Recombinant DNA Advisory Committee - 10/7-8/91 
I. CALL TO ORDER 
Dr. McGarrity (Chair) called the meeting to order at 9:00 a.m., on October 7, 1991. He 
noted that due notice of the meeting was published in the the Federal Register dated 
September 3, 1991, and that a quorum was present. This committee serves as advisor to 
the Director of the National Institutes of Health (NIH). The Director has three options. 
She may accept the committee's recommendation, she may reject the recommendation, 
or she may send the committee's actions and votes back to the committee for further 
deliberation. Dr. McGarrity introduced the ad hoc consultant to the committee, Dr. 
LeRoy Walters, who is the Chair of the Human Gene Therapy Subcommittee (HGTS). 
II. MINUTES OF THE MAY 30-31, 1991, MEETING 
Dr. McGarrity called on Ms. Buc to comment on the minutes of the May 30-31, 1991, 
meeting of the RAC. Ms. Buc said she had read through the minutes, and they were 
accurate. She moved they be approved. Dr. McGarrity noted the second reviewer, Dr. 
Hirano, was not present. He asked Dr. Wivel to appoint another member to review the 
minutes and defer approval of the minutes until tomorrow morning, October 8. 
III. PROPOSED AMENDMENT TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING HUMAN GENE TRANSFER PROTOCOL ENTITLED GENE 
TRANSFER FOR THE TREATMENT OF CANCER 
Dr. Gellert noted this proposal was considered by the HGTS at its meeting in July. The 
protocol is designed to kill ovarian cancer cells using gene therapy. The patient will be 
infused with tumor cells which have been transduced with the herpes simplex virus 
(HSV) thymidine kinase gene (TK). These cells are now exquisitely sensitive to killing 
by the drug, ganciclovir. However, there is a possibility that neighboring cells will also 
be killed. 
Dr. Gellert said the investigators had performed animal experiments in which tumor cells 
were infused into mice. Shortly thereafter, the gene-modified tumor cells were 
introduced, and the mice were then treated with ganciclovir. Following the 
administration of ganciclovir, a small proportion of non gene-modified tumor cells were 
also killed. He said the mouse model did not meet the criterion of being the most 
appropriate animal model as is required in the Points to Consider for the Design and 
Submission of Protocols for the Transfer of Recombinant DNA into the Genome of Human 
Subjects because no attempt was made to treat mice that had a solid tumor mass. The 
experiments submitted by the investigator only dealt with cell suspensions. Entirely 
different effects might have been seen if mice with established ovarian tumors were 
treated. The proposed experiments should be done before this protocol is approved by 
the RAC. 
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Recombinant DNA Research, Volume 15 
