6 
rr. Anderson said a virus should probably possess the three characteristics of 
infectivity, oncoqenicity , and broad host-ranae before BL3 containment is 
required. 
Dr. Gottesman said the working group also addressed the issue of vhether Appen- 
dix B, "Classification of Microorganisms on the Basis of Hazard," of the NIH 
Guidelines should be modified. Appendix B does not classify retroviruses 
although other types of viruses are classified in this appendix. The working 
group discussion indicated a preference for language describing the consider- 
ations involved in using retroviruses rather than a specific classification of 
retroviruses in Appendix R of the NIH Guidelines. They felt descriptive 
language miaht be more flexible than a listing in Appendix B. 
Dr. Walters said a portion of the November 12, 1985, meeting of the Working 
Group on Viruses was devoted to the vectors to be used in human gene therapy. 
The working group discussed : (1) vector recombination, and (2) insertional 
activation or inactivation of chromosomal genes. Dr. Walters said the 
consensus was that the "Points to Consider in the Design and Submission of 
Human Somatic-Cell Gene Therapy Protocols" adequately address these issues. 
Dr. Gottesman said the Working Group on Viruses agreed insertional activation 
or inactivation by human gene therapy vectors are low probability events. 
They noted, however, that high levels of recombination occur with retroviruses, 
and this high level of recombination should be considered in developing human 
gene therapy vectors, Dr. Grobstein said a fourth item of concern may exist, 
activation of chromosomal genes which are not proto-oncogenes through retrovirus 
insertion. 
Dr. Motulsky said many aspects of retroviral biology are unknown; he questioned 
whether human gene therapy vectors might produce surprises. He offered the 
example of HTLV III/LAV; at this time it is not known why certain T-cells are 
infected and destroyed by the virus while in other patients neural tissue is 
the target. 
Dr. Anderson said HTLV III/LAV has a regulatory system different from that of 
other retroviruses; the tat gene of HTLV III/LAV is a post-transcriptional 
activator and apparently activates translation of both its own and the products 
of other genes. Dr. Gottesman agreed that investigators do not know all the 
rules reaulating retroviral behavior. 
Mr. Capron asked whether investigators believe the current hypothetical model of 
retrovirus functioning is correct. Dr. Anderson felt the model is probably 
correct since investigators can generally predict the results of experiments 
based on this model. 
Transgenic Animal Studies 
Dr. Walters said Dr. Scangos would describe transgenic experiments involving 
the introduction of foreign DNA into animal genomes. 
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