A teenager's death during a gene therapy experiment at the University of Pennsylvania was caused by the treatment but not by any errors by the research team, according to the preliminary findings of a two-month internal investigation.

The death is the first attributed to gene therapy, a nine-year-old field of research that is trying to find a way to use genes to overcome inherited diseases, cancer and other problems.

The findings were disclosed in a brief summary report released yesterday by the researchers who conducted the experiment. The researchers declined to provide the supporting documentation until next week, when they make a public presentation before a federal oversight board looking into the death.

The experiment had been controversial even before the death of Jesse Gelsinger, an 18-year-old Tucson resident, because it tested unusually large doses of a gene-altered virus on relatively healthy volunteers with a rare liver disorder.

"The findings suggest that the experimental drug used in the trial--a modified cold virus, or vector, incorporating a potentially corrective gene for Mr. Gelsinger's genetic disease--initiated an unusual and deadly immune-system response that led to multiple organ failure and death," the report states.

However, the researchers say they still don't know why the virus, known as an adenovirus, triggered a lethal reaction in Gelsinger.

Gelsinger received a significantly larger dose of vector than all but one of the other participants. But there were no early warnings of trouble in the other volunteer who received the high dose or in 16 earlier volunteers who received smaller doses, the report states.

The report acknowledges that some participants suffered temporary liver damage but says a review of patient data and of animal studies performed before the clinical trial "revealed no information that would have predicted the events that led to Mr. Gelsinger's death."

"There was no evidence of human error in his clinical management," the report says.

The Washington Post reported last week that monkeys given a high dose of a genetically engineered virus by the Penn team a few years ago had died in a manner similar to Gelsinger. Penn researchers subsequently developed what they considered to be a safer version of the virus for the experiment.

However, some scientists, citing a growing body of evidence that adenovirus in any form causes serious side effects, have questioned the wisdom of using it to treat genetic diseases. The risk might be warranted if the participants were dying and had exhausted conventional treatments, they said. But the Penn team chose to experiment on adults with a mild form of a liver disorder--ornithine transcarbamylase deficiency--who either suffered no symptoms or had them under control with drugs and diet.

The report states that the researchers were mindful of the potential side effects and "carefully monitored all patients for liver inflammation and/or injury using liver-function tests and liver biopsies. While there was evidence of liver inflammation in some patients, all such episodes proved transitory in nature," and their livers returned to normal within two weeks.

Gelsinger died within four days of receiving the infusion on Sept. 13. His decline began within a day, as he developed a systemic blood clotting disorder followed by respiratory distress and then liver and kidney failure on Sept. 17.

In the investigation that ensued, Penn researchers checked the vector for abnormalities but found none, according to their summary. All laboratory data that they reviewed pointed to an unusually severe reaction to the genetically altered virus, the report says.

"In the context of this unexpected tragedy, the researchers--Dr. James Wilson, Dr. Steve Raper, and Dr. Mark Batshaw--remain committed to fully evaluating all potential leads," the report states. "The purpose of these efforts is to understand the precise nature of Mr. Gelsinger's unfortunate death, and to share the knowledge gained with the research community and the public in order to prevent another such occurrence."

Gelsinger's death prompted the Office of Biotechnology Activities at the National Institutes of Health to call on all researchers using adenoviruses to report any ill effects that might shed light on his death or prevent future injuries.

The results of that solicitation and of the Penn investigation will be presented next week in Bethesda to a special NIH advisory committee that monitors gene therapy experimentation.

CAPTION: Jesse Gelsinger, 18, died during a gene therapy experiment.