Evelyn Witkin
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Evelyn M. Witkin ( Maisel; March 9, 1921 – July 8, 2023) was an American bacterial
geneticist A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic process ...
at
Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, botany, genomics, and quantitative biology. It is located in Laurel Hollow, New York, in Nassau County, on ...
(1944–1955),
SUNY Downstate Medical Center SUNY Downstate Health Sciences University is a public medical school and hospital in Brooklyn, New York. It is the southernmost member of the State University of New York (SUNY) system and the only academic medical center for health education, ...
(1955–1971), and
Rutgers University Rutgers University ( ), officially Rutgers, The State University of New Jersey, is a Public university, public land-grant research university consisting of three campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's C ...
(1971–1991). Witkin was considered innovative and inspirational as a scientist, teacher and mentor. Her work on DNA damage and DNA repair in bacteria is foundational to our understanding of such processes in living organisms. Her work has direct application to the effects of aging and to the diagnosis and treatment of human diseases such as cancer. Witkin was awarded the
National Medal of Science The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral science, behavior ...
in 2002 for her pioneering work on DNA
mutagenesis Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using lab ...
and
DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...
.Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the Lasker Award, prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Phys ...
"for discoveries concerning the DNA-damage response - a fundamental mechanism that protects the genomes of all living organisms."


Career

Witkin grew up in Queens, New York. She commuted to attend high school in Manhattan at Washington Irving High School, then an all-girls school, where she was encouraged to pursue her interest in science. Witkin earned a bachelor’s degree from
New York University New York University (NYU) is a private university, private research university in New York City, New York, United States. Chartered in 1831 by the New York State Legislature, NYU was founded in 1832 by Albert Gallatin as a Nondenominational ...
in 1941, majoring in biology. She intended to remain there for graduate work, but after she helped to organize protests against the school's policy of not allowing black athletes to play at Southern colleges, she was suspended for three months and an offer for a graduate position was withdrawn. After receiving her bachelor's degree, Witkin applied to
Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...
where she received her master's degree in 1943. She did her Ph.D. work with
Theodosius Dobzhansky Theodosius Grigorievich Dobzhansky (; ; January 25, 1900 – December 18, 1975) was a Russian-born American geneticist and evolutionary biologist. He was a central figure in the field of evolutionary biology for his work in shaping the modern ...
, who recommended her for
Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, botany, genomics, and quantitative biology. It is located in Laurel Hollow, New York, in Nassau County, on ...
(CSHL). Witkin spent the summer of 1944 at CSHL, where she learned genetics techniques for working with bacteria, a new field of research. During her stay she isolated a
UV radiation Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of t ...
-resistant mutant of ''E. coli''; this was the first time mutations conferring UV radiation-resistance were isolated. She returned to CSHL in 1945 and stayed there to complete her PhD research. Her degree was conferred in 1947. After completing her degree she was employed by the Carnegie Institution of Washington to continue work at CSHL until 1955.
Vannevar Bush Vannevar Bush ( ; March 11, 1890 – June 28, 1974) was an American engineer, inventor and science administrator, who during World War II, World War II headed the U.S. Office of Scientific Research and Development (OSRD), through which almo ...
, President of the Carnegie Institution, arranged for her to come in part-time after her children were born, an extremely unusual arrangement at that time. Witkin spent her official working hours in the lab, and did planning, data analysis and writing at home. In 1949, she was approached by
Leo Szilard Leo Szilard (; ; born Leó Spitz; February 11, 1898 – May 30, 1964) was a Hungarian-born physicist, biologist and inventor who made numerous important discoveries in nuclear physics and the biological sciences. He conceived the nuclear ...
and Bernard Davis to organize and edit the ''Microbial Genetics Bulletin''. Witkin edited the publication from 1950 to 1964. From 1955 to 1971, Witkin worked at the State University of New York's Downstate Medical Center in Brooklyn. In 1971 Witkin was appointed Professor of Biological Sciences at Douglass College,
Rutgers University Rutgers University ( ), officially Rutgers, The State University of New Jersey, is a Public university, public land-grant research university consisting of three campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's C ...
. She was named
Barbara McClintock Barbara McClintock (June 16, 1902 – September 2, 1992) was an American scientist and cytogenetics, cytogeneticist who was awarded the 1983 Nobel Prize in Physiology or Medicine. McClintock received her PhD in botany from Cornell University ...
Professor of Genetics in 1979, before moving to the Waksman Institute at Rutgers as Laboratory Director in 1983. She held that position until her retirement in 1991, when she became a professor emerita at Rutgers.


