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NOTICES 
comport with requirements o f the NIH 
guidelines. 
The guidelines are also applicable to 
projects done abroad if they are sup- 
ported by NIH funds. If the host coun- 
try has established rules (or the con- 
duct of recombinant DNA projects, 
then a certificate of compliance with 
the host country rules may be submit- 
ted to NTH in lieu of compliance with 
the fruid.elines. NIH reserves the right 
to withhold funding if the safety prac- 
tices to be employed are not reason- 
ably consistent with the NIH guide- 
lines. In any case, a memorandum of 
understanding and agreement (MUA) 
shah be sucmitted to NIH for pur- 
poses of regist ration. 
I-D Prohibitions. The following ex- 
periments are not to be initiated at 
the present time: 
I-D-l. Formation of recombinant 
DNA's derived from the pathogenic or- 
ganisms classified) 1) as class 3. 4. or 
5(3) or from cells Itnown to be Infected 
with such agents, regardless of the 
host vector system used. 
I-D-2. Deliberate formation of re- 
combinant DNA's containing genes for 
the biosynthesis of potent toxins (e.g.. 
botulinum or diphtheria toxins; 
venoms from Insects, snakes, etc.). 
I-D-3. Deliberate creation by the use 
of recombinant DNA of a plant patho- 
gen with increased virulence and hast 
range beyond that which occurs by 
natural genetic exchange. 
I-D-4. Deliberate release Into the en- 
vironment of any organism containing 
recombinant DNA. 
I-D-5. Deliberate transfer of a drug 
resistance trait to micro-organisms 
that are not known to acquire it natu- 
rally. if such acquisition could compro- 
mise the use of a drug to control dis- 
ease agents In human or veterinary 
medicine or agriculture. 
I-D-6. Large-scale experiments (e.g., 
more than 10 liters of culture) with or- 
ganisms containing recombinant 
DNA's. unless the recombinant DNA's 
are rigorously characterized and are 
shown to be free of harmful genes. (3) 
We differentiate between small- and 
large-scale experiments with organ- 
isms containing recombinant DNA's 
because the probability of escape from 
containment barriers normally In- 
creases with increasing scale. 
Experiments in these categories may 
be excepted) 4) from the prohibitions 
(and will at that time be assigned ap- 
propriate levels of physical and bio- 
logical containment) provided that 
these experiments are expressly ap- 
proved by the Director. NIH. on rec- 
ommendation of the Recombinant 
DNA Advisory Committee after appro- 
priate notice and opportunity for 
public comment. In making such ex- 
ceptions. weight will be given both to 
scientific and societal benefits and to 
potential risks. 
I-E. Exemptions. It must be empha- 
sized that the following exemptions!'*) 
are not meant to apply to experiments 
described in the section I-D as being 
prohibited. 
The following recombinant DNA 
molecules are exempt from these 
guidelines, and no registration with 
NIH is necessary: 
I-E-l. Those that are not in organ- 
isms or viruses.! 5) 
I-E- 2. Those that consist entirely of 
DNA segments from a single nonehro- 
mosorr.a.1 or viral DNA sources, though 
one or more of the segments may be a 
synthetic equivalent. 
I-E-3. Those that consist entirely of 
DNA from a prokaryotic host, includ- 
ing i-s indigenous plasmids or virsuses. 
when propagated only in that host (or 
closely related strain oi the same spe- 
cies); also those that consist entirely 
of ENA from a eukaryotic host, in- 
cluding its chioropie-sts. mitochondria, 
or plasmids (but excluding viruses), 
when propagated oniy in that host (or 
a closely related strain of the same 
species). 
I-E-4. Certain specified recombinant 
DNA molecules that consist entirely of 
DNA segments from different species 
that exchange DNA by known physio- 
logical processes, though one or more 
of the segments may be a synthetic 
equivalent. A list of such exchangers 
will be prepared and periodically re- 
vised by the Director. NIH. on the rec- 
ommendation of the Recombinant 
DNA Advisory Committee, after ap- 
propriate notice and opportunity for 
public comment. Certain classes are 
exempt as of publication of these re- 
vised guidelines. The list In appendix 
A. An updated list may be obtained 
from the Office of Recombinant DNA 
Activities. National Institutes of 
Health. Bethesda, M J. 20014. 
I-E-5. Other classes of recombinant 
DNA molecules if the Director. NIH. 
on the recommendation of the Recom- 
binant DNA Advisory Committee, 
after appropriate notice and opportu- 
nity for public comment, finds that 
they do not present a significant risk 
to health or the environment. 
I-F. General Definitions. The follow- 
ing terms, which are used throughout 
these guidelines, are defined as fol- 
lows: 
I-F-l. "DNA'' means deoxyribo- nu- 
cleic acid. 
I-F-2. "Recombinant DNA mole- 
cule” means either <i) molecules which 
are constructed outside living cells by 
joining natural or synthetic DNA seg- 
ments to DNA molecules that can rep- 
licate in a living cell, or (ii) DNA mole- 
cules which result from the replication 
of a molecule described in (i) above. 
I-F-3. "Director" means the Director 
of the National Institutes of Health 
(NIH) and any other officer or em- 
ployee of NIH to whom authority has 
been delegated. 
I-F-4. "Institution" means any 
public or private entity (including Fed- 
eral. State, and local government 
agencies). 
I-F-5. Memorandum of Under- 
standing and Agreement" or "MUA" 
means an institution's certification to 
NIH that the project will comply with 
the guidelines. See appendix C regard- 
ing the form and contents of an MUA. 
I-F-6. "Institutional Biosafety Com- 
mittee" or IBC" is discussed in detail 
in section IV-A-2. 
I-F-7. “Area Biosafety Committee" 
or "ABC" means that in special cir- 
cumstances. in consultation with the 
NIH Office of Recombinant DNA Ac- 
tivities. an Area Biosafety Committee 
may be formed, composed of members 
from the institution and other organi- 
zations beyond its own staff, as an al- 
ternative to an IBC when additional 
expertise outside the institution is 
needed for the indicated reviews. 
I-F-8. "Recombinant DNA Advisory 
Committee" or "RAC" means the 
public advisory committee that shall 
advise the Secretary, Assistant Secre- 
tary for Health, and the Director of 
the National Institutes of Health, con- 
cerning recombinant DNA research. 
The RAC shall consist of members 
who shall be selected from persons 
knowledgeable in the fields of recom- 
binant DNA technology, biological 
safety, ar.d community interests. 
Nominations for the RAC may be sub- 
mitted to ORDA and will be consid- 
ered in accordance with established 
nomination procedures for NIH peer 
review groups. 
I-F-9. "NIH Office of Recombinant 
DNA Activities” or "ORDA" means 
the office within NIH with responsibil- 
ity to (i) review and coordinate all ac- 
tivities of NIH related to the guide- 
lines: (li) foster the interrelationships 
between NIH and other (Jovemment 
agencies, private foundations, profes- 
sional societies and industry, in order 
to assure coordination of activities; 
(Hi) promote international coopera- 
tion: (iv) review the composition of In- 
stitutional Biosafety Committees: (v) 
review MUA's: < vi ) develop registries 
of activities related to recombinant 
DNA research (laboratories, projects, 
new containment facilities, etc.); and 
(vii) prepare regular reports. 
II. Containment 
Effective biological safety programs 
have been operative in a variety of lab- 
oratories for many years. Considerable 
information therefore already exists 
for the design of physical containment 
facilities and the selection of labora- 
tory procedures applicable to organ- 
isms carrying recombinant DNA’s. (6- 
19) The existing programs rely upon 
mechanisms that, for convenience, can 
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