Human Gene Therapy Subcommittee - 4/5/91 
Mr. Capron agreed with Dr. Leventhal's assessment of what this experiment could hope 
to produce in terms of future therapy and treatment. The techniques being employed in 
this protocol involve trade-offs, including purging the bone marrow, which are aimed at 
therapy, but this protocol is purely and simply a scientific experiment using a human 
model. 
Dr. Walters asked for an explanation of the differences between these protocols and Dr. 
Brenner's acute myelogenous leukemia (AML) protocol which was approved earlier by 
the subcommittee. He asked if the key difference was the efficiency of transduction. Dr. 
Parkman said Drs. Brenner and Ihle had shown that 30% of AML colonies were 
transduced, whereas the transduction efficiency in the case of neuroblastoma would be 2- 
3 logs lower than that of the AML protocol. 
Dr. Leventhal felt that patients should be given some guarantee that something could be 
learned from this study, despite the individual patient's outcome. It is unlikely that the 
study would produce an answer as to whether the relapse came from residual bulk cells 
in the body or from the bone marrow. Therefore, this would not produce any evidence 
to judge whether a particular bone marrow purging method had any advantage over 
another. 
Dr. Mclvor said that one of his concerns in the AML protocol was the low transduction 
frequency, and this was an even more acute point in this protocol. He requested an 
estimate of how many patients with negative results would be necessary before the 
investigators would consider the treatment regimen unsuccessful. Since an assessment of 
clonality would depend on performing inverse PCR, an update on any advances on this 
technique from the investigators' laboratory would be necessary. 
Ms. Meyers expressed her disappointment with the various cancer protocols that had 
come before the subcommittee, which offered no direct benefit to the patients. In her 
opinion, it might be more important to study inherited diseases, rather than try to answer 
questions about cancer, which could perhaps be better addressed in animals. 
Dr. Kelley disagreed with this position. Experiments in the area of bone marrow 
transplantation are justified, and the question of whether relapse is coming from the 
marrow or from bulk disease is an appropriate and important question to answer. It 
would be unfair to limit human gene therapy to the narrow focus of genetic disease, 
because as the technology grows, its applications will apply to both genetic and acquired 
diseases. 
Dr. Leventhal felt the goal of using a gene marker to study the effects of other therapies 
should not be rejected. She agreed that it is unwise to limit human gene therapy 
research to inherited diseases, because doing so would limit the potential of gene therapy 
[568] 
Recombinant DNA Research, Volume 14 
