Gene Therapy Marches on Despite Setbacks

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Sept. 15, 2000 (Washington) -- Ten years after the first use of gene therapy to treat a patient, the field is continuing to advance despite a scandal that threatened to cripple it, researchers here said Thursday.

"As time goes on, gene therapy should become relatively inexpensive. It's costly in development, but 10 or 15 years from now, it will be an inexpensive way of curing disease," W. French Anderson, MD, said at a conference Thursday sponsored by the National Foundation for Cancer Research to celebrate the 10th anniversary of gene therapy. Anderson is considered the father of gene therapy, which involves injecting genetic information into cells to alter their function. He is the director of the gene therapy laboratories at the University of Southern California Keck School of Medicine in Los Angeles.

Anderson reflected on the death 1 year ago of 18-year-old Jesse Gelsinger, a gene therapy patient at the University of Pennsylvania. Investigators have said that Gelsinger, who had a rare genetic disorder called ornithine transcarbamylase deficiency, died after suffering an immune system failure. "What caused Jesse's death is still unknown," Anderson said. "He probably had an underlying infection that damaged his bone marrow."

What was scary about Gelsinger's death, Anderson said, is that it cannot be attributed to any obvious errors by the researchers who were running the study. "If the Pennsylvania team had made a mistake, we'd all be a lot more comfortable. But it was something unpredictable, and it could happen to any of us at any time. That's what's really frightening."

As a result of the outcry following Gelsinger's death, the government has issued more stringent guidelines for gene therapy research. The guidelines "make doing gene therapy trials more expensive and difficult," he said. "But on the positive side, I think gene therapy trials are now done better [because] they're more closely monitored. It will be better science."

Despite the increased difficulty, gene therapy trials are continuing, with about 100 under way worldwide, says Anderson. One trial that Anderson is overseeing involves an injectable form of gene therapy for treating patients with gastrointestinal cancers that have spread to the liver.

Making gene therapy injectable, rather than something that requires transfusions in the hospital, will be key to spreading the technology across the population, Anderson said. "So long as gene therapy is being done in hospitals, it's not going to reach millions of people. It's got to be an injection. That's the Holy Grail."

Researchers also are looking at ways to prevent disease in patients with genetic deficiencies, and that will change the way medicine is practiced, predicted Martyn Smith, PhD, professor of toxicology at the University of California at Berkeley. "In the first part of the century, health care was sick care," he said. "Then people wanted to cut costs, so now there's managed care. But a new kind of care is coming -- preventive care -- where tests will be done to predict who will get a disease. It will change the way doctors do a lot of their business."

Danny Welsh, PhD, a cell biologist at the Pennsylvania State University College of Medicine in State College, said physicians also will be better able to target their treatments based on the particular type of disease a patient has. "There are eight or nine different types of breast cancer, and yet people want to treat all breast cancers the same way," he said. "But within the next decade or so, the ability to [type diseases better] will allow physicians to make informed choices rather than just guessing."

One of the patients attending the conference was 5-year-old Taylor Daley, the first person to receive a successful in utero, or before-birth, bone marrow transplant to cure severe combined immune deficiency syndrome (SCIDS) -- a rare disorder that has forced some children to live in a virtual "bubble" because they can't fight off even minor infections. The disorder had been detected through a prenatal test. "We didn't look at it as being pioneers," said Taylor's mother, Heather Daley. "We just had to try everything possible to save our child." Although SCIDS itself is not a cancerous ailment, it makes patients more vulnerable to contracting certain cancers.

Another participant at the conference was 14-year-old Ashanthi DeSilva, the first successful gene therapy recipient. DeSilva, who also has SCIDS, said she remembered little of the events surrounding her therapy 10 years ago, but she is thankful for the researchers' work. "I was always grateful, but now I realize it more," DeSilva told WebMD.

Anderson said that when he was giving DeSilva the therapy, he had only one thing on his mind. "My feeling was 'Don't mess up,'" he said. "For several days before, I tried to think of everything that could go wrong and figure out a back-up. We were all very much aware that this was a momentous event. If anything had happened to Ashanthi, it would have been the end of our careers."

Kenneth Culver, MD, another member of the team that treated DeSilva, noted that he got involved with gene therapy because it seemed like the only hope for SCIDS patients. "Every kid I'd treated with immune deficiency had died," he said, his voice breaking. "That was enough."

Culver, who is now an executive director of pharmacogenetics at Novartis Pharmaceuticals in East Hanover, N.J., urged high school students attending the conference to consider careers in genetics. "Genetics is part of everything," he said. "Pick something that will help move the whole area along. If there is a component where you are helping other people, you'll never run out of the dedication and energy to make it happen."


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