It looked safe. It was presented as safe. And it was going to the benefit of everyone." That's how Paul Gelsinger, a father of four from Tucson, Ariz., explained in an emotional appearance before a Senate subcommittee last week why he supported the decision made by his 18-year-old son Jesse to undergo gene therapy for a rare metabolic disorder Jesse had suffered from since birth.
Now, four months after Jesse's untimely death, Gelsinger and much of the scientific community are struggling to understand what went wrong. For while Jesse didn't count on personally benefiting from the treatment he underwent at the University of Pennsylvania--he did it mostly to help other youngsters--neither did he expect to die from it. "We gave our consent," Paul Gelsinger testified, "but in no way was it informed."
The Gelsinger case has called much needed attention to the dark side of gene therapy, which--no less than other experimental treatments--has the power to harm as well as help. Ironically, the recriminations over Jesse's death are occurring just as gene therapy appears to be fitfully inching toward the sort of success that has eluded it for so long. In December, only a month before Jesse's death prompted the U.S. Food and Drug Administration to shut down all gene-therapy research at the University of Pennsylvania, reports were circulating in scientific circles that a team from the Necker Hospital for Sick Children in Paris had achieved heartening results in a gene-therapy trial designed to cure severe combined immunodeficiency (SCID), an inherited disorder that, left untreated, is fatal.
Pending publication of their results in a scientific journal, the Necker researchers are reluctant to divulge details. However, it appears that two 18-month-old boys with SCID remain healthy nine months after undergoing gene therapy. Their newfound ability to ward off infections that plagued them as infants appears to be a direct consequence of their receiving functioning copies of a gene that is crucial to the body's ability to fight disease.
This development comes amid other signs suggesting that gene therapy may be on the verge of delivering on at least some of its unfulfilled promise. The replacement of faulty genes, for example, appears to have reduced the need for transfusion in patients with hemophilia. Drugs designed using the principles of gene therapy also seem to be shaping up as promising weapons against certain forms of cancer. But in all these cases the number of patients who have experienced improvements is too small to establish whether the same procedures will prove broadly beneficial or whether adverse effects will overshadow possible benefits.
Jesse's death, for example, may have occurred because his immune system reacted violently not to the gene the scientists infused but to the virus that carried it into the cells of his liver. While deactivated, the virus--a form of the adenovirus that causes the common cold--still retained some properties capable of triggering an immune response. Indeed, what has alarmed officials at the National Institutes of Health is how common such reactions to adenovirus appear to be--and how seldom researchers have reported them to the NIH. Out of 93 gene-therapy trials using adenovirus, it was recently revealed, there were 691 instances of adverse effects. Of those, the NIH was promptly notified of only 39--about 5% of the total.