After receiving the AdCFTR experimental treatment, the risk to the environment 
while the patient is on the 7 West ward will be negligible, based on the 
isolation procedures and patient rooms as described in section 5.6.4. In the 
context that the patient will not be discharged until shedding from blood, 
urine, nose, pharynx, or rectal sites has been documented not to occur on 
three separate days, the risk to the environment after discharge is limited to 
the possibility that the individual will become infected with a virus that 
will either complement or recombine with AdCFTR DNA still present in this 
individual. From the data available (see sections 4.1, 4.5, 4.7, 4.8, 4.9 and 
Table 5.2-A), this is very unlikely, but cannot be proven impossible without 
carrying out the human trial. 
If complementation were to occur, the risk to the environment might be small 
amounts of AdCFTR released. Since AdCFTR is replication deficient, this will 
have limited spread. If an individual (other than the original patient) were 
to be exposed, in the context that animal studies show no risk from the 
exogenous gene (the CFTR cDNA) , there should be no risk, particularly in the 
context that shedding will be associated with far less amounts of AdCFTR that 
will be administrated to the study individuals. 
If recombination were to occur, the most likely possibility is that it would 
occur from a crossover between the left end of the new infecting virus 
(providing the missing El functions) and the right end of AdCFTR i.e., (this 
would produce a replication competent E3~ Ad5) . As discussed in section 4.8, 
this should be no different, and likely less virulent, than a replication 
competent E3 + adenovirus . This concept is supported by a human trial with 
oral administration of a replication competent E3~ recombinant hepatitis 
adenovirus vaccine (Tacket et al . , 1992). 
In the event that AdCFTR continues to be shed from the study individual 
following administration, or AdCFTR recombines with another virus or other 
genetic information to create a new replication competent virus that continues 
to be shed by the study individual, it is theoretically possible that either 
AdCFTR or a new replication competent virus could be released to the 
environment. Together, the available data argues that this theoretical 
possibility does not pose a risk to the environment should it occur. The 
unlikely scenario of the study individual insisting on leaving the isolation 
conditions with the knowledge of shedding of either AdCFTR or a new virus is 
discussed in detail in section 5.2 and in the Consent Form (section 5.13), as 
are the possible recourses of the physicians caring for the individual if they 
felt the study individual posed a risk for society. 
5.9 Risk-Benefit Considerations for the Patient 
The risks to the patient, and the efforts made to minimize those risks, are 
detailed in sections 5. 1-5. 6. Cystic fibrosis is a fatal disease with no 
alternative therapies other than transplantation, a high risk, unproven and 
costly procedure (see sections 1.1-1. 5). The definite benefits of this initial 
toxicity/eff icacy study are minimal, although there is a possibility that the 
AdCFTR experimental treatment will stabilize the respiratory disease, at least 
in one lung. These risk-benefit considerations are detailed for the patient in 
the Informed Consent. 
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