2 
Dr. Gottesman convened the meeting of the Working Group on Viruses at 9:00 a.m. 
on November 12, 1985. She said this working group was formed to: (1) address 
the impact of recent discoveries in virology on the National Institutes of 
Health (NIH) Guidelines for Research Involving Recanbinant DNA Molecules; and 
(2) respond to scientific issues originating in a memorandum from the Department 
of Health and Human Services (DHHS) . 
In April 1984, the Assistant Secretary for Planning and Evaluation, DHHS, sent 
a memorandum to the Assistant Secretary for Health, DHHS. This memorandum 
transmitted to the Assistant Secretary for Health a list of issues in recanbinant 
DNA technology. The Assistant Secretary for Health forwarded this memorandum 
for comment to several DHHS agencies: the Food ard Drug Administration (FDA), 
the Centers for Disease Control (CDC), and the National Institutes of Health 
(NIH). The Director, NIH, subseguently asked the Recanbinant DNA Advisory 
Committee (RAC) Risk Assessment Subcommittee to formulate a response to the 
memorandum. The Risk Assessment Subcommittee upon evaluation of the memorandum 
suggested sane issues involving use of viral vectors should be evaluated in 
greater detail by a working group of virologists. 
Dr. Gottesman said containment conditions and review procedures for experiments 
involving viral genes are specified in several sections of the NIH Guidelines: 
(1) Under Appendix C in certain conditions, viral genes may be cloned in E. 
coli , S. cerevisiae , and subtilis host-vector systems. These experiments 
are exempt. (2) Under Section III-B, viruses classified in Appendix B can be 
used under specified containment which ranges fran Biosafety Level (BL) 2 to 
BL3. The Institutional Biosafety Canmittee (IBC) must approve of the experiments 
before initiation. Many retroviruses have not, however, been classified in 
Appendix B although seme have been listed in this appendix. (3) Under Section 
III-C, Experiments That Require IBC Notice Simultaneously With Initiation of 
Experiments , experiments involving viruses are also covered. Section III-C 
contains a caution which reads as follows: 
"Experiments Involving Formation of Recombinant DNA Molecules Containing 
No More Than Two-Thirds of the Genome of Any Eukaryotic Virus. Recanbinant 
DNA molecules containing no more than two-thirds of the gencme of any 
eukaryotic virus (all viruses frem a single Family (17) being considered 
identical (19)) may be propagated and maintained in cells in tissue 
culture using BLl containment. For such experiments, it must be shown 
that the cells lack helper virus for the specific Family of defective 
viruses being used. If helper virus is present, procedures specified 
under Section III-B- 3 should be used. The DNA may contain fragments of 
the genome of viruses fran more than one Family but each fragment 
must be less than two-thirds of a genome." 
Dr. Gottesman said the NIH Guidelines define a defective virus as consisting 
of less than two-thirds of a virus gencme. 
Dr. Gottesman said the working group would address several specific issues at 
this meeting. One issue is whether Appendix B should be revised to reflect 
more accurately the situation with retroviruses. A second issue is whether 
the NIH Guidelines should be modified to cover explicitly recanbinant RNA. 
[441] 
