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 Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

. 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, r ...

, an

X-linked Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome ( autosome). Genes situated on the X-chromosome are thus termed X-linked, and ...

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 chromosome abnormality. Although polygenic disorders are ...

of the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, the symptoms of which include an inability to metabolize

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

– a byproduct of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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 which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism is ...

. 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 (Penn or UPenn) is a Private university, private Ivy League research university in Philadelphia, Pennsylvania, United States. One of nine colonial colleges, it was chartered in 1755 through the efforts of f ...

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 respo ...

(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 Queb ...

(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 of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

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

{{DEFAULTSORT:Gelsinger, Jesse 1981 births 1999 deaths Clinical trial disasters History of biotechnology Human subject research in the United States Famous patients