Recombinant DMA Advisory Committee - 5/30-31/91 
saying that the LNL6 system is the marking system of choice where there is anything but a 
very obvious alternative. He said he was comfortable in doing this in this case, in light of the 
risl« and problems of the children, but nevertheless he felt it would be very difficult in the 
future to say no to the use of this vector in any situation. 
In regards to the informed consent, Mr. Barton said the assent form needed to describe the 
marking procedure and a statement outlining the altruistic nature of the assent should be 
included. On the main consent form he said he felt the vector was being compared to routine 
vaccines for mumps and measles and that he was uncomfortable with this because it suggested 
a degree of familiarity or routineness of the procedure which was unfounded. He urged that 
the investigators remove that sentence from the consent form. 
Dr. McGarrity then asked if other members of the RAC had questions that needed to be 
responded to by the investigators. 
Dr. Krogstad asked the investigators to address the issue of whether hepatocyte cell lines were 
currently available to the investigators. 
Dr. Post noted that the proposed dosage was 2 X 10® cells per kilogram and asked whether 
this constituted the maximum tolerated dose since this was the highest dosage noted in the 
preclinical data. He asked Dr. Ledley to comment on dose selection. 
Dr. Atlas said that he noted that in the preclinical data there appeared to be a time when the 
surgical procedures were changed and resulted in an increased survival of the animals. He 
asked what change in procedure caused this increased survival. 
Dr. Walters said that he had noticed that the consent form lumped hepatocellular 
transplantation, bone marrow grafts and gene marking together and asked whether patients 
would be allowed to receive one without the other. 
And Dr. R. Murray noted that the consent form (page 1455, paragraph 6) referred to risks 
associated with blood and blood products in a transplanted patient. He noted that it stated: 
"These risks will be the same as those associated with whole organ transplan- 
tation and will be explained to you by the transplant team." 
He said he did not see any other mention of these risks in the consent form and asked why 
they were set apart and what assurances existed that these issues will be addressed by the 
transplant team. 
Dr. Ledley noted that the issue of scale was very important. He said the most critical step was 
in the hepatocyte preparation. He said they had gone ahead and prepared a whole organ just 
to prove it could be done and used the same type of conditions that were planned to be used 
in the protocol for the infection, although they limited numbers of plates for cost purposes. 
Recombinant DNA Research, Volume 14 
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