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THE GENE WARS PT 5.Pdf 8.8 Mb PART FIVE Ethical, Legal, and Social Issues A New Social Contract ANCY SABIN WEXLER radiates openness, integrity, and com- N mitment; she is a doer with a big heart. Her passion for the science of genetics is grounded in personal experience. Her mother, Leonore Sabin Wexler, died of Huntington's disease, as did her uncles Jesse, Seymour, and Paul, and their father, Abraham Sabin (Nancy's maternal grandfather). As Alzheimer's disease did in the Ross family, Huntington's disease cut a wide swath through the Wexler family. Nancy, her sister, Alice, and her father, Milton, watched as Leonore, a woman of formidable intellect, developed uncontrollable movements and deteriorated mentally. On May 14, 1978, it was over. Her body was cremated, according to her wish. The funeral was strictly family. We spent the time reading letters she had written in the early days of her marriage. They were cheerful, exuberant, and full of intelligence. They recreated the woman who had been vibrant and alive. Now that it was finally over, we could afford to remember her when she was healthy and allow ourselves to feel the enormity of the loss.1 When Milton Wexler first discovered the diagnosis in 1968, he called Nancy and Alice home to Los Angeles and explained the prospects. Nancy was in London at the Hampstead Clinic Child Psychoanalytic Training Institute, having just graduated from Radcliffe. She went on to do graduate work in psychology at the University of Michigan, and wrote her dissertation on how 232 The GENE WARS those at risk lived with the threat of Huntington's disease. She then taught for two years at the New School for Social Research in New York City. Opportunity knocked for Nancy Wexler at age thirty, when she was hired as executive director of the Congressional Commission for the Control of Huntington's Disease and Its Consequences (the Huntington's Commission). The history of the commission is another story of a woman's persistence. After singer Woody Guthrie died of Huntington's disease, his wife, Marjorie, formed the Committee to Combat Huntington's Disease to focus attention on the disease and to lobby for action in Washington. Congress subsequently created the Huntington's Commission, which was housed at the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) within the National Institutes of Health (NIH). The commission's task was to rec- ommend what Congress should do to combat Huntington's disease. Milton Wexler had formed the Hereditary Disease Foundation in 1968, to focus on the science,2"4 and Nancy's expertise and family background made her a logical candidate to direct the commission. The commission published its report in 1978,5 and Wexler went to work at NINDS to implement its recommendations. She became the impresario of Huntington's research, enticing the best scientists she could find into the field. It became an American success story, balancing the strengths of the public and private sectors. The Hereditary Disease Foundation was the private arm that could move quickly. It convened a series of informal workshops that would have been more difficult to engineer under federal auspices. NINDS had much deeper pockets, and the infrastructure to cultivate the best science through grants. In 1979, the Hereditary Disease Foundation held a workshop on applying recombinant DNA technology to search for the Huntington's gene. Alan Tobin, a UCLA researcher and the foundation's scientific director, was con- vinced that direct study of DNA was the fastest route to solving the problem of Huntington's disease.3 It seemed farfetched to many,6 but the idea of a genetic linkage map of the human genome had begun to grow among a small group of cognoscenti. A group in Boston that included David Housman (MIT) and Joseph Martin (Massachusetts General Hospital) was thinking seriously about genetic linkage mapping as part of a nascent Huntington's research center.3 The Botstein et al. paper was not yet published, but the notion was becoming known, particularly in Boston. Arlene Wyman and Ray White were just beginning work to find the first DNA marker in nearby Worcester, in collaboration with Botstein at MIT.7;8 Botstein came to the workshop, where he scribbled furiously on the board in a persuasive display of intellectual pyrotechnics. The foundation placed a bet on genetic linkage map- ping. P. Michael Conneally at the University of Indiana searched for linkage between Huntington's disease and protein markers, while a team led by James Gusella began to work with the new DNA markers. Gusella was a graduate A New Social Contract 233 student with David Housman at MIT and later went to work at the new Huntington's Center Without Walls at Massachusetts General Hospital. The