Recombinant DNA Advisory Committee - 12/1-2/94 
I. CALL TO ORDER 
Dr. Walters (Chair) called the meeting to order and stated that the notice of the meeting and proposed actions 
were published in the Federal Register on November 8, 1994 (59 FR 55796) as required by the National 
Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). 
He noted that a quorum was present and outlined the order in which speakers would be recognized: the 
primary reviewers, other RAC members, and ad hoc experts, followed by responses from the principal 
investigators (Pis). The Chair will recognize other NIH and Federal employees, and the public who have 
submitted written statements prior to the meeting, followed by the public at large. 
Dr. Walters welcomed Joseph C. Glorioso, Ph.D., as a new scientific member of the RAC. Dr. Glorioso is 
Professor and Chair of the Department of Molecular Genetics and Biochemistry at the University of 
Pittsburgh, Pittsburgh, Pennsylvania. 
Dr. Walters stated that 4 major items of business would be discussed during this meeting: (1) the review of 6 
new human gene therapy protocols, (2) review and discussion of the December 1994 Data Management 
Report, (3) a presentation on in utero somatic cell and gene therapies by Dr. Amy Patterson of the Food and 
Drug Administration (FDA), and (4) discussion of the proposed amendments to Appendix B of the NIH 
Guidelines , "Classification of Etiologic Agents and Oncogenic Viruses on the Basis of Hazard." 
Dr. Walters made the following announcements: (1) A public FDA meeting on somatic cell and gene therapy 
production issues will be held at the end of the first day of the RAC meeting. (2) Dr. David CurieFs human 
gene transfer protocol entitled: Phase I Trial of a Polynucleotide Vaccine to Human Carcinoembryonic Antigen 
in Patients with Metastatic Colorectal Cancer (Protocol #9406-073) was recommended for approval with 
contingencies by the RAC at its June 1994 meeting; however, Dr. V arm us deferred approval of Dr. Curiel’s 
protocol based on insufficient preclinical data. (3) The ad hoc RAC review committee proposed by Dr. 
Varmus at the September 1994 RAC meeting is currently being formed and a tentative agenda approved. The 
first meeting of this ad hoc committee will be held in late January or early February. Several meetings of this 
ad hoc committee are expected, at least one of which will coincide with a RAC meeting. 
Dr. Walters noted that on September 28, 1994, a congressional hearing was held on the subject, "Human Gene 
Therapy-Status, Prospects for the Future, and Government Policy Implications," before the Committee on 
Science, Space, and Technology, chaired by Representative George Brown. Drs. Wivel, Philip Noguchi (FDA), 
and Walters testified before the committee. At this hearing, Ms. Ashanti DeSilva, an adenosine deaminase 
deficiency (ADA) patient entered on Dr. Michael Blaese’s Protocol #9007-002, Mr. DeSilva (her father), and 
Dr. Kenneth Culver were present at the hearing and testified. Dr. Walters informed the RAC that an article 
entitled: "Gene Techniques and the Shape of Future Generations," was printed on the front page of the 
November 22, 1994, New York Times in response to a study by Ralph Brinster of the University of 
Pennsylvania published in Proceedings of the National Academy of Sciences, U.SA. in November 1994. Dr. 
Brinster’s study involved the introduction of genetic modifications into the murine spermatogonia that develop 
into mature sperm cells. He stated that the National Academy of Sciences Institute of Medicine is considering 
funding for a report designed to analyze the implications of human germ line genetic intervention. This report 
would be considered a companion report to a study that was recently published by a National Academy of 
Sciences committee (Chaired by Dr. Motulsky) entitled: "Assessing Genetic Risks." 
Dr. Walters noted that a total of 93 human gene transfer protocols (68 gene therapy and 25 gene marking) 
have been reviewed and recommended for approval by the RAC to date (See Attachment II-Human Gene 
Therapy Protocols). Forty-three are targeted at cancer, 5 directed towards human immunodeficiency virus 
(HIV) infection, 18 for inherited genetic disorders, and 2 other therapeutic interventions. The NIH Director 
has approved 81 of the 93 RAC-approved studies following review and submission of data submitted in 
response to the RAC’s stipulation requirements. Dr. Motulsky inquired about the reason for the discrepancy 
in the number of protocols approved by the RAC and that approved by the NIH Director. Dr. Wivel 
explained that most protocols are approved by the RAC, contingent on the review of data submitted in 
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Recombinant DNA Research, Volume 20 
