Research must be seen to be accountable, even if that means hanging on to redundant reviews.
All scientists must contend with regulation and bureaucracy, despite their frequent complaints that such processes stifle and slow their work. US researchers in gene therapy perhaps feel the pressure of red tape more than most. Is now the right time to ease that burden?
The US Institute of Medicine wants to find out. This week, it kicked off a review of an oversight committee that many in gene therapy argue is redundant. They might be right, but when it comes to medical ethics, it is not enough for scientists to do the right thing — they must also be seen to do so.
The Recombinant DNA Advisory Committee (RAC) was set up within the National Institutes of Health (NIH) in 1974 as a direct response to public concerns about the ethics and safety of research involving lab-assembled DNA sequences. After devising guidelines for this research, the committee gained the power to approve or reject proposed experiments in humans. As the field has grown, so has the number of experiments that must be given the green light by the RAC, including those that fall under the umbrella of gene therapy.
The problem, as gene therapists see it, is that many other parallel regulatory hurdles have been erected in the meantime. The US Food and Drug Administration (FDA) must approve clinical trials of gene therapy in humans. And institutions have their own biosafety committees and institutional review boards.
Naturally, the RAC disagrees from time to time with the findings of the other scrutineers. When it does, the delays can drag on.
Enough, said the American Society of Gene and Cell Therapy last March. It told the NIH that in recent decades, more than 1,000 gene-therapy clinical trials have been conducted. The worst fears of the public — that gene therapy would lead to alterations of the human genome, or to the release of genetically modified super microbes — have not come to pass. The society told the NIH that the RAC should no longer review individual gene-therapy protocols, and should instead “identify new areas of research that require a public forum for discussion and review”.
The gene-therapy field is not free from the risk of adverse events, but the RAC has never claimed to be able to prevent them. Instead, it has had a crucial role in helping the field to learn from setbacks.
“ It is a tricky time to argue that any public-review process in medical research should be scaled back. ”
After the death of US teenager Jesse Gelsinger in a gene-therapy trial in 1999, for instance, the RAC adopted rules that compel investigators to report all serious adverse events that occur during gene-therapy trials. When children who had been cured of severe combined immunodeficiency by gene therapy developed leukaemia in 2001, the RAC investigated how gene therapy might have contributed to the problem and recommended action to stop it recurring.
Researchers feel strongly that RAC review of individual protocols no longer serves an important purpose, and they resent being at the mercy of the committee’s ability to call them out on questions that they often perceive as tangential to their research. Yet it is a tricky time to argue that any public-review process in medical research should be scaled back. Witness the storm of public outrage in the past decade over pharmaceutical companies’ failure to report side effects of drugs for conditions from diabetes to depression (see Nature 431, 122–124; 2004). Long after these drugs were approved, it was revealed that their sponsors had held back crucial information about their safety.
Gene-therapy clinical trials have proceeded with an unusually high degree of openness, and that has been crucial in helping the field to gain public confidence and acceptance. Such a role should be emulated in other areas of research, rather than eliminated. Apart from the RAC review, none of the oversight required for gene therapy is public. FDA review includes public meetings, but the formal review process allows investigators to keep many of their data secret.
The question is how to preserve the openness that the RAC has enabled without bogging down progress. Perhaps now is the right time to scale back the RAC’s purview, but it will be imperative to do so while maintaining the committee’s moral authority. That position may feel burdensome, but without it, the field could not have got to where it is today.