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DNA Fragments. Nature 251. 476-481. 
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Sites Only in the Non-Essential Region of the 
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Bleche, K. Denniston-Thompson, H. E. Faber, 
L A. Furlong, D. J. Gunwald, D. O. Kiefer, D. 
j D. Moore J. W. Shumm, E. L Sheldon, and O. 
Smithies (1977). Charon Phages; Safer 
Derivatives of Bacteriophage Lambda for 
DNA Cloning. Science 196, 163-169. 
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An Improved Lambda Vector Construction of 
Model Recombinants Coding for Kanamycin 
Resistance, Gene 1, 209-227. 
(13) Leder, P., D. Tiemeier and L Enqulst 
(1977). EK2 Derivatives of Bacteriophage 
Lambda Useful in the Cloning of DNA from 
Higher Organisms: The ??????? WES System. 
Science 196, 175-177. 
(14) Skalka, A. (1978). Current Status of 
Coliphage, EK2 Vectors. 
(15) Szybalski, W., A. Skalka, S. 
Gottesman, A. Campbell, and D. Botstein 
i (1978). Standardized Laboratory Tests for 
EK2 Certification. Gene 3, 36-38. 
Appendix J — Federal Interagency 
Advisory Committee on Recombinant 
I DNA Research 
Appendix J-I. Federal Interagency 
Advisory Committee. The Federal 
Interagency Advisory Committee on 
Recombinant DNA Research advises the 
Secretary of the Department of Health 
and Human Services, the Assistant 
Secretary for Health, and the Director, 
National Institutes of Health, on the 
coordination of those aspects of all 
Federal programs and activities relating 
to recombinant DNA research. The 
committee provides for communication 
and exchange of information necessary 
to maintain adequate coordination of 
such programs and activities. The 
committee is responsible for facilitating 
compliance with a uniform set of 
guidelines in the conduct of this 
research in the public and private 
sectors and, where warranted, to 
suggest administrative or legislative 
proposals. 
The Director of the NIH, or his 
designee, serves as chairman, and the 
committee includes representation from 
all Departments and Agencies whose 
programs involve health functions or 
responsibilities as determined by the 
Secretary. 
Departments and agencies which have 
representation on this committee as of 
December 1980 are: 
Department of Agriculture 
Department of Commerce 
Department of Defense 
Department of Energy 
Environmental Protection Agency 
Executive Office of the President 
Department of Health and Human 
Services 
Office of the Assistant Secretary for 
Health 
Centers for Disease Control 
Food and Drug Administration 
National Institutes of Health 
Department of the Interior 
Department of Justice 
Department of Labor 
National Aeronautics and Space 
Administration 
National Science Foundation 
Nuclear Regulatory Commission 
Department of State 
Department of Transportation 
Arms Control and Disarmament Agency 
Veterans Administration 
At the second meeting of the 
committee on November 23, 1976, all of 
the Federal agencies endorsed the 
Guidelines, and Departments which 
support or conduct recombinant DNA 
research agreed to abide by the 
Guidelines}!). 
Appendix J— II. — Footnote of Appendix J 
(!) Minutes of the First eight meetings of the 
Federal Interagency Advisory Committee on 
Recombinant DNA Research are reproduced 
in Recombinant DNA Research, Volume 2, 
Documents Relating to “NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules," June 1976 — November 1977. 
Appendix K — Physical Containment for 
Large-Scale Uses of Organisms 
Containing Recombinant DNA 
Molecules 
This part of the Guidelines specifies 
physical containment guidelines for 
large-scale (greater than 10 liters of 
culture) research or production involving 
viable organisms containing 
recombinant DNA molecules. It shall 
apply to large-scale research or 
production activities as specified in 
Section III— B— 5 of the Guidelines. 
AlLprovisions of the Guidelines shall 
apply to large-scale research or 
production activities with the following 
modifications: 
• Appendix K shall replace Appendix 
G when quantities in excess of 10 liters 
of culture are involved in research or 
production. 
• The institution shall appoint a 
Biological Safety Officer (BSO) if it 
engages in large-scale research or 
production activities involving viable 
organisms containing recombinant DNA 
molecules. The duties of the BSO shall 
include those specified in Section IV-B- 
4 of the Guidelines. 
• The institution shall establish and 
maintain a health surveillance program 
for personnel engaged in large-scale 
research or production activities 
involving viable organisms containing 
recombinant DNA molecules which 
require BL3 containment at the 
laboratory scale. The program shall 
include: preassignment and periodic 
physical and medical examinations; 
collection, maintenance and analysis of 
serum specimens for monitoring 
serologic changes that may result from 
the employee’s work experience; and 
provisions for the investigation of any 
serious, unusual or extended illnesses of 
employees to determine possible 
occupational origin. 
Appendix K-I. Selection of Physical 
Containment Levels. The selection of 
the physical containment level required 
for recombinant DNA research or 
production involving more than 10 liters 
of culture is based on the containment 
guidelines established in Part III of the 
Guidelines. For purposes of large-scale 
research or production, three physical 
containment levels are established. 
These are referred to as BLl-LS, BL2- 
LS, and BL3-LS. The BL-LS level of 
physical containment is required for 
large-scale research or production of 
viable organisms containing 
recombinant DNA molecules which 
require BLl containment at the 
laboratory scale. (The BLl-LS level of 
physical containment is recommended 
for large-scale research or production of 
viable organisms for which BLl is 
recommended at the laboratory scale 
such as those described in Appendix C.) 
The BL2-LS level of physical 
containment is required for large-scale 
research or production of viable 
organisms containing recombinant DNA 
molecules which require BL2 
containment at the laboratory scale. The 
BL3-LS level of physical containment is 
required for large-scale research or 
production of viable organisms 
containing recombinant DNA molecules 
which require BL3 containment at the 
laboratory scale. No provisions are 
made for large-scale research or 
production of viable organisms 
containing recombinant DNA molecules 
which require BL4 containment at the 
laboratory scale. If necessary, these 
requirements will be established by NIH 
on an individual basis. 
Appendix K-II. BLl-LS Level. 
Appendix K-II-A. Cultures of viable 
orgainsma containing recombinant DNA 
molecules shall be handled in a closed 
system (e.g., closed vessel used for the 
propagation and growth of cultures) or 
other primary containment equipment 
(e.g., biological safety cabinet containing 
a centrifuge used to process culture 
fluids) which is designed to reduce the 
potential for escape of viable organisms. 
Volumes less than 10 liters may be 
handled outside of a closed system or 
other primary containment equipment 
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