Posted on March 22, 2007

A Visionary Who Led A Genetic Revolution

Elaine Woo, Los Angeles Times, March 22, 2007

[Milton] Wexler, 98, who died of respiratory failure Friday at his Santa Monica home, ignored the scientific wisdom of the time and poured his energy into unlocking the mysteries of one of the most enigmatic and crippling of diseases, 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 bright young scientists willing to gamble on a longshot to workshops aimed at finding a cure. The freewheeling workshops—structured like the group therapy sessions Wexler ran in his Westside practice—stressed brainstorming and were unlike anything the scientists had ever experienced.

In 1983, after a decade of struggle in laboratories around the country, the scientists nurtured by Wexler—and later also by [his 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.

Wife dies of the disease

These milestones in the genetics revolution did not help Leonore Wexler, who died of Huntington’s on Mother’s Day in 1978—10 years after her diagnosis. 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 entire 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 leading 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 ferment that Milton and Nancy created,” said Collins, now director of the government-supported National Human Genome Research Institute in Bethesda, Md.

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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 get a doctorate in psychology at Columbia University. He also studied under Theodor Reik, a Sigmund Freud disciple who helped legitimize the practice of psychoanalysis by non-physicians 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 renowned 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.

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Transferring the group therapy method of free association to solving the quandary of Huntington’s was, Gehry added, “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 postdoctoral 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.

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A family project

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When the Wexler daughters learned that they might have inherited their mother’s defective gene, they decided not to have children. When the procedure for detecting the gene was developed, in part through their brave efforts, they chose not to undergo it, believing that testing positive could raise more questions than they could handle.

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