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protocol. Nonetheless, a trial use could be justified in a last hope case. 
Ms. Areen felt that it was time to move forward; the subcommittee should not seek to answer 
these questions, which the principal investigator (PI) should address. Additional information may 
prove unnecessary. If the questions were different, perhaps reviewers’ responses would be as 
well; some reviewers disapproved of a "general protocol." Dr. Parkman’s points revealed a more 
complex situation regarding PEG-ADA therapy; the protocol may have to provide greater 
discussion of alternative therapies. He noted that both an Institutional Review Board (IRB) and 
an Institutional Biosafety Committee (IBC) would have to approve a "real protocol." Perhaps the 
subcommittee should approve both a PEG-ADA trial and a human gene therapy protocol. 
Dr. Parkman believed that if the patient dies, risk would be irrelevant. The safety issue arises 
exclusively if drugs are used. The subcommittee then took a coffee break. 
After the coffee break, Dr. Walters asked if the subcommittee could agree on a set of issues 
considered important and identify data that could help to resolve outstanding questions. Mr. 
Capron, Drs. Gartland, and McCarthy agreed that they could develop a report and publish it in 
the Guide for Grants and Controls. 
Dr. Cook-Deegan asked whether the subcommittee needed to consider a totally new vector 
system. While these issues required discussion, conflict between the subcommittee’s time frame 
and "compassionate use" was growing. Perhaps the development of guidelines would be a 
useful step. 
Dr. Epstein felt that they were really discussing a ‘decision tree", which would offer a more flexible 
approach. Specific answers to questions on safety, risks and alternatives were required. Ms. 
Areen believed that it may prove difficult to identify patients in the "last hope" category. Dr. 
Parkman stated that the fourth part is the actual protocol. 
Dr. Miller believed that "compassionate use" was an inappropriate expression. He had a great 
deal of experience at Institutional Review Boards and the Food and Drug Administration, for 
example with AZT, IL-2, and cardiac transplants. 
Dr. Gottesman noted that lists were being developed, though an absolute hierarchy could not 
be made. Regarding safety issues, it was unclear that all questions are either short term or long 
term. She asked: (1) whether some issues extend beyond the patient; (2) what information is 
available on safety issues and, if so, whether it is theoretical or hard data. Furthermore, the 
subcommittee has not addressed packaging systems and whether alternatives existed without 
packaging systems. Regarding efficacy issues, animal models might answer certain questions, 
but she questioned whether they are feasible. Perhaps, in certain situations, data must come 
exclusively from human studies. 
Dr. Mulligan turned the discussion to different vector systems. Chemical methods of transfection, 
such as through protoplast electroporation, remain inefficient; lipofection, with an artificial 
membrane, works well in the short term. In addition, the retrovirus-infection method raises certain 
questions: (1 ) what target cell will be chosen; (2) because the cell must have a renewal capacity, 
it may not be necessary to infect totipotent cells; (3) what Dr. Anderson will infect; and (4) 
whether evidence exists to prove that the cells are replicating. 
Recombinant DNA Research, Volume 13 
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