[Federal Register Volume 68, Number 219 (Thursday, November 13, 2003)]
[Notices]
[Pages 64350-64351]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-28377]


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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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