By Lisa Seachrist

Washington Editor

BETHESDA, Md. - In the wake of the death of a teen-ager enrolled in a gene therapy protocol, the National Institutes of Health's Recombinant Advisory Committee (RAC) began a three-day examination of the incident with an exhaustive review of the science.

The panel listened to gene therapy researchers describe the promises and pitfalls of using an adenovirus vector to deliver therapeutic genes. In addition, the researchers described the common adverse events associated with adenovirus vectors.

"The main purpose of this meeting is to learn and gather information so we can gain insight into what happened and in turn do better clinical trials," said Claudia Mickelson, biosafety officer in the department of environmental medical service at the Massachusetts Institute of Technology in Boston.

The death of 18-year-old Jesse Gelsinger has focused the committee on the safety of adenoviral vectors. Gelsinger, a Tucson, Ariz., native, enrolled in a gene therapy study at the University of Pennsylvania aimed at treating partial ornithine transcarbamylase deficiency, an inherited metabolic disorder that inhibits the breakdown of ammonia byproducts.

Following an infusion of replication-incompetent adenovirus carrying the gene to correct the disorder, Gelsinger became ill, and died in September. The fact that the genetically modified virus was infused directly into Gelsinger's liver when adenovirus is known to cause serious hepatitis in patients with compromised immune systems raised questions about whether such a procedure is safe.

"For the first time in gene therapy, a patient's life has been lost not as a direct result of the disease being treated but likely as a direct result of his participation in a gene therapy clinical trial," said Amy Patterson, director of biotechnology activities at NIH. "The challenge now is to apply our knowledge and reason in order to understand the risks involved in this type of gene therapy as well as understand this young man's death."

The RAC will take up the specifics of the Penn study today, with presentations from both the FDA and Penn researchers. On Friday, the committee will turn its attention to proposed rules concerning the reporting of adverse events.

"I think there are two points that need to be made about the [Penn study]," said gene therapy pioneer W. French Anderson, now at the University of Southern California. "The first is that medical research is risky. The second is that Jesse Gelsinger is a hero - he gave his life for something he believed in."