Recombinant DNA Advisory Committee- 9/12-13/94 
reviewed by RAC members if necessary. Dr. Straus emphasized that if adverse events can 
be avoided in the future by a minor change of the procedure or premedication, no 
revision of the Informed Consent document is needed. 
Dr. Walters welcomed Ms. Daryl A (Sandy) Chamblee, Acting Deputy Director for 
Science Policy and Technology Transfer at NIH and Dr. Harold Varmus, the NIH 
Director, to the meeting. 
VI. DISCUSSION REGARDING CRITERIA FOR RAC REVIEW AND APPROVAL OF 
HUMAN GENE TRANSFER PROTOCOLS/DR VARMUS 
Dr. Walters welcomed Dr. Varmus, the NIH Director, to the RAC noting that Dr. Varmus 
has a longstanding interest in gene therapy and was one of the original members of 
Human Gene Therapy Subcommittee of the RAC. Dr. Varmus made a proposal to form 
an ad hoc committee to review RAC activities, particularly the criteria by which RAC 
approves human gene therapy protocols. The reason for making this suggestion was 
threefold. First, during a meeting of the National Task Force on AIDS Drug 
Development chaired by Dr. Philip R. Lee, Assistant Secretary for Health, Department of 
Health and Human Services, which was held on July 18, 1994, at Arlington, Virginia, many 
concerns were raised regarding the slowness of the review process that affects investigators 
initiating gene therapy protocols to study aquired immune deficiency syndrome (AIDS). 
The current multiple procedures to review these protocols by both the RAC and the FDA 
were seen as unnecessarily slow. A one-stop shopping mechanism for consolidated review 
of human gene transfer protocols was proposed by Dr. Wivel, Director of ORDA at the 
NIH and Dr. Philip Noguchi, Director of the Division of Cellular and Gene Therapies of 
FDA The proposal was endorsed by the AIDS Task Force. Second, many investigators 
have complained about undue delays in review of gene therapy protocols; for example, the 
review criteria are unclear as to the permissibility to use certain vectors. The third reason 
derived from Dr. Varmus’ review of a disputed protocol which was approved by a split 
vote at the June 1994 RAC meeting (Protocol #9406-073 by David Curiel). Dr. Varmus 
was concerned about lack of consensus in review criteria for approval of this protocol, i.e., 
the minimum criterion of no harm to the subjects or the additional requirement that 
useful scientific information to be obtained from the experiment in order to justify the 
study. He was disturbed by the lack of adequate information to make this decision. 
Relevant information of a human study of the same gene by other researchers was not 
made available to the investigators in this case, and there were significant questions 
regarding the preclinical experiments in mice. 
Dr. Varmus proposed the formation of an ad hoc group that could include current or past 
RAC members, and those who previously served on the Human Gene Therapy 
Subcommittee. At least two major areas would be reviewed. The first area concerns the 
domain of RAC activities and the composition of its membership (scientific and public). 
The second task is to define the criteria by which gene therapy protocols are evaluated, 
e.g., safety, scientific credibility, scientific utility or therapeutic promise. Another issue is 
coordination of an application to the RAC with an application to NIH for extramural 
funding that is reviewed by an initial scientific merit review group. Should RAC require 
[ 20 ] 
Recombinant DNA Research, Volume 20 
