Human Gene Therapy Subcommittee - 11/21-22/91 
Another consideration is gene insertion into ova and sperm. What is state-of-the-art 
technology? 
In addition to the scientific questions, the working group noted that the HGTS would 
need extensive education regarding the ethical implications of germ line therapy. Since 
the effects of germ line intervention will be on the individual as well as on future 
generations, the criteria for risk-benefit assessment will have to be reconsidered. Do 
models exist for the assessment of long-term implications of genetic intervention? 
Dr. Parkman stated that the HGTS should establish a format for these discussions. 
Should an additional day be added to the next meeting? Should afternoon sessions be 
devoted to these topics? Should the subcommittee invite a series of speakers to address 
these pertinent issues over a period of time? 
Dr. Parkman suggested that these manipulations would be more accurately described as 
germ line intervention or germ line effects rather that germ line therapy. Although there 
will be adventitious effects, these effects may not be therapeutic in the strictest sense. 
There are clearly many different categories that can be considered. 
Mr. Capron said that a useful exercise may be to develop several hypothetical cases for 
discussion in order to guide the decision-making process. With this format, the HGTS 
could begin to discuss ethical issues, risks and benefits, and the ability of individuals to 
provide consent. It will be critical for the subcommittee to articulate to the scientific 
community and the public what kinds of standards will be applied in the review of 
human germ line experiments. Dr. Zallen added that it will be important that as these 
discussions advance, the general public is provided the opportunity for input on the 
pertinent issues. Dr. Parkman asked for suggestions regarding other areas of scientific 
interest that should be included for discussion. 
Dr. Epstein said that the areas that were defined by the working group were an 
appropriate starting point. He agreed that a critical issue to consider will be germ line 
intervention as a primary effect versus a secondary effect, such as in pre-implantation 
intervention. Dr. Epstein suggested that the subcommittee should discuss the issue of 
homologous recombination. It is critical that the HGTS be brought up to date on the 
current status of site-specific integration and the possibility of homologous 
recombinational events. 
Dr. Leventhal stated that the RAC should initially review information regarding 
adventitious germ line effects that have been observed in mature animals. Dr. Parkman 
suggested another consideration would be the reported incidence of secondary germ line 
effects resulting from somatic cell intervention. Dr. Epstein added that vast amounts of 
literature exist regarding viral mutagenesis, radiation mutagenesis, and chemical 
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