Two US institutions that ran a gene therapy trial in which a teenager died in 1999 agreed to pay more than $1 million in a civil settlement last week. The government had alleged that the researchers, based at the University of Pennsylvania and the Children's National Medical Center, had failed to protect patients who volunteered for the experimental treatment. At the age of 18, Jesse Gelsinger took part in a gene therapy trial at the University of Pennsylvania for an inherited liver disorder called ornithine transcarboxylase deficiency (OTCD), but he died from multiple organ failure four days after beginning the treatment.
The allegations included charges of failure to halt the experiment when serious side effects first arose, failure to flag up the potential dangers of the study to participants, and falsely suggesting that earlier patients had benefited from the therapy. Under the terms of the settlement, the University of Pennsylvania team, lead by James Wilson, do not admit any wrongdoing. However, the University will pay a fine of $517, 496 to the government, while the Children's National Medical Center will pay $514,622. Wilson is barred from carrying out further experiments on humans until 2010, a ban which has been in place since 2000. His colleagues Mark Batshaw and Steven Raper will also have restrictions placed on their work.
Gelsinger's death was thought to have been caused by an immune response to the adenovirus used to deliver the therapeutic gene to his body. At the time, the Food and Drug Administration (FDA) immediately halted all gene therapy trials at the university, while an investigation was carried out. It revealed that the trial in which Gelsinger took part had not been properly supervised or monitored. The resulting public and scientific outcry triggered a reappraisal of the way in which 'adverse events' in gene therapy trials are reported in the US, and the National Institutes of Health called for gene therapy researchers to report all their past failures as well as successes. By February 2000, this request had brought to light 692 'serious adverse events' in gene therapy trials, only 39 of which had been reported previously.
It is not known how many of these failed experiments, which involved either serious deterioration or, in a few cases, death, were caused by the gene therapy itself. Patients enrolling on gene therapy trials are often terminally ill, and have not responded to any other form of treatment. However, some researchers feared that poor results were sometimes being kept under wraps because of the potential financial damage they might cause the funding companies. In March 2000, the FDA announced its new gene therapy clinical trial monitoring plan, designed to increase the level of scrutiny of gene therapy experiments. And new regulations unveiled in January 2001 include the requirement that researchers must publish details of any potential risks on the FDA's website.
Paul Gelsinger, Jesse's father, said that the rule changes for research involving humans that followed his son's death offered some consolation. But he told the Washington Post that he thought the government's decision not to pursue criminal charges or impose stricter penalties was disappointing. 'I wanted some accountability, and that's not going to happen', he said. He is also upset that none of the documents relating to the case are being released to the public, a move which he said would have ensured that 'real changes could be made in the way human research is conducted in this country'. David Hoffman, a prosecutor for the US Attorney's office, said that the fine would serve as a warning to researchers to comply with government regulations. 'The money is significant money', he said, adding ' but most important to me, quite frankly, is ensuring that research participant safety is number one'.