Human Gene Therapy Subcommittee - July 29-30, 1991 
Dr. D. Miller said the definition of gene therapy should be slightly broadened to 
include all therapy, e.g., cancer therapy, AIDS therapy, infectious disease therapy, and 
any other form of genetic therapy. There are unique problems associated with these 
therapies. An example would be the potential to modify the germ line and the lasting 
changes in the somatic cells of an individual. Germ line modifications will raise a 
whole spectrum of different issues that need to be addressed. 
Mr. Capron added that the HGTS had originally wanted the investigators to address 
the question of germ line modifications in order to prepare the scientific conununity for 
the day when germ line experiments would become feasible. Then it was decided that 
the HGTS could handle this task more efficiently. The HGTS has not attended to that 
task. The HGTS has stated that it would not entertain germ line gene therapy 
protocols, but will discuss with the investigators the question of germ line modifications 
that might arise from their work. 
Dr. Parkman said there are major biological differences between marking TIL cells, 
which have a relatively short half-life, and marking neuroblastoma cells in the normal 
bone marrow, where there is a high probability of marking some cells that may have a 
very long life span. Therefore, there are some marking experiments that require 
review by the HGTS because they have far reaching implications. The subcommittee 
has two functions: (1) to serve as quality control for a review process that currently is 
not working as efficiently as it should (if the review process were efficient, every 
protocol submitted would be sent directly to the RAC, making the HGTS unnecessary); 
and (2) to address the issue of germ line modification. Some protocols have addressed 
the possibility that the germ line may be affected. The HGTS must begin to discuss 
how it is going to approach this possibility. 
Dr. Leventhal said that all clinical research protocols have to go through an extensive, 
time-consuming review process. The gene therapy review system is not different or 
unduly rigid. As long as the protocols still need work and contain levels of uncertainty, 
the HGTS is still needed. 
Dr. Mclvor said the purpose of the RAC is to evaluate the effects of recombinant 
DNA. The purpose of the HGTS is to evaluate the effects of recombinant DNA in 
human beings. A risk-benefit ratio needs to be determined, on a case-by-case basis, 
and the HGTS has the expertise to evaluate these protocols. Eventually, there will be 
situations where certain protocols become routine and will not have to come to the 
HGTS. Gene marking protocols will possibly be the first types of protocols that will 
qualify for exemption. 
Ms. Meyers said that investigators with approved protocols should report their results 
to the HGTS. To avoid unnecessary experimentation in humans, the HGTS should not 
approve other closely related protocols that will not add to the knowledge base. 
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Recombinant DNA Research, Volume 14 
