Rachel Fuller Brown
Encyclopedia
Rachel Fuller Brown was a chemist best known for her long-distance collaboration with microbiologist Elizabeth Lee Hazen
Elizabeth Lee Hazen
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 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
New York State Department of Health
The New York State Department of Health, ', is the governmental body responsible for public health in the state of New York. The cabinet-level department is headed by the Health Commissioner, a position held since January 24, 2011 by Nirav R. Shah, M.D., M.P.H.....

. Brown received her B.A. from Mount Holyoke College and her Ph.D from the University of Chicago. She was inducted into the National Inventors Hall of Fame
National 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.

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...

, still produced today under various trade names, not only cures a variety of potentially devastating fungal infections, but has also been used to combat Dutch Elm disease in trees and to restore artwork damaged by water and mold.

Early life

Rachel Fuller Brown was born on November 23, 1898 in Springfield, Massachusetts
Springfield, Massachusetts
Springfield is the most populous city in Western New England, and the seat of Hampden County, Massachusetts, United States. Springfield sits on the eastern bank of the Connecticut River near its confluence with three rivers; the western Westfield River, the eastern Chicopee River, and the eastern...

 to parents George Hamilton Brown, a real estate and insurance agent, and Annie Fuller, a director of religious education. They later moved to Missouri
Missouri
Missouri is a US state located in the Midwestern United States, bordered by Iowa, Illinois, Kentucky, Tennessee, Arkansas, Oklahoma, Kansas and Nebraska. With a 2010 population of 5,988,927, Missouri is the 18th most populous state in the nation and the fifth most populous in the Midwest. It...

 where, at the age of fourteen, Brown’s parents separated and her father left the family with almost no money. So her family of three moved back to Springfield.

Education

Upon the family’s return to Springfield, Rachel enrolled in Commercial High School, but her mother forced her to transfer to Central High School for a more traditional education.

Brown’s hard work and determination to go to college impressed Henriette F. Dexter, a friend of her grandmother, who decided to pay for Brown to attend Mount Holyoke College
Mount Holyoke College
Mount Holyoke College is a liberal arts college for women in South Hadley, Massachusetts. It was the first member of the Seven Sisters colleges, and served as a model for some of the others...

. Though she originally chose to major in history, she fell in love with chemistry, a strong field at Mount Holyoke, after taking a required science course. Brown earned her A.B. in chemistry and history in 1920.

After working as a laboratory assistant for some time, Brown eventually began her graduate work and earned an M.S. in organic chemistry from the University of Chicago in 1921. She then taught for three years at the Frances Shimer School near Chicago, a school and junior college for girls.

After taking some language courses and chemistry at Harvard, Brown returned to the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...

 for additional graduate work in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...

 and bacteriology
Bacteriology
Bacteriology is the study of bacteria. This subdivision of microbiology involves the identification, classification, and characterization of bacterial species...

. After successfully completing her research project and the required course work in 1926, she submitted her Ph.D thesis. However, due to some complications in scheduling her oral examinations and the depletion of her savings, Brown was forced to leave Chicago without her Ph.D to find a job at the Division of Labor and Research in Albany, New York
Albany, New York
Albany is the capital city of the U.S. state of New York, the seat of Albany County, and the central city of New York's Capital District. Roughly north of New York City, Albany sits on the west bank of the Hudson River, about south of its confluence with the Mohawk River...

.

Early career

The Division of Labor and Research, a major arm of the New York Department of Health, was famous for its research of human disease-causing agents and the creation of antiserums and vaccines. There Brown worked for seven years without her Ph.D until her return to Chicago
Chicago
Chicago is the largest city in the US state of Illinois. With nearly 2.7 million residents, it is the most populous city in the Midwestern United States and the third most populous in the US, after New York City and Los Angeles...

 for a scientific meeting, at which point Brown arranged to take her oral examinations and was awarded her Ph.D.

At the division’s laboratory, Brown focused on identifying the types of bacteria that caused pneumonia, helping develop a pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

 vaccine still in use today. Additionally, she researched ways to improve the test for syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

.

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
Elizabeth Lee Hazen
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...

, 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
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 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
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

, which could lead to sore mouths or upset stomachs. Other fungal diseases without cures including infections attacking the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

, 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
United States Postal Service
The United States Postal Service is an independent agency of the United States government responsible for providing postal service in the United States...

 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
Chromatography
Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures....

