WASHINGTON _ In a controversial but long-anticipated move,National Institutes of Health (NIH) director Harold Varmus proposedthe elimination of the Recombinant DNA Advisory Committee(RAC) on Monday.
A July 8, 1996, notice in the Federal Register outlined Varmus'proposal to scrap RAC and replace it with a much smaller committeethat will neither conduct case-by-case reviews of gene therapyprotocols nor cast votes to approve or reject them.
"All approval responsibilities for recombinant DNA experimentsinvolving human gene transfer will be relinquished to the FDA whichretains statutory authority for such approval," stated the proposedamendments to the NIH Guidelines.
Varmus has proposed a new organizational structure to insurecontinued NIH oversight of scientific and societal issues raised bygene therapy. His proposal would establish a new charteredcommittee, the Office of Recombinant DNA Activities (ORDA)Advisory Committee (OAC), that would consist of between six to 10standing members (vs. RAC's 25 members) representing thescientific, legal, ethical and public advocacy communities. OACwould meet four times a year to advise ORDA regarding "relevantgene therapy issues," to identify and prioritize topics for periodicpublic gene therapy conferences and to periodically review andanalyze data submitted to the NIH gene therapy database.
In addition to OAC, Varmus proposes to convene a Gene TherapyPolicy Conference three to four times per year for in-depth, expertdiscussions of "a single issue relevant to scientific merit and/or safetyas it relates to human gene therapy clinical trials." Finally, Varmus'sproposal includes the ORDA's continued maintenance of the publiclyavailable, comprehensive NIH database of human gene transferclinical trials.
Varmus Skeptical Of Gene Therapy
Lana Skirboll, director of the NIH's Office of Science Policy, saidVarmus's proposal stems in part from his discomfort with the RAC'sauthority to confer the NIH's stamp of "approval" on gene therapyprotocols. Skirboll, speaking at an FDA-sponsored gene therapyconference on Thursday, said Varmus sees the NIH's mission as thenation's arbiter of "meritorious science" in conflict with the RAC'smission to merely review the safety of proposed experiments.
Indeed, Varmus was so concerned about what he perceives as thequestionable scientific merit of most gene therapy protocols that heconvened a panel of experts last year to scrutinize the quality ofresearch in the NIH's own portfolio. The NIH spends roughly $200million per year supporting gene therapy experiments. The panelconcluded that the NIH should focus its efforts on gene discovery,diagnosis and disease pathogenesis rather than on expanding genetherapy in humans.
The December 1995 report noted that, despite the hype, clinicalefficacy has not been definitively proven in any gene therapyprotocol to date.
Experts said Varmus is convinced that continued RAC "approval" ofgene therapy protocols amounts to a squandering of the NIH'sscientific imprimatur. Even more disturbing to Varmus: after RACvotes on a given protocol, he must sign off on the experiments sinceRAC's role is only advisory.
"Varmus is a superb basic scientist and he doesn't like having to signoff on clinical protocols that he considers aren't cutting edgescience," explained French Anderson, director of the gene therapylaboratory at the University of Southern California in Los Angeles."He has very high standards and I applaud his standards, but hedoesn't understand that clinical research is not as elegant as basicscience."
RAC Supporters Decry Its Demise
Anderson, one of the pioneers of gene therapy, said he opposesVarmus's proposal to replace RAC with a "quasi-RAC" that has noreal authority. "It's undisputed that no other human being, living ordead, has had more static from RAC than I have," Anderson toldBioWorld Today. "But the RAC has a 20-year proven history ofbeing a superb and highly respected public oversight committee. Thisnew committee is just window dressing."
Anderson supported the "consolidated review" reforms that tookeffect last year and stipulated that RAC only review protocols fornovel gene therapy experiments. After those reforms were enacted,about 75 percent of all protocols went directly to the FDA becausethey were similar to previously approved experiments. At FDA, genetherapy protocols go through the standard investigational new drugapplication (IND) process.
But Anderson insists that the RAC should retain full review andvoting authority on truly novel gene therapy techniques, such as hisown current research on the viability of fetal gene therapy. AbbeyMyers, president of the National Organization for Rare Disorders anda long-time RAC member, agrees. In a strongly worded July 10,1996, letter to Varmus, she argued that the consequences of newapproaches such as germ line, in utero or cosmetic gene therapycould have "profound implications for the human race."
"The FDA is required by statute to confine its decisions solely tosafety and efficacy measures, and it is not empowered to deny anIND based on ethical factors," wrote Myers. "Until there are laws orFDA regulations to prevent scientists from performing unethicalexperiments, only NIH's RAC has the ability to bring these issues tothe public's attention and veto any protocol that is ethicallyquestionable."
Of course, not everyone views the Varmus proposal negatively. RACmember Robertson Parkman, head of the division of researchimmunology at the Childrens Hospital of Los Angeles, told BioWorldToday that OAC keeps intact the most valuable aspect of RAC _public discussion. "The FDA could still rely on [OAC] as a publicforum and if this group of six or 10 individuals says a certainexperiment is not scientifically or ethically justifiable, I can't believethat won't have an impact," said Parkman. "The new structure doesnot per se prohibit OAC from being effective."
The NIH's Skirboll said Varmus welcomes public comments on hisproposal. The public comment period extends until Aug. 7, 1996. n
-- Lisa Piercey Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.