The Biotech Death of Jesse Gelsinger

The jagged peak of Mount Wrightson towers 9,450 feet above Tucson, overlooking a deep gorge where the prickly pear cactus that dots the desert floor gives way to a lush forest of ponderosa pine. It is said that this is as close to heaven as you can get in southern Arizona. Jesse Gelsinger loved this place. So it was here, on a clear Sunday afternoon in early November, that Paul Gelsinger laid his 18-year-old son to rest, seven weeks after a gene-therapy experiment cost him his life.

The ceremony was simple and impromptu. Two dozen mourners -- Jesse's father; his mother, Pattie; his stepmother, Mickie; and two sisters, a brother, three doctors and a smattering of friends -- trudged five miles along a steep trail to reach the rocky outcropping at the top. There, Paul Gelsinger shared stories of his son, who loved motorcycles and professional wrestling and was, to his father's irritation, distinctly lacking in ambition. Jesse was the kind of kid who kept $10.10 in his bank account -- You need $10 to keep it open,'' Gelsinger explained -- but those assembled on the mountaintop agreed that he had a sharp wit and a sensitive heart.

At Gelsinger's request, the hikers had carried Jesse's medicine bottles filled with his ashes, and now they were gathered at the edge of the peak. Steve Raper, the surgeon who gave Jesse what turned out to be a lethal injection of new genes, pulled a small blue book of poetry from his pocket. ''Here rests his head upon the lap of Earth,'' Raper read, reciting a passage from an elegy by Thomas Gray, ''a youth to Fortune and Fame unknown./Fair Science frowned not on his humble birth.'' Then the surgeon, the grieving father and the rest scattered Jesse's ashes into the canyon, where they rose on a gust of wind and fell again in a powerful cloud of fine gray dust. ''I will look to you here often, Jess,'' Paul Gelsinger said sadly.

Jesse Gelsinger was not sick before died. He suffered from ornithine transcarbamylase (OTC) deficiency, a rare metabolic disorder, but it was controlled with a low-protein diet and drugs, 32 pills a day. He knew when he signed up for the experiment at the University of Pennsylvania that he would not benefit; the study was to test the safety of a treatment for babies with a fatal form of his disorder. Still, it offered hope, the promise that someday Jesse might be rid of the cumbersome medications and diet so restrictive that half a hot dog was a treat. ''What's the worst that can happen to me?'' he told a friend shortly before he left for the Penn hospital, in Philadelphia. ''I die, and it's for the babies.''

As far as government officials know, Jesse's death on Sept. 17 was the first directly related to gene therapy. The official cause, as listed on the death certificate filed by Raper, was adult respiratory distress syndrome: his lungs shut down. The truth is more complicated. Jesse's therapy consisted of an infusion of corrective genes, encased in a dose of weakened cold virus, adenovirus, which functioned as what scientists call a vector. Vectors are like taxicabs that drive healthy DNA into cells; viruses, whose sole purpose is to get inside cells and infect them, make useful vectors. The Penn researchers had tested their vector, at the same dose Jesse got, in mice, monkeys, baboons and one human patient, and had seen expected, flulike side effects, along with some mild liver inflammation, which disappeared on its own. When Jesse got the vector, he suffered a chain reaction that the testing had not predicted -- jaundice, a blood-clotting disorder, kidney failure, lung failure and brain death: in Raper's words, ''multiple-organ-system failure.'' The doctors are still investigating; their current hypothesis is that the adenovirus triggered an overwhelming inflammatory reaction -- in essence, an immune-system revolt. What they do not understand yet is why.

Every realm of medicine has its defining moment, often with a human face attached. Polio had Jonas Salk. In vitro fertilization had Louise Brown, the world's first test-tube baby. Transplant surgery had Barney Clark, the Seattle dentist with the artificial heart. AIDS had Magic Johnson. Now gene therapy has Jesse Gelsinger.