M.J. Welsh and A.E. Smith, RAC Application 
vi. Venipuncture to obtain the blood samples produces minimal risks that are well-known. 
vii. Arterial puncture for measurement of blood gases includes the risk of bleeding and 
bruise formation and pain at the time of the procedure. The procedure is standard and done 
frequently on outpatients. 
viii. Pulmonary function studies are routine on outpatients with a variety of lung diseases. 
There are no anticipated short or long term risks. 
ix. Chest and sinus X-rays carry the risk of radiation exposure; we anticipate that a subject 
will have three chest X-rays and two computerized tomographic X-rays of the sinuses 
during the course of the studies. Although there are no known adverse effects of this 
amount of radiation, the long term effects of such radiation are not known with certainty. 
x. Emotional discomfort related to respiratory isolation in a hospital room for two weeks 
may occur. We will provide reading material, VCRs, an exercise bicycle, etc. to the 
patient. If required we will provide psychological support. 
B.3.h. If a treated patient dies, what special post mortem studies will be performed? 
It is not anticipated that death should occur during participation in the trial. Should it occur 
for any unforeseen reason, we will request an autopsy. This is discussed in the Information 
Summary for Informed Consent. 
B.4. Public Health Considerations 
Describe any potential benefits and hazards of the proposed therapy to persons other 
than the patients being treated. Specifically: 
B.4.a. On what basis are potential public health benefits or hazards postulated? 
The knowledge obtained from this study could lead to a significant improvement in the care 
of patients with CF. Thus, because CF is a common, chronic, debilitating disease which is 
usually lethal, it could have a significant beneficial public health impact. 
There is a risk that the virus could be passed to another person. This could occur if a 
caregiver or visitor is exposed to the virus we apply to the patient or exposed to virus that 
had replicated in the patient. Wild- type adenovirus 2 causes mild disease. Because 
Ad2/CFTR-1 is replication impaired and because our experimental results have 
demonstrated no virus replication, the possibility that an exposed person will develop 
clinical disease is very remote. 
Were environmental release to occur, the most likely virus involved would be wild-type 
adenovirus that had overgrown the Ad2/CFTR-1 or a recombinant with no biological 
activity other than that associated with wild-type virus. Recombinant and wild-type 
adenovirus has been used previously in human populations (93,146). 
B.4.b. Is there a significant possibility that the added DNA will spread from the patient to 
other persons or to the environment? 
Both theoretical considerations and experimental results suggest that the risk of spread to 
other persons or to the environment is very low. a) Our data indicate that viral replication 
in the patient is very unlikely. Thus, given the low amounts of virus used, it is unlikely that 
the virus will spread, b) As indicated below, we will take precautions to decrease the risk 
Recombinant DNA Research, Volume 16 
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