Human Gene Therapy Subcommittee - 4/5/91 
Dr. R. Murray moved that the protocol be approved. Ms. Meyers seconded the motion. 
She added that the children who can't get a liver transplant have absolutely no chance. 
There is nothing else that can be done for them. 
Dr. Mclvor said that if the combination of the frequency of donor cells in the liver and 
the transduction frequency amounted to greater than 1 in 10^, that would probably be 
indicative of a positive outcome. He said that transduction frequencies and the 
differences in the sizes of the liver are issues requiring further discussion. 
Dr. Epstein said he would be willing to approve the protocol with the caveat that the 
investigators supply the RAC with more in vitro data. They need to determine the 
efficiency of transduction in primary human hepatocytes with this vector and demonstrate 
their ability to detect it. 
Dr. Ledley said he would provide more human data. He stressed that the protocol 
proposes only the addition of the neo gene. The dangerous part is the hepatocyte 
transplant itself. 
Dr. Parkman said it was inappropriate for the investigators to appear without having 
adequate data on the transfection efficiency of human hepatocytes. Dr. Ledley 
responded that they have shown data using four vector systems in human cells. While 
this is not quantitative data, there has been no difficulty in infecting these cells. 
Dr. Epstein said that due to the state-of-the-art nature of these experiments, the 
committee needs to see that the experiment really can be performed. The burden is on 
the investigators, not the committee, to show that they can transduce the cells with a 
sufficient titer, that they can use a detection system to allow sufficient quantitation for 
the generic marking experiments. He amended the motion to be provisional approval 
with the stipulation that the investigators supply additional data to the RAC. 
Specifically, data need to be supplied on the transduction of human hepatocytes with the 
proposed vector, evidence of the ability to quantitatively detect the number of transduced 
cells in those samples, and, by inference, in the transplanted liver. Also, the informed 
consent issues mentioned should be resolved. 
Dr. Walters noted that there was a motion on the floor to approve the protocol 
provisionally with stipulations regarding additional data to be provided in advance of the 
RAC meeting, and revisions in the consent form. 
Dr. R. Murray added that, as a procedural matter, members of the subcommittee ought 
to be supplied with the additional data. 
Dr. Walters called for a vote on the motion for provisional approval with the stipulation 
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Recombinant DNA Research, Volume 14 
