Year after year for two decades, Nancy Wexler led medical teams into remote villages in Venezuela, where extended families lived in stilt houses on Lake Maracaibo and, for generations, had suffered from a hereditary disease that causes brain degeneration, disability and death.
Neighbors shunned the sick, fearing they were contagious. “Doctors wouldn’t treat them,” Wexler said. “Priests wouldn’t touch them.”
She began to think of the villagers as family, and started a clinic for them. Over time, she coaxed elite scientists to collaborate rather than compete to find the cause of the disorder, Huntington’s disease, and she raised millions of dollars for research.
Her work led to the discovery in 1993 of the gene that causes Huntington’s, to the identification of other genes that may have moderating effects and, at long last, to experimental treatments that have begun to show promise.
Now, at 74, Wexler has decided it’s time to acknowledge publicly that she has the disease she has spent her life studying and that killed her mother, uncles and grandfather.
“There is such stigma, and such ostracization,” said Wexler, a professor of neuropsychology at the College of Physicians and Surgeons at Columbia University. “I think it’s important to destigmatize Huntington’s and make it not as scary. Of course it is scary. Having a fatal disease is scary, and I don’t want to trivialize that. But if I can say, I’m not stopping my life, I’m going to work, we’re still trying to find a cure.”
Among her greatest concerns are the thousands of Venezuelans whose willingness to donate blood and skin samples, and the brains of deceased relatives, made it possible to find the gene. But they live in an impoverished region, and, Wexler said. The clinic that she and her colleagues opened has been shut down by Venezuela’s government.
“We share DNA,” she said. “They’re part of my family. They are super-stigmatized. So I thought, this is part of my decision to come out, about me — which I still find hard to do without breaking into tears.”
Although Wexler has not talked about her diagnosis until now, it is no surprise to friends or colleagues. For at least a decade, her symptoms were noticeable. Her gait is unsteady, her speech is sometimes slurred, she loses her temper. She needs a walker to get around outside the Manhattan apartment she shares with Dr. Herbert Pardes.
But her mind is sharp and her will is strong, and she has chosen to deal with the disease on her own terms and in her own good time.
“She’s a remarkable human being who’s been an incredible leader of a scientific initiative,” said Dr. Francis Collins, director of the National Institutes of Health, who was among those she recruited to help find the Huntington’s gene.
The specter of the disease has been hanging over Wexler since 1968, when she was 22. One morning, a police officer accused her mother, Leonore, of being drunk as she crossed a street in Los Angeles on the way to jury duty. She had not realized she was staggering.
Leonore Wexler’s father and all three of her brothers had died from Huntington’s. She was a geneticist, a field she had chosen in hopes of finding a way to save her brothers, Nancy Wexler said.
Huntington’s is caused by a dominant gene: If one parent has the disease, every child has a 50-50 chance of having it, too. The disease is rare. About 30,000 people in the United States have it, and another 200,000 are at risk. It is the disease that killed folk singer Woody Guthrie in 1967.
When Leonore’s disease was diagnosed, there was no test for the gene. People could only wait to see whether they fell ill. The symptoms usually appear when patients are in their 30s or 40s. Leonore was 53 when her illness was identified.
After the diagnosis, Leonore’s former husband, Milton Wexler, told their daughters, Nancy and her older sister, Alice, that they were at risk of getting the disease, too. But he insisted they would be spared.
But looking back at that day, Nancy Wexler said she felt that, in an instant, three generations had been wiped out: Her mother, herself and the children she had hoped to have. She and her sister decided that they would not have children. Wexler said it is a decision that she regrets.
Determined to find a cause and cure, or at least a treatment, Milton Wexler started the Hereditary Disease Foundation to raise money and recruit researchers. Nancy decided to devote her career to Huntington’s.
Leonore Wexler’s condition worsened and she died on Mother’s Day in 1978, 10 years after the diagnosis.
The next year, Nancy Wexler made her first trip to Venezuela to study an extended family believed to have the world’s highest prevalence of Huntington’s. She knew that to find the gene, scientists would need DNA samples from as many affected people and their healthy relatives as possible. Wexler told them that she and they were related, that her family had the disease, too.
For 20 years, she returned with teams that ultimately collected 4,000 blood samples. They traced the path of the disease through 10 generations in a family tree that included more than 18,000 people.
In 1983, just four years after the first trip, the team found a marker, a stretch of DNA that was not the gene but nearby. It took a half dozen high-powered research groups — picked by Wexler and her father — 10 more years to find the gene, on chromosome 4, one of the 23 pairs of chromosomes found in most cells in the body.
The discovery was a landmark in genetics, one that scientists say would never have happened without Wexler. The gene contains the blueprint for a protein that the researchers named Huntingtin. Its role in the brain is not understood. But in people with the disease, a series of three DNA building blocks — represented by the letters CAG — is repeated too many times. The repeats lead to an abnormal form of Huntingtin, which poisons nerve cells in the brain.
Nancy Wexler holds out hope for the work on new drugs. She said she still has a great deal of work to do.
“Enjoy life while you can,” she advised. “Find what gives you some pleasure and go for it. Don’t get kidnapped by this.”