Human Gene Therapy Subcommittee - 4/5/91 
of this approach is that all of the donor liver cells would be marked, and this could be 
used to evaluate engraftment. 
Dr. Childress praised the clarity and comprehensiveness of the proposal in terms of the 
issues he was competent to address. He raised the question of the relationship between 
the hepatocellular transplantation and the use of the gene marker, and how to relate the 
two investigational procedures. It is impossible to separate them fully and the committee 
should think about the genetic markers in relation to the other experimental procedure. 
He questioned the distinction between primary and secondary benefits. He understood 
the protocol to be directed primarily at determining the efficacy of hepatocellular 
transplantation, with a secondary benefit being the identification of some possible 
contribution to the care of the particular patient. Another possible secondary benefit 
involves developing the methods of gene transfer. However, the presentation of these 
benefits to the subjects in the consent form is problematic. The sub-theme of the 
consent form- "This may not be effective or beneficial in the case of your child" should 
be shifted to reflect the projected benefits. 
Dr. Childress expressed concern with the voluntariness of consent, but not with the 
information component. The protocol seems to suggest that this treatment would be 
directed at patients who did not qualify on medical grounds for liver transplantation, or 
did not qualify on financial grounds, or for whom a liver could not be found. He asked 
whether offering this procedure to those who could not qualify on financial grounds for 
liver transplantation, a very expensive procedure, would in effect constitute a form of 
undue pressure, incentive, or perhaps an exploitation. He felt comfortable that the 
investigators have procedures in place to continue to refine this problem and develop the 
delicate balance between taking advantage of the patient's situation on the one hand, 
and, on the other hand, not excluding patients from the therapy. 
Ms. Meyers said that the informed consent needed to be brought down more towards the 
eighth-grade level. Also, the language in the reimbursement area should explain that the 
insurance company is not going to know which part of the liver transplantation 
procedures is experimental; there needs to be a statement that the institution will 
reimburse for this. 
Dr. Parkman asked about the investigator's transduction rate in primary human 
hepatocyte cultures and why they chose to look for a marker gene that is in only a 
percentage of the cells as opposed to a marker gene that is in 100% of the cells. 
Dr. Ledley emphasized that the protocol is part of what they perceive to be a much 
larger clinical and basic research effort, directed ultimately at gene therapy. There are a 
variety of other pediatric problems which can be addressed along the way. The research 
is directed at hepatocellular transplantation for liver disease, as well as hepatic gene 
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