Recombinant DNA Advisory Committee - 12/3-4/92 
The issue of recruitment presents several difficulties. The majority of problems that 
have been encountered focus on the referring physician, who is known and trusted by 
these individuals. In certain circumstances, however, there are problems associated with 
misinformation on the part of the patient's physician. Despite the time that is taken to 
thoroughly explain the protocol to the primary physician, the information is not always 
relayed adequately to the patient. To avoid this situation. Dr. Wilson said that he or one 
of his co-investigators visits the referring physician when feasible. Travel is not always 
possible, e.g., the patient identified in Cyprus. 
Dr. Wilson responded to the RACs concerns regarding pre-screening for El sequences. 
Data suggests that El sequences can be found by PCR in pulmonary cells recovered 
from the lung. PCR analysis would provide misleading information and suggested that 
patients should be evaluated for any overt clinical infections through culture techniques. 
In regard to the length of time patients will be required to stay in the negative pressure 
facility, Dr. Wilson stated that patients will be released after 3 consecutive negative 
cultures. Dr. Wilson called on his collaborator, Dr. Richard Simon, a pulmonologist, to 
respond to the issue of damage to the lung caused by the proposed procedures. 
Dr. Simon explained that only 5 % of the patient's total airway will be occluded. This 
temporary loss of ventilation should not cause any significant problem to the patient. 
Any signs of hypoxia will be easily detectable because these patients will be monitored 
continuously for arterial saturation with a finger oximeter. The period of time that will 
be required for occlusion is 10 minutes in order to achieve excellent gene transfer. 
Dr. Walters asked if the volume to be administered to the patient has been reduced 
from the 50 ml volume that was proposed originally. Dr. Wilson stated that the volume 
has been reduced to 20 ml. Dr. Walters asked Dr. Wilson if he would agree to move the 
expected benefit section of the informed consent as discussed earlier. Dr. Wilson agreed 
to move the statement to the front section of the document. 
Dr. D. Miller noted that it is important for the RAC to remember that Dr. Crystal and 
Dr. Wilson are proposing vectors that have slightly different promoters. What is the 
level of CFTR expression from the proposed vector compared to the endogenous level? 
Dr. Wilson responded that the level of expression depends on the specific cell type. The 
level of expression in epithelial cells is greater than endogenous expression in most cases; 
however, probably not more that a 10-fold increase. 
Committee Motion 
A motion was made by Dr. Zallen and seconded by Dr. D. Miller to approve the 
protocol with the following stipulations: (1) delete the inclusion/exclusion criteria that 
Recombinant DNA Research, Volume 16 
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