[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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