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Creation and Use of Recombinant DNA Molecules in Research
The following information is from the NIH Guidelines for Research Involving Recombinant DNA Molecules
In the context of the NIH Guidelines, recombinant DNA molecules are defined as either: (i) molecules that are constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or (ii) molecules that result from the replication of those described in (i) above.
Synthetic DNA segments which are likely to yield a potentially harmful polynucleotide or polypeptide (e.g., a toxin or a pharmacologically active agent) are considered as equivalent to their natural DNA counterpart. If the synthetic DNA segment is not expressed in vivo as a biologically active polynucleotide or polypeptide product, it is exempt from the NIH Guidelines.
Genomic DNA of plants and bacteria that have acquired a transposable element, even if the latter was donated from a recombinant vector no longer present, are not subject to the NIH Guidelines unless the transposon itself contains recombinant DNA.
Section I-C-1. The NIH Guidelines are applicable to:
Section I-C-1-a. All recombinant DNA research within the United States (U.S.) or its territories that is within the category of research described in either Section I-C-1-a-(1) or Section I-C-1-a-(2).
Section I-C-1-a-(1). Research that is conducted at or sponsored by an institution that receives any support for recombinant DNA research from NIH, including research performed directly by NIH. An individual who receives support for research involving recombinant DNA must be associated with or sponsored by an institution that assumes the responsibilities assigned in the NIH Guidelines.
Section I-C-1-a-(2). Research that involves testing in humans of materials containing recombinant DNA developed with NIH funds, if the institution that developed those materials sponsors or participates in those projects. Participation includes research collaboration or contractual agreements, not mere provision of research materials.
Section I-C-1-b. All recombinant DNA research performed abroad that is within the category of research described in either Section I-C-1-b-(1) or Section I-C-1-b-(2).
Section I-C-1-b-(1). Research supported by NIH funds.
Section I-C-1-b-(2). Research that involves testing in humans of materials containing recombinant DNA developed with NIH funds, if the institution that developed those materials sponsors or participates in those projects. Participation includes research collaboration or contractual agreements, not mere provision of research materials.
Section I-C-1-b-(3). If the host country has established rules for the conduct of recombinant DNA research, then the research must be in compliance with those rules. If the host country does not have such rules, the proposed research must be reviewed and approved by an NIH-approved Institutional Biosafety Committee or equivalent review body and accepted in writing by an appropriate national governmental authority of the host country. The safety practices that are employed abroad must be reasonably consistent with the NIH Guidelines.
As a condition for NIH funding of recombinant DNA research, institutions shall ensure that such research conducted at or sponsored by the institution, irrespective of the source of funding, shall comply with the NIH Guidelines.
Information concerning noncompliance with the NIH Guidelines may be brought forward by any person. It should be delivered to both NIH/OBA and the relevant institution. The institution, generally through the Institutional Biosafety Committee, shall take appropriate action. The institution shall forward a complete report of the incident recommending any further action to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD 20892-7985, 301-496-9838/301-496-9839 (fax) (for non-USPS mail, use zip code 20817).
In cases where NIH proposes to suspend, limit, or terminate financial assistance because of noncompliance with the NIH Guidelines, applicable DHHS and Public Health Service procedures shall govern.
The policies on compliance are as follows:
Section I-D-1. All NIH-funded projects involving recombinant DNA techniques must comply with the NIH Guidelines. Non-compliance may result in: (i) suspension, limitation, or termination of financial assistance for the noncompliant NIH-funded research project and of NIH funds for other recombinant DNA research at the institution, or (ii) a requirement for prior NIH approval of any or all recombinant DNA projects at the institution.
Section I-D-2. All non-NIH funded projects involving recombinant DNA techniques conducted at or sponsored by an institution that receives NIH funds for projects involving such techniques must comply with the NIH Guidelines. Noncompliance may result in: (i) suspension, limitation, or termination of NIH funds for recombinant DNA research at the institution, or (ii) a requirement for prior NIH approval of any or all recombinant DNA projects at the institution.
The following terms, which are used throughout the NIH Guidelines, are defined as follows:
Section I-E-1. An "institution" is any public or private entity (including Federal, state, and local government agencies).
Section I-E-2. An "Institutional Biosafety Committee" is a committee that: (i) meets the requirements for membership specified in Section IV-B-2, Institutional Biosafety Committee (IBC), and (ii) reviews, approves, and oversees projects in accordance with the responsibilities defined in Section IV-B-2, Institutional Biosafety Committee (IBC).
Section I-E-3. The "Office of Biotechnology Activities (OBA)" is the office within the NIH that is responsible for: (i) reviewing and coordinating all activities relating to the NIH Guidelines, and (ii) performing other duties as defined in Section IV-C-3, Office of Biotechnology Activities (OBA).
Section I-E-4. The "Recombinant DNA Advisory Committee" is the public advisory committee that advises the Department of Health and Human Services (DHHS) Secretary, the DHHS Assistant Secretary for Health, and the NIH Director concerning recombinant DNA research. The RAC shall be constituted as specified in Section IV?C?2, Recombinant DNA Advisory Committee (RAC).
Section I-E-5. The "NIH Director" is the Director of the National Institutes of Health, or any other officer or employee of NIH to whom authority has been delegated.
Section I-E-6. "Deliberate release" is defined as a planned introduction of recombinant DNA-containing microorganisms, plants, or animals into the environment.
Section I-E-7. “Enrollment” is the process of obtaining informed consent from a potential research participant, or a designated legal guardian of the participant, to undergo a test or procedure associated with the gene transfer experiment.
Section II-A. Risk Assessment
Section II-A-1. Risk Groups
Risk assessment is ultimately a subjective process. The investigator must make an initial risk assessment based on the Risk Group (RG) of an agent (see Appendix B, Classification of Human Etiologic Agents on the Basis of Hazard). Agents are classified into four Risk Groups (RGs) according to their relative pathogenicity for healthy adult humans by the following criteria: (1) Risk Group 1 (RG1) agents are not associated with disease in healthy adult humans. (2) Risk Group 2 (RG2) agents are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available. (3) Risk Group 3 (RG3) agents are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available. (4) Risk Group 4 (RG4) agents are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available.
Section II-A-2. Criteria for Risk Groups
Classification of agents in Appendix B, Classification of Human Etiologic Agents on the Basis of Hazard, is based on the potential effect of a biological agent on a healthy human adult and does not account for instances in which an individual may have increased susceptibility to such agents, e.g., preexisting diseases, medications, compromised immunity, pregnancy or breast feeding (which may increase exposure of infants to some agents).
Personnel may need periodic medical surveillance to ascertain fitness to perform certain activities; they may also need to be offered prophylactic vaccines and boosters (see Section IV-B-1-f, Responsibilities of the Institution, General Information).