Recombinant DNA Advisory Committee - 12/3-4/92 
experiments indicate that even under the least optimal conditions the wild-type 
adenovirus rapidly outgrows the E3 negative adenovirus, In contrast, E3 positive 
adenoviruses out compete the wild-type virus. One of the products of the E3 positive 
virus, gpl9, reduces the expression of Class I MHC antigens on the cell surface. E3 
negative viruses produce increased inflammatory responses as demonstrated in the lungs 
of the cotton rat. 
Dr. Welsh explained that the patient compensation concerns noted by Ms. Meyers were 
addressed by the Institutional Biosafety Committee, not the IRB. Although the exclusion 
of compensation for non-negligent injury is standard practice (both at the national and 
university level), there is a moral obligation to make every attempt to care for the 
patient and minimize any potential financial consequences in the event of untoward 
research-related consequences. 
Dr. Welsh said that although the possibility of a patient excreting or secreting virus after 
4 weeks is remote, precautions will be taken to avoid the spread of virus to other 
individuals and the environment in the case that a patient was positive after this period 
of time. 
Dr. Gregory addressed the issue of stability of the DNA and the copy number per cell, 
specifically, the increase in viral molecules from an MOI of 50 to 550. El deleted 
viruses can replicate and DNA synthesis can occur at high MOIs. The observed increase 
most likely results from the E2 transcription unit of the virus not being completely 
quiescent in the absence of Ela. The E2 transcription unit encodes DNA polymerase 
and other associated proteins needed for viral DNA replication. The major issue is that 
DNA replication is not necessarily related to virus replication. No evidence of 
recombinant vims has ever been observed in these cells. There is a low level of DNA 
synthesis, which is in the order of 1,000 to 10,000-fold less than would occur with the 
wild-type vims. 
In response to Ms. Meyers concern about financial compensation for participation in this 
protocol, Dr. Welsh said that the amount of compensation should not be a persuasive 
factor. Patients will receive a minor reimbursement, $75 per day for the inconvenience 
they incur as a result of their 10 day to 3 week hospitalization. 
Discussion 
Ms. Meyers asked Dr. Welsh about the course of action that would be taken in the event 
that one of these patients were to develop a very unusual type of pneumonia following 
treatment and their insurance company refused to compensate for treatment after their 
participation in this experimental protocol. Dr. Welsh said that since these patients 
already have mild to moderate lung disease, it is possible that they may develop a 
Recombinant DNA Research, Volume 16 
[ 579 ] 
