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Federal Register / Vol. 45. No. 20 / Tuesday, January 29, 1980 / Notices 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
National Institutes of Health 
Guidelines for Research Involving 
Recombinant DNA Molecules 
January 1980. 
Contents 
I. Scope of the Guidelines 
I-A. Purpose 
I-B. Definition of Recombinant DNA 
Molecule 
I-C. General Applicability (see IV-B) 
I-D. Prohibitions 
I-E. Exemptions 
I- F. General Definitions (see IV-C) 
II. Containment 
II— A. Standard Practices and Training 
II— B. Physical Containment Levels 
II— B— 1. PI Level 
II-B-l-a. Laboratory Practices 
II— B — 1— b. Containment Equipment 
II-B-l-c. Special Laboratory Design 
II— B — 2. P2 Level 
Il-B-2-a. Laboratory Practices 
II— B— 2— b. Containment Equipment 
II-B-2-c. Special Laboratory Design 
II— B— 3. P3 Level 
II-B-3-a. Laboratory Practices 
II— B— 3— b. Containment Equipment 
II-B-3-c. Special Laboratory Design 
II— B — 4. P4 Level 
II-B-4-a. Laboratory Practices 
II-B-4-b. Containment Equipment 
II-B-^4-c. Special Laboratory Design 
Il-C. Shipment 
II— D. Biological Containment 
Il-D-1. Levels of Biological Containment 
Il-D-l-a. HVl 
II-D-l-b. HV2 
II-D-l-c. HV3 
II— D— 2. Certification of Host-Vector 
Systems 
II-D-2-a. Responsibility 
II-D-2-b. Data To Be Submitted for 
Certification 
II- D-3. Distribution of Certified Host- 
Vectors 
III. Containment Guidelines for Covered 
Experiments 
III— O. Classification of Experiments Using 
the E. coli K-12 Host-Vector Systems 
III— A. Classification of Experiments Using 
Certain HVl and HV2 Systems 
III-A-1. Shotgun Experiments 
III-A-l-a. Eukaryotic DNA Recombinants 
III— A— 1— b. Prokaryotic DNA Recombinants 
III-A-2-a. Viruses of Eukaryotes 
III-A-2-b. Eukaryotic Organelle DNAs 
III-A-2-c. Prokaryotic Plasmid and Phage 
DNAs 
III— A— 3. Lowering of Containment Levels 
for Characterized or Purified DNA 
Preparations and Clones 
III-A-3-a. Purified DNA Other than 
Plasmids, Bacteriophages, and Other 
Viruses 
III-A-3-b. Characterized Clones of DNA 
Recombinants 
III— B. Experiments with Prokaryotic Host- 
Vectors Other than E. coli K-12 
III— 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 
III— C. Experiments with Eukaryotic Host- 
Vectors 
III— C— 1. Vertebrate Host-Vector Systems 
III— C— 1— a. Polyoma Virus 
III— C— 1— b. Simian Virus 40 
III— C— 1— c. Human Adenoviruses 2 and 5 
III— C— 1— d. Murine Adenovirus Strain FL 
III— C— 1— e. All Other Potential Viral Vectors 
III— C— 1— f. Nonviral Vectors 
III— C— 2. Invertebrate Host-Vector Systems 
III— C— 2— a. Insect Viral Vectors 
III— C— 2— b. Nonviral Vectors 
III— C— 3. Plant Viral Host-Vector Systems 
III— C— 4. Plant Host-Vector Systems Other 
than Viruses 
III— C— 5. Fungal or Similar Lower 
Eukaryotic Host-Vector Systems 
III— C— 6. Return of DNA Segments to a 
Higher Eukaryotic Host of Origin 
III— 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 
III— D. Complementary DNAs 
III— E. Synthetic DNAs 
IV. Roles and Responsibilities 
IV- A. Policy 
IV-B. General Applicability 
IV-C. General Definitions 
IV-D. Responsibilities of the Institution 
IV-D-1. (General) 
IV-D-2. Membership and Procedures of the 
IBC 
IV-D-3. Functions of the IBC 
IV-D-4. Biological Safety Officer 
IV-D-5. Principal Investigator 
IV-D-5-a. PI — General 
IV-D-5-b. Submissions by the PI to NIH 
IV-D-5-c. Submissions by the PI to the IBC 
IV-D-5-d. PI Responsibilities After 
Approval but Prior to Initiating the 
Research 
IV-E. Responsibilities of NIH 
IV-E-1. Director 
IV-E-l-a. General Responsibilities of the 
Director, NIH 
IV-E-l-b. Specific Responsibilities of the 
Director, NIH 
IV-E-2. Recombinant Advisory Committee 
IV-E-3. The Office of Recombinant DNA 
Activities 
IV-E-4. Other NIH Components 
IV-F. Registration 
IV-F-1. Required Registration 
IV-F-2. Federal Agency Registration 
IV-F-3. Voluntary Registration and 
Certification 
IV-F-4. Disclosure of Information 
IV-G. Compliance 
VI. Voluntary Compliance 
VI-A. Basic Policy 
VI-B. IBC Approval 
VI-C. Registration 
VI-D. Cetification of Host-Vector Systems 
VI-E. Requests for Exceptions, Exemptions, 
Approvals 
VI-F. Protection of Proprietary Data 
Appendix A — List of Exchangers. 
Appendix B — Classification 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 III— A. 
Appendix E — Certain Actions Taken with 
Regard to the Guidelines. 
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. Definitioi\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-l. Formation of recombinant 
DNAs derived from the pathogenic 
organisms classified ( 1 ) as Class 3, 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 potent for 
vertebrates [2A) (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 pathogen 
with increased virulence and host range 
beyond that which occurs by natural 
genetic exchange. { 2A ) 
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. [2 A) 
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 (5). (See Section IV-E-l-b- 
(3)— (d).) 
We differentiate between small- and 
large-scale experiments with organisms 
containing recombinant DNAs because 
the probability of escape from 
containment barriers normally increases 
with increasing scale. 
Experiments in Categories I-D-l 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) provided 
that these experiments are expressly 
approved by the Director, NIH, with 
advice of the Recombinant DNA 
Advisory Committee after appropriate 
notice and opportunity for public 
[16] 
