Human Gene Therapy Subcommittee - 11/30/90 
be conducted in adults where informed consent could be obtained from the patient 
undergoing the procedure. 
Dr. Mclvor questioned why unsuccessful previous bone marrow transplant should be 
an exclusion criteria for the protocol. The informed consent should specifically 
indicate what is happening to the cells that are reinfused into the patient. 
Dr. Walters called on Dr. Parkman to lead a discussion of the letter from Dr. 
Mulligan. Dr. Parkman said that Dr. Mulligan's comments were similar to his 
comments on the University of Wisconsin protocol. Dr. Mulligan had the following 
concerns: (1) What are the precise conditions under which the in vitro transfection 
will occur? (2) What attempts will be made to look for other gene abnormalities 
such as rearrangements, besides looking for the neomycin resistance gene? (3) Is the 
biological assay for determining the presence of the neomycin resistance gene 
adequate and would PCR be a better technique to employ for this purpose? and (4) 
Will mutagenesis occur and will the use of growth factors in vitro in any way increase 
the probability of mutagenesis? 
Dr. Epstein asked if there were any substantive differences between this protocol 
and the protocol of Dr. Cornetta. Dr. Mclvor said that the focus of this protocol 
was on AMI^ whereas the earlier protocol was not limited and would look at both 
AML and ALL. In this protocol, 30% of marrow cells will be transduced, whereas 
in the previous protocol only 10% would undergo transduction. Also, this protocol 
presented more preclinical data than the previous protocol, including data on 
detection of the neomycin resistance gene and labeling of different progenitor cells 
as well as transduction of AML blast colonies. 
Dr. Parkman said the major difference was that the preclinical data included an 
experiment in which human bone marrow cells were infected and grown with and 
without G418 to study differentiation in normal myeloid progenitor cells versus AML 
cells in terms of their growth characteristics in vitro. There is a question whether 
enough leukemic cells were marked to obtain requested data concerning transfection 
rates as noted in the preclinical data. 
Dr. Mclvor asked how the distinction was made between the morphology of AML 
blast cells and normal cell colonies. Dr. Parkman added that he wanted to know 
how the investigators were going to proceed if the experiment provided a positive 
result. 
Dr. Walters called on Dr. Brenner to reply to the written critiques of the reviewers 
as well as to questions which had been brought up during the meeting. Dr. Brenner 
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Recombinant DNA Research, Volume 14 
