E7-14215. Office of Biotechnology Activities; Recombinant DNA Research: Proposed Actions Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines)

ACTION:

Notice of consideration of proposed actions under the NIH Guidelines.

SUMMARY:

Proposals to conduct research involving the deliberate transfer of a chloramphenicol resistance trait to Rickettsia typhi and conorii has been submitted to the NIH Office of Biotechnology Activities (OBA). The acquisition of this antibiotic resistance trait could possibly compromise the use of a class of antibiotics for the treatment of Rickettsia infections in humans. Under the NIH Guidelines, these experiments can proceed only after they are reviewed by the NIH Recombinant DNA Advisory Committee (RAC) and specifically approved by the NIH Director as Major Actions. These proposals will be discussed at the September 17-19, 2007 RAC meeting.

DATES:

The public is encouraged to submit written comments on these proposed actions. Comments may be submitted to the OBA in paper or electronic form at the OBA mailing, fax, and e-mail addresses shown below. Comments submitted by September 6, 2007 will be reproduced and distributed to the RAC for consideration at its September meeting. In addition, an opportunity for public comment will be provided at that meeting. All written comments received in response to this notice will be available for public inspection at the NIH OBA office, 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892 (telephone, 301-496-9838), weekdays between the hours of 8:30 a.m. and 5 p.m.

FOR FURTHER INFORMATION CONTACT:

Contact OBA by e-mail at [e-mail], or telephone at 301-496-9838, if you have questions, or require additional information about these proposed actions. Comments may be submitted to the same e-mail address or by fax at 301-496-9839 or sent by U.S. mail to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, Maryland 20892. For additional information about the RAC meeting at which these proposed actions will be deliberated, please visit the NIH OBA Web site at: http://www4.od.nih.gov/​oba/​.

SUPPLEMENTARY INFORMATION:

OBA has received information regarding proposed experiments, which, to proceed, would require Major Actions under Section III-A-1-a of the NIH Guidelines. Under this section, if the deliberate transfer of a drug resistance trait to micro-organisms could compromise the use of the drug to control disease in humans, veterinary medicine, or agriculture the experiment must be reviewed by the RAC. Dr. David Walker, Chairman, Pathology Department, University of Texas Medical Branch, proposes to introduce DNA constructs encoding resistance to the antibiotic chloramphenicol into Rickettsia conorii and Rickettsia typhi with the goal of developing genetic tools to study the biology of these organisms and in particular the genes associated with virulence. Dr. Abdu Azad, Professor of Microbiology, University of Maryland proposes a similar experiment in R. typhi. Dr. Walker's ultimate goal is to develop a vaccine for Rickettsia prowazekii, a Select Agent that causes epidemic typhus.

Rickettsiae are spread to humans by arthropods and human to human transmission does not occur directly. R. conorii causes Mediterranean Spotted Fever, a disease endemic to southern Europe and Africa. Clinically, it typically presents with high fever, flu-like symptoms, headache and a maculopapular rash. The disease is generally mild but severe forms include major neurological manifestations and multi-organ failure with a mortality rate estimated up to 2.5%. R. typhi is found in the United States and many other parts of the world, although it is relatively uncommon. The clinical presentation in humans includes fever, headache, other constitutional symptoms and, in up to 40% of adults, neurological symptoms. Although generally mild it has a 1-4% mortality rate. Current first-line treatment for R. typhi and R. conorii is doxycycline or chloramphenicol. Due to its safety profile, doxycycline is the preferred antibiotic but chloramphenicol is indicated in certain patients. Background information may be obtained by contacting NIH OBA via e-mail at [e-mail]. Alternatively, information is available on the OBA Web site at http://www4.od.nih.gov/​oba/​rac/​latestnewsrac.htm.

Dated: July 17, 2007.

Amy P. Patterson,

Director, Office of Biotechnology Activities, National Institutes of Health.