Gene-therapy trials must proceed with caution

Jesse Gelsinger was 18 and healthy when he died in 1999 during a gene-therapy experiment. He had a condition called ornithine transcarbamylase deficiency (OTC), but it was under control through a combination of diet and medication. Like others with the disorder, Gelsinger lacked a functional enzyme involved in breaking down ammonia, a waste product of protein metabolism that becomes toxic when its levels become too high. The gene therapy that he received used a viral vector to introduce a normal gene for the enzyme.

Gene therapy remains an obvious route to treat OTC. Simply adding the missing gene has been shown to repair metabolism in mice. But the memory of what happened to Gelsinger has slowed progress in gene therapy for any condition.

That memory was firmly on the agenda at a meeting of the US National Institutes of Health’s Recombinant DNA Advisory Committee (RAC) last week. The RAC evaluates proposals to use modified DNA in human trials, and presenting to it were Cary Harding, a medical geneticist at Oregon Health and Science University in Portland, and Sam Wadsworth, chief...