E8-12924. Office of the Director, Office of Biotechnology Activities; Recombinant DNA Research: Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines)

AGENCY:

National Institutes of Health (NIH), DHHS.

ACTION:

Notice of a final action under the NIH Guidelines and notice of additions to Appendix D of the NIH Guidelines.

SUMMARY:

Proposal to conduct research involving the deliberate transfer of a drug resistance trait to a microorganism that causes disease in humans has been reviewed by the Recombinant DNA Advisory Committee (RAC) and approved by the NIH Director.

DATES:

The final action is effective April 7, 2008.

FOR FURTHER INFORMATION CONTACT:

Background documentation and additional information can be obtained from the Office of Biotechnology Activities (OBA), National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, Maryland 20892-7985; e-mail at [e-mail], or telephone at 301-496-9838. The NIH/OBA Web site is located at: http://www4.od.nih.gov/​oba/​.

SUPPLEMENTARY INFORMATION:

This final action allows Dr. David Walker, University of Texas Medical Branch at Galveston to deliberately introduce a gene encoding chloramphenicol resistance into Rickettsia conorii. This approval is specific to Dr. Walker. His research with these resistant organisms may only occur under the conditions outlined below. It should be noted that any work involving the introduction of chloramphenicol resistance into R. conorii by other investigators would need to be reviewed by the RAC and specifically approved by the NIH Director.

Background Information and Response to Comments: On July 24, 2007, background on the proposed action and information on how to submit public comment, was published in the Federal Register (72 FR 40320). On September 17, 2007, and December 5, 2007, the RAC discussed this proposed action and a proposed action to allow the transfer of chloramphenicol resistance into R. typhi. The RAC reviewed the three public comments received regarding the transfer of chloramphenicol resistance to R. conorii and to R. typhi. The RAC unanimously recommended that the transfer of chloramphenicol resistance to R. conorii be approved at this time and the majority of the members present did not recommend the transfer of chloramphenicol resistance to R. typhi. On April 7, 2008, the NIH Director approved the transfer of chloramphenicol resistance to R. conorii with the following containment provisions/stipulations:

(1) Perform all research involving the introduction of chloramphenicol resistance into Rickettsia conorii at minimum biosafety level 3 (BL-3) containment. Access will therefore be restricted to well-trained personnel whose presence is required for the conduct of this work. In addition, there must be a standard training procedure to make sure that personnel are trained and training is ongoing.

(2) Maintain at least one back-up power source to insure computer based security remains in place at all times.

(3) Include a signature nucleic acid sequence (“bar-code”) to allow identification of laboratory-created (chloramphenicol resistant) strains.

(4) Incorporate the following elements into a health surveillance program for individuals working with chloramphenicol resistant R. conorii:

(a) Exclude those with a known allergy or sensitivity to tetracycline, and in particular doxycycline, from working with chloramphenicol resistant R. conorii;

(b) Obtain and store a baseline blood sample from laboratory workers;

(c) Do not permit pregnant individuals to work in any laboratory in which chloramphenicol resistant rickettsia is being handled;

(d) Provide workers education on the possible clinical manifestations of a rickettsial laboratory acquired infection;

(e) Develop a medical card that would be carried by all laboratory workers that includes at a minimum the following:

(i) Identification of the organism to which the labworker has been exposed;

(ii) Identification of key personnel responsible for providing diagnosis and treatment;

(iii) A CDC telephone number for reporting the infection and obtaining treatment recommendations; and

(iv) A twenty-four hour contact number for the principal investigators.

(5) Have a detailed standard operating procedures outlining the specific steps to be taken in the case of a laboratory exposure or infection containing at a minimum:

(a) Identification of key personnel who would provide diagnostic testing and treatment; and

(b) Instructions on managing exposures or infections discovered during off hours (after close of business, holidays, weekends, etc.).

Additions to Appendix D of the NIH Guidelines: In accordance with Section III-A of the NIH Guidelines, Appendix D of the NIH Guidelines will be modified as follows to reflect the recent approvals for the transfer of drug resistance traits to microorganisms. Specifically, Appendix D will be modified to include approval of experiments to be conducted by Dr. Daniel Rockey, Oregon State University and Dr. Walter Stamm, University of Washington in which tetracycline resistance will be transferred into Chlamydia trachomatis (72 FR 61661) and approval of the Dr. Walker's experiment to transfer chloramphenicol resistance to Rickettsia conorii.

Appendix D-116. Dr. Daniel Rockey at Oregon State University and Dr. Walter Stamm at the University of Washington may conduct experiments to deliberately transfer a gene encoding tetracycline resistance from Chlamydia suis (a swine pathogen) into C. trachomatis (a human pathogen). This approval is specific to Drs. Rockey and Stamm and research with these resistant organisms may only occur under the conditions specified by the NIH Director. It should be noted that any work involving the introduction of tetracycline resistance into C. trachomatis by other investigators would need to be reviewed by the RAC and specifically approved by the NIH Director. This approval was effective as of September 24, 2007 (72 FR 61661).

Appendix D-117. Dr. David Walker at the University of Texas Medical Branch at Galveston may conduct experiments to deliberately introduce a gene encoding chloramphenicol resistance into Rickettsia conorii. This approval is specific to Dr. Walker and research with these resistant organisms may only occur under the conditions specified by the NIH Director. It should be noted that any work involving the introduction of chloramphenicol resistance into R. conorii by other investigators would need to be reviewed by the RAC and specifically approved by the NIH Director. This approval was effective as of April 7, 2008.

Dated: June 3, 2008.

Amy P. Patterson,

Director, Office of Biotechnology Activities.