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Federal Re|$ister / Vol. 46. No. 233 / Friday. December 4. 1981 / Notices 
Containment levels for other classes 
of experiments involving non-HVl 
systems may be expressly approved by 
the Director, NIH. (See Sections IV-E-1- 
b-OHb). IV-E-l-b-{2Hc). and IV-E-1- 
b-{3Hb).) 
Ill-C-6. Return of DNA Segments to a 
Higher Eukaryotic Host of Origin. DNA 
from a higher eukaryote (Host D) may 
be inserted into a vector and propagated 
in E coli K-12. Subsequently, this 
recombinant DNA may be returned to 
Host D and propagated under conditions 
of physical containment comparable to 
Pi and appropriate to the organism 
under study. (2A| 
IJl-C-7. Transfer of Cloned DNA 
Segments to Eukaryotic Organisms 
llI-C-7-a. Transfer to Non-human 
Vertebrates. D.NA from any 
nonprohibited source (Section 1-D), 
except for greater than one quarter of a 
eukaryotic viral genome, which has 
been doned and propagated in £. coii 
K-12. may be transferred with E coli 
vector used for doning to any 
eukaryotic cells in culture or to any non- 
human vertebrate organism and 
propagated under conditions of physical 
containment comparable to Pi and 
appropriate to the organism under 
study(2]. Transfers to any other host will 
be considered by the RAC on a case-by- 
case basis|45|. 
in-C-7-b. Transfer to Higher Plants. 
DNA from any nonprohibited source 
(Section I-D] which has been doned 
and propagated in £. coH K-12 or 5. 
cerevisiae. may be transferred with the 
£. coli or S. cerevisiae vector used for 
cloning to any higher plant organisms 
(Angiosperms and Cymnosperms) and 
, propagated under conditions of physical 
containment comparable to Pi and 
appropriate to the organism under study 
(2A|. Intact plants or propagative plant 
parts may be grown under Pi conditions 
described under Section Ill-C-3. 
Containment must be modihed to ensure 
L that the spread of pollen, seed or other 
I propagules is prevented. This can be 
accomplished by conversion to negative 
pressure In the growth cabinet or 
greenhouse or by physical entrapment 
by "bagging" of reproductive structures. 
Transfers to any other plant organisms 
will be considered on a case-by-case 
basis|4S|. 
lll-C-7-c. Transfer to Invertebrates. 
DNA from any nonprohibited source 
. (Section I-D), except for greater than 
one quarter of a eukaryotic viral 
genome, which has been cloned and 
propagated in E coli K-12. may be 
transferred with the E ccH vector used 
for cloning to any eukaryotic cells in 
culture or to any invertebrate organism 
and propagated under conditions of 
physical containment comp.irable to Pi 
and appropriate to the organism under 
study (2A). Transfers to any other host 
will be considered by the RAC on a 
case-by-case basis (45). 
Ill-D. Complementary DNAs. Specific 
contaiiunent levels are given in Section 
IU-A-2-a (see also last column of Table 
III) for complementary DNA (cDNA) of 
viral mRNA. For the other Sections of 
the Guidelines, where applicable, 
cDNAs synthesized in vitro are included 
within each of the above classifications. 
For example, cDNAs formed from 
cellular RNAs that are not purified and 
characterized are included under III-A- 
1, shotgun experiments; cDNAs formed 
from purified and characterized RNAs 
are included under llJ-A-3: etc. 
Due to the possibility of nucleic acid 
contamination of enzyme preparations 
used in the preparation of cDNAs, the 
investigator must employ purified 
enzyme preparations that are free of 
viral nucleic acid. 
111-E. Synthetic DNAs. If the synthetic 
DNA segment is likely to(2AJ yield a 
potentially harmful polynucleotide or 
polypeptide (e.g.. a toxin or a 
pharmacologically active agent), the 
contaiiunent conditions must be as 
stringent as would be used for 
propagating the natural DNA 
counterpart 
If the synthetic DNA sequence codes 
for a harmless product(2A] it may be 
propagated at the same contaiiunent 
level as its purified natural DNA 
counterpart. For example, a synthetic 
DNA segment which corresponds to a 
nonharmful gene of birds, to be 
propagated in Saccharamyces 
cerevisiae, would require P2 physical 
containment plus an HVl host-vector, or 
Pi -t- HV2. 
If the synthetic DNA segment is not 
expressed in vivo as a polymucleotide or 
polypeptide product, the organisms 
containing the recombinant DNA 
molecule are exempt(4) from the 
Guidelines. 
rV. Roles and Responsibilities 
rV-A. Policy. Safety in activities 
involving recombinant DNA depends on 
the individual conducting them. The 
Guidelines cannot 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 
or final, since all conceivable 
experiments involving recombinant 
DNA caiuiot be foreseen. Therefore, it is 
the responsibility of the Institution and 
those associated with it to adhere to the 
purpose of the Guidelines as well as to 
their specifics. 
Each Institution (and the IBC acting 
on its behalf) is responsible for ensuring 
that recombinant DNA activities comply 
with the Guidelines. General recognition 
of institutional authority and 
responsibility properly establishes 
accountability for safe conduct of the 
research at the local level. 
The following roles and 
responsibilities constitute an 
administrative framework in which 
safety is an essential and integral part of 
research involving recombinant DNA 
molecules. Further clarifications and 
interpretations of roles and 
responsibilities will be issued by NIH as 
necessary. 
IV-B. General Applicability. The 
Guidelines are applicable to all 
recombinant DNA research within the 
United States or its territories which is 
conducted at or sponsored by an 
Institution that receives any support for 
recombinant DNA research from NIH. 
This includes research by NIH directly. 
An individual receiving support for 
research involving recombinant DNA 
must be associated with or sponsored 
by an Institution that can and does 
assume the responsibilities assigned in 
these Guidelines. 
The Guidelines are also applicable to 
projects done abroad if they are 
supported by NIH funds. If the host 
country, however, has established rules 
for the conduct of recombinant DNA 
projects, then a certificate of compliance 
with those rules may be submitted to 
NIH in lieu of compliance with the NIH 
Guidelines. NIH reserves the right to 
withhold funding if the safety practices 
to be employed abroad are not 
reasonably consistent with the NIH 
Guidelines. 
IV-C. General Definitions. The 
following terms, which are used 
throughout the Guidelines, are defined 
as follows: 
IV-C-1. "DNA" means 
deoxyribonucleic acid. 
IV-C-2. "Recombinant DNA" or 
"recombinant DNA molecules" means 
either (i) molecules which are 
constructed outside living cells by 
joining natural or synthetic DNA 
segments to DNA molecules that can 
replicate in a living cell, or (ii) DNA 
molecules which result from the 
replication of a molecule described in (i) 
above. 
IV-C-3. [Deleted) 
IV-C-4. "Institution" means any 
public or private entity (including 
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