Nancy Wexler

Nancy Wexler (born 19 July 1945) FRCP MEASA is an American geneticist and the Higgins Professor of Neuropsychology in the Departments of Neurology and Psychiatry of the Columbia University College of Physicians and Surgeons, best known for her involvement in the discovery of the location of the gene that causes Huntington's disease. She earned a Ph.D. in clinical psychology but instead chose to work in the field of genetics.

The daughter of someone exhibiting Huntington's, she led a research team into a remote part of Venezuela where the disease is prevalent. She visited the villages of Laguneta, San Luis, and Barranquitas. She obtained samples of DNA (deoxyribonucleic acid) from a large family with a majority of the members having Huntington's disease. The samples her team collected were instrumental in allowing a global collaborative research group to locate the gene that causes the disease. Wexler participated in the successful effort to create a chromosomal test to identify carriers of Huntington's disease.

Early life and education Nancy Wexler was born 19 July 1945, in Washington, D.C., and grew up in Pacific Palisades, California and Topeka, Kansas. Wexler's father, Dr. Milton Wexler, was a psychoanalyst and clinical psychologist, and her mother was a geneticist who taught biology before her children were born. Both parents taught the girls different areas of science, including the environment, nature, physics, and astronomy. Wexler's grandfather died when her mother, Leonore, was only 15 years old. Leonore looked up Huntington's disease (HD) at the library and read that it was a fatal, inherited disease, and (incorrectly) that it only affecting men. Years later, Nancy became involved in the Venezuela research. While studying for her A.B. she was required to take an introductory biology course, which constitutes "[her] only formal education in biology."

Her sister, Alice Wexler is three years older, and has her PhD in History and also contributed to the field of Huntington's. Nancy Wexler and the rest of the Wexler family feature prominently in Alice's book, Mapping Fate -A Memoir of Family, Risk, and Genetic Research that describes how the Wexlers coped with an affected mother while simultaneously trying to spearhead HD research. Alice Wexler also wrote a book on the social history of HD. The discovery that the gene was on the tip of chromosome 4 led to the development of a test for the disease. For her work, she has been awarded the Mary Woodard Lasker Award for Public Service, the Benjamin Franklin Medal in Life Science (2007), and honorary doctorates from New York Medical College, the University of Michigan, Bard College and Yale University.

Wexler's mother's symptoms progressed from fingers moving constantly, to uncontrollable motions. Nancy explains, “When she sat, her spasmodic body movements would propel her chair along the floor until it reached a wall, her head would bang repeatedly against the wall. To keep her from hurting herself at night, her bed was padded with lamb’s wool.” She continued to lose weight; she needed to consume at least 5,000 calories a day because of her unique metabolism. She died on Mother's Day, 1978.

Wexler continued her research of the HD disease and credits her ambition and motivation to her father, Milton Wexler; he and her sister Alice worked closely with her for years until her father turned his work over to her and her colleagues, feeling that science had become too complicated for him.

Wexler has held many public policy positions, including: Chair of the Joint NIH/DOE Ethical, Legal and Social Issues Working Group of the National Human Genome Research Institute; Chair of HUGO, the Human Genome Organization; and member of the Institute of Medicine. She has served on the American Association for the Advancement of Science board of directors, and the advisory committee on Research on Women's Health, NIH. . An episode of The Gene also tells the story of her learning she has Huntington's disease after years of not getting tested . Wexler has written a memoir about her experience as a scientist in search of a cure for the disease that now affects her My Life, My Science: Pursuing a Cure for Huntington's Disease.

Huntington's disease location In taking over the work of her father, Nancy Wexler met with many issues and difficulties. The goal of Wexler's research was to continue the work. For years the researchers used DNA to study DNA of Huntington's disease patients.

Nancy Wexler first encountered the idea of using polymorphisms as markers in October 1979. She was hosting a workshop and listened as key theorists explained their visions of gene hunting and was struck with the idea. It was from her idea that James F. Gusella focused on finding HD markers. He quickly hit upon the marker that would determine if a person had HD. Wexler gave Gusella samples of blood that she had collected from people in Venezuela and one after another, the samples confirmed the early finding. The HTT gene is located on the short arm of chromosome 4 at 4p16.3. HTT contains a sequence of three DNA bases—cytosine-adenine-guanine (CAG)—repeated multiple times (i.e. ... CAGCAGCAG ...), known as a trinucleotide repeat. CAG is the genetic code for the amino acid glutamine, so a series of them results in the production of a chain of glutamine known as a polyglutamine tract (or polyQ tract), and the repeated part of the gene, the PolyQ region.

Presymptomatic and prenatal testing Since 1986, presymptomatic and prenatal testing for HD has been available internationally. Nancy Wexler served as a director of a program that provided presymptomatic and prenatal testing for Huntington's disease. She also worked as a counselor in this program and had the opportunity to speak with over 100 individuals regarding testing. Regarding prenatal testing, Wexler believes that in-depth and detailed counseling must accompany both disclosing and nondisclosing testing.

Because the disease had no treatment or cure it was hard to get participants for many of the research studies. Patients would sometimes become depressed and even suicidal, not wanting to deal with 50 – 90% chance of inheriting the disease. Thus, the client can be told the test is noninformative.

Wexler and her sister Alice never wanted to know the results of the testing. Wexler learned that the disease was usually detected in midlife, but was sometimes found in children as young as two years old. The disease would affect the muscles that control swallowing. “When my sister and I both decided not to have children,” she says, “neither of us ever expected anything to happen in our lifetime that might change that.” The test provides 96% accuracy whether or not a person will develop the disease.

Personal views on genetic counseling Wexler believes that people who come for presymptomatic testing will benefit from intensive counseling, sometimes in lieu of the test itself. Her beliefs regarding counseling stem from her own experience regarding presymptomatic testing and also talking with colleagues in other programs. Being at risk has had a profound effect on most people's lives. They may have had an ill parent, with whom they may or may not have had contact, and perhaps other relatives who have had HD. Almost all welcome the opportunity to talk with someone knowledgeable about the experience that they are going through. Wexler states that, “The genetic test gives people a crystal ball to see the future: will the city be free of bombs from now on or will a bomb crash into their home, killing them and jeopardizing their children?”