Recombinant DMA Advisory Committee - 
Dr. Mclvor asked Dr. Anderson if he had ever done the calculations on the likelihood of 
insertional mutagenesis. Dr. Anderson tried, but there are many assumptions that are 
necessary for each particular cancer. Dr. Mclvor was looking for information on how 
many integration events in a cell population would be necessary before the activation of 
two oncogenes could be observed. Dr. Ihle said that several experiments had been done 
in this regard and that the frequency of activating of an oncogene is something on the 
order of 10‘^. Therefore, the frequency of activating two oncogenes would be In 
regard to these experiments, the vast number of cells will not reconstitute in the long- 
term, and only a very small percentage of stem cells would contribute to cancer. It 
would be very difficult to calculate the risk of oncogenesis in such experiments. 
Dr. Carmen suggested the following wording be inserted in the informed consent 
document under the heading of Bone Marrow Transplant Procedure, found on page 31 
of the protocol (page 109 of the mailing): 
The current sentence beginning, "If you agree, one-third of the marrow will be treated 
with..." should be reworded as follows: 
"If you agree, one-third of the marrow will be treated with a marker bacterial 
gene, attached to a disabled mouse virus, to carry it into the cell." 
Further, on page 33 of the protocol (page 111 of the mailing) under the heading of 
Marrow Marking, the third line, insert the word "mouse" between the words "the" and 
"virus" to make the sentence read: 
"For example, although the mouse virus containing the marker has been greatly 
disabled and is considered harmless, it is conceivable that changes might occur in 
the cells in which it is placed, which would allow the virus to recover, grow and 
potentially even cause cancer." 
Dr. Walters said that one other piece of information was received via FAX from Dr. 
Mulligan during the morning and it states: 
"IVe read the response of Dr. Brenner, et aLy to my comments on the clinical 
protocol....and believe they have adequately addressed my concerns. My vote 
would now be to approve the protocol." 
Dr. McGarrity asked if Dr. Brenner had any comments on Dr. Carmen's suggestions on 
the informed consent. Dr. Brenner said it looked fine and would be incorporated in the 
informed consent document. 
Dr. Mclvor moved that the protocol be approved with Dr. Carmen's revisions with the 
Recombinant DNA Research, Volume 14 
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