Research

Before DNA was definitively identified as hereditary material, Witkin began to study central problems in genetics involving the duplication of genes and the mechanisms by which genetic changes propagate. When Witkin began her research, it was assumed that agents such as UV directly caused mutations that were responsible for developing resistance. Witkin and others discovered out that the bacteria actively responded to DNA damage in a variety of ways. Through these protective activities, bacteria were themselves shaping the genetic changes that occurred in responses to DNA damage. During her first summer as a student at Cold Spring Harbor, Witkin worked with bacteria, which had recently been identified as having genes and being capable of viral resistance. Given that there were no published survival curves for the mutation of ''
E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
'' using
ultraviolet light Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of th ...
(UV), Witkin initially chose doses that turned out to be quite high. Most of her colonies died, but four survived on one plate. When compared to the parent strain, those bacteria showed a much higher tolerance to
UV radiation Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of t ...
. She also noted that there were differences in the strain's behavior compared to wild strains: the resistant strains did not display a delay before cell division and the development of elongated and filamentous strands, both of which were seen in UV-sensitive strains. Witkin was the first researcher to isolate a mutation conferring UV radiation-resistance. While at Downstate, Witkin discovered that UV mutagenesis in E. coli could be reversed, a phenomenon she called "dark repair". She was the first to describe the processes of mutation frequency decline (MFD). She observed a decrease in damage-induced suppressor mutations when protein synthesis was transiently inhibited as a result of UV irradiation. Witkin concluded that MFD occurs as a result of rapid enzymatic repair before replication in cases where protein synthesis is inhibited or delayed. In the case of potentially mutagenic UV photoproducts (lesions), a failure to replicate is lethal to the bacterium. If another DNA polymerase is able to copy past an area of damage, the bacterium survives, but with a higher likelihood of errors having occurred during the DNA synthesis and repair. In her 1967 paper, Witkin proposed that UV exposure blocked cell division by inhibiting a DNA replication enzyme that would introduce mutations during the replication process if it was left active. Mutants lacking excision repair processes were highly sensitive to the effects of radiation, and survivors of radiation exposure had many radiation-induced mutations. It was later determined that this type of excision repair is mediated in bacteria by a transcription-repair coupling factor (TRCF), which is produced by the MFD gene. In this and other research, Witkin inferred processes based on careful observation and experiment with populations of bacteria, that would only be directly observed and confirmed years later after the development of new technologies. In 1970,
Miroslav Radman Miroslav Radman (born April 30, 1944) is a Croatian biologist. Biography Radman was born in Split, PR Croatia, Yugoslavia. From 1962–1967 he studied experimental biology, physical chemistry and molecular biology at the University of Zagreb an ...
, a recent graduate of the Free University of Brussels, circulated a memorandum to Witkin in which he proposed a model for "SOS replication". He theorized that sudden and extensive DNA damage could trigger an inducible stress response, genetically controlled and involving synthesis of new proteins. Witkin looked for evidence for a common control mechanism to underlie and explain the variety of cellular responses that she had observed in her work with UV mutagenesis in bacteria. She proposed that UV-damaged DNA generates a regulatory signal that activates a large number of genes. Her findings supported the idea of a control mechanism involving lexA, which normally represses SOS response genes, and recA, which eliminates lexA repression in response to DNA damage. Such an upregulation of proteins for DNA protection and repair represents a trade-off between accuracy of replication and immediate survival. Witkin's research since the completion of her PhD was based on DNA mutagenesis, her mutagenesis work led to her work on DNA repair. Through this work she articulated the
SOS response The SOS response is a global transcriptional response to DNA damage in prokaryotes, in which the cell cycle is arrested and DNA repair mechanisms (error-free as well as error-prone) are induced. The regulation of this response is driven by two p ...
. Later, by characterizing the phenotypes of mutagenised ''E. coli'', she and Radman detailed the SOS response to UV radiation in bacteria. Witkin continued to work on the mechanism of the SOS response until her retirement. The SOS response to DNA damage was a seminal discovery because it was the first coordinated stress response to be elucidated.


