Jesse Gelsinger

{{Short description|American man who died during a clinical trial (1981–1999)}}

File:JesseGelsingerROIsmall.tif

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.{{Cite magazine |last=Stolberg |first=Sheryl Gay |date=November 28, 1999 |title=The Biotech Death of Jesse Gelsinger |url=https://www.nytimes.com/1999/11/28/magazine/the-biotech-death-of-jesse-gelsinger.html |magazine=The New York Times Magazine |language=en-US |access-date=July 5, 2018}}

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,{{cite web|url=http://www.upenn.edu/almanac/between/FDAresponse.html |title=Institute for Human Gene Therapy Responds to FDA – Almanac Between Issues |publisher=Upenn.edu |date=2000-02-14 |access-date=2010-11-16}} but the university and Children's National Medical Center each agreed to pay more than $500,000 to the government.{{cite journal |last1=Branca |first1=MA |title=Gene therapy: cursed or inching towards credibility? |journal=Nature Biotechnology |date=May 2005 |volume=23 |issue=5 |pages=519–21 |doi=10.1038/nbt0505-519 |pmid=15877060|s2cid=6628811 }} Both Wilson and the University are reported to have had financial stakes in the research.Greenberg, Daniel S. Science for Sale. The Perils, Rewards, and Delusions of Campus Capitalism. Chicago: U. Chicago Press, 2007, 324pp., pages 104–106.{{cite web |url=http://www.law.virginia.edu/html/news/2008_spr/milstein.htm |title=Don't Compromise Ethics in Human Experiments, Bioethics Expert Says |publisher=Law.virginia.edu |date=2008-04-18 |access-date=2010-11-16 |archive-url=https://web.archive.org/web/20091014162046/http://www.law.virginia.edu/html/news/2008_spr/milstein.htm |archive-date=2009-10-14 |url-status=dead }} After his death, all gene therapy trials in the United States halted for a time.{{cite web|url=https://learn.genetics.utah.edu/content/genetherapy/challenges/ |title=Challenges in Gene Therapy |publisher=University of Utah |access-date=2020-11-02}} The Gelsinger case was a severe setback for scientists working in the field and a reminder of the risks involved.{{cite journal|url=https://www.science.org/doi/full/10.1126/science.1174935 |title=A History Lesson for Stem Cells |publisher=Sciencemag.org |date=2009-05-08 |doi=10.1126/science.1174935 |access-date=2012-02-29|last1=Wilson |first1=James M. |journal=Science |volume=324 |issue=5928 |pages=727–728 |pmid=19423804 |bibcode=2009Sci...324..727W |s2cid=206520573 }}