Death Points to Risks in Research

"The company was talking about lucrative markets and a promising product much too soon," said Marcy Darnovsky, associate executive director of the Center for Genetics and Society, an Oakland, Calif.-based public interest group that focuses on genetic technologies.

Company officials said the drug does show promise by some measures. "We don't know what the best indication of efficacy is yet," said Barrie Carter, the company's chief scientific officer.

Finally, on July 20, a day after Mohr's emergency transport to Chicago and four days before she died, the company sent a "serious adverse event" report to the FDA and suspended the study, conceding that her life-threatening symptoms were "possibly" due to the treatment.

Three weeks after Mohr got the injection that she had hoped would cure her, she was unconscious and beyond hope of recovery. With family and friends gathered around, her life support was removed.

"Basically, I told my daughter that her mommy has died and gone to live with Jesus," Robb Mohr said. "She prays every night that Jesus will make her better so she can come back home."

Tests on Jolee's Mohr's tissues may tell the story of what happened, but for now scientists say they are scratching their heads.

One reassuring aspect of tgAAC94's engineering is that genes required for replication have been removed, so the viruses cannot make more of themselves. But animal studies conducted by the company have shown that the product can escape from the joint space and travel about the body, perhaps catching the attention of the immune system. In general, the immune system mounts much more robust -- sometimes dangerously robust -- responses after a second exposure. In fact, both shots Mohr got were the real thing, the company said.

Further complicating matters, Mohr was on three conventional but potent arthritis drugs, each of which can cause serious side effects.

Years ago, when Targeted Genetics first sought permission to test tgAAC94 in people, federal reviewers approved a single dose in patients who were not taking other drugs but said they would think twice about approving multiple shots or testing in people taking other arthritis medications. Some questioned whether the risk of even a single shot was worth it for a non-life-threatening disease such as arthritis, according to the minutes of meetings at the National Institutes of Health, which used to review, in public, every proposed human gene therapy experiment.

After completing its initial study of single shots, Targeted Genetics sought permission to start giving two -- and to patients taking other drugs. Whatever discussion led up to that approval is hidden from the public because of a federal rule change in 2000 that placed most such follow-on studies under confidential FDA review rather than a public NIH process.

In testimony before a congressional subcommittee in 2000, a chief executive representing the Biotechnology Industry Organization spoke out for the rule change, to streamline oversight and harmonize NIH and FDA regulations. Among other things, the change gave companies up to a year to report serious adverse events as long as the doctor overseeing the study does not think the problem is caused by the test product.

The chief executive was H. Stewart Parker of Targeted Genetics.

Staff researcher Madonna Lebling contributed to this report.