Recombinant DNA Advisory Committee - 6/9-10/94 
Dr. Miller said that this issue is basically academic since current rephcation-competent 
retrovirus (RCR) assays adequately test for the recombination events alluded to by Dr. 
Temin. The standard S'^L' marker rescue assays and the Mus dunni co-cultivation assay 
are sensitive enough to detect RCR both in the vector preparations and viruses 
generated following cell infection. Dr. Parkman concurred with Dr. Miller's statement. 
Dr. Post said that the question raised by Dr. Temin was not stated explicitly; and 
unfortunately, the question cannot be clarified since Dr. Temin is recently deceased. Dr. 
Post speculated that if the helper virus RNA is co-packaged with the vector RNA in 
virus particles, recombination might occur between these two RNA species upon 
infection of target cells to generate a novel retrovirus. Dr. Miller said that the current 
packaging cell fines are constructed with a split helper virus genome in order to reduce 
the probability of such a recombination event. Dr. Straus said that the question raised 
by a prominent scientist and Nobel laureate such as Dr. Temin could possibly be more 
profound that it initially appears. Perhaps, Dr. Temin was speculating about the 
possibility of generating RCR upon infection of sensitive cells in vivo, i.e., in the patient's 
body, as a result of recombination between the vector sequences and some endogenous 
elements within the target cells. Dr. Straus said that this issue should be carefully 
considered by the RAC to assure that current safeguards and testing procedures are 
adequate. Dr. Miller said that the current RCR testing procedures are designed to 
screen for such recombination events both before and after infection with the vector 
preparations. Dr. Philip Noguchi, Director of the Division of Cellular and Gene 
Therapies, Food and Drug Administration (FDA), agreed with Dr. Miller's statement 
that current testing procedures can adequately detect most occurrences of RCR; 
however, remote recombination events do occur during large-scale vector production. 
Dr. Noguchi encouraged the RAC to continue its discussion of this safety issue. 
Update on Accelerated Review Procedures 
Dr. Walters inquired about the status of the Accelerated Review procedures approved by 
the RAC at its March 1994 meeting. Dr. Wivel responded that these actions are 
included in the new incorporated version of the NIH Guidelines, which is in the final 
stage of approval by the NIH Director. The 1994 NIH Guidelines include new 
Appendices P and Q that address physical and biological containment for transgenic 
plants and animals in the greenhouse and animal facility settings. The environmental 
assessment for these new appendices has been recently approved. 
Continuation of Discussion on Compensation for Research-Related Injuries 
In regard to the RACs earlier discussion regarding the provision of medical care to 
subjects injured during the course of their participation in research. Dr. Walters asked 
Dr. Smith to comment on Yale University's program for compensation for research- 
related injuries. Dr. Smith responded that Yale University provides coverage for all 
costs related to research-related injuries. Although he did not have data regarding the 
number and amounts of payments for claims under the program, he understands that the 
claims have not been overwhelming. 
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