NINCDS-sponsored program grew out of the Huntington's Commission recommendations; its NIH project officer turned out to be Nancy Wexler. The DNA marker project took several years to get up to speed. By then, the prospects had brightened considerably, although DNA markers had never been used to find disease genes, and many doubted they could be. David Housman and Richard Mulligan chaired a May 1983 workshop convened by the Hereditary Disease Foundation in Cambridge, Massachusetts. The topic was "What Can Be Learned About Huntington's Disease Once the Gene Has Been Located?" According to one report, the meeting ended "on a note of sobriety for the distance to be traveled and genuine offers of assistance some five or ten years hence when a marker would be found."9 Wrong. Barely three months later, Gusella's group turned up a promising lead. They found a possible linkage between Huntington's disease and a marker on chromosome 4. This marker, designated G8, was among the first tested.3;4;10 (Thereafter, Gusella was known as "Lucky Jim."4) An August workshop, titled "Clinical Impact of Recombinant DNA Research on Neurogenetic Diseases" and once thought premature, was suddenly playing catch-up.n That workshop took place "in an atmosphere of elation and stunned disbelief."9 The results were published in Science that November, by which time the linkage was well established.12 A November workshop focused on issues that might emerge as the marker was used to predict who might develop Huntington's disease.11 At a January 1984 workshop, just months after Gusella and others found the approximate chromosomal location of the Huntington's gene, a consor- tium of laboratories formed spontaneously to search for the gene itself and the DNA alteration that caused the disease. Wexler and the Hereditary Disease Foundation were the spokes supporting the wheel. The consortium held to- gether through the 1980s and into the 1990s. Other groups outside the con- sortium—such as Rick Myers and David Cox in San Francisco, Michael Hayden and his coworkers in Vancouver British Columbia, and groups in Europe and Asia—continued in generally friendly competition for a decade, until the gene was found.3 Once the gene's location was found, many hoped it would be only a few years until the gene were found. The hunt for the gene itself proved much more arduous. It took a decade of dedicated work, but Gusella's group did lead the effort that eventually uncovered the gene and the nature of the muta- tion causing Huntington's disease.13 The gene was more elusive than some because it was embedded in a complex and confusing region. In the end, the article announcing the end of the search was authored by the entire Hunting- ton's Disease Research Group, which by then included fifty-eight authors in six groups spanning the Atlantic. The hunt for the Huntington's disease gene was far more than luck. It involved a large international collaboration and a decade of intensive work 234 The GENE WARS A New Social Contract 235 with many false starts. Another critical factor was the discovery of a large family with Huntington's disease living near Lake Maracaibo in Venezuela. This family had been discovered by a Venezuelan physician, Americo Ne- grette. Wexler flew down to investigate in 1979. It turned out to be an enor- mous pedigree, containing thousands of living members, with an immense toll of Huntington's disease. Thus began an annual rite of visitation that continues to this day. Wexler became a local fixture, known as La Catira ("the Blonde"), and the Venezuelan families became an extension of Wexler's family—a group with whom she shared an emotional bond deepened by mutual suffering and the fierce struggle against a common enemy.2 Dr. Negrette described the feeling of working among the Maracaibo families in the company of La Catira: I arrived in their homes and their shacks, and left feeling destroyed inside because I felt incapable of solving the problems. ... At times I would distance myself from them— for years.. and feel guilty. But now as I grow older I have become more sensitive to the pain of others. So much so that it now no longer feels apart. It is my pain, this pain that they feel. And it is for this that I love La Catira. Because she comes every year, for more than ten years to battle. She brings them medicines and she brings them projects for their social welfare. But she brings them something more precious yet. She brings them an immeasurable love. She pours on them a warm contagious care. I have seen her embracing women and embracing men and kissing children. Without theater, without simulation, without pose. With a tenderness that jumps from her eyes. And her fingers are claws of love mingling with tenderness and passion...
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