DEPARTMENT OF HEALTH & HUMAN SERVICES 
November 8, 1985 
Executive Secretary 
Recombinant DNA Advisory Committee 
Preposed Modifications of the Guidelines 
to Include Reference to Recombinant FNA 
The Record 
Attachment II - Page 1 
Public Health Service 
National Institutes of Health 
Memorandum 
Drs. Gottesman, Martin, Talbot, and I spoke by conference call on November 4, 
1985, to consider possibilities for including specific reference to 
recombinant RNA in the NIH Guidelines for Research Involving Recombinant CNA 
Molecules. This arose from discussions by the Reccmhinant Advisory 
Committee as to whether there should be an explicit statement that retro- 
viruses cure covered by the Guidelines, particularly in the case of hunan 
gene therapy protocols, vhich require rc/iew and specific approval by the NIH 
under Section III-A of the Guidelines. 
After discussing alternative ways of including reference to recombinant RNA. 
in the Guidelines, it was proposed that reference to recombinant RIsA. be 
added to sections III-A-4, III-B-3, and III-B-4-a. The sections would be 
revised to read as follows (revised wording is underlined): 
III-A-4. Deliberate transfer of recombinant CNA or CNA or IRNA derived 
from recombinant DNA into human subjects (21). The requirement for 
RAC review should not be considered to preonpt any other required review 
of experiments with human subjects. Institutional Review Board (IRB) 
review of the proposed should be completed before submission to NIH. 
III-B-3. Experiments Involving the Use of Infectious Animal or Plant 
CNA or RNA Viruses or Defective Animal or Plant CNA or RNA Viruses 
in the Presence of Helper Virus in Tissue Culture Systems. 
Caution: Special care should be used in the evaluation of containment 
levels for experiments vhich cure likely to either enhance the patho- 
genicity (e.g., insertion exf a host oncogene) or to extend the host 
range (e.g., introduction of novel control elements) of viral vectors 
under conditions \*hich permit a productive infection. In such cases, 
serious consideration should be given to raising the physical contain- 
ment by at least one level . 
Note. — Recombinant DNA molecules or RNA molecules derived therefrom 
^hich contain less than two-thirds of the genome of any eukaryotic 
virus (all virus from a single Family (17) being considered identical 
(19) may be considered defective and can be used in the absence of 
helper under the conditions specified in Section III-C. 
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