Human Gene Therapy Subcommittee - 11/21-22/91 
gene transfer occurred in vitro not in vivo. There is an extremely remote likelihood that 
genes could enter the germ line of patients whose cells were transduced in vitro. Dr. 
Parkman added that a more likely candidate for such concerns is Dr. Gary Nable's in 
vivo liposome transfection; however, since the transfection is highly targeted, germ line 
effects should not be a concern. 
Ms. Meyers said that the majority of protocols that have been reviewed to date have 
been approved for the treatment of cancer, usually in people beyond the child-bearing 
age. Dr. Parkman added that the inclusion criteria for Dr. Nabel's liposome protocol 
required that women be post-menopausal, thereby eliminating any potential risk 
associated with germ line transfer. If the issues regarding germ line gene transfer are 
resolved, in vivo gene therapy protocols will not be restricted to such small patient 
populations. Dr. Anderson reminded the HGTS that two of the cancer patients treated 
on Dr. Rosenberg's tumor infiltrating lymphocyte protocol were premenopausal and 
capable of becoming pregnant. Dr. Walters said that it is the desire of the HGTS and 
the RAC that these terminally ill patients get well and survive. Germ line transfer is not 
an issue if the therapy is not curative. 
Mr. Capron said that the HGTS must become educated, so that it will be prepared to 
entertain germ line proposals when the time comes. Inviting experts on background 
mutational rates is an excellent area in which to initiate ethical considerations. If it can 
be determined that the possibility of germ line effect is less than or equal to the 
background mutational rate, than there is statistically no increased risk to the patient. 
Dr. Epstein asked the subcommittee to consider a patient that has received intense 
therapy with highly mutagenic drugs for a malignancy. A high degree of mutagenesis is 
allowable, using current therapeutic approaches to cancer treatment. In addition, there 
are no exclusion criterion for these therapies pertaining to the age of a woman, i.e., her 
reproductive capacity. 
Dr. Walters summarized by stating that it is the consensus of the subcommittee to invite 
an expert on background mutational rates to the next meeting, in order to initiate 
discussions regarding human germ line gene therapy. Dr. Zallen asked if the speaker 
would be announced in the Federal Register. If so, it might be useful for the HGTS to 
consider how it would interface with the public regarding the issue since the subject is 
usually viewed as emotional and perceptions are polarized? Mr. Capron noted that the 
Federal Register announcements notify the public that they may comment on the 
proposed agenda items. Dr. Leventhal suggested that future discussions should include 
individuals that have been diagnosed as having hereditary diseases. It would be useful to 
obtain responses from the patient population to which such therapies will be targeted. 
Perhaps, there could be a targeted mailing of the Federal Register announcement. Ms. 
Meyers suggested contacting these patients, as well as the Ethical, Legal, and Social 
Implications Working Group of the National Center for Human Genome Research 
Recombinant DNA Research, Volume 15 
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