Recombinant DMA Advisory Oimmittee - 5/30-31/91 
done in such-and-such a model," and that the reviewers will not accept the model which was 
deemed most appropriate by the investigator. 
Mr. Barton suggested, as a friendly amendment to Dr. Mclvor's motion, that the word "most" 
be dropped from the wording. Dr. Mclvor said he would accept this as a friendly amendment 
and that he felt it still expressed the intent of the proposed wording. Dr. R. Murray 
suggested, in the form of a friendly amendment, that the last sentence be modified to read, 
"...the models chosen are appropriate for the protocol." He felt that this wording would force 
the investigator to prove that the model proposed was appropriate for that protocol and that, 
at the same time, it would not restrict the investigator to a single model. 
A lengthy discussion ensued centering on the specific connotation of the term "efficacy" as to 
whether this implied "therapeutic efficacy." It was determined that the term "efficacy" in this 
sentence should be taken as the efficacy of insertion of the marker, rather than therapeutic 
efficacy for the patient. 
Dr. McGarrity then restated the proposed wording, as amended, as follows: 
"Preclinical Studies Including Risk Assessment Studies: Provide results that 
demonstrate the safety, efficacy and feasibility of the proposed procedures using animal 
and/or cell culture model systems and explain why the models chosen are appropriate 
for the protocol." 
There being no further discussion. Dr. McGarrity called for a vote on Dr. Mclvor's motion. 
The motion passed a vote of 17 in favor, 1 opposed and no abstentions. 
Dr. McGarrity then called on Dr. Ledley to present the next agenda item. 
PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A 
HUMAN GENE TRANSFER PROTOCOL ENTITLED HEPATOCELLULAR TRANSPLAN- 
TATION IN ACUTE HEPATIC FAILURE AND TARGETING GENETIC MARKERS TO 
HEPATIC CELLS: 
Dr. Ledley said the research being proposed, in the broader sense, was to treat a genetic 
disease of the liver by removing cells from a patient by partial hepatectomy, growing 
hepatocytes in culture, transducing them with a vector to repair the genetic defect in the cells, 
perhaps selecting for the cells in which the defect has been repaired and then transplanting 
those cells back into the patient. 
Dr. Ledley said the proposal is to find children who have fulminant hepatic failure or life- 
threatening liver disease for whom transplant is not available in time to save their lives or to 
prevent severe mental retardation, and to try hepatocellular transplantation either to palliate 
their hepatic failure and provide a bridge to recovery or to perhaps even reconstitute the liver 
with donor cells. He noted that the LNL6 vector will be introduced as the genetic marker to 
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