Recombinant DNA Advisory Committee - 10/7-8/91 
Mr. Capron said that it is likely that once a patient comes to the University of Michigan 
at the university's expense, the patient may not feel the freedom to decline treatment. 
Ms. Buc asked if the investigators will also pay the for the patient to return home if it is 
decided not to continue the therapy. Dr. Wilson said that the full cost of all pre- 
evaluations will be paid by the university. 
Dr. McGarrity said he hoped that patients would be able to walk away, think about it, 
talk to other people who can help make a decision, return to continue the educational 
process, officially enroll, and sign the consent form. Dr. Wilson said he is quite 
comfortable with Dr. McGarrity's suggestion of giving the patient time to decide. 
Dr. Doi asked about the half-life of a hepatocyte cell that has been transfused back into 
the animals. Dr. Wilson said it has been a very difficult question to address, but he had 
read estimates of anywhere between one month and a year. 
Dr. Leventhal asked about long-term follow-up for the baboons. She noted that Dr. 
Wilson is planning to biopsy the human patients at three months, and asked what else he 
is planning for the patient's follow-up. 
Dr. Wilson replied that the long-term follow-up for the baboons will consist of clinical 
evaluations, chemistries, hematology, tests for replication competent virus, and probably 
one percutaneous liver biopsy for gross histopathology, as well as some specific 
immunocytochemical staining for viral antigens. The patient long-term follow-up is 
essentially metabolic with one percutaneous liver biopsy. 
Dr. Leventhal noted that in a couple of committee reviews, there were concerns about 
the possible carcinogenesis of this procedure. She asked if there was any experimental 
basis for that concern. Dr. Wilson said it is theoretically possible. The simple 
cultivation in vitro and potential insertional mutagenesis could potentially predispose the 
reinfused cells to carcinogenesis. He stressed that these are theoretical concerns. In his 
experience in hepatology, it has been very difficult to transform hepatocytes since they 
are terminally differentiated cells. Carcinogenesis in rodent and rabbit experiments has 
not been observed. 
Dr. Doi asked about the relatively short hepatocyte half-life and the need for subsequent 
infusion of modified hepatocytes. Dr. Wilson said they could repeat the treatment. The 
investigator's goal is to cryopreserve cells and simply reintroduce them. What poses a 
scientific hurdle is the ability to expand hepatocytes in vitro. This has not been done. It 
is currently possible, however, to cryopreserve hepatocytes and reinfuse them. 
Dr. Atlas asked what the investigators plan to do if there is an immunologic response in 
the receptor-negative patients. Dr. Wilson said that the potential effect of the therapy 
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Recombinant DNA Research, Volume 15 
