria in them would kill the Cryptococcus neoformans fungus, which infects lungs, skin and nerves, or the Candida albicans fungus, which infects the lungs, skin, mouth, nails and vagina. If she found something that stopped the spread of the fungus, she would grow a batch and mail it to Brown. In Albany, Brown would extract ingredients that seemed to be acting as fungicides and mail them back to Hazen in Manhattan for more tests – had Brown succeeded in isolating the active substance and, if so, how concentrated did it have to be to work?
Bacteria have developed many effective fungicidal poisons, the pair found, but most were too poisonous. Again and again, Brown would analyze a batch of bacteria that Hazen sent her, purify the active chemical and mail it back. Again and again, Hazen found that the compound would poison not just fungi, but laboratory animals too.
One strain of bacteria that they called Microorganism No. 47205 was promising – it seemed not to strong, not too weak -- but tests eventually showed that it too was toxic to mice. Hazen and Brown didn’t give up. Hazen kept analyzing new samples of dirt and sending the new fungicides north. Brown kept refining out the active compounds and sending them south.
After visiting friends on a farm near Warrenton, Va., Hazen tested dirt she had collected there. It showed promise, so she grew the bacteria from that soil and shipped the batch to Brown under the name Microorganism No. 48240. Brown analyzed it and shipped back two active chemicals – Fraction A and Fraction AN. When Hazen tested Fraction A, she found that it was too powerful. But Fraction AN worked well. At low concentrations it would kill Cryptococcus, Candida and 14 other types of fungus, but it didn’t harm test animals – or humans.
In 1949, Hazen and Brown reported their findings to their bosses. Instead of calling their discovery “Fraction AN of Microorganism No. 48240,” they named it “Nystatin” in honor of New York State and the N.Y. State Division of Laboratories and Research. They had found the world’s first useful fungus-killing antibiotic, a discovery that they patented in 1951, when they were ages 66 and 53. The U.S. Food and Drug Administration approved it for sale in 1954. Before the patent expired in 1974, Nystatin royalties totaled $13.4 million, but neither Hazen nor Brown sought any profit from their discovery. They gave half the royalties to a non-profit group that subsidized scholarly research. The other half went to a new Brown-Hazen Fund, which supported medicine and biology research, especially for female scientists.
Hazen remained active in fungus research for a decade after discovering Nystatin. She and Brown uncovered two further fungicidal antibiotics, neither of which was suitable for medical use. At age 70, she and a colleague published a guide for other fungus researchers and technicians, Laboratory Identification of Pathogenic Fungi Simplified. In her early 70s, she worked on an updated edition of the book. At age 75, she returned to Columbia as emeritus research professor, but remained a mycology consultant for the state Division of Laboratories and Research.
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