Gene therapy under a cloud

Trials: A teen-ager's death prompts a Senate probe and casts a pall over a promising avenue of research.

February 02, 2000|By Jonathan Bor | Jonathan Bor,SUN STAFF

When Paul Gelsinger agreed to withdraw life support for his teen-age son, the victim of a gene therapy experiment gone awry, he vowed to stand by the scientists who administered the tests "until my dying day."

His resolve didn't last long.

First came the news reports, then a federal report alleging that the University of Pennsylvania failed to disclose crucial information to test subjects -- such as the fact that the gene product had killed monkeys who were given higher doses. Then in December, three months after his son died, federal officials ordered the experiment and seven others at the center shut down until further notice.

Today, accompanied by a lawyer, the Tucson, Ariz., handyman is poised to tell a Senate subcommittee that the doctors deceived him. He says his son, Jesse, an 18-year-old supermarket clerk who suffered from a mild form of a rare liver disease, might not have enrolled in the trial if told the truth.

"Put yourself in my shoes," said Gelsinger, asked in an interview why he has turned so publicly against the doctors. "Try to imagine walking your child into something like this. My boy relied on my judgment and trusted me. And I trusted the doctors."

"I should have known everything," he said. "I had a right to know, and my son had a right to know what he had gotten into fully. I had to find out from other sources besides [University of Pennsylvania]. I had a lot of faith in these guys, and I trusted them with my son's life."

Gelsinger is one of seven witnesses scheduled to testify before the Senate Subcommittee on Public Health and Safety, which will consider whether federal agencies and medical institutions are doing enough to monitor the safety of gene therapy experiments. The inquiry -- along with probes by the FDA, the National Institutes of Health and the hospital itself -- isn't just about a Tucson teen-ager but the future of gene therapy trials in general.

"Those in the gene therapy community who think, `This won't affect me,' that's absolutely not true," said Dr. Arthur Caplan, who heads the medical ethics program at the University of Pennsylvania. "It's absolutely devastating."

Mounting concerns over the safety of gene therapy experiments -- and the truthfulness of doctors conducting them -- could cause the government and private foundations to shy away from funding the trials, he said. Scientists who receive grants will likely have to slog through additional paperwork to satisfy regulators.

That might make critics feel better, he said, but slow progress.

Though gene therapy hasn't yet cured anyone of any disease, many researchers believe it will someday revolutionize the way patients are treated for conditions ranging from cystic fibrosis to cancer. Gene therapies are based on a common strategy: supplying patients with healthy genes that might go on to produce substances they lack.

Jesse Gelsinger suffered from ornithine transcarbamylase deficiency, known as OTC, a rare disease marked by the dangerous build-up of ammonia in the bloodstream and brain. He had a mild form and controlled it with drugs and diet. But he enrolled in the trial in the hope of helping babies who are afflicted with the full-blown disease and usually die within a few years.

His father, who was divorced but had custody over Jesse and three other children, said he and Jesse read a lengthy consent form that warned of hepatitis and other possible side effects. But he said the risks were posed as theoretical. Never, he said, was he told that earlier volunteers had suffered liver toxicity severe enough to warrant the trial's suspension.

Nor, he said, was he told that monkeys given higher doses in earlier experiments had died. Gelsinger said he learned of these lapses in newspaper articles that appeared last fall in the Washington Post and the New York Times and in a December hearing held by the National Institutes of Health.

"I discovered things at the [NIH] meeting in early December that opened my eyes up fully," Gelsinger said.

Harris Pogust, an attorney with the firm Gelsinger has hired, said the immediate goal is to help him through the hearing. And the firm is investigating the case to determine whether to file suit.

Jesse Gelsinger, a soft-spoken young man who loved motorcycles and professional wrestling, suffered a lethal chain reaction after receiving injections of the gene product. He developed jaundice, a clotting disorder and kidney failure -- and lapsed into coma.

Although doctors do not know what led to his death, they believe Jesse's immune system mounted an exaggerated response to the altered cold virus that was used as a "vector" to carry the gene to Jesse's tissues.

Lately, his doctors have declined comment. Ken Wildes, a spokesman, said the university is conducting reviews and decided not to participate in today's hearing because it had not completed its response to the FDA critique.

"Our thoughts and prayers are with him and his family," Wildes said.

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