Thursday, March 22, 2007

Obit: Huntington's Disease Pioneer Milton Wexler, 98

By Elaine Woo Los Angeles Times

LOS ANGELES -- Devastating health news to his ex-wife almost 40 years ago sent Milton Wexler, a lay psychoanalyst popular with actors and artists, on a journey to the edge of a scientific frontier. He would emerge a hero.

Wexler, 98, who died of respiratory failure Friday at his Santa Monica, Calif., home, ignored the scientific wisdom of the time and poured his energy into unlocking the mysteries of Huntington's disease, a rare, incurable genetic disorder often described as a time bomb because the mental and physical havoc it wreaks typically does not surface until midlife.

In the early 1970s, after starting what is now the Hereditary Disease Foundation, he began to recruit young scientists willing to gamble on a longshot to workshops aimed at finding a cure. The workshops -- structured like the group therapy sessions Wexler ran in his Los Angeles practice -- stressed brainstorming and were unlike anything the scientists had experienced.

In 1983, after a decade of struggle in laboratories around the country, the scientists nurtured by Wexler -- and later also by daughter Nancy, a clinical psychologist -- achieved the breakthrough few people believed possible: They found the genetic marker for Huntington's. In 1993, they located the gene itself.

These milestones in the genetics revolution did not help Leonore Wexler, Milton Wexler's ex-wife who died of Huntington's 10 years after her diagnosis -- on Mother's Day in 1978. But they would have a profound impact on others.

Discovering the gene not only represented an enormous step toward finding a cure for Huntington's, but it demonstrated the feasibility of mapping the array of 30,000 human genes.

Wexler ``proved it could be done,'' said Dr. Francis Collins, who was a junior professor at the University of Wisconsin when he joined Wexler's workshops in the mid-1980s. Collins helped develop the methods for identifying the genes responsible not only for Huntington's disease but for cystic fibrosis before going on to lead the successful effort to complete the genome blueprint in 2003.

``The search for the Huntington's gene became the paradigm for all such gene hunts. ... That all came out of that wonderful intellectual foment that Milton and Nancy created,'' said Collins, director of the government-supported National Human Genome Research Institute in Bethesda, Md.

Anne B. Young, a Harvard Medical School professor and chief of neurology at Massachusetts General Hospital, said Wexler was ``a visionary ... He was the guru and the glue'' who held together a project that many eminent scientists had deemed foolish.

``Today we have the gene. We have an inkling of what the gene does. It wouldn't have happened without Milton,'' Young said. ``He was a catalyst for all of that.''

Born in San Francisco but reared in New York City, Wexler entered Syracuse University at 16 and earned a law degree from New York University. But he hated practicing law and abandoned it in 1937 to obtain a doctorate in psychology at Columbia University. He also studied under Theodor Reik, a disciple of Sigmund Freud, who helped legitimize the practice of psychoanalysis by nonphysicians in the United States.

Wexler followed Reik's path and became one of the country's first lay psychoanalysts. After serving in the Navy during World War II, he joined the staff of the Menninger Foundation, a psychiatric research and treatment center in Topeka, Kan., where his success treating schizophrenics gained attention. He gave his patients round-the-clock care, even taking a small group of them on vacation with his family so their treatment would not be interrupted.

``He was an organizing force in their life. A lot of people got better,'' Nancy Wexler said.

In 1951, he left Menninger and moved to Los Angeles to begin a more lucrative private practice that would enable him to help support his wife's three brothers, who had been diagnosed with Huntington's the year before. He found success treating clients who were well-known in Hollywood. He even wrote a screenplay with director Blake Edwards, the husband of actress Julie Andrews, for the movie ``The Man Who Loved Women.''

He also accepted many struggling artists into analysis and by the early 1960s treated them free in groups.

Transferring the group therapy method of free association to solving the quandary of Huntington's was, former patient architect Frank Gehry said, ``sheer genius.''

Several principles guided the workshops. The priority was to encourage a free flow of bold ideas, so written lectures and slide presentations were banned because they stifled interaction. The groups were kept small -- usually no more than 20 participants -- with an emphasis on post-doctoral students and young scientists who were less likely to be bound by orthodoxy. Wexler also invited established scientists -- including Nobel laureate and DNA pioneer James Watson -- who functioned as living encyclopedias across a wide range of disciplines. Scientists who ordinarily would not be in the same room together -- geneticists who studied worms and flies side-by-side with neurologists and psychologists -- shared thoughts.

Wexler ``had an ability to bring together a room full of disparate people and basically remove the walls. He was a master of the creative,'' said David E. Housman, a biologist who played a crucial role in the collaborative effort that led to the identification of the Huntington's gene.

The spirit of cooperation was so strong that when the scientists published their findings, the authorship was given to the Huntington's Disease Collaborative Research Group.

By then the effort had become a Wexler family project. Nancy, a professor at Columbia, recruited scientists, led workshops and collected blood samples in a remote village in Venezuela where the world's largest family with Huntington's disease lived. She succeeded her father as president of the foundation. Daughter Alice, a historian, wrote ``Mapping Fate,'' a 1995 memoir of her family's struggle.

When the Wexler daughters learned that they might have inherited their mother's defective gene, they decided not to have children. When the test to detect the gene was developed, in part through their efforts, they chose not to take it, believing that the wrong answer could raise more questions than they could handle.

Their father agreed with their decision. They were the reason he got into the fight in the first place.

``I became an activist because I was terribly selfish,'' he once said. ``I was scared to death that one of my daughters would get it too.''

Now in their 60s, they have remained free of the disease.

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