[Federal Register Volume 75, Number 99 (Monday, May 24, 2010)]
[Notices]
[Page 28811]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-12453]
[[Page 28811]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
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 a proposed action under Section III-
A-1 of the NIH Guidelines.
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SUMMARY: The NIH Guidelines requires certain recombinant research to be
reviewed by the NIH Recombinant DNA Advisory Committee and approved by
the NIH Director (Section III-A-1). Such research involves the
introduction of drug resistance into a microorganism if the
introduction of that drug resistance trait can compromise the ability
to treat disease caused by the microorganism in humans, animals or
agriculture. In order to meet the threshold for consideration under
Section III-A-1, the microorganism must be able to cause disease in
humans, animals or agriculture.
A proposal to deliberately transfer a chloramphenicol resistance
trait into an attenuated strain (CO92 lcr-) of Yersinia pestis has been
submitted to the NIH Office of Biotechnology Activities (OBA) by the
Institutional Biosafety Committee at Lawrence Livermore National
Laboratory (LLNL). Treatment guidelines recommend streptomycin as the
first-line antibiotic for treatment of disease caused by wild type Y.
pestis, and gentamicin is recommended when streptomycin is not
available. Doxycycline and chloramphenicol are also effective and
ciprofloxacin is recommended as prophylaxis and has been shown to treat
disease in animal models. The LLNL investigators will be using Y.
pestis CO92 lcr- strains that have already been made resistant to
ciprofloxacin or doxycycline through exposure of these attenuated
strains to these antibiotics. The proposed research involves the
addition of chloramphenicol resistance into these strains, thereby
creating lcr- Y. pestis strains that are resistant to multiple
antibiotics used to treat disease caused by this organism.
A fundamental question with respect to this line of proposed
research is whether this specific strain (lcr-) has the ability to
cause disease in humans and therefore should be subject to Section III-
A-1 of the NIH Guidelines. While there is evidence that the strain is
attenuated, this does not necessarily mean the strain is avirulent, and
the RAC will review the evidence regarding the ability of this strain
to cause disease. The recent death of a researcher at the University of
Chicago while working with an attenuated strain of Yersinia pestis
highlights that attenuated strains may be pathogenic in certain
populations. If a determination is made that that lcr- strains do pose
a potential public health risk, then these experiments will be
considered at this meeting under Section III-A-1 of the NIH Guidelines.
A recommendation will then be made as to whether this research should
be allowed to proceed and, if so, under what containment conditions.
The RAC will review of this proposed work at its June 16-17, 2010
meeting, which will be held at the Hilton Washington DC/Rockville Hotel
1750 Rockville Pike, Rockville, MD and is open to the public. The
public may also submit written comments.
DATES: The public is encouraged to submit written comments on this
proposed action. Comments may be submitted to the OBA in paper or
electronic form at the OBA mailing, fax, and e-mail addresses shown
below under the heading FOR FURTHER INFORMATION CONTACT. All comments
should be submitted by June 10, 2010. All written comments received in
response to this notice will be available for public inspection in the
NIH OBA office, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD
20892-7985, (Phone: 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
[email protected], or telephone at 301-496-9838, if you have questions, or
require additional information about this line of research. For
additional information about the RAC meeting at which this line of
research will be discussed, please visit the NIH OBA Web site at:
http://oba.od.nih.gov/oba/index.html.
SUPPLEMENTARY INFORMATION: Yersinia pestis is the causative organism
for plague and it regulated by the Department of Health and Human
Services (HHS) as a Select Agent pursuant to the Select Agent
Regulations (42 CFR part 73). There are a number of attenuated strains
of Yersinia pestis that do not contain certain virulence factors. The
strain that will be used in the proposed research, Yersinia pestis CO92
lcr-, lacks the plasmid called pCD1 or the ``low calcium response-lcr''
plasmid since it confers calcium dependence for growth at 37[deg] C.
Loss of the pCD1 plasmid is accompanied by a concomitant loss of
virulence as indicated in studies using several animal models. This
strain is excluded from the HHS list of Select Biological Agents and
Toxins http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20Exclusions.html#hhsAgents.
Additional background information may be obtained by contacting NIH
OBA via e-mail at [email protected] or by going to the OBA Web site at
http://oba.od.nih.gov/rdna/news_events_oba.html#RAC.
Dated: May 17, 2010.
Jacqueline Corrigan-Curay,
Acting Director, Office of Biotechnology Activities, National
Institutes of Health.
[FR Doc. 2010-12453 Filed 5-21-10; 8:45 am]
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