Federal Register / Vol. 45, No. 20 / Tuesday, January 29, 1980 / Notices 
6725 
comment. (See Section IV-E-l-b-(l)- 
(e).) 
Experiments in Categories I-D-l, I-D- 
2, I-D-3, 1-D-5, and experiments 
involving “wild type" host-vector 
systems are excepted 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 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 determined, the clones will 
be destroyed after the completion of the 
experiment rather than retaining them in 
the 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^) are not meant to apply to 
experiments described in the Sections I- 
D-l to I-D-5 as being prohibited. 
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-3. Those that consist entirely of 
DNA from a prokaryotic host, including 
its indigenous plasmids or viruses, when 
propagated only in that host (or 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 Recombinant DNA 
Advisory Committee, 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. 
I-E-5. Other classes of recombinant 
DNA molecules, if the Director, NIH, 
with advice of the Recombinant DNA 
Advisory Committee, 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. 
I-F. General Definitions. See Section 
IV-C. 
II. 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-JS) 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 
genetically 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 
that investigators and institutional 
biosafety committees recommend 
changes in the Guidelines to permit their 
use. 
II-A. Standard Practices and 
Training. The first principle of 
containment is a strict adherence to 
good microbiological practices. (0-75) 
Consequently, all personnel directly or 
indirectly involved in experiments on 
recombinant DNAs must receive 
adequate instruction. (See Sections IV- 
D-l-g, IV-D-5-d and IV-D-8-b.). This 
shall as a minimum include instructions 
in aseptic techniques and in the biology 
of the organisms used in the 
experiments, so that the potential 
biohazards can be understood and 
appreciated. 
Any research group working with 
agents with a known or potential 
biohazard shall have an emergency plan 
which describes the procedures to be 
followed if an accident contaminates 
personnel or the environment. The 
principal investigator must ensure that 
everyone in the laboratory is familiar 
with both the potential hazards of the 
work and the emergency plan. (See 
Sections IV-D-5-e and IV-D-3-d.) If a 
research group is working with a known 
pathogen where there is an effective 
vaccine it should be made available to 
all workers. Where serological 
monitoring is clearly appropriate it shall 
be provided. (See Sections IV-D-l-h 
and IV-D-8-c.) 
II— B. Physical Containment Levels. 
The objective of physical containment is 
to confine organisms containing 
recombinant DNA molecules, and thus 
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