before you are given the altered virus. The wait from the time of enrollment into the 
study and administration of the altered virus will be at least three weeks, but could be 
significantly longer. Most of the tests will be repeated just before you are given the 
altered virus, and some will be repeated during the visits between enrollment into the 
study and administration of the virus. 
The virus, known as adenovirus 2, is a common virus that is found in human airways and 
can cause a "cold". The virus that you will receive has been altered so that it cannot 
reproduce normally. These changes limit its ability to cause disease, to grow, and to 
spread. The normal gene for the cystic fibrosis protein, CFTR, has been inserted into the 
virus. In the laboratory, it has been shown that this altered virus can enter the cells that 
form the lining of the human nose and deposit the normal gene, so that normal CFTR is 
produced by the cells. Studies with laboratory animals suggest that the altered virus does 
not cause disease or illness. They also indicate that the virus can carry a new gene into 
the cells of the airway. However, there is no guarantee that the virus will behave the 
same way in humans. 
The day the virus is applied, you will be admitted to the hospital. The virus you will 
receive has been prepared at Genzyme Corporation in Framingham, Massachusetts. To 
put the virus into the lining of the nose, we will use a small tube to place a few drops into 
the nose on one side. On the other side, we will place a few drops of a salt solution, for 
purposes of comparison. The application procedure will last about 30 or 40 minutes. We 
will give you a mild tranquilizer that will reduce anxiety and help you sit still. Each time 
we repeat the treatment we will use a higher dose of the virus. In this way we can learn if 
the virus is safe. We plan to administer the virus five times at approximately one month 
intervals. We expect that the entire study will take about six months. This procedure is 
experimental. 
To determine whether the virus carrying CFTR is safe and can correct the cystic fibrosis 
respiratory abnormalities, we will perform several studies on days 1, 3, 7, 14 and 21 after 
the treatment. We will take swabs from both nostrils and your throat. The nasal and 
throat swabs are performed by gently rubbing a cotton-tipped applicator in the inside of 
your nose and in your throat. These procedures are commonly performed to diagnose 
"strep throat" and are not harmful or painful. 
Because this is an experimental virus, there is a possibility that inflammation of the lining 
of the nose may occur. It is possible that redness and pain could occur or that you could 
develop symptoms similar to those experienced when you have a cold: that is a stuffy or 
runny nose. To determine if any harm was done to the area of nose where the virus was 
given, we will perform a nasal biopsy. Prior to the biopsy, an anesthetic to numb the 
feeling in the area will be used. A small area (about half the size of a dime) will be 
removed from the lining of both sides of your nose by an Ear, Nose and Throat doctor. 
This will be done after the completion of all the treatments or earlier if we find any 
evidence of injury from the virus. 
To learn whether the experimental virus can correct cystic fibrosis respiratory 
abnormalities, we will measure the voltage across the lining of the nose. This involves 
the insertion of a needle into the skin on your arm, and touching the inner surface of the 
nose with a small rubber catheter. The rubber catheter and the needle will be connected 
to a voltmeter. A voltmeter is a recording device and does not deliver any electricity to 
your nose. Two different drugs at very low doses will be perfused onto the lining of the 
nose for approximately 30 minutes. These drugs are terbutaline (which is used to treat 
asthma), and amiloride (which is used to treat heart and kidney problems). These drugs 
Recombinant DNA Research, Volume 18 