Honors

Witkin was elected as a member of the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
in 1977. At the time she was one of the few women elected to the Academy. She also became a Fellow of the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...
(1978), a Fellow of the
American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is a United States–based international nonprofit with the stated mission of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsib ...
(1980); and a Fellow of the American Academy of Microbiology. She was awarded the 2000
Thomas Hunt Morgan Medal The Thomas Hunt Morgan Medal is awarded by the Genetics Society of America (GSA) for lifetime contributions to the field of genetics. The medal is named after Thomas Hunt Morgan, the 1933 Nobel Prize winner, who received this award for his work w ...
and her contributions to science have been recognized by the United States government as she was awarded the
National Medal of Science The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral science, behavior ...
in 2002:
For her insightful and pioneering investigations on the genetics of DNA mutagenesis and DNA repair that have increased our understanding of processes as varied as evolution and the development of cancer.The President's National Medal of Science: Recipient Details
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In 2015, she was awarded The
Wiley Prize The Wiley Prize in Biomedical Sciences is intended to recognize breakthrough research in pure or applied life science research that is distinguished by its excellence, originality and impact on our understanding of biological systems and processes. ...
in Biomedical Sciences and was named as one of ''
The Forward ''The Forward'' (), formerly known as ''The Jewish Daily Forward'', is an American news media organization for a Jewish American audience. Founded in 1897 as a Yiddish-language daily socialist newspaper, ''The New York Times'' reported that Set ...
'' 50. Also in 2015, Witkin won the Lasker Award for Basic Medical Research, with Stephen J. Elledge, "for discoveries concerning the DNA-damage response - a fundamental mechanism that protects the genomes of all living organisms." In 2021,
Rutgers University Rutgers University ( ), officially Rutgers, The State University of New Jersey, is a Public university, public land-grant research university consisting of three campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's C ...
and the Waksman Institute of Microbiology held "Symposium Celebrating 100th Birthday and Research Accomplishments of Dr. Evelyn M. Witkin", a public symposium and dedication ceremony of a new research laboratory named after her. Kenneth Irvine, interim director of the Waksman Institute, said, “The laboratory is being named after Dr. Witkin because she was an outstanding scientist. But certainly it’s important to note that she was a pioneering woman scientist, working at a time when science was dominated by men.”


Personal life

Evelyn Witkin was married to psychologist
Herman Witkin Herman A. Witkin (2 August 1916 – 8 July 1979) was an American psychologist who pioneered the development of cognitive theories, especially as they pertained to learning. While many cognitive psychologists diagnosed learning disabilities with qu ...
; their sons were: Joseph Witkin, an emergency physician and founding member of
Sha Na Na Sha Na Na was an American rock and roll and doo-wop revival group formed in 1969. The group performed a song-and-dance repertoire based on 1950s hit songs that both revived and parodied the music and the New York City street culture of the 1 ...
, and Andy Witkin (d. 2010), a computer scientist. She was also the grandmother of four. She
turned 100 A centenarian is a person who has reached the age of 100. Because life expectancies at birth worldwide are well below 100, the term is invariably associated with longevity. The United Nations estimated that there were 316,600 living centenarian ...
in 2021. Witkin died of complications from a fall in
Plainsboro Township, New Jersey Plainsboro Township is a Township (New Jersey), township situated in southern Middlesex County, New Jersey, Middlesex County, in the U.S. state of New Jersey. Centrally located in the Raritan River, Raritan Valley region, the township is an ou ...
, on July 8, 2023, at the age of 102.


Selected publications

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References

{{DEFAULTSORT:Witkin, Evelyn M. 1921 births 2023 deaths American geneticists American women centenarians Rutgers University faculty Fellows of the American Academy of Arts and Sciences Fellows of the American Association for the Advancement of Science Members of the United States National Academy of Sciences National Medal of Science laureates Columbia University alumni Scientists from New York City Recipients of the Albert Lasker Award for Basic Medical Research