Elizabeth Lee Hazen
Encyclopedia
Elizabeth Lee Hazen born in Mississippi is most known for her contribution to the development of nystatin
. Her education focused on science and research where she developed a passion for microbiology. Her peers and teachers knew her as a quick learner and a bright student. In 1948, she teamed up with Rachel Fuller Brown
to develop nystatin
, the first non-toxic drug treatment for fungal infections in humans. Her research had multiple applications ranging from saving infected trees to restoring paintings and artwork damaged due to mold.
(then Mississippi Industrial Institute and College), and obtained a Bachelor of Science degree there in 1910. While teaching biology and high school physics in Jackson, Mississippi
, she continued her education by attending summer schools at the University of Tennessee
and University of Virginia
. Following her teaching job, Hazen applied and was accepted into Department of Biology at Columbia for graduate studies. She completed a Master's of Biology at Columbia University
in 1917 and a Ph.D. in microbiology there in 1927, one their first female doctoral students. She served as an Army
diagnostic laboratory technician during World War I
. In the 1920s, while studying at Columbia University
, Hazen worked with Ricin
and its effect on Clostridium botulinum toxin
.
From there she worked at the New York office of the Division of Laboratories and Research of the State Department of Public Health
. There she learned, trained, and studied about fungi and fungal diseases. She had picked up a project there and started producing her own culture collection. This collection and the research along with it helped place her name in the National Inventors Hall of Fame.
(Hazen), a biochemist
was also needed, and Rachel Fuller Brown
was chosen. Hazen started researching and studying fungus diseases, specifically ones that had been widespread in the city. This included diseases such as pneumonia, and moniliasis (thrush), a mouth condition that makes swallowing painful. She had a growing collection of fungus and was studying the effects and possible antifungal agents. However, Elizabeth needed someone to identify and isolate the antifungal activity occurring within samples. She was introduced by Dalldorf, the direction of the Division in Albany, in 1948 to Rachel Fuller Brown who had a laboratory in Albany.
Their research started by collecting soil samples from all over the country. Dr. Hazen cultured actinomycetes (microorganisms most frequently having antifungal properties) from each sample and tested on them to see if there was any fungal activity. If there was any activity, it was shipped to Albany where Dr. Brown prepared samples and extracts from the cultures. She would do this by isolating the chemical agents that appeared to have the property of killing fungi. These new samples would then be shipped back to New York City where Hazen would test the samples again for toxicity. She would expose the organisms against two fungi, Candida albicans
and Cryptococcus neoformans
. She would then purify promising samples for further test of fungistatic and fungicidal activity.
In 1948, Hazen and Brown began searching for an effective anti-fungal agent. Hazen found a promising micro-organism in the soil of a friend's dairy farm. She named it named Streptomyces noursei, after William Nourse, the farm's owner. Streptomyces noursei was found to produce two anti-fungal substances. One turned out to be toxic for mice, but the other, when purified, turned out to be effective against candidiasis
and a fungus that invaded the lungs and central nervous system. In 1950 they presented their discovery, the first safe and effective anti-fungal antibiotic, to the National Academy of Sciences
. They originally named it fungicidin, but later re-named it nystatin
, in honor of their employer, the New York State Department of Public Health.
In fall 1950, Dr. Hazen and Dr. Brown announced at a National Academy of Sciences meeting that they had successfully produced two antifungal agents from an antibiotic. This led to their development of nystatin (named in honor of the New York State Public Health Department), the first fungicide safe for treating humans. After several animal and human studies proved satisfactory to the FDA, nystatin was put to into the market through E.R. Squibb & Sons in 1954 and earning over $135,000 in its first year. Hazen and Brown donated their royalties, over $13 million, to a trust fund that was established under both Hazen and Brown for science and advancing women in science.
Patent Number: 2,797, 183
A patent was filed in late 1950 for nystatin. It took Hazen, Brown, and Squibb Research Company six and half years to secure a patent for the invention. There were two reasons for the delay. First, testing had to be done to prove the utility of the product. This required FDA approval of animal and human trials to be conducted. Nystatin was granted approval by the FDA
and released by Squibb
in 1954. In addition, there was an article published in Journal of Investigative Dermatology in 1954 that suggested Hazen and Brown exposed methods of nystatin in another article previously published in 1949. If this were the case, then it would have been over a year before a patent was filed, rendering the pending patent useless. However, after research and a signature by the author of the 1954 article stating there was no connection, the U.S. Patent Office issued a patent on June 25, 1957. It covered nystatin and the method of preparation for the next seventeen years.
