Recombinant DNA Advisory Committee - 12/3-4/92 
Ms. Buc noted that the issue has become confused during the discussion. The issue is 
reimbursement for costs associated with non-negligent research-related injury, not 
differential access due to the cost of the procedure. With regard to informed consent, 
there appears to be an underlying notion that some patients are able to consent to 
procedures but not others. This hypothesis is unacceptable. If a patient is not capable 
of consenting to the risks of a protocol, then he/she should not participate in it. The 
financial status of a patient does not determine their ability to provide consent. 
Dr. Murray recommended that Drs. Walters, Zallen, Geiduschek, and Ms. Meyers should 
take the committee's comments and suggestions into consideration in preparing a revised 
version of the letter to the NIH Director. This revised letter will be discussed later on in 
the meeting. 
V. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: GENE THERAPY OF THE 
RESPIRATORY MANIFESTATIONS OF CYSTIC FIBROSIS USING A REPLICATION 
DEFICIENT RECOMBINANT ADENOVIRUS TO TRANSFER THE NORMAL HUMAN 
CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR cDNA TO 
THE AIRWAY EPITHELIUM /DR. CRYSTAL 
Review-Dr. Parkman 
Dr. Murray called on Dr. Parkman to present his primary review of the protocol 
submitted by Dr. Ronald G. Crystal of the National Institutes of Health, Bethesda, 
Maryland. Dr. Parkman summarized the objectives of the protocol. This protocol is 
uniquely different from other protocols that have been previously reviewed by the RAC 
because: (1) the first time that cystic fibrosis (CF) has been proposed as a target disease 
for human gene therapy, and (2) the first time that an adenovirus has been proposed as 
a vector for the in vivo transduction of human cells. 
Cystic fibrosis is the most common serious genetic disorder among whites and Hispanics; 
1 in 10 individuals are carriers of this gene and 1 in 3,000 live births result in the 
manifestation of the disease. Three major organ systems are involved: the lungs, liver, 
and gastrointestinal tract. The gastrointestinal tract is affected due to the decreased 
production of enzymes that are necessary for food digestion; therefore, many individuals 
are malnourished. Patients exhibiting gastrointestinal effects traditionally undergo 
enzyme replacement therapy. The major clinical manifestation of cystic fibrosis is thick 
mucous secretions resulting from the defective cystic fibrosis transmembrane conductance 
regulator (CFTR) gene. The thickened secretions cause the bronchi and bronchioli to 
become obstructed. Infection of these secretions often leads to severe scarring of the 
patient's airways. 
Recombinant DNA Research, Volume 16 
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