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Gene Therapists Ask to Be Released From the RAC


The main U.S. professional society representing gene therapists argued this week that clinical trials in their maturing field should no longer be required to undergo review by a special federal advisory committee. Although others disagree, many say it's time to take a fresh look at the role of the venerable Recombinant DNA Advisory Committee (RAC).

RAC was created in 1974 to oversee all gene splicing experiments, then later shifted its focus mainly to human gene therapy. In the mid-1990s, then-National Institutes of Health (NIH) Director Harold Varmus questioned whether RAC was needed, and its mission was changed from approving protocols to offering advice. But any NIH-funded researcher who proposes a gene therapy trial is still required to send a thick application to the RAC's 21 researchers, ethicists, public representatives, and others for review. The committee selects about 20% of the 50 to 100 protocols it receives each year for discussion at its public meetings. The RAC also oversees institutional biosafety committees and updates NIH's guidelines for working with recombinant DNA.

But now after 20 years of experience, more than 1000 U.S. trials, and a growing number of gene therapy successes in the clinic, some researchers say it's time to end RAC review of gene therapy protocols. One big reason, they say, is that the proposals are already reviewed by the U.S. Food and Drug Administration and institutional ethics and biosafety boards, which now have plenty of experience with the field. "Gene therapy is overregulated to the point where it's crippling progress," says Xandra Breakefield of Massachusetts General Hospital in Charlestown, president-elect of the American Society of Gene and Cell Therapy (ASGCT).

ASGCT says that the two main safety concerns—altering germline DNA or creating a novel pathogenic vector—haven't materialized for the vectors that most trials now use. In a recent letter to the RAC and a statement that Breakefield read at a RAC meeting yesterday, the society says that instead of reviewing individual protocols, RAC should instead focus on "new areas of research."

This proposal got a mixed reaction from RAC members and others who submitted comments online. While many gene therapists agree—including the ASGCT's European counterpart—some have suggested that RAC reviews remain valuable for assessing the safety and ethics of novel therapies and can actually speed review by other bodies. Commenters also lauded RAC's value as a forum for public discussions that doesn't exist in other areas of clinical research. "It would be a mistake to underestimate the importance," said Claudia Mickelson, biosafety officer at the Massachusetts Institute of Technology in Cambridge.

The chair of RAC, Yuman Fong of Memorial Sloan-Kettering Cancer Center in New York City, urged caution: "To go from reviewing most things to reviewing nothing is a big step." He also noted that because no gene therapy treatments have yet been approved by the FDA, public trust is "very important." At the same time, he agrees that the RAC should have "a dialogue" about whether it should "pare back" its role.

Amy Patterson, NIH associate director for science policy, said that NIH has no plans to do away with the RAC: "We still believe it's important to have that transparent forum." But she says NIH is "happy to think about ways to streamline the RAC process," and is likely to host a broader discussion.