In memoriam

时间:2019-03-07 03:17:04166网络整理admin

By Nell Boyce in Washington DC RARELY can one death in a clinical trial have caused so much soul-searching. Three months after 18-year-old Jesse Gelsinger died during an experimental gene therapy for his liver disorder, the tragedy has prompted US officials to draft tough new rules for reporting side effects in gene therapy trials. It has also now emerged that Gelsinger should never have been entered into the trial in the first place, because his liver wasn’t functioning well enough. Gene therapists and biotech companies complain that the proposed rules would create an unmanageable mountain of paperwork. But given the latest revelation, officials are under pressure to tighten regulation of the field. Occasional deaths from unexpected side effects are part and parcel of clinical research. But until 17 September, no such problems had been reported for any gene therapy trial. Gelsinger’s death changed all that, following a trial designed to correct a genetic defect that makes livers unable to break down ammonia (New Scientist, 9 October, p 11). James Wilson of the University of Pennsylvania in Philadelphia, who led the trial, last week appeared before the National Institutes of Health’s Recombinant DNA Advisory Committee (RAC) near Washington DC. In front of a packed auditorium, he said that the precise cause of Gelsinger’s death remains a mystery. The modified virus used to transport the therapeutic gene into Gelsinger’s liver was injected directly into the circulation of the liver. Yet Wilson told the RAC that significant amounts of the virus showed up in other organs. Gelsinger also did not appear to have hepatitis, which had been considered the most likely side effect. But he did have bone marrow abnormalities and persistently high levels of IL-6, a protein that promotes inflammatory reactions. Rises in IL-6 levels in some other patients during the trial were only transient. Prior to Wilson’s appearance before the RAC, the Food and Drug Administration (FDA) announced that his team had disobeyed several of the rules laid down for patients in the trial. Blood ammonia levels, for example, were supposed to be less than 0.7 micrograms per millilitre, but Gelsinger’s levels ranged from 0.91 to 1.14 in the four days before he entered the trial. The researchers also failed to notify the FDA that two patients had experienced side effects including fever. The RAC was also kept in the dark. Indeed, its members are alarmed that they are routinely not being told of complications emerging in gene therapy trials (New Scientist, 13 November, p 15). Last week, the RAC discussed new rules that would require researchers to rapidly and publicly disclose all severe complications. Critics argue that this would overwhelm the RAC’s limited resources. Robert Spiegel, chief medical officer with the Schering-Plough Research Institute in Kenilworth, New Jersey, warned the RAC to expect “a deluge of uninterpretable reports”. H. Stewart Parker, of the Biotechnology Industry Organization in Washington DC,