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.[1]
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,[2] but the university and Children's National Medical Center each agreed to pay more than $500,000 to the government.[3] Both Wilson and the University are reported to have had financial stakes in the research.[4][5] After his death, all gene therapy trials in the United States halted for a time.[6] The Gelsinger case was a severe setback for scientists working in the field and a reminder of the risks involved.[7]
Notes
[edit]- ↑ Stolberg, Sheryl Gay (November 28, 1999). "The Biotech Death of Jesse Gelsinger". The New York Times Magazine. Retrieved July 5, 2018.
- ↑ "Institute for Human Gene Therapy Responds to FDA". The University of Pennsylvania Almanac. University of Pennsylvania. February 14, 2000. Retrieved 2010-11-16.
- ↑ Branca, MA (May 2005). "Gene therapy: cursed or inching towards credibility?". Nature Biotechnology. 23 (5): 519–21. doi:10.1038/nbt0505-519. PMID 15877060. S2CID 6628811.
- ↑ Greenberg, Daniel S. (October 2007). Science for Sale: The Perils, Rewards, and Delusions of Campus Capitalism. Chicago: University of Chicago Press. p. 104–106. ISBN 9780226306254.
- ↑ Reitz, Ken (April 18, 2008). "Don't Compromise Ethics in Human Experiments, Bioethics Expert Says". University of Virginia School of Law. University of Virginia. Archived from the original on 2009-10-14. Retrieved 2010-11-16.
- ↑ "Challenges in Gene Therapy". Learn.Genetics. University of Utah. December 1, 2012. Retrieved 2020-11-02.
- ↑ Wilson, James M. (2009-05-08). "A History Lesson for Stem Cells". Science. 324 (5928). Sciencemag.org: 727–728. Bibcode:2009Sci...324..727W. doi:10.1126/science.1174935. PMID 19423804. S2CID 206520573. Retrieved 2012-02-29.
Further reading
[edit]- Gelsinger, Paul. Helms, Robert (ed.). "Jesse's Intent". Guinea Pig Zero. No. 8. New Orleans: Garrett County Press. Jesse's father Paul tells of Jesse's death.
- Philipkoski, Kristen (October 1, 1999). "Another Chance For Gene Therapy?". Wired.
- Baker, Dennis E. (February 8, 2002). "DHHS-FDA Notice of Opportunity for Hearing; James M. Wilson, M.D., Ph.D." Food and Drug Administration.
- "Trial and Error". Horizon. BBC. February 27, 2003.
- Milstein, Alan (January 29, 2008). "On gene therapy and informed consent". blog.bioethics.net. American Journal of Bioethics. Archived from the original on 2012-02-16.
- Gelsinger, Paul (January 31, 2008). "A comment from Paul Gelsinger on gene therapy and informed consent". Bioethics Today. American Journal of Bioethics.
