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At 18, Ashanthi DeSilva of suburban Cleveland is a living symbol of one of the great intellectual achievements of the 20th century. Born with an extremely rare and usually fatal disorder that left her without a functioning immune system (the "bubble-boy disease", named after an earlier victim who was kept alive for years in a sterile plastic tent), she was treated beginning in 1990 with a revolutionary new therapy that sought to correct the defect at its very source, in the genes of her white blood cells. It worked. Although her last gene-therapy treatment was in 1992, she is completely healthy with normal immune function, according to one of the doctors who treated her, W. French Anderson of the University of Southern California. Researchers have long dreamed of treating diseases from hemophilia to cancer by replacing mutant genes with normal ones. And the dreaming may continue for decades more. "There will be a gene-based treatment for essentially every disease," Anderson says, "within 50 years. "
It’s not entirely clear why medicine has been so slow to build on Anderson’s early success. The National Institutes of Health budget office estimates it will spend $ 432 million on gene-therapy research in 2005, and there is no shortage of promising leads. The therapeutic genes are usually delivered through viruses that don’t cause human disease. "The virus is sort of like a Trojan horse," says Ronald Crystal of New York Presbyterian/Weill Cornell Medical College. "The cargo is the gene. "
At the University of Pennsylvania’s Abramsoh Cancer Center, immunologist Carl June recently treated HIV patients with a gene intended to help their cells resist the infection. At Cornell University, researchers are pursuing gene-based therapies for Parkinson’s disease and a rare hereditary disorder that destroys children’s brain cells. At Stanford University and the Children’s Hospital of Philadelphia, researchers are trying to figure out how to help patients with hemophilia who today must inject themselves with expensive clotting drugs for life. Animal experiments have shown great promise.But somehow, things get lost in the translation from laboratory to patient. In human trials of the hemophilia treatment, patients show a response at first, but it fades over time. And the field has still not recovered from the setback it suffered in 1999, when Jesse Gelsinger, an 18-year-old with a rare metabolic disorder, died after receiving an experimental gene therapy at the University of Pennsylvania. Some experts worry that the field will be tarnished further if the next people to benefit are not patients but athletes seeking an edge. This summer, researchers at the Salk Institute in San Diego said they had created a "marathon mouse" by implanting a gene that enhances running ability; already, officials at the World Anti-Doping Agency are preparing to test athletes for signs of "gene doping". But the principle is the same, whether you’re trying to help a healthy runner run faster or allow a muscular-dystrophy patient to walk. "Everybody recognizes that gene therapy is a very good idea," says Crystal. "And eventually it’s going to work. \

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