NIH's RECOMBINANT DNA ADVISORY COMMITTEE SHOULD CONTINUE TO REVIEW GENE THERAPY AS GERMLINE AND SOCIETAL ISSUES ARISE, RAC AD HOC GROUP CONCURS

Issues related to germline therapy warrant the continued existence of the Recombinant DNA Advisory Committee, ad hoc RAC review committee members agreed at their second meeting March 8 on the National Institutes of Health campus.

Robertson Parkman, MD, Children's Hospital, Los Angeles, maintained that the field is moving to the point "where germline intervention becomes either a programmatic goal or a result of therapy, where no longer will the consequences of what is done be limited to an individual." The consequences of such therapy will be "societal," Parkman commented, and therefore there is a "need to have a mechanism where society is saying: `Is this worthwhile?' rather than just a few individuals or parents."

Noting that the initial review of somatic cell gene therapy was driven by political forces, Parkman observed that "in reality, particularly in retrospect, the scientific issues of release and other things were minimal." In contrast, he said, "now...the scientific consequences of what we do are going to become more societal. And, as they become more societal, then you need a forum to address that."

While acknowledging the importance of RAC's future oversight for germline gene therapy, Charles Epstein, MD, University of California-San Francisco, repeatedly asked the committee to explain why somatic cell gene therapy should still be reviewed by RAC. "What are the residual issues that require this level of oversight?" he asked.

RAC Chairman LeRoy Walters, MD, Georgetown University, commented that while the "frontier issue" is germline intervention, "what if an investigator proposes to repair early gene defects in a human embryo -- what will the RAC say about that [and] what will society think about that idea?"

Commenting that there could be germline aspects to somatic gene therapy, Parkman used an example of the discovery of genes involved in determination of height. He noted that an investigator could propose to genetically correct height deficiencies. "Does that now become a medical decision...to cure short stature? The issue of how you decide to use that technology in a somatic sense [seems] to be a societal question," he stated.

Walters maintained that "the other issue I see coming down the pike is genetic enhancement, and there it could even take a health-related form. What if someone came forward with a proposal, for example, to enhance the function of a normal immune system so that it would be more efficient at warding off disease later in life than most of our immune systems are as our bodies wind down?"

Addressing the societal impact of gene therapy, Walters added: "Once in a while there is a biomedical innovation that comes along that should have a public accompaniment during the first few years of being in effect." He cited in vitro fertilization research as an area where "it would have been useful to have some kind of public advisory committee going with the technology, perhaps reducing the hype that surrounded the first years of the technology. Part of the role of the RAC in the next year or two will be to provide a reality check to claims that are going beyond the evidence."

Walters also noted that in the area of somatic cell gene therapy, RAC plays an international role in serving as a model review system. "Investigators and members of committees analogous to RAC in other countries regularly come to RAC meetings and many of them have said: `Please continue to meet in public because we take what we learn at your meetings back to our own countries,'" he stated.

Epstein argued that if the committee is going to recommend to NIH Director Varmus that the RAC should proceed "with these functions, I think you have to present him with arguments as to why." He recommended that the final draft of recommendations to Varmus should contain "a series of reasons why the committee feels...the continued existence of the RAC, in whatever form, is justified."