Washington

The director of the gene therapy institute where a patient died during treatment last September has admitted errors in the administration of its trials, but denies that they led to the patient's death.

The US Food and Drug Administration (FDA) recently shut down five clinical trials at the University of Pennsylvania's Institute of Human Gene Therapy (IHGT) after an investigation found 18 possible violations in the way the institute had run and monitored an earlier trial (see Nature 403, 354; 2000).

Wilson: admits that procedures were lax. Credit: UNIV. PENNSYLVANIA

In a letter to the FDA, James Wilson, director of the institute, acknowledges errors in the trial — the first in which a death has been attributed directly to the experimental treatment (see Nature 401, 517; 1999).

Wilson does not not accept all 18 of the FDA's preliminary findings, but he admits perhaps the most serious charge: that the institute failed to contact the FDA when two patients who received an adenoviral vector with a therapeutic gene for a liver-enzyme deficiency experienced adverse effects.

Under the protocol, the IHGT should have notified the FDA immediately. Wilson says that the institute had reported similar effects in two previous patients, and that the FDA had allowed the trial to resume in both cases. He points out that the FDA received written records of those adverse effects before permitting the IHGT to use higher doses on other patients, but wrote that “IHGT should not have proceeded as it did”.

But Wilson denies several other serious charges. For example, he says that Jesse Gelsinger, the Arizona man who died in the experiment, was eligible for treatment despite having a high level of ammonia before the treatment. The protocol specified only that the enzyme level should be normal at the time of enrolment, not treatment, and it is “common” for such enzyme levels to fluctuate, Wilson says in his letter.

Also, he says that the researchers did not inform Gelsinger of the deaths of two primates because they were models for a different disease and received a different therapeutic gene.

Finally, the university report contradicts Paul Gelsinger, Jesse's father, who, at a recent Senate hearing, said that investigators did not follow procedures for informed consent properly (see Nature 403 , 583; 2000). “Each and every patient in the … trial gave clear and unambiguous consent to participate.”

Wilson declined to comment further. But Kenneth Wildes, a university spokesman, says: “We made some mistakes, but those mistakes did not lead to the death of Jesse Gelsinger.” Wildes adds: “We're not minimizing the conduct of researchers at Penn. They should be held to the highest standards.”

Wilson says in his letter that, if allowed to resume its suspended trials, IHGT would be willing to be more closely monitored, and to follow more stringent reporting requirements.