[Federal Register: November 13, 2003 (Volume 68, Number 219)]
[Notices]
[Page 64350-64351]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr13no03-58]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Office of the Secretary
Findings of Scientific Misconduct
AGENCY: Office of the Secretary, HHS.
ACTION: Notice.
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SUMMARY: Notice is hereby given that the Office of Research Integrity
(ORI)
[[Page 64351]]
and the Assistant Secretary for Health have taken final action in the
following case:
Timothy R. Smith, Ph.D., Michigan State University: Based on the
findings of Michigan State University, the respondent's admission, and
analysis conducted by ORI in its oversight review, the U.S. Public
Health Service (PHS) found that Timothy R. Smith, Ph.D., former
Postdoctoral Fellow, Department of Biochemistry and Molecular Biology
at Michigan State University, engaged in scientific misconduct in
research supported by National Institute of General Medical Sciences
(NIGMS), National Institutes of Health (NIH) grant P01 GM57323,
entitled ``Oxygen utilizing membrane heme proteins.''
Specifically, PHS found that Dr. Smith falsified and fabricated
data involving research into the physical interaction of prostaglandin
endoperoxide synthase-2 (PGHS-2) with cell membranes, and the effects
of arachidonate and nonsteroidal anti-inflammatory drugs (NSAIDs) on
PGHS-2 structure.
Dr. Smith committed scientific misconduct by falsifying and
fabricating data for the following tables and figures in his 2000
doctoral dissertation and in a paper in the Journal of Biological
Chemistry (275:40407-40415, 2000) entitled ``Arachidonic Acid and
Nonsteroidal Anti-inflammatory Drugs Induce Conformational Changes in
the Human Prostaglandin Endoperoxide H2 Synthase-2
(Cyclooxygenase-2)'' (JBC paper):
I. JBC paper Table II, entitled ``Comparison of inter-residue
distances as determined by EPR spectroscopy and as calculated from the
x-ray crystal structures'' (and corresponding Dissertation Table 6
entitled ``EPR determined and X-ray crystal modeled inter-nitroxide
distances of PGHS-2 MBD mutants'');
II. JBC paper Table III entitled ``Changes in inter-nitroxide
differences between PGHS-2 holoenzyme and the apoenzyme, and the
arachidonate, flurbiprofen, and SC58125 complexes'' (and corresponding
Dissertation Table 7), entitled ``Relative changes in inter-nitroxide
distances for NSAID and arachidonate complexes compared to the
unliganded enzyme'');
III. JBC paper Figure 4 (binding curves) (and corresponding
Dissertation Figure 20 entitled ``Binding curves for the association of
heme, flurbiprofen and arachidonic acid with PGHS-2 double mutants'');
IV. Dissertation Table 8 entitled ``EPR determined inter-nitroxide
distances for NSAID and arachidonate complexes of PGHS-2 MBD mutants;'
V. Dissertation Table 9 entitled ``Relative changes in inter-
nitroxide distances for NSAID and arachidonate complexes compared to
the unliganded enzyme;'
VI. Dissertation Table 10 entitled ``Kinetic properties and NSAID
sensitivities of PGHS-2 active site mutants;''
VII. Dissertation Table 12 entitled ``Relative PGHS-2 protein
incorporation of PGHS-2 into lipsomes of varying composition;''
IX. Dissertation Table 13 entitled ``EPR determined inter-nitroxide
distances for detergent solubilized and lipsome reconstituted PGHS-2
mutants;'' and
X. Dissertation Figure 27 entitled ``Lipid and activity profile of
sucrose gradient fractions.''
The research misconduct was significant for several reasons. First,
the JBC paper was novel in that it reported that binding of
arachidonate and NSAIDs induced structural changes in PHS-2. For the
naturally occurring fatty acid arachidonate, this had not previously
been shown. These results could be interpreted as having important
implications for understanding the catalytic mechanism of this enzyme.
In addition, a considerable expenditure of other researchers' time and
resources was prompted by using results generated from the falsified
and fabricated data in the JBC paper.
Dr. Smith has entered into a Voluntary Exclusion Agreement
(Agreement ) in which he has voluntarily agreed:
(1) to exclude himself from serving in any advisory capacity to PHS
including but not limited to service on any PHS advisory committee,
board, and/or peer review committee, or as a consultant for a period of
three (3) years, beginning on October 27, 2003;
(2) to exclude himself voluntarily from any contracting or
subcontracting with any agency of the United States Government and from
eligibility or involvement in nonprocurement programs of the United
States Government defined as ``covered transactions'' in the debarment
regulations at 45 CFR part 76 for a period of three (3) years,
beginning on October 27, 2003. During the three (3) year period of
voluntary exclusion, PHS grant funds may be used to pay for page
charges for any written work currently being prepared for submission
and/or publication on which Dr. Smith is listed as an author only if
(i) such written work is unrelated to the misconduct findings described
in the Agreement, (ii) Dr. Smith is not listed as first author, and
(iii) the publication does not state that Dr. Smith was supported by a
PHS grant. Dr. Smith must certify that all data supporting such written
work is true and accurate to the best of his knowledge; and
(3) to submit a letter within 30 days of notification of this
action to JBC requesting retraction of the following paper: Smith, T.,
McCracken, J., Shin, Y.K., & DeWitt, D. ``Arachidonic Acid and
Nonsteroidal Anti-inflammatory Drugs Induce Conformational Changes in
the Human Prostaglandin Endoperoxide H2 Synthase-2
(Cyclooxygenase-3).'' J. Biol. Chem. 275:40407-40415, 2000. Dr. Smith
agreed that the retraction will state that he alone was responsible for
the falsification and fabrication of the results and will specifically
list the falsified figures delineated on page 1 of the Agreement
(Findings I, II, and III). Dr. Smith must submit a draft of the
retraction letter for ORI approval prior to sending it to JBC. This
requirement for retraction will be noted on the ALERT System until Dr.
Smith sends a copy of the retraction letter to ORI.
FOR FURTHER INFORMATION CONTACT: Director, Division of Investigative
Oversight, Office of Research Integrity, 1101 Wootton Parkway, Suite
750, Rockville, MD 20852, (301) 443-5330.
Chris B. Pascal,
Director, Office of Research Integrity.
[FR Doc. 03-28377 Filed 11-12-03; 8:45 am]
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