Human Gene Therapy Subcommittee - 4/5/91 
the next agenda item. 
III. AMENDMENT TO THE POINTS TO CONSIDER IN THE DESIGN AND 
SUBMISSION OF PROTOCOLS FOR THE TRANSFER OF RECOMBINANT DNA 
INTO THE GENOME OF HUMAN SUBJECTS: 
Dr. Mclvor said that this proposal had arisen from a retrospective look at the four 
protocols which the Human Gene Therapy Subcommittee (HGTS) and the Recombinant 
DNA Advisory Committee (RAC) had approved. In all cases, there was a minimum of 
preclinical data; and in particular, minimal data from animal studies. This was often 
justified as in the case of the vectors that were used in the first three protocols for 
mediated gene transfer into human lymphocytes; these vectors do not function in mouse 
lymphocytes, making murine experiments impossible. He raised the concern that a major 
policy was being set as a result of the case-by-case discussion of these protocols. This 
policy needs to be considered because of the expectations of the subcommittee and the 
RAC that preclinical studies would be performed prior to initiating human trials. 
There is an expectation in evaluating new therapies for human disease that experiments 
in animals or in vitro are of the utmost importance to demonstrate that proposed 
experiments are feasible and reasonable. However, the subcommittee needs to clarify its 
expectations with regard to human gene therapy experiment so that current and future 
proposals will meet the needs of the subcommittee and the RAC. 
Dr. Mclvor felt the best way to deal with this issue was through a modification of the 
Points to Consider document. He noted that the current wording requests only that the 
investigator provide results addressing the efficacy and safety of the gene transfer system 
in a relevant preclinical model. The proposed modification would go further to state 
that such results were expected. He moved that the following sentence be added to the 
Points to Consider: 
"Results demonstrating the safety, efficacy and feasibility of the proposed 
procedures using the most relevant animal model and/or cell culture model 
systems should be included." 
Dr. Parkman seconded Dr. Mclvor's motion. Dr. Parkman supported this idea and noted 
that one of the major factors leading to the approval of the ADA protocol was the 
submission of preclinical data from Dr. Bordignon. In the future, such data should be 
part of any proposal for human gene therapy. He stressed the necessity of having some 
demonstration of efficacy in an animal model or in cell culture before moving to human 
subjects. He defined "efficacy" as a demonstration that the cells of origin that were to be 
genetically altered could be modified with a level of efficiency likely to result in a clinical 
outcome that was measurable and quantifiable. Dr. Parkman further proposed that 
[564] 
Recombinant DNA Research, Volume 14 