Hazen and Brown obtained the patent in 1957.
in 1994.
Nystatin
Nystatin is a polyene antifungal medication to which many molds and yeast infections are sensitive, including Candida. Due to its toxicity profile, there are currently no injectable formulations of this drug on the US market...
. Her education focused on science and research where she developed a passion for microbiology. Her peers and teachers knew her as a quick learner and a bright student. In 1948, she teamed up with Rachel Fuller Brown
Rachel Fuller Brown
Rachel Fuller Brown was a chemist best known for her long-distance collaboration with microbiologist Elizabeth Lee Hazen in developing the first useful antifungal antibiotic, Nystatin, while doing research for the Division of Laboratories and Research of the New York State Department of Health....
to develop nystatin
Nystatin
Nystatin is a polyene antifungal medication to which many molds and yeast infections are sensitive, including Candida. Due to its toxicity profile, there are currently no injectable formulations of this drug on the US market...
, the first non-toxic drug treatment for fungal infections in humans. Her research had multiple applications ranging from saving infected trees to restoring paintings and artwork damaged due to mold.
Early life
Elizabeth Lee Hazen was born on August 24, 1885, in Rich, Mississippi, to William Edgar Hazen and Maggie Harper Hazen. She was their second daughter and middle of three children. Her parents died when she was four, and the three children were adopted by an aunt and uncle.Education
Hazen attended the Mississippi University for WomenMississippi University for Women
Mississippi University for Women, also known as MUW or simply the "W" is a four-year coeducational public university located in Columbus, Mississippi. It was formerly known as Industrial Institute and College and later Mississippi State College for Women...
(then Mississippi Industrial Institute and College), and obtained a Bachelor of Science degree there in 1910. While teaching biology and high school physics in Jackson, Mississippi
Jackson, Mississippi
Jackson is the capital and the most populous city of the US state of Mississippi. It is one of two county seats of Hinds County ,. The population of the city declined from 184,256 at the 2000 census to 173,514 at the 2010 census...
, she continued her education by attending summer schools at the University of Tennessee
University of Tennessee
The University of Tennessee is a public land-grant university headquartered at Knoxville, Tennessee, United States...
and University of Virginia
University of Virginia
The University of Virginia is a public research university located in Charlottesville, Virginia, United States, founded by Thomas Jefferson...
. Following her teaching job, Hazen applied and was accepted into Department of Biology at Columbia for graduate studies. She completed a Master's of Biology at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
in 1917 and a Ph.D. in microbiology there in 1927, one their first female doctoral students. She served as an Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...
diagnostic laboratory technician during World War I
World War I
World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...
. In the 1920s, while studying at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
, Hazen worked with Ricin
Ricin
Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose as small as a few grains of salt can kill an adult. The LD50 of ricin is around 22 micrograms per kilogram Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally...
and its effect on Clostridium botulinum toxin
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
.
Post-graduation
With her strong science background and experience in the field, Hazen continued her research in bacteria and immunology. She was presented with an opportunity in 1931 to work with the New York State Department of Health. She accepted and worked in the Bacterial Diagnosis Laboratory Division in New York City. She had several major accomplishments there in the field of bacterial diagnosis. Among her work there included tracing an outbreak of anthrax, locating sources of tularemia, and tracing the source of food poising from improperly preserved foods.From there she worked at the New York office of the Division of Laboratories and Research of the State Department of Public Health
Wadsworth Center
The Wadsworth Center, located in Albany, New York, is the research-intensive public health laboratory of the New York State Department of Health. The Wadsworth Center is dedicated to science in the pursuit of health.-History:...
. There she learned, trained, and studied about fungi and fungal diseases. She had picked up a project there and started producing her own culture collection. This collection and the research along with it helped place her name in the National Inventors Hall of Fame.
Development of nystatin
In 1944 she was chosen by Augustus Wadsworth, founder and head of the division, to be in charge of an investigation into fungi and its relation to bacteria and other microbes. In addition to a microbiologistMicrobiologist
A microbiologist is a scientist who works in the field of microbiology. Microbiologists study organisms called microbes. Microbes can take the form of bacteria, viruses, fungi, and protists...
