Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

. Gelsinger suffered from

ornithine transcarbamylase deficiency Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, re ...

, an

X-linked Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...

genetic disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

of the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

, the symptoms of which include an inability to metabolize

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

– a byproduct of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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 Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized e ...

. 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 The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...

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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) investigation concluded that the scientists involved in the trial, including the co-investigator

James Wilson James Wilson may refer to: Politicians and government officials Canada *James Wilson (Upper Canada politician) (1770–1847), English-born farmer and political figure in Upper Canada * James Crocket Wilson (1841–1899), Canadian MP from Quebe ...

(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

levels that should have led to his exclusion from the trial. *Failure by the university to report that two patients had experienced serious

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s 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. After his death, all gene therapy trials in the United States halted for a time. The Gelsinger case was a severe setback for scientists working in the field and a reminder of the risks involved.

Notes

External links

* Another Chance For Gene Therapy?: https://www.wired.com/1999/10/another-chance-for-gene-therapy/ * Paul Gelsinger, Jesse's father, tells of Jesse's death: http://www.guineapigzero.com/jesses-intent.html * On gene therapy and informed consent (2008 debate): http://blog.bioethics.net/2008/01/on-gene-therapy-and-informed-consent/#comments * BBC Horizon Trial and error – the rise and fall of genome therapy: http://www.bbc.co.uk/science/horizon/2003/trialerror.shtml * FDA Notice Of Opportunity for Hearing to James Wilson: https://www.fda.gov/regulatoryinformation/foi/electronicreadingroom/ucm144564.htm {{DEFAULTSORT:Gelsinger, Jesse 1981 births 1999 deaths Clinical trial disasters History of biotechnology Human subject research in the United States