The University of Pennsylvania announced yesterday that it had reached an out-of-court settlement with the family of Jesse Gelsinger, the Tucson teenager whose death in a gene therapy experiment 14 months ago prompted a national reassessment of protections for research volunteers.

Details of the settlement, which grew out of a civil suit the family filed in a Pennsylvania state court in September, were not disclosed.

Gelsinger, who was 18 and had an inherited liver disorder, died Sept. 17, 1999, just four days after getting an experimental infusion of trillions of genetically engineered viruses. Researchers had hoped the treatment might lead to a cure for his disease, ornithine transcarbamylase deficiency, and other ailments.

A subsequent investigation by the Food and Drug Administration found numerous breaches of federal research rules. The study was also widely criticized because of apparent financial conflicts of interest through which one of the principal investigators, Penn researcher James Wilson, stood to profit from the experiment through a biotechnology company he had founded, Genovo of Sharon Hill, Pa.

Paul Gelsinger, Jesse's father, said yesterday he had undergone a painful change of heart in the year after his son's death, at first fully trusting the researchers and holding them blameless and then gradually, as disclosures of apparent wrongdoing emerged, concluding that he had been duped by scientists who cared more about profits than safety.

"Dealing with the money end of this [settlement] was probably one of the most difficult aspects of this because this experiment was all about money, and it was never about money for Jesse," Gelsinger said.

Gelsinger was the first person known to have died directly as a result of gene therapy, an experimental approach that seeks to cure diseases by giving people new genes. The field, which has yet to enjoy a proven long-term success after more than a decade of efforts in thousands of patients, has been criticized over the years for moving too quickly from animal studies to humans--a trend that has coincided with increasing investment from biotechnology and pharmaceutical companies.

Gelsinger's death drew widespread attention to shortcomings in the federal system for protecting research volunteers. It prompted several congressional hearings and various ongoing efforts by the FDA, the National Institutes of Health and the Department of Health and Human Services to improve human subject protections.

In January, as a result of its investigation, the FDA suspended all human experiments at Penn's Institute for Human Gene Therapy, once considered one of the world's premier gene therapy centers. Among its findings:

* Four patients who had enrolled ahead of Gelsinger suffered reactions to the treatment so serious as to require, according to rules Penn had agreed to in advance, that the study be halted and the FDA notified immediately. But the agency was not notified at the time nor was the study halted.

* Informed consent forms that were supposed to tell volunteers about the potential risks of participation were changed without the knowledge of the FDA to eliminate all mention of monkeys that had died after getting a similar treatment.

* Gelsinger was given the experimental treatment even though his blood ammonia levels--a measure of liver failure--were higher than the highest allowable level deemed safe for the experiment. Moreover, that highest allowable level had previously been raised by the researchers without the knowledge or permission of the FDA.

In May, the university announced that, rather than comply with all of the FDA's demands for changes, human experiments would no longer be conducted at the institute and Wilson would limit his studies to animals. But even that level of work came into question in July, when FDA investigators announced they had uncovered serious lapses in the institute's animal research as well.

Parties to yesterday's settlement include Penn, Genovo, Wilson and his co-workers Mark L. Batshaw and Steven E. Raper, and those two colleagues' institutions, Children's National Medical Center of Washington and Children's Hospital of Philadelphia, respectively.

The Gelsinger family released two other defendants from the suit: Penn bioethicist Arthur Caplan, who had provided controversial advice that led to the experiment's focus on relatively healthy adults such as Gelsinger instead of critically ill newborns as originally planned, and former Penn medical dean William Kelley, who held key patents on the gene therapy technique.

Paul Gelsinger said he planned to use some of the settlement money to fund research on Jesse's disease and to foster public awareness of the need to protect human subjects. He said he hoped to do that through groups such as the National Organization for Rare Disorders in New Fairfield, Conn., and Citizens for Responsible Care & Research, an advocacy group in New York City.

In a brief statement, Penn said the settlement will "enable Penn to concentrate on moving forward with its aggressive efforts to improve its oversight and monitoring of human subject research, an effort to which the university has already devoted substantial resources of time, energy, and money."

The university also said it hoped the agreement would "enable the Gelsingers to bring a small measure of closure to their loss."

Gelsinger said closure was unlikely. "There's never really any satisfaction to be had," he said. But he said he was gratified that in the aftermath of Jesse's death, some wheels of change had begun to turn.

"I am just amazed at the impact that my boy has had," he said.