(Hazen), a biochemist
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
was also needed, and Rachel Fuller Brown
Rachel Fuller Brown
Rachel Fuller Brown was a chemist best known for her long-distance collaboration with microbiologist Elizabeth Lee Hazen in developing the first useful antifungal antibiotic, Nystatin, while doing research for the Division of Laboratories and Research of the New York State Department of Health....
was chosen. Hazen started researching and studying fungus diseases, specifically ones that had been widespread in the city. This included diseases such as pneumonia, and moniliasis (thrush), a mouth condition that makes swallowing painful. She had a growing collection of fungus and was studying the effects and possible antifungal agents. However, Elizabeth needed someone to identify and isolate the antifungal activity occurring within samples. She was introduced by Dalldorf, the direction of the Division in Albany, in 1948 to Rachel Fuller Brown who had a laboratory in Albany.
Their research started by collecting soil samples from all over the country. Dr. Hazen cultured actinomycetes (microorganisms most frequently having antifungal properties) from each sample and tested on them to see if there was any fungal activity. If there was any activity, it was shipped to Albany where Dr. Brown prepared samples and extracts from the cultures. She would do this by isolating the chemical agents that appeared to have the property of killing fungi. These new samples would then be shipped back to New York City where Hazen would test the samples again for toxicity. She would expose the organisms against two fungi, Candida albicans
Candida albicans
Candida albicans is a diploid fungus that grows both as yeast and filamentous cells and a causal agent of opportunistic oral and genital infections in humans. Systemic fungal infections including those by C...
and Cryptococcus neoformans
Cryptococcus neoformans
Cryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in pigeon excrement....
. She would then purify promising samples for further test of fungistatic and fungicidal activity.
In 1948, Hazen and Brown began searching for an effective anti-fungal agent. Hazen found a promising micro-organism in the soil of a friend's dairy farm. She named it named Streptomyces noursei, after William Nourse, the farm's owner. Streptomyces noursei was found to produce two anti-fungal substances. One turned out to be toxic for mice, but the other, when purified, turned out to be effective against candidiasis
Candidiasis
Thrush redirects here. For the hoof infection see Thrush .Candidiasis or thrush is a fungal infection of any of the Candida species , of which Candida albicans is the most common...
and a fungus that invaded the lungs and central nervous system. In 1950 they presented their discovery, the first safe and effective anti-fungal antibiotic, to the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
. They originally named it fungicidin, but later re-named it nystatin
Nystatin
Nystatin is a polyene antifungal medication to which many molds and yeast infections are sensitive, including Candida. Due to its toxicity profile, there are currently no injectable formulations of this drug on the US market...
, in honor of their employer, the New York State Department of Public Health.
In fall 1950, Dr. Hazen and Dr. Brown announced at a National Academy of Sciences meeting that they had successfully produced two antifungal agents from an antibiotic. This led to their development of nystatin (named in honor of the New York State Public Health Department), the first fungicide safe for treating humans. After several animal and human studies proved satisfactory to the FDA, nystatin was put to into the market through E.R. Squibb & Sons in 1954 and earning over $135,000 in its first year. Hazen and Brown donated their royalties, over $13 million, to a trust fund that was established under both Hazen and Brown for science and advancing women in science.
Patent
Nystatin (Antifungal / Antibiotic)Patent Number: 2,797, 183
A patent was filed in late 1950 for nystatin. It took Hazen, Brown, and Squibb Research Company six and half years to secure a patent for the invention. There were two reasons for the delay. First, testing had to be done to prove the utility of the product. This required FDA approval of animal and human trials to be conducted. Nystatin was granted approval by the FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
and released by Squibb
Bristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
in 1954. In addition, there was an article published in Journal of Investigative Dermatology in 1954 that suggested Hazen and Brown exposed methods of nystatin in another article previously published in 1949. If this were the case, then it would have been over a year before a patent was filed, rendering the pending patent useless. However, after research and a signature by the author of the 1954 article stating there was no connection, the U.S. Patent Office issued a patent on June 25, 1957. It covered nystatin and the method of preparation for the next seventeen years.
Hazen and Brown obtained the patent in 1957.
Later life
Dr. Hazen continued to do research in laboratory in her later years as her experience and skills were very useful and beneficial to those around her. She continued to study the several uses of nystatin for other diseases and conditions.Awards
Towards the end of her life, she received a series of awards for her success. Those awards included: The Squibb Award in Chemotherapy, The Sara Benham Award of the Mycological Society of the Americas, An honorary degree from Hobart and William Smith Colleges, and The Chemical Pioneer Award of the American Institute of Chemists. After her death, Elizabeth Hazen was nominated and accepted into the National Inventors Hall of FameNational Inventors Hall of Fame
The National Inventors Hall of Fame is a not-for-profit organization dedicated to recognizing, honoring and encouraging invention and creativity through the administration of its programs. The Hall of Fame honors the men and women responsible for the great technological advances that make human,...
in 1994.