Recombinant DNA Advisory Committee - 12/2-3/93 
A motion was made by Ms. Grossman and seconded by Dr. Secundy to defer the 
protocol based on the lack of in vivo data. Dr. Walters invited discussion on this motion. 
Dr. Post said that although the ongoing murine studies will address several safety issues, 
the data are incomplete. Dr. Post urged the investigators to further characterize the 
ongoing experiments in order to demonstrate the safety of FACC gene expression in 
mice. 
Ms. Meyers commented that Fanconi anemia is a very rare disease, and little is known as 
compared to other more common genetic disorders. She expressed concern that there 
may never be an adequate amount of data to address all the RAC's concerns. She 
suggested that a more appropriate motion would be to approve the protocol contingent 
upon receipt of data derived from ongoing animal studies. 
Dr. Parkman expressed concern that approval of this protocol, which involves gene 
transfer for the treatment of a genetic disease that has not been previously reviewed by 
the RAC, would set a precedent for other novel protocols. Although the investigators 
have submitted efficacy data based on an in vitro model, little is known about the safety 
of long-term expression of the FACC gene in hematopoietic stem cells. Dr. Parkman 
noted that similar murine experiments were not required for RAC approval of other 
protocols, such as the adenosine deaminase (ADA)-deficiency protocol which also 
involved stem cell transduction. 
Dr. Smith stated he is in favor of approving the protocol contingent on the submission of 
the additional data noted by Dr. Dunbar and review and approval of data obtained from 
the ongoing murine experiments. Dr. Post stated his view that the protocol should be 
deferred until the investigators return to the full RAC with the additional safety data. 
Dr. Miller stated that the protocol should be approved contingent on the submission of 
data from ongoing experiments; and recommended a 4 month follow-up for toxicity 
experiments would be adequate. Dr. Liu responded that 8 mice have been followed for 
a period of 3 months. 
Dr. Walters asked Dr. Miller if he would like to offer a substitute motion for the original 
deferral motion made by Ms. Grossman. 
Committee Motion #2 
A substitute motion was made by Dr. Miller and seconded by Dr. DeLeon to 
conditionally approve this protocol contingent upon the receipt of the murine safety data 
to be reviewed by a subcommittee that includes the primary reviewers. Dr. Miller said 
that this motion will not delay initiation of the protocol. The RAC voted to accept Dr. 
Miller's substitute motion by a vote of 9 in favor, 6 opposed, and no abstentions. 
Dr. Leventhal expressed her reservation about allowing a subcommittee to review the 
requested data. The RAC meets every 3 months; therefore, there is no reason that the 
investigators cannot present data derived from the ongoing studies at the next RAC 
meeting. Dr. Smith agreed that full RAC review would afford a more detailed 
Recombinant DNA Research, Volume 18 
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