Seventeen-year-old Jesse Gelsinger (pictured at the left) had a genetic disease called ornithine transcarbamylase (OTC) deficiency. He had trouble metabolizing ammonia, a waste product made by the body. This can have severe health effects, as buildup of ammonia can result in death at a young age. However, one can enforce dietary restrictions, such as a strict non-protein diet, for the rest of one's life to improve conditions.
Meanwhile, Dr. James Wilson was conducting a clinical trial at the University of Pennsylvania. He aimed to test a new gene therapy approach towards OTCD, where he would devise a way of delivering normal OTC genes into liver cells through an adenovirus factor. He hoped to restore the activity of this gene in patients with OTCD, which would prevent ammonia buildup in result. This study was in its early stages, so it aimed to test the safety and dosage of the therapy rather than its effectiveness. Wilson looked to recruit volunteers, with Jesse Gelsinger being one of them.
Gelsinger flew to Philadelphia in September 1999 to receive the gene therapy. Compared to the previous patients, Gelsinger received the highest dose of the injection. Other patients, albeit having lower doses, had moderate side effects but had recovered within days. Gelsinger, on the other hand, had a severe reaction within hours of receiving the injection. Developing a high fever, jaundice, coagulation, and organ failure, Gelsinger was admitted to the ICU and put on life support. He died four days later.
What Happened to Jesse?
A key piece of information found was that Gelsinger had been exposed to adenoviruses before, and had developed antibodies against them! Because of this, the antibodies Gelsinger developed would enhance his immune reaction to the virus if it ever entered his body again, explaining his severe reaction to the adenovirus injection from the trial. The cause of his death was a massive immune response from the injection he received. Even though blood testing was available, Wilson and his team had not checked Gelsinger’s blood for antibodies before enrolling him in the trial.
The many, many problems associated with this trial
Wilson and his team had failed to inform the FDA of the adverse events experienced by participants after the injection.
Researchers went ahead with the injection even though Gelsinger’s liver function was not within the study’s limits (his ammonia levels were too high).
Dr. Wilson had financial interests in the trial, meaning that he had a financial stake in the study. He did not disclose this.
The University of Pennsylvania did not properly monitor the trial, as they did not ensure the trial was approved as independent and free of conflicts of interest.
The FDA did not inspect the trial’s site or data before Gelsinger’s death.
The Outcome of Estate of Gelsinger v. Trustees of University of Pennsylvania
Paul Gelsinger (Jesse Gelsinger’s father) sued the researchers for breach of these sanctions and wrongful death. The University of Pennsylvania and the Children’s National Medical Center, which were involved in the trial, settled and paid fines.
Gelsinger’s death was a tragic lesson. It pointed out ethical and regulatory issues with the conduct of human research. High standards must be set when it comes to studies, such as transparent communication, proper review, and respect for human dignity. Jesse Gelsinger was a courageous and generous research volunteer, willing to take risks for the sake of advancing medical knowledge and helping others.