Jesse Gelsinger

Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for gene therapy. Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, the symptoms of which include an inability to metabolize ammonia – a byproduct of protein breakdown. The disease is usually fatal at birth, but Gelsinger had a milder form of the disease, in which the ornithine transcarbamylase gene is mutated in only part of the patient's cells, a condition known as somatic mosaicism. As his deficiency was partial, Gelsinger managed to survive on a restricted diet and special medications.

Gelsinger joined a clinical trial run by the University of Pennsylvania that aimed at developing a treatment for infants born with the severe form of the disease. On September 13, 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure. He died four days later at the age of 18, on September 17, apparently having suffered a massive immune response triggered by the use of the viral vector to transport the gene into his cells, leading to multiple organ failure and brain death.

A Food and Drug Administration (FDA) investigation concluded that the scientists involved in the trial, including the co-investigator James Wilson (Director of the Institute for Human Gene Therapy), broke several rules of conduct:

• Inclusion of Gelsinger as a substitute for another volunteer who dropped out, despite Gelsinger's having high ammonia levels that should have led to his exclusion from the trial.
• Failure by the university to report that two patients had experienced serious side effects from the gene therapy.
• Failure to disclose, in the informed-consent documentation, the deaths of monkeys given a similar treatment.

The University of Pennsylvania later issued a rebuttal, but the university and Children's National Medical Center each agreed to pay more than $500,000 to the government. Both Wilson and the University are reported to have had financial stakes in the research.The Gelsinger case was a severe setback for scientists working in the field and a tragic reminder of the risks involved.