Recombinant DMA Advisory Committee - 
Dr. McGarrity noted that traditionally prior to 1981 RAC review was entirely scientific in 
scope. However, after the publication of the National Academy of Sciences' document 
entitled Splicing Life, it became apparent that ethical issues needed to be considered in 
review of human gene therapy protocols. Dr. Walters noted that it was the President's 
Commission on Bioethics that produced the report, Splicing Life. Although it contained 
a thorough discussion of the philosophical aspects of human gene therapy research, it 
was the result of a request by the then-Chair of the RAC, Mr. Robert Mitchell, that the 
RAC began discussing human gene therapy research. As a result of this discussion, the 
Points to Consider document was developed to look at the scientific issues as well as 
social and ethical considerations such as informed consent, privacy, and confidentiality. 
Dr. McGarrity then summarized what had been requested from Dr. Lotze thus far. 
Further issues for discussion were gene transduction efficiency, informed consent, and 
patient costs. He also noted that on page 16 of tab 1413, the final paragraph, as it was 
stated: 
"Although we plan to use LNL6 for the protocol submitted, if a superior 
vector becomes available we would use it. We would make this 
substitution only with the approval of the FDA and notification of the 
RAC." 
Dr. McGarrity said that such a change would require not only notification of the RAC 
but approval of the RAC. 
Dr. Anderson said that this particular wording was taken directly from the N2/TIL 
protocol and was a result of HGTS insistence that the investigators switch to the LNL6 
vector, rather than using the N2 vector, despite lack of FDA approval of the LNL6 
vector. This had set a precedent, which he had included in several documents after that 
point, that the replacement of a superior vector is not even a minor amendment that 
requires approval. The intention was to allow use of safer vectors as they are developed, 
and to be able to substitute them with FDA approval. 
Dr. McGarrity said this particular substitution of vectors had been the basis for the 
development of the rapid review process for minor changes. In light of this new process 
now being in place it would be the one that should be followed. Dr. Anderson said that 
several other protocols, including Dr. Brenner's, contain the exact same wording. Since 
it is recognized now that such a vector substitution is a minor modification, the wording 
will have to be modified in these protocols. 
Dr. McGarrity called on Dr. Lotze to present the protocol and respond to the questions 
put forward by the conunittee. Dr. Lotze said he would try to discuss comments that 
arose both in the meeting of the HGTS and in this meeting. 
Recombinant DNA Research, Volume 14 
[463] 
