Recombinant DNA Advisory Committee - 06/1-2/92 
encodes the glycosylated GAG protein of the Moloney murine leukemia virus 
(MoMuLV). There is a large open reading frame in this portion that would terminate in 
the neomycin resistance coding region. Therefore, there is an additional protein present 
that may cause unknown effects, positive or negative. The RAC must decide whether or 
not this additional protein may influence the outcome of the protocol. 
Dr. Haselkorn asked if the whole GAG region is present? Dr. D. Miller responded that 
it is not the entire GAG protein. The investigators discovered that a portion of the 
GAG region of the MoMuLV enhances viral titers. 
Dr. Parkman commented on the standard of preclinical data required to justify a Phase I 
versus a Phase II clinical trial. The RAC has discussed this issue in the past; the 
consensus has been that the standard of preclinical efficacy should be the same for Phase 
I as for Phase II. 
Ms. Meyers discussed the issue of research related costs. There is a section in the 
informed consent document for the twin protocol that says if there are injuries as a result 
of your participation in this study, the medical expenses will be billed to the patient. 
This statement is unacceptable. 
Ms. Meyers said that informed consent document states, "In addition, no adverse effects 
on cell growth or function were observed following our gene therapy procedure" should be 
expanded to include the exact procedures, i.e., animals, test tubes, etc. 
Ms. Meyers noted that the informed consent document states that patients treatment will 
be decided by random assignment. Since these patients are probably going to die, there 
is no need to have a control group. Additional areas are not addressed such as handling 
of the press, long term follow-up, a request for autopsy, or birth control. 
Mr. Capron asked the investigators to address the presentation of the informed consent 
option to the patient. In the twin protocol particularly, will these options be presented in 
advance of the twin acknowledgement of participation? Have the proposed patients 
already participated in the bone marrow transplantation process with their twin? 
Dr. Leventhal responded to Ms. Meyers statement regarding the use of controls in this 
protocol. Just because all of the patients with this disease are going to die, does not 
mean that controlled studies should not be performed. In addition, Dr. Leventhal asked 
the investigators how they arrived at the number of patients to be treated, i.e., 15 
autologous patients and 15 controls? 
Dr. Leventhal noted that the investigators have included a stopping rule as part of the 
protocol; however, they failed to include this in the informed consent document. Dr. 
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Recombinant DNA Research, Volume 15 
