60108 
NOTICES 
[41 10-08-M] 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
National Inditutai of Health 
GUIDELINES FOR RESEARCH INVOLVING 
RECOMBINANT DNA MOLECULES 
December 1978. 
Contents 
I. SCOPE OF THE GUIDELINES 
I-A. Purpose 
I-B. Definition of Recombinant DNA Mol- 
ecules 
III-D. 
I-C. 
General Applicability (see IV-B) 
III-E. 
I-D. 
Prohibitions 
I-E. 
Exemptions 
I-F. 
General Definitions (see IV-C) 
rv-A. 
IV-B. 
II. CONTAINMENT 
IV-C. 
II-A. 
Standard Practices and Training 
IV-D. 
II-B. Physical Containment Levels 
II-B-1. PI Level 
II-B-l-a. Laboratory Practices 
II-B-l-b. Containment Equipment 
II-B-l-c. Special Laboratory Design 
II-B-2. P2 Level 
II-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 
II-C. Shipment 
II-D. Biological Containment 
II-D-1. Levels of Biological Containment 
II-D- 1 -a. HV1 
II-D-l-b. HV2 
II-D-l-c. HV3 
II-D-2. Certification of Host-Vector Sys- 
tems 
II-D-2-a. Responsibility 
II-D-2-b. Data To Be Submitted for Certi- 
fication 
II-D-3. Distribution of Certified Host-Vec- 
tors 
III. CONTAINMENT GUIDELINES FOR COVERED 
EXPERIMENTS 
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-l-c. Human Adenoviruses 2 and 5 
III-C-1-d. Murine Adenovirus Strain PL 
III-C-1-e. All Other Potential Viral Vec- 
tors 
III-C-2. Invertebrate Host- Vector Systems 
in Which Insect Viruses Are Used to Prop- 
agate Other DNA Segments 
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 Eukaryo- 
tic Host- Vector Systems 
IV. ROLES AND RESPONSIBILITIES 
IV-D-1. (General) 
IV-D-2. Membership and Procedures of 
the IBC 
1V-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 Ap- 
proval but Prior to Initiating the Re- 4 
search 
IV-D-5-e. PI Responsibilities During the 
Conduct of the Approved Research 
IV-E. Responsibilities of NIH 
IV-E-1. Director 
rV-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 Certi- 
fication 
IV-F-4. Disclosure of Information 
IV-G. Compliance 
V. FOOTNOTES AND REFERENCES 
III-A. Classification of Experiments Using 
the E. Coli K-12 Host-Vector Systems 
III-A- 1. Shotgun Experiments 
m-A-l-a. Eukaryotic DNA Recombinants 
III-A-l-b. Prokaryotic DNA Recombinants 
III-A-2. Plasmids, Bacteriophages, and 
Other Viruses 
III-A-2-a. Viruses of Eukaryotes 
III-A-2-b. Eukaryotic Organelle DNA’s 
III-A-2-c. Prokaryotic Plasmid and Phage 
DNA’s 
III-A-3. Lowering of Containment Levels 
for Characterized or Purified DNA Prep- 
arations and Clones 
III-A-3-a. Purified DNA Other than Plas- 
mids, Bacteriophages, and Other Viruses 
III-A-3-b. Characterized Clones of DNA 
Recombinants 
III-B. Experiments with Other Prokaryo- 
tic Host-Vectors 
III-B-1. HV1 Systems 
III-B-2. Return of DNA Segments to Non- 
HV1 Host of Origin 
III-B-3. Non-HVl Systems 
Appendix A: List of Exchangers 
Appendix B: Classification of Microorga- 
nisms on the Basis of Hazard 
I. Scope of the Guidelines 
I-A. Purpose. The purpose of these 
Guidelines is to specify practices for 
constructing and handling (i) recom- 
binant DNA molecules and (ii) organ- 
isms and viruses containing recombin- 
ant DNA molecules. 
I-B. Definition of Recombinant DNA 
Molecules. In the context of these 
Guidelines, recombinant DNA mole- 
cules are defined as either <i) mole- 
cules which are constructed outside 
living cells by joining natural or syn- 
thetic DNA segments to DNA mole- 
cules that can replicate in a living cell, 
or (ii) DNA molecules that result from 
FEDERAL REGISTER, VOL. 43, NO. 247— FRIDAY, DECEMBER 
[ 30 ] 
the replication of those described in (i) 
above. 
I-C. General Applicability. See Sec- 
tion IV-B. 
I-D. Prohibitions. The following ex- , 
periments are not to be initiated at 
the present time: 
I-D-l. Formation of recombinant 
DNAs derived from the pathogenic or- 
ganisms classifiedil] as Class 3, 4, or 
5[21 or from cells known C2A] to be in- 
fected with such agents, regardless of 
the host-vector system used. 
I-D-2. Deliberate formation of re- 
combinant DNAs containing genes for 
the biosynthesis of toxins potent for 
vertebrates [2A] (e.g., botulinum or 
diphtheria toxins; venoms from in- 
sects, snakes, etc.). 
I-D-3. Deliberate creation by the use 
of recombinant DNA of a plant patho- 
gen with increased virulence and host 
range beyond that which occurs by 
natural genetic exchange. [2A1 
I-D-4. Deliberate release into the en- 
vironment of any organism containing 
recombinant DNA. 
I-D-5. Deliberate transfer of a drug 
resistence trait to microorgansims 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 medi- 
cine or agriculture. [2 A] 
I-D-6. Large-scale experiments (e.g., 
more than 10 liters of culture) with or- 
ganisms containing recombinant 
DNAs, unless the recombinant DNAs 
are rigorously characterized and the 
absence of harmful sequences estab- 
lished [31. (See Section IV-E-l-b-(3)- 
(d).) 
We differentiate between small- and 
large-scale experiments with organ- 
isms containing recombinant DNAs be- 
cause the probability of escape from 
containment barriers normally in- 
creases with increasing scale. 
Experiments in these categories may 
be excepted[41 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, with 
advice of the Recombinant DNA Advi- 
sory Committee after appropriate 
notice and opportunity for public com- 
ment. (Section IV-E-l-b-G)-(e).) 
I-E. Exemptions. It must be empha- 
sized that the following exemptions[41 
are not meant to apply to experiments 
described in the Section 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-l. Those that are not in organ- 
isms or viruses. [51 
I-E-2. Those that consist entirely or 
DNA segments from a single nonchro- 
mosomal or viral DNA source, though 
22, 1978 
