July 30, 1990, Hunan Gene Therapy Subconmi ttee 
based on: whether there was some expectation that this therapy would work; whether it 
was safe; whether the use of children was acceptable; and finally issues of informed 
consent. 
Dr. Childress said he found the revised informed consent document well organized and 
said that the addition of headings had helped. He said it had been appropriately 
expanded but without providing excessive detail. It was generally concise and clear. 
However, he noted there was some confusion as to whether infusions would continue 
indefinitely or for a period of two years. He presented a written critique including the 
notation of typographical errors he had found in the document. He said he had no 
suggestions for revisions to the children's assent form. Both the assent form and the 
revised consent form were deemed to be splendid documents. 
Dr. Mclvor said he also had some concerns with the preclinical data presented from the 
Milan experiments. He said one of his main concerns was the overall efficiency of the 
gene transfer process being used. Only two of four animals showed human DNA 
sequences in spleen. Further, he said Figure 2, as provided, was uninterpretable as to 
levels of ADA activity. However, Figure 5 convinced him there was no problems with 
ADA expression. Further concerns in the experiments were: 
1. Control levels of CD4^ human T cells in the mice; 
2. Levels of human immunoglobulins obtained when normal peripheral blood 
lymphocytes are provided to the animals; and, 
3. The heterogeneity of types of cells being accessed and provided to the 
animals. 
Dr. Mclvor said he believed the subcommittee would have to deal with two main issues: 
1. Do the data support a sufficient T and B cell responsiveness to warrant an 
attempt at therapy in humans at this point? 
2. Are the Milan and NIH protocols analogous enough to predict an 
efficacious outcome from the NIH protocol? 
Dr. Mulligan said he viewed the data from the perspective of whether it added anything 
to the existing data. He said the following issues were still difficulties in the protocol: 
1. Whether the T cell repertoire would be maintained, as was the case in the 
enzyme replacement approach; 
2. Whether culture conditions are good for preserving function of T cells and 
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