Jesse Gelsinger
Encyclopedia
Jesse Gelsinger was the first person publicly identified as having died in a clinical trial for gene therapy
.
He was 18 years old. 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 not inherited the disease; in his case it was the result of a genetic mutation and as such was not as severe - some of his cells were normal which enabled him 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 severe 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, September 17, at 2:30 pm, apparently having suffered a massive immune response triggered by the use of the viral vector used 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 lead researcher Dr. James M. Wilson (U Penn), broke several rules of conduct:
The University of Pennsylvania later issued a rebuttal but paid the parents an undisclosed amount in settlement. 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.
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
.
He was 18 years old. Gelsinger suffered from ornithine transcarbamylase deficiency
Ornithine transcarbamylase deficiency
Ornithine transcarbamylase deficiency , the most common of the urea cycle disorders, is a rare metabolic disorder, occurring in one out of every 80,000 births...
, an X-linked
Sex linkage
Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...
genetic disease
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, the symptoms of which include an inability to metabolize ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
- a byproduct of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
breakdown. The disease is usually fatal at birth, but Gelsinger had not inherited the disease; in his case it was the result of a genetic mutation and as such was not as severe - some of his cells were normal which enabled him to survive on a restricted diet and special medications.
Gelsinger joined a clinical trial run by the University of Pennsylvania
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...
that aimed at developing a treatment for infants born with severe disease. On September 13, 1999, Gelsinger was injected with an adenoviral vector
Adenoviridae
Adenoviruses are medium-sized , nonenveloped icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome...
carrying a corrected gene to test the safety of the procedure. He died four days later, September 17, at 2:30 pm, apparently having suffered a massive immune response triggered by the use of the viral vector used to transport the gene into his cells, leading to multiple organ failure and brain death.
A Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) investigation concluded that the scientists involved in the trial, including the lead researcher Dr. James M. Wilson (U Penn), broke several rules of conduct:
- Inclusion of Gelsinger as a substitute for another volunteer who dropped out, despite 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 paid the parents an undisclosed amount in settlement. 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.
External links
- Another Chance For Gene Therapy?: http://www.wired.com/news/technology/0,1282,31613,00.html
- Paul Gelsinger, Jesse's father, tells of Jesse's death: http://www.guineapigzero.com/jesse.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