33084 
NOTICES 
III C-4. Plant Host- Vector Systems 
Other than Viruses. Organelle, plas- 
mid. and chromosomal DMA s may be 
used as vectors. DNA recombinants 
formed between such vectors and host 
DNA. when propagated only In that 
host for a closely related strain of the 
same species), are exempt from these 
Guidelines (see section 1-E). DNA re- 
combinants formed between such vec- 
tors and DNA from cells other than 
the host species require P2 physical 
containment. The development and 
use of host-vector systems that exhibit 
a high level of biological containment, 
such as those using protoplasts or un- 
differentiated cells in culture, permit a 
decrease in the physical containment 
to PI. 
Intact plants or propagative plant 
parts which because of their large size 
cannot be grown in a standard P2 lab- 
oratory may be grown under the PI 
conditions described above in section 
III-C-3 except that (1 > sterilization of 
run-off water Is required where this Is 
a plausible route for secondary infec- 
tion and <U) the standard P2 practices 
are adopted for microbiological work. 
IH-C-5. Fungal or Similar Lower 
Eukaryotic Host-Vector Systems. The 
containment criteria for DNA recom- 
binant experiments using these host- 
vector* most closely resemble those 
for prokaryotes, rather than those for 
the preceding eukaryotes, since the 
host cells usually exhibit a capacity 
for dli -err.! nation outside the labora- 
tory that Is similar to that for bacte- 
ria Therefore, the procedures estab- 
lished for certification of HV systems 
other than F. coli K-12 (sec. II-D-2) 
will also apply to these fungal or simi- 
lar lower eukaryotic host-vector sys- 
tems 
Once an HV1 system Is approved by 
N1H. it may be used under P2 contain- 
ment for sho’gun experiments with 
phag*s. plasmids, and DNA from Class 
1 prokaryotes 1) and 'ewer eukaryote* 
that do not produce polypeptide 
toxins.(J4) Other classes of recombin- 
ant DNA experiments with these HV1 
systems will require prior approval 
and classification by NTH. Should HV2 
or HV3 systems of this type be devel- 
oped and approved by NIH. guidelines 
for their use In other types of recom- 
binant DNA experiments will also be 
established. 
In addition to the experiments de- 
scribed above, the following experi- 
ments maybe carried out without the 
eukaryotic host 'Host C> hav'ng been 
approved as an HV1 host: DNA from 
Host C may be Inserted Into a vector 
from a certified EX2 host-vector 
system and propagated in E. coli K-12 
under the appropriate containment 
conditions [see Section III-A-l-(a»- 
($>) Subsequently, this recombinant 
DNA may be returned to Host C and 
propagated there under PI conditions. 
( 43 ) 
ITI-D. Complementary DNA’s. Spe- 
cific containment levels are given in 
Section III-A-2-a (see also last column 
of Table m) for complementary DNA 
(cDNA) of viral mRNA. For the other 
Sections of the Guidelines, where ap- 
plicable. cDNA’s synthesized in vitro 
are included within each of the above 
classifications. For example. cDNA’s 
formed from cellular RNA's that are 
not purified and characterized are in- 
cluded under III-A-1. shotgun experi- 
ments; cDNA's formed from purified 
and characterized RNA’s are included 
under III-A-3; etc. 
Due to the possibility of nucleic add 
contamination of enzyme preparations 
used in the preparation of cDNA’s. the 
investigator must employ purified 
enzyme preparations that are free of 
viral nucleic add. 
III-E Synthetic DSA 's If the syn- 
thetic DNA segment could yield a po- 
tentially harmful polynucleotide or 
polypept.de (e.g . a toxin or a pharma- 
cologically active agent), the contain- 
ment 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, it may be 
propagated at the same containment 
level as Its purified natural DNA coun- 
terpart. For example, a synthetic DMA 
segment, to be propagated in E coli 
K-12. which corresponds to a non- 
harmful gene of birds, would require 
P2 physical containment plus an EK1 
host-vector, or PI ♦ EX2. 
If the synthetic DNA segment is not 
expressed is rtro as a polynucleotide 
or polypeptide product, the organisms 
containing the recombinant DNA mol- 
ecules are exempt'/) from the Guide- 
line*. 
IV. Roles axd Rzsrowsiaiunzs 
8afety Involving recombinant DNA 
molecules depends primarily on the in- 
dividuals conducting the research ac- 
tivities The guidelines cannot antici- 
pate every possible situation. Motiva- 
tion and good judgment are the keys 
to protection of health and the envi- 
ronment. 
The guidelines are designed to help 
the principal Investigator determine 
the safeguards that should be imple- 
mented. They wGl never be complete 
and final, since all conceivable experl- 
menu Involving recombinant DNA 
cannot be foreseen. Therefore, it is the 
principal Investigator’s responsibility 
to Insure that the purpose of the 
guidelines is fulfilled. 
The institution, and the Institution- 
al Biosafety Committee (IBC) acting 
on it* behalf, are given responsibility 
for seeing that recombinant DNA ac- 
tivities comp' y with the guidelines. 
This delegation of authority will serve 
the scientific process and at the same 
time properly focus accountability for 
safe conduct of the research. 
The following roles and responsibil- 
ities constitute an administrative 
framework in which safety is an essen- 
tial and Integral part of research In- 
volving recombinant DNA molecules. 
Detailed administrative procedures de- 
signed to implement this framework 
are provided in Appendix C. Further 
clarifications and interpretations of 
roles and responsibilities will be issued 
by NIH as necessary. 
IV- A. Responsibilities of the Institu- 
tion 
IV-A-1. Institution. The institution 
bears primary responsibility for estab- 
lishing and implementing policies for 
the safe conduct of researen involving 
recombinant DNA molecules. These 
shall be policies that assure compli- 
ance with the NIH Guidelines. In car- 
rying out iu responsibilities, the Insti- 
tution shall: 
IV-A-l-a. establish an Institutional 
Biosafety Committee (IBC) and insure 
that it is fulfilling its respond bill Lies: 
rV-A-l-b. report to the NIH Office 
of Recombinant DNA Activities 
(ORDA) the names of members of its 
IBC and relevant information on 
them; 
IV A-l-c. submit to NIH for regis- 
tration a Memorandum of Under- 
standing and A g ree m ent (MUA) or 
equ' valent information (in the case of 
non NIH supported recombinant DNA 
projects), approved by the IBC. for all 
recombinant DNA research at an insti- 
tution receiving any NIH funds for re- 
combinant DNA research 'see section 
IV -C and Appendix C for NIH policies 
on MU As end other required docu- 
mentation); 
IT-A-l-d. Assume responsibility for 
insuring compliance of recombinant 
DNA projects with the procedures and 
standards of the NIH Guidelines. If. 
upon registration and review. NIH 
(ORDA) finds that IBC approved pro- 
tocols do not conform with standards 
set forth in the NIH Guidelines. the 
institution will be notified by NIH and 
shall take appropriate action to bring 
the protocols into compliance <see Ap- 
pendix C for additional Information). 
Further, the institution shall insure 
that ail principal investigators, irre- 
spective of source of funding, have 
agreed to carry out their responsibil- 
ities under the Guidelines; 
IV-A-1 -e. Determine, in connection 
with each project, the necessity for 
medical surveillance of recombinant 
DNA research personnel before, 
during, and after their tavolvment in 
this research. Where possible, each in- 
stitution should cooperate with the 
local public health department. An in- 
stitution's medical surveillance pro- 
gram might include, for example, rec- 
ords of agents handled, active investi- 
FIMUL IKr'STH VOL 43. MO. 14S— JIX Y 3*. 1V71 
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