1. Overview of the NIH Guidelines for Research Involving Recombinant DNA Molecules
This is an edited combination of Haverford College’s IBC training materials and training materials from the NIH; by Gretchen Hofmeister, April 2017

2. NIH Guidelines for Research Involving Recombinant DNA Molecules
These guidelines specify practices for constructing and handling:
Recombinant DNA (rDNA) molecules
Organisms and viruses containing rDNA molecules
History:
Guidelines originally established in 1975 at the Asilomar Conference on Recombinant DNA
Established recommendations to perform rDNA experiments in a manner safe for researchers and the public
Revised as needed, most recently in April 2016

3. Why does Carleton need to oversee rDNA research?
Carleton receives NSF funding for non-exempt projects involving rDNA research, therefore:
ALL researchers at Carleton must comply with the NIH Guidelines
Even those not directly receiving NIH funding
AND
Just one non-compliant researcher could jeopardize NIH grant funding for the entire college

4. How can Carleton and St. Olaf stay in compliance with the NIH Guidelines?
The NIH Office of Biotechnology Activities (OBA) fosters awareness of and adherence to the NIH Guidelines
OBA periodically conducts site visits to review how institutions follow the NIH Guidelines
Compliance with the NIH Guidelines is the responsibility of:
The Institution
The Institutional Biosafety Committee (IBC)
The Principal Investigator

5. The Institution’s Responsibilities
Provide training tools to researchers on the safe use of rDNA
Inform Principal Investigators of their responsibilities outlined in the guidelines
Form an Institutional Biosafety Committee (IBC)

6. Institutional Biosafety Committee (IBC) Responsibilities
On behalf of the institution, the IBC is responsible for:
Reviewing rDNA research conducted at or sponsored by the institution
Setting containment levels
Notifying PI of the results of the IBC’s review and approval
Reporting significant problems or violations with the NIH guidelines to NIH/OBA
Developing emergency plans covering accidental spills and personnel contamination resulting from rDNA research

7. Institutional Biosafety Committee (IBC)
Functions to review, approve, and oversee projects in accordance with the responsibilities defined in NIH Guidelines Section IV-B-2
Committee membership requirements:
Individuals with expertise in rDNA technology
Individuals with expertise in human gene transfer*
Individual with expertise in plant containment*
Scientist with expertise in animal containment*
Biosafety officer¶
Community members not affiliated with institution
*when experiments involve plants, animals, or humans
¶For research at BL3 or BL4

8. What are rDNA molecules?
Definition of rDNA molecules:
Molecules constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell
Synthetic DNA segments, likely to yield a potentially harmful polynucleotide or polypeptide, are considered equivalent to their natural DNA counterpart.
Examples:
Human gene transfer
Cloning plasmids
Viral or bacterial vectors
Transgenic animals
Genetically modified cell lines

9. NIH Guidelines – Section II
Safety Considerations
Risk assessments: (Appendix B)
RG RG RG RG 4
Agents that are not associated with disease in healthy adult humans
Agents that are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available
Agents that are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available (high individual risk but low community risk)
Agents that are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available (high individual risk and high community risk)

10. NIH Guidelines – Section II
Safety Considerations
Containment
Physical (Appendix G)
Practices
Equipment
Facilities
Biological (Appendix I)
Survival
Transmission
BSL4
BSL3
BSL2
BSL1

11. Section III - Levels of Review
IBC, RAC, NIH Director
IBC, OBA (in consult with experts)
IBC, IRB, RAC
IBC
IBC (notification)
Exempt
RISK

12. NIH Guidelines - Section III Levels of Review
Level of review
Example of types of research covered
Relevant section(s) of the NIH Guidelines
IBC, RAC review, and NIH Director review and approval
Experiments that compromise the control of disease agents in medicine through deliberate transfer of a drug resistance trait
III-A
IBC approval and NIH review for containment determinations
Experiment involving the cloning of toxin molecules with LD50 of less than 100 nanograms per kilogram of body weight
III-B
IBC and IRB approval and NIH review before research participant enrollment
Experiments involving the deliberate transfer of recombinant or synthetic nucleic acid molecules into a human research participant
III-C
IBC approval before initiation
Creating stable germline alterations of an animal’s genome, or testing viable recombinant or synthetically modified microorganisms on whole animals, where BL-2 containment or greater is necessary
III-D
IBC notice at initiation
Creating stable germline alterations of rodents by introduction of recombinant or synthetic nucleic acid molecules when these experiments require only BL-1 containment
III-E
Exempt from the NIH Guidelines. IBC registration not required if experiment not covered by Sections III-A, III-B, or III-C
Purchase or transfer of transgenic rodents
III-F

13. Exempt rDNA Experiments
NIH Guidelines “Section III-F” covers exempt experiments
Registration with the IBC is not required
Exempt experiments are those involving rDNA molecules that:
III-F-1: are not in organisms or viruses
III-F-2: consist entirely of DNA from single nonchromosomal or viral DNA source
III-F-3: consist entirely of DNA from a prokaryotic host when propagated only in that host
III-F-4: consist entirely of DNA from an eukaryotic host when propagated only in that host (excluding DNA from viruses)
III-F-5: consist entirely of DNA from different species that exchange DNA by known physiological processes (list periodically updated in Appendices A-I through A-VI)
III-F-6: do not present significant risk to health or to the environment as determined by NIH Director with the advice of RAC

14. Training Requirements
All personnel who are listed on a registration document must complete training, including: PI
Anyone directly involved in rDNA experiments
Registrations will not be approved until all training is complete
This module satisfies the knowledge portion of training on the NIH Guidelines
PI is responsible for “hands-on” training of personnel

15. Carleton’s rDNA Registration Review Process
Submit the completed and signed registration forms to the chair of the IBC (Associate Dean of the College)
A member of the IBC will review the registration form and contact you with any questions or necessary revisions
The IBC reviews registrations as needed
The IBC is not permitted to review registrations outside of a fully convened meeting SO
Please be sure to submit registrations in a timely fashion, allowing enough time for a full meeting of the IBC to be arranged and convened

16. Carleton’s rDNA Registration Review Process
If the IBC approves your registration, you will receive an approval letter with:
IBC registration number (ex. #11-805)
The biosafety level (BSL) required
The animal biosafety level (ABSL) required (if applicable)
Registrations must be renewed every 3 years
If your registration is for work requiring IBC approval BEFORE initiation (Sections III-A, III-B, III-C, III-D), you may not start work until an official approval letter has been received

17. Additional Resources to Foster NIH Guideline Understanding
Office of Biotechnology Activities website
NIH Guidelines
Office of Environmental Health and Radiation Safety’s (EHRS) website for Biological Safety at U. Penn
St. Olaf College Biosafety Information
Contact Carleton or St. Olaf IBC members