Recombinant DNA Advisory Committee - 12/2-3/93 
vector. The present study is to test toxicity associated with multiple dosing of the vector. 
Dr. Welsh responded to the question of vector-induced inflammation. The data derived 
from animal and human experiments is variable. Variations have been observed 
between laboratories. Possible explanations for these variations are different vector 
constructs, different animal species or strains, and the purity of the vector preparations. 
Dr. Welsh presented data from his murine study in which vector purity affected the 
outcome of the experiment. At high doses, pure clinical grade vector preparations 
caused no evidence of inflammation; however, the lesser purity preparations caused 
peribronchial inflammation. Different animal species appeared to be a variable factor, 
e.g., the inflammation observed in BALB/c mice was not present in C57/B1 mice. 
In regard to Informed Consent document issues, Dr. Welsh stated that contraception will 
be recommended for both females and males throughout the active phase of the study 
and for 1 month after this period. Dr. Chase recommended that a letter be sent to Dr. 
Welsh's IRB about provision of compensation in the event of research-related injury. 
Dr. Walters inquired about the degree of discomfort experienced by patients undergoing 
biopsy of their maxillary sinus. Dr. Scott Graham (an otolaryngologist and co- 
investigator on this protocol) responded that biopsy of the maxillary sinus is a procedure 
commonly performed under local anesthesia. A slight degree of discomfort is associated 
with the procedure; however, the tissue obtained is crucial to understanding pathogenesis 
if an adverse reaction is encountered. 
Committee Motion 
A motion was made by Dr. Post and seconded by Dr. DeLeon to approve the protocol 
with the following stipulations: (1) the investigator retains the option to use either the 
AD2-ORF6/PGK-CFTR (new) or AD2/CFTR-1 (old) adenovirus vectors, and (2) 
patients will be isolated for a period of 24 hours following vector administration; 
however, if a single patient demonstrates virus shedding at 24 hours, the investigator will 
immediately notify the RAC for reconsideration of the isolation period. The motion to 
approve the protocol passed by a vote of 1 1 in favor, 1 opposed, and 3 abstentions. 
The RAC recommended that a letter be sent by ORDA to the IRB of the University of 
Iowa requesting that the following statement be deleted from the Informed Consent 
document: 
"I understand that in the event of physical injury resulting directly from the 
research procedures, no compensation will be available in the absence of 
j negligence by a state employee. However, medical treatment is available at the 
University Hospitals and Clinics, but I will be responsible for making 
arrangements for payment of the expenses of such treatments..." 
XXI. AMENDMENTS TO SECTIONS III, IV, V OF THE NIH GUIDELINES AND THE 
POINTS TO CONSIDER REGARDING NIH (ORDA) REVIEW AND APPROVAL OF 
Recombinant DNA Research, Volume 18 
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