Recombinant DNA Advisory Committee - 12/3-4/92 
complication of their disease during the course of this study that is unrelated to the 
treatment. In such an instance, the patient would be cared for, but the usual 
mechanisms of cost-reimbursement would be applied. Ms. Meyers asked if the 
pneumonia were to persist for a long period of time and the patient was not able to pay 
for medical treatment, would he/she be turned away? Dr. Welsh explained that this 
question is very difficult to answer, and that he has discussed it with the director of 
clinical research, university lawyers, and the local IRB. He said that he could not be any 
more specific than to state that every attempt will be made to minimize any financial 
\ 'den in the event of adverse consequences. 
u(. Walters noted that both the title and the introduction of the informed consent 
document do not clearly explain that this is a preliminary study to test what happens in 
the nasal epithelium, and that there will be no direct benefit as a result of participation 
in this study. The use of the words gene therapy and efficacy is a concern. In addition, 
the introduction explains the ultimate purpose of the research, and patients may 
misunderstand the expected benefit of this particular protocol. Dr. Welsh offered to 
incorporate a statement in the introduction that states that this treatment will not be 
efficacious to the patient. However, the patient needs to be made aware that he/she will 
derive no therapeutic benefit by the fact that this procedure will be performed on the 
nasal epithelium, not the lung. Dr. Walters suggested including the statement, It is 
unlikely that participation in this study will directly benefit you, should be inserted into the 
introduction section of the informed consent document. Dr. Welsh agreed to include this 
statement. 
Dr. Ginsberg stated that it should be recognized in terms of safety, the results obtained 
regarding inflammation in the nasal epithelium may not necessarily translate to those 
effects that may be observed in the lung. However, he acknowledged that the nasal 
epithelium is a good site for the initial administration. Individuals who possess 
antibodies may have a dormant adenovirus infection in the lymph nodes and lymphatic 
cells. Even in the most severe adenovirus pneumonias, viremia has never been 
demonstrated; so the problem of viremia is not an important issue. Approximately 1 in 
10 6 lymphoid cells of antibody positive individuals contains adenovirus DNA. 
Dr. Michel Perricaudet of the National Center for Scientific Research, Paris, asked if the 
expression of E3 proteins has been studied in the absence of Ela. Dr. Welsh responded 
that these experiments have not been performed. 
Dr. Murray asked Dr. Ginsberg if he could anticipate any difficulties that could arise in 
future protocols regarding recombination and aerosol administration. Dr. Ginsberg said 
that because Type 5 and Type 2 adenoviruses do not produce severe disease in adults, 
there will probably not be any serious problems associated with the aerosol 
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Recombinant DNA Research, Volume 16 