 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
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 the New York State Division of Laboratories and Research.

Nystatin

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...

 is a polyene
Polyene
Polyenes are poly-unsaturated organic compounds that contain one or more sequences of alternating double and single carbon-carbon bonds. These double carbon-carbon bonds interact in a process known as conjugation, which results in an overall lower energy state of the molecule.Organic compounds with...

 antifungal drug to which many molds and yeast infections are sensitive. It was also the first antifungal antibiotic to be safe and effective in treating human diseases. Not only did it cure many serious fungal infections of the skin, mouth, throat, and intestinal tract, but it could also be combined with antibacterial drugs to balance their side effects. Over the years, Nystatin proved effective not only in fighting human diseases, but was also used to stop fungal growth on flood-damaged works of art in Florence, Italy. It also showed effectiveness in slowing the spread of Dutch Elm Disease
Dutch elm disease
Dutch elm disease is a disease caused by a member of the sac fungi category, affecting elm trees which is spread by the elm bark beetle. Although believed to be originally native to Asia, the disease has been accidentally introduced into America and Europe, where it has devastated native...

, a fungal disease of elm trees spread by the elm bark beetle.

Announcement and Production

Brown and Hazen presented their work at 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...

 regional meeting in 1950. The subsequent report by the New York Times started a flurry of calls from pharmaceutical companies, interested in the commercial possibilities of Nystatin. The pharmaceutical industry had the manufacturing capabilities and ability to test the compound on humans. However, to license the substance, control the purity, and protect the financial interests of the developers, Gilbert Dalldorf, the division director of the laboratory in which Hazen and Brown worked, assigned patent royalties to the Research Corporation of New York, a nonprofit foundation created for the advancement of science. The production license was awarded to E. R. Squibb & Sons, who developed a safe method of mass production and produced the first sale of the tablets, named Mycostatin, for human use in 1954.

Later years

In 1951, the Department of Health and Laboratories promoted Brown to associate biochemist. Brown and Hazen, in continuing their research, discovered two additional antibiotics—phalmycin and capacidin. The two continued to work closely together in making additional minor contributions to the field of bacteriology until their retirement.

Brown died on January 14, 1980 at the age of 81 in Albany, New York.

Awards and recognition

Royalties for Nystatin totaled $13.4 million. As Brown and Hazen did not want any of the money for themselves, the philanthropic Research Corporation used half for grants to further scientific research and the other half to support what became known as the Brown-Hazen Fund.

Both Brown and Hazen received many awards for their collaborative work, the first major prize being the Quibb Award in Chemotherapy in 1955. Brown was also elected fellow of the New York Academy of Sciences
New York Academy of Sciences
The New York Academy of Sciences is the third oldest scientific society in the United States. An independent, non-profit organization with more than members in 140 countries, the Academy’s mission is to advance understanding of science and technology...

 in 1957. On Brown’s retirement in 1968, she received the Distinguished Service Award of the New York Department of Health. In 1972, she was also given the Rhoda Benham Award of the Medical Mycological Society of the Americas. Brown and Hazen were the first women ever to receive, in 1975, the American Institute of Chemists’ Chemical Pioneer Award.

Brown was inducted into the National Inventors Hall of Fame
National 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.

Philanthropy

Brown was a member of St. Peter’s Episcopal Church since she first arrived in Albany. There she met Dorothy Wakerley, a woman who became her lifelong friend and companion. They shared a house, and like many other unmarried women during their time, they cared for an extended family over the years. They lived with Brown’s grandmother, mother, and various nieces as well as nephews. Brown also invited a succession of visiting women scientists from China. Brown continued her active community life in retirement, becoming the first female vestry, or administrative member, of her Episcopalian church. She also taught Sunday school for many years.

Between 1957 and 1978, the Brown-Hazen Fund supported training and research in biomedical sciences and encouraged women to take up careers in science. For several years the fund was the largest single source of nonfederal funds for medical mycology in the United States.

For over fifty years, Brown was also an active member of the American Association of University Women, strongly supporting the participation of women in science.

By her death, Brown had not only paid back Henriette Dexter, the wealthy woman who made it possible for her to attend college, but possibly more important, the money she earned from royalties allowed her to create new funds for scientific research and scholarships to provide other scientists with the same opportunities.

In a statement published in the Chemist the month of her death, Brown said she hoped for a future of “equal opportunities and accomplishments for all scientists regardless of sex.”

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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