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Federal Renter / Vol. 47. No. 102 / Wednesday. May 26. 1982 / Notices 
must be carried out under NIH specified 
conditions as described in Appendix P. 
IH-B-2-b. Containment conditions for 
experiments in which DNA from Class 5 
agents is transferred into nonpathogenic 
prokaryotes or lower eukaryotes will be 
determined by ORDA following a case- 
by-case review. A USOA permit is 
required for work with Class 5 agents 
(18. 20|. 
ni-B-3. Experiments Involving the 
Use of Infectious Animat or Plant 
Viruses or Defective Animal or Plant 
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 which are likely to 
either enhance the pathogenicity (e.g.. 
insertion of a host oncogene) or to 
extend the host range (e.g.. introduction 
of novel control elements) of viral 
vectors under conditions which permit a 
productive infection. In such cases, 
serious consideration should be given to 
raising the physical containment by at 
least one level. 
Note. — Rtcombtnsni DNA moUculet which 
contain less than Iwo-lhlrds of the lenoo* of 
any eukaryotic virus (all virus fro«n a tingle 
Family (17) being considered Indentical (19|) 
may be constdei^ defective and can be 
used. In the absence of helper, under the 
conditions spedfled In Section ID-C 
Ql-B-8-a. Experiments involving the 
use of infectious Qass 2 animal viruses 
(1). or defective Class 2 animal viruses 
in the presence of helper virus, can be 
performed at P2 containment. 
lIl-B-8-b. Experiments Involving the 
use of Infectious Qass 3 animal viruses 
(1|. or defective Qass 3 animal viruses 
in the presence of helper virus, can be 
carried out at P3 containment. 
U1-B-3-C Experiments involving the 
use of infectious Qass 4 viruses (1), or 
defective Qass 4 viruses in the presence 
of helper virus, may be carried out under 
P4 containment. 
ni-&-3-d. Experiments Involving the 
use of infectious Qass 5 [1] viruses, or 
defective Qass 5 viruses in the presenct 
of helper virus will be determined on a 
case-by-case basis following ORDA 
review. A USOA permit is required for 
work with Qass 5 pathogens [16.20]. 
UI-B-3-e. Experiments involving the 
use of Infectious animal or plant viruses, 
or defective animal or plant viruses in 
the presence of helper virus, not covered 
by Sections IU-B-3^. IIl-B-3-b. IIl-B- 
8^ or IQ-B-^-d may be carried out 
under Pi containment. 
UI-B-4 Recombinant DNA 
Experiments Involving Whole Animals 
or Plants. 
ni-B-4-a. DNA from any source 
, except for greater than two-thirds of a 
eukaryotic viral genome may be 
transferred to any non-human 
vertebrate organism and propagated 
under conditions of physical 
containment comparable to Pi and 
appropriate to the organism under study 
[2]. It is important that the investigator 
demonstrate that the fraction of the viral 
genome being utilized does not lead to 
productive infection. 
Ill-B-4-b. For all experiments 
involving whole animals and plants and 
not covered by IU-B-4-a. the 
appropriate containment will be 
determined by the IBC 
-B-5. Experiments Involving More 
than 10 Liters of Culture. The 
appropriate containment will be decided 
by the IBC. Where appropriate, the 
large-scale containment 
recommendations of the NIH should be 
used (45 FR 24966). 
Ul-C. Experiments that Require IBC 
Notice Simultaneously with Initiation of 
Experiments. Experiments not included 
in Sections III - A. UI-B. Ul-D. and 
subsections of these Sections are to be 
considered in Section lU-C All such 
experiments can be carried out at Pi 
containment. For experiments in this 
category, a registration document as 
describ^ in Action Ill-B must be dated 
and signed by the Investigator and filed 
«vith the local IBC The IBC shall review 
all such proposals, but IBC review prior 
to Initiation of the experiment is not 
required. 
For example, experiments in which all 
components derive from non-pa thogenic 
prokaryotes and non-pathogenic lower 
eukaryotes fall under Section IIl-C and 
can be carried out at Pi containment. 
Caution: Experiments Involving 
Formation or Recombinant DNA 
Molecules Containing no more Than 
Two-Thirds of the Genome of any 
Eukaryotic Virus. Recombinant DNA 
molecules containing no more than two- 
thirds of the genome of any eukaryotic 
virus (all viruses from a single Family 
(17) being considered identical (19]) may 
be propagated and maintained in cells in 
tissue culture using Pi containment. For 
such experiments, it must be shoivn that 
the cells lack helper virus for the 
specific Families of defective viruses 
being used. If helper virus is present, 
procedures spedhed under Section III- 
B-3 should be used. The DNA may 
contain fragments of the genome of 
viruses from more than one Family but 
each fragment must be less than two- 
thirds of a genome. 
IIl-D. Exempt Experiments. The 
following recombinant DNA molecules 
are exempt from these Guidelines and 
no registration with the IBC is 
necessary. 
IlI-D-1. Those that are not in 
organisms or viruses. 
UI-D-2. Those that consist entirely of 
DNA segments from a single 
nonchromosomal or viral DNA source, 
though one or more of the segments may 
be a synthetic equivalent 
III-D-3. Those that consist entirely of 
DNA from a prokaryotic host, including 
its indigenous plasmids or viruses, when 
propagated only in that host (or a 
closely related strain of the same 
spcdes) or when transferred to another 
host by well established physiological 
means; also those that consist entirely of 
DNA from an eularyotic host including 
its chloroplasts, mitochondria, or 
plasmids (but excluding viruses), when 
propagated only in that host (or a 
closely related strain of same species). 
Ill-D-4. Certain specified recombinant 
DNA molecules that consist entirely of 
DNA segments from different species 
that exchange DNA by known 
physiological processes, though one or 
more of the segments may be a synthetic 
equivalent. A list of such exchangers 
will be prepared and periodically 
revised by the Director, NIH. with 
advice of the RAC, after appropriate 
notice and opportunity for public 
comment (See Section IV-C-l-b-(l}- 
(c).) Certain classes are exempt as of 
publication of these Revised Guidelines. 
The list Is In Appendix A. An updated 
list may be obtained from the Office of 
Recombinant DNA Activities. National 
Institutes of Health, Bethesda, Maryland 
20205. 
III- D-5. Other classes of recombinant 
DNA molecules. If the Director, NIH, 
with advice of the RAC, after 
appropriate notice and opportunity for 
public comment, finds that they do not 
present a significant risk to health or the 
environment. (See Section IV-C-l-b- 
(l)-(c).) Certain classes are exempt as of 
publication of these Revised Guidelines. 
The list is in Appendix C. An updated 
list may be obtained from the Office of 
Recombinant DNA Activities. National 
Institutes of Health, Bethesda. Maryland 
20205. 
IV. Roles and Responsibilities 
IV- A. Policy. Safety in activities 
involving recombinant DNA depends on 
the Individual conducting them. The 
Guidelines carmot anticipate every 
possible situation. Motivation and good 
judgment are the key essentials to 
protection of health and the 
environment. 
The Guidelines are intended to help 
the Institution, the Institutional 
Biosafety Committee (IBC), the 
Biological Safety Officer, and the 
Principal Investigator determine the 
safeguards that should be implemented. 
These Guidelines will never be complete 
[441] 
