Human Gene Therapy Subcommittee - 11/30/90 
Dr. Walters asked Ms. Meyers to make a motion on the protocol. Ms. Meyers 
moved to table discussion on the protocol until such time as additional information 
can be received. Dr. Mclvor seconded the motion. 
Dr. Walters called for discussion on the motion to table discussion. Dr. Mclvor said 
that there were two main issues: (1) a concern that the proposal will not provide 
efficient enough transfer to generate an informative result; and (2) questions about 
the endpoint and evaluation of whether or not to proceed with bone marrow purging 
procedures. Any data presented should mimic as closely as possible what is 
proposed with the donor marrow so that results could be analyzed using techniques 
proposed in the protocol. There is still the question of which cells, host cells or 
donor cells, caused a relapse. If it is a mixture of the two, then it becomes a 
question of how much of the relapse is contributed by each cell type. 
Dr. Kelley said that feasibility studies, rather than a model system, would be 
appropriate for this experiment. The investigators could perform mixing experiments 
to look at hematologic malignancy in animals. Dr. Mclvor agreed that such 
experiments would bolster his confidence that informative results could be obtained 
in humans. More detailed information is needed about the absolute number of cells 
to be transduced and the post-transplant molecular analysis to be conducted. 
Mr. Capron said the detailed discussion of specific scientific points had become 
complex and confusing. He asked whether the criterion for approving the protocol 
was based upon the "best possible science" or if it was something that may provide 
results that credible scientists could believe had some value. 
Dr. Parkman said that the basic question was whether other scientists believed that 
such an experiment, conducted with the demonstrated level of competence, was 
likely to provide meaningful scientific results. 
Mr. Capron asked whether making the requested additional refinements would make 
the experiment any more meaningful. Dr. Parkman said that with the efficiency of 
insertion that had been presented (i.e., one-tenth of the cells being labeled), no 
meaningful results will be obtained from the experiment. Mr. Capron said that 
perhaps the easiest way to resolve the dilemma before the HGTS would be to define 
the level of results necessary before any approval would be granted rather than to 
ask to see the results of certain studies. 
Dr. Parkman said that the preclinical data were too minimal ( 1 % labeling in 1 
patient) to answer any questions. For this experiment to be likely to succeed. 
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