The National Institutes of Health (NIH) and the Food and Drug Administration (FDA) have played key roles in the emergence of safe and effective human gene therapies. Now, we are proposing new efforts to encourage further advances in this rapidly evolving field.
The potential to alter human genes directly was first recognized nearly 50 years ago, around the same time as initial groundbreaking advances were being made in recombinant DNA technology. After intense discussions regarding the ethical, legal, and social implications of this technology, conversations were initiated at the NIH that led to the establishment of the Recombinant DNA Advisory Committee (RAC) in 1974. The RAC’s mission was to advise the NIH director on research that used emerging technologies involving manipulation of nucleic acids — a mission that was eventually expanded to encompass the review and discussion of protocols for gene therapy in humans. In 1990, the FDA oversaw the first U.S. human gene-therapy trial, which involved pediatric patients with adenosine deaminase deficiency and was conducted at the NIH Clinical Center in Bethesda, Maryland.
Although no major safety concerns were initially reported, over the course of the 1990s it became evident that many questions regarding the safety and efficacy of gene therapy remained unanswered. These unknowns were brought into sharp focus in 1999 when Jesse Gelsinger died of a massive immune response during a safety trial of gene therapy for ornithine transcarbamylase deficiency.1 This tragic death led to closer scrutiny of the field, including a greater focus on open dialogue and increased regulatory oversight.