Federal Register / Vol. 46, No. 126 / Wednesday, July 1, 1981 / Notices 
34463 
I-D-4. Deliberate release into the 
environment of any organism containing 
recombinant DNA. 
I-D-6. Deliberate transfer of a drug 
resistance trait to microorganisms that 
are not known to acquire it naturally, if 
such acquisition could compromise the 
use of a drug to control disease agents in 
human or veterinary medicine or 
agriculture. [2A] 
I-D-6. Large-scale experiments (e g., 
more than 10 liters of culture) with 
organisms containing recombinant 
DNAs. unless the recombinant DNAs 
are rigorously characterized and the 
absence of harmful sequences 
established (J). (See Section IV-E-l-b- 
(3Hd).) 
1-D (1-6). Experiments in Categories 
1-D-l to l-D-6 may be excepted’ (4) from 
the prohibitions (and will at that time be 
assigned appropriate levels of physical 
and biological containment) provided 
that these experiments are expressly 
approved by the Director, National 
Institutes of Health (NIH), with advice 
of the Recombinant DNA Advisory 
Committee (RAC), after appropriate 
notice and opportunity for public 
comment. (See Section IV-E-l-b-(l)- 
(e).) 
Experiments in Categories 1-D-l, I-D- 
2, l-D-5. and experiments involving 
"wild type" host-vector systems are 
expected from the prohibitions, provided 
that these experiments are designed for 
risk-assessment purposes and are 
conducted within the NIH high- 
containment facilities located in 
Building 41-T on the Bethesda campus 
and in Building 550 located at the 
Frederick Cancer Research Center. The 
selection of laboratory practices and 
containment equipment for such 
experiments shall be approved by the 
Office of Recombinant DNA Activities 
(ORDA) following consultation with the 
RAC Risk Assessment Subcommittee 
and the NIH Biosafety Committee. 
ORDA shall inform RAC members of the 
proposed risk-assessment projects at the 
same time it seeks consultation from the 
RAC Risk Assessment Subcommittee 
and the NIH Biosafety Committee. If a 
major biohazard is detemined. the 
clones will be destroyed after the 
completion of the experiment rather 
than retaining them in high containment 
facility. Other clones that are non- 
hazardous or not of major hazard will be 
retained in the high containment. 
I-E. Exemptions. It must be 
emphasized that the following 
exemptions (4) are not meant to apply to 
experiments described in the Sections 1- 
D-1 to I-D-5 as being prohibited. In 
addition, any recombinant DNA 
molecules involving DNA from Class 3 
organisms (7) or cells known to be 
infected with these agents, or any 
recombinant DNA molecules which 
increase the virulence and host-range of 
a plant pathogen beyond that which 
occurs by natural genetic exchange, are 
not exempt unless specifically so 
designated by NIH under Section I-E-5. 
Also. Appendix G overrides the 
exemptions for specified experiments 
involving genes coding for toxins. 
The following recombinant DNA 
molecules are exempt from these 
Guidelines, and no registration with NIH 
is necessary. 
I-E-1. Those that are not in organisms 
or viruses. (5) 
I-E-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. 
I-E-^. 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 
species) or when transferred to another 
host by well established physiological 
means; also those that consist entirely of 
DNA from a eukaryotic host, including 
its chloroplasts, mitochondria, or 
plasmids (but excluding viruses), when 
propagated only 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 
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-E-l-b-(l)- 
(d).) 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. 
l-E-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-E-l-b- 
(l)-(d).) 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. 
1-F. General Definitions. See Section 
IV-C. 
n. Containment 
Effective biological safety programs 
have been operative in a variety of 
laboratories for many years. 
Considerable information, therefore, 
already exists for the design of physical 
containment facilities and the selection 
of laboratory procedures applicable to 
organisms carrying recombinant DNAs. 
(6-79) The existing programs rely upon 
mechanisms that, for convenience, can 
be divided into two categories: (i) a set 
of standard practices that are generally 
used in microbiological laboratories, 
and (ii) special procedures, equipment, 
and laboratory installations that provide 
physical barriers which are applied in 
varying degrees according to the 
estimated biohazard. 
Experiments on recombinant DNAs. 
by their very nature, lend themselves to 
a third containment mechanism — 
namely, the application of highly 
specific biological barriers. In fact, 
natural barriers do exist which limit 
either (i) the infectivity of a vector, or 
vehicle, (plasmid or virus) for specific 
hosts or (ii) its dissemination and 
survival in the environment. The vectors 
that provide the means for replication of 
the recombinant DNAs and/or the host 
cells in which they replicate can be 
geneticaly designed to decrease by 
many orders of magnitude the 
probability of dissemination of 
recombinant DNAs outside the 
laboratory. 
As these three means of containment 
are complementary, different levels of 
containment appropriate for 
experiments with different recombinants 
can be established by applying various 
combinations of the physical and 
biological barriers along with a constant 
use of the standard practices. We 
consider these categories of 
containment separately here in order 
that such combinations can be 
conveniently expressed in the 
Guidelines. 
In constructing these Guidelines, it 
was necessary to define boundary 
conditions for the different levels of 
physical and biological containment and 
for the classes of experiments to which 
they apply. We recognize that these 
definitions do not take into account all 
existing and anticipated information on 
special procedures that will allow 
particular experiments to be carried out 
under different conditions than 
indicated here without affecting risk. 
Indeed, we urge that individual 
investigators devise simple and more 
effective containment procedures and 
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