Federal Register / Vol. 46, No. 233 / Friday. December 4, 1981 / Notices 
59399 
ni-A-l-b Prokaryotic DNA 
Recombinants 
lU-A-2-a Viruses of Eukaryotes 
IIl-A-2-b Eukaryotic Organelle DNAs 
IU-A-2-C Prokaryotic Plasmid and Phage 
DNAs 
III-A-3 Lowering of Containment Levels 
for Characterized or Purified DNA 
Preparations and Clones 
IIl-A-3-a Purified DNA Other Than 
Plasmids, Bacteriophages, and Other 
Viruses 
lIl-A-3-b Characterized Clones of DNA 
Recombinants 
IIl-B Experiments with Prokaryotic Host- 
Vectors Other than E. colt K-12 
m-B-1 HVl and HV2 Systems 
III-B-2 Return of DNA Segments to 
Prokaryotic Non-HVl Host or Origin 
III-B-3 Non-HVl Systems 
IIl-C Experiments with Eukaryotic Host- 
Vectors 
IIl-C-1 Vertebrate Host-Vector Systems 
Ill-C-l-a Polyoma Virus 
Ill-C-l-b Simian Virus 40 
III-C-l-c Human Adenoviruses 2 and 5 
lll-C-l-d Murine Adenovirus Strain FL 
Ill-C-l-e All Viral Vectors 
Ill-C-l-f Nonviral Vectors 
Ill-C-2 Invetebrate Host-Vector Systems 
IU-C-2-a Invertebrate Viral Vectors 
III-C-2-b Nonviral Vectors 
ni-C-3 Plant Viral Host-Vector Systems 
IIl-C-4 Plant Host-Vector Systems Other 
than Viruses 
ni-C-5 Fungal or Similar Lower 
Eukaryotic Host-Vector Systems 
III-C-6 Return of DNA Segments to a 
Higher Eukaryotic Host of Origin 
lII-C-7 Transfer of Cloned DNA 
Segments to Eukaryotic Organisms 
III-C-7-a Transfer to Non-human 
Vertebrates 
III-C-7-b Transfer to Higher Plants 
IU-C-7-c Transfer to Invertebrates 
III-D Complementary DNAs 
III- E Synthetic DNAs 
IV. Roles and Responsibilities 
IV- A Policy 
rV-B General Applicability 
rV-C General Definitions 
IV-D Responsibilities of the Institution 
lV-D-1 (General) 
IV-D-2 Membership and Procedures of 
the IBC 
rV-D-3 Functions of the IBC 
IV-D-4 Biological Safety Officer 
rV-D-5 Principal Investigator 
rV-D-5-a PI — General 
lV-D-5-b Submissions by the PI to NIH 
1V-D-5-C Submissions by the PI to the 
IBC 
IV-D-5-d PI Responsibilities After 
Approval but Prior to Initiating the 
Research 
lV-D-5-e PI Responsibilities During the 
Conduct of the Approved Research 
IV-E Responsibilities of NIH 
lV-E-1 Director 
IV-E-l-a General Responsibilities of the 
Director, NIH 
rV-E-l-b Specific Responsibilities of the 
Director, NIH 
IV-E-2 Recombineint Advisory 
Committee 
IV-E-3 The Office of Recombinant DNA 
Activities 
IV-E-4 Other NIH Components 
IV-G Compliance 
V. Footnotes and References 
VI. Voluntary Compliance 
VI-A Basic Policy 
VI-B IBC Approval 
VI-D Certification of Host-Vector 
Systems 
Vl-E Requests for Exceptions. 
Exemptions, Approvals 
Vl-F Protection of Proprietary Data 
Appendix A — Exemptions Under I-E-4 
Appendix B — Glassification of 
Microorganisms on the Basis of Hazard 
Appendix C — Exemptions Under I-E-5 
Appendix D — HVl and HV2 Host-Vector 
Systems Assigned Containment Levels 
as Specified in the Subsections of 
Section Ill-A 
Appendix E — Actions Taken Under the 
Guidelines 
Appendix F — Certified Host-Vector Systems 
Appendix G — Containment Conditions for 
Cloning of Genes Coding for the 
Biosynthesis of Toxins for Vertebrates 
Appendix H — Experiments Covered by 
Section Ill-O 
I. Scope of the Guidelines 
I-A. Purpose. The purpose of these 
Guidelines is to specify practices for 
constructing and handling (i) 
recombinant DNA molecules and (ii) 
organisms and viruses containing 
recombinant DNA molecules. 
1-B. Definition of Recombinant DNA 
Molecules. In the context of these 
Guidelines, recombinant DNA molecules 
are defined as 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 that result from the 
replication of those described in (i) 
above. 
I-C. General Applicability. See 
Section IV-B. 
I-D. Prohibitions. The following 
experiments are not to be initiated at the 
present time: 
I-D-1. Formation of recombinant 
DNAs derived from the pathogenic 
organisms classifed [1] as Class 4 or 5 
[2] or from cells known [2A] to be 
infected with such agents, regardless of 
the host-vector system used. 
I-D-2. Deliberate formation of 
recombinant DNAs containing genes for 
the biosynthesis of toxins lethal for 
vertebrates at an LDs« of less than 100 
nanograms per kilogram body weight 
(e.g., the botulinum toxins, tetanus toxin, 
diphtheria toxin. Shigella dysenteriae 
neurotoxin). Guidelines for the cloning 
of DNAs containing genes coding for the 
biosynthesis of toxins which are lethal 
to vertebrates at 100 nanograms to 100 
micrograms per kilogram body weight 
are specified in Appendix G, which 
overerides other parts of the Guidelines 
(e.g.. exemptions, return to host of 
origin, etc.). 
I-D-3. [Deleted], 
I-D-4. Deliberate release into the 
environment of any organism containing 
recombinant DNA 
I-D-5. 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 other than those listed in 
Appendix C, Section 2, 3, and 4 of the 
Guidelines, unless the recombinant 
DNAs are rigorously characterized and 
the absen''e of harmful sequences 
established [3]. [See Section IV-E-l-b- 
(3)-[d).) 
I-D [1-6). Experiments in Categories 
I-D-1 to I-D-6 may be excepted [4] from 
the prohibitions [and will at that time be 
assigned appropriate levels of physical 
and biological containment) provide 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 I-D-1, 1-D- 
2, I-D-5, and experiments involving 
“wild type” host-vector systems are 
excepted from the prohibitions, provided 
that these experiments are designed for I 
risk-assessment purposes and are | 
conducted within the NIH high- 
containment facilities located in ' 
Building 41-T on the Bethesda campus i 
and in Building 550 located at the r 
Frederick Cancer Research Center. The ^ 
selection of laboratory practices and i; 
containment equipment for such ' 
experiments shall be approved by the y 
Office of Recombinant DNA Activities 
(ORDA) following consultation with the J, 
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 seks consultation from the ^ 
RAC Risk Assessment Subcommittee I, 
and the NIH Biosafety Committee. If a ^ 
major biohazard is determined, the 
clones will be destroyed after the i||| 
completion of the experiment rather i i 
than retaining them in the high « i 
containment facility. Other clones that 
are non-hazardous or not of major )|j 
hazard will be retained in the high yi 
containment. 
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