5 
Group on Viruses. The Wbrking Group on Viruses thought the proposal was 
appropriate. This proposal will be presented to the RAC for consideration 
at the January 27, 1986, meeting. 
Dr. Gottesman reported that the Working Group on Viruses felt it would tie 
appropriate to modify the NIH Guidelines to exempt tissue culture experiments 
involving small fragments of viral genomes. An argument for exempting small 
pieces of viruses is that few mechanisms exist for spread of these small pieces, 
and a modification exempting tissue culture experiments involving small pieces of 
viral gencmes would reduce the Institutional Riosafety Ccmmittee ( IBC) workload. 
Dr. Gottesman reported that three important issues were raised during the 
working group discussion of the status of retroviruses under the NIH Guidelines: 
(1) Is the virus an infectious or a defective virus? An infectious virus is 
capable of multiple rounds of replication. Defective viruses usually can only 
go through one round of replication. Recombinant vectors, including retroviral 
vectors, are generally defective since the added genetic material replaces 
information necessary for replication. The NIH Guidelines are generally less 
concerned about the potential hazard associated with defective viruses. Retro- 
viruses recombine at high frequency, however; and this aspect of their behavior 
may permit then to qenerate infectious particles throuqh recombination with 
helper viruses or endogenous retroviral sequences. The consensus of the group 
was that while recombination frequency in retroviruses is high, the probability 
of recombination and the products of such recombinations can generally be 
predicted. (2) Vfoat is the host range of the retrovirus and the derived vector? 
.Rome retroviruses have a narrow host range; other retroviruses have a broad 
host range. Those retroviruses possessing a broad host range present a qreater 
concern. (3) What are the effects of the retroviruses or the derived vectors 
on the host? For example, is the virus oncogenic or cytotoxic? 
nr. Gottesman said the discussion on appropriate safety levels for research 
involving retroviruses indicated that most laboratories use Biosafety Level 
(BL) 2 containment for research involving retroviruses. Same laboratories in 
addition employ BL3 practices for research with certain viruses. Cr. Gottesman 
said the Office of Reccmbinant CNA Activities (ORDA) currently recommends BL2 
conditions for research involving retroviral agents. 
Dr. Gottesman said no clear consensus emerged at the November 12, 1985, meeting 
on how the NIH Guidelines should deal with retroviruses or retroviral vectors. 
All working group members, however, felt some combinations of characteristics 
should be carefully evaluated. Dr. Gottesman suggested experiments involving 
retroviruses could be performed under BL2 containment. However, if the vector 
possesses two of the three characteristics of infectivity, oncogenicity and 
broad host ranqe, consideration should be given to rising containment to BL3. 
Dr. Pobert Cook-Deeqan of the Office of Technology Assessment asked how Rous 
sarcoma virus (RSV) would be treated under this proposal. RSV is infectious 
and oncogenic, but because its host range does not include humans it is not 
considered a danger to investigators. 
[571] 
