[Federal Register Volume 67, Number 174 (Monday, September 9, 2002)]
[Notices]
[Pages 57239-57241]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-22794]


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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) and the Assistant Secretary for Health have taken final action in 
the following case:
    Zhenhai Yao, M.D., Ph.D., The University of North Carolina at 
Chapel

[[Page 57240]]

Hill: On August 20, 2002, the U.S. Public Health Service (PHS) entered 
into a Voluntary Exclusion Agreement with The University of North 
Carolina at Chapel Hill (UNC) and Zhenhai Yao, M.D., Ph.D., an 
Associate Professor of Anesthesiology, School of Medicine at UNC. Based 
on the UNC Report, the respondent's admissions, and additional analysis 
conducted by ORI in its oversight review, PHS found that Dr. Yao 
engaged in scientific misconduct in research funded by the National 
Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health 
(NIH).
    Specifically, PHS and UNC found that Dr. Yao:
    (1) Falsified two flourescent micrographs for figures presented in 
three NIH grant applications:
    A. Figure 5, p. 28, in a funded grant application in 1 R01 
HL067416-01, ``Mechanism of Preconditioning and Cardiac Apoptosis,'' 
submitted to NIH on May 31, 2000;
    B. Figure 6, p. 33, in a funded grant application in 1 R01 HL68250-
01, ``Free Radicals, PKC[delta] Signal Acetylcholine Preconditioning,'' 
submitted to NIH on September 9, 2000; and
    C. Figure 7, p. 25, in an unfunded grant application in 1 R01 
HL66230-01A1, ``Nitric Oxide and Opioid Preconditioning,'' Submitted to 
NIH on July 2, 2001.
    Dr. Yao falsely claimed that two fluorescent micrographs in the 
figure represented neonatal rat cells transfected with an adenovirus-
derived vector, when the cells actually were chick cells transfected 
with a cytomegalovirus-based vector, which he had taken from another 
scientist at the University of Chicago.
    (2) Falsified the same two fluorescence micrographs of CMV-
transfected chick cells described in Issue 1, above, by misrepresenting 
their description as embryonic chick cells transfected with pcDNA, with 
and without green fluorescent protein, for Figure 13 on p. 30 in an 
unfunded NIH grant application, 1 R01 HL66230-01, ``Molecular 
Mechanisms of Opioids in Myocardial Ischemia,'' submitted January 21, 
2000.
    (3) Falsified a flow cytometry histogram in Figure 1B on p. 22 of 
NIH application R01 HL66230-01A1, by claiming the histogram represented 
results with rat myocardiocyte cultures treated with an opiate 
antagonist (staurosporine).
    However, this histogram had been published by Liu, H., McPherson, 
B.C., & Yao, Z. ``Preconditioning Attentuates Apoptosis and Necrosis: 
Role of Protein Kinase C[egr] and -[delta] Isoforms.'' Am. J. 
Physiology Heart Circ Physiol. 281:H404-H410, 2001, as Figure 1f 
showing the result from embryonic chick cells treated for 12 hours with 
deoxy-glucose in the absence of oxygen (simulated ischemia).
    (4) Falsified claims about research results in NIH grant 
application R01 HL66230-01A1, by claiming that data in Figure 3 on p. 
23 represented experiments on cultures of neonatal rat cardiomyocytes 
as an in vitro model of hypoxia-reoxygenation, shown as data from four 
separate experiments measuring apoptosis by different means.
    The data in the four separate experiments portrayed in Figure 3 are 
identical to Figure 1, p. 2009, in the publication by Liu, H., Zhang, 
H.Y., McPherson, B.C., Baman, T., Roth, S., Shao, Z., Zhu, X., & Yao, 
Z. ``Role of Opioid [delta]1 Receptors, Mitochondrial 
KATP Channels, and Protein Kinase C during Cardiocyte 
Apoptosis. J. Mol. Cell. Cardio. 33:2001-2014, 2001, which were 
reported as the results from experiments on cultures of embryonic chick 
cardiocytes.
    (5) Falsified the micrographs in panels a and d, Figure 1, p. 2009, 
in the publication by Liu, H. et al., J. Mol. Cell. Cardiol. 33:2001-
2014, 2001, by claiming they represented TUNEL data showing normal 
media and opioid antagonist (BTNX)-treated cultures of chick 
cardiocytes, respectively.
    The same micrographs had been reported by Liu, H. et al., Am. J. 
Physiology Heart Circ Physiol. 281:H404-H410, 2001, in Figure 1 (panels 
a and e) and in Figure 2 (panels a and b), as representing cardiocyte 
cultures exposed for 24 hours to deoxy-glucose and no oxygen (simulated 
ischemia).
    (6) Falsified the physiological effects of gene transduction into 
hearts, by copying and re-using the same pressure tracing for untreated 
rats as he did for rats purportedly treated by intracardial injection 
with adenovirus (AdEGFP) in:
    A. Figure 11, p. 26, in unfunded NIH grant application R01 HL66230-
01A1;
    B. Figure 9, p. 30, in funded NIH grant application R01 HL67416-01;
    C. Figure 9, p. 34, in funded NIH grant application R01 HL68250-01; 
and
    D. Figure 8, p. 30, in funded NIH grant application 1 K08 HL03881-
01.
    (7) Falsified data in panels c and d in Figure 13, p. 26, in NIH 
grant application R01 HL66230-01A1. Dr. Yao claimed that panel c 
represented a TUNEL assay on histological sections of myocardium from a 
rat transfected with Ad.[beta]gal and subjected to ischemia-reperfusion 
and that panel d represented a tissue section from a rat transfected 
with Ad.PKC[delta]-FL.
    Panel c is a horizontally compressed copy of panel b, purported to 
be a non-transfected rat subjected to ischemia-reperfusion, and panel d 
is a horizontally expanded version of panel a, purported to be a sham-
operated, non-transfected control.
    (8) Falsified the claims about the micrograph of ischemic data 
(``panel b'' in issue 7, above) reported as:
    A. Figure 11, p. 31, in R01 HL67416-01 (submitted May 31, 2000); 
and
    B. Figure 12, p. 35, in R01 HL68250-01 (submitted September 29, 
2000).
    In both examples, the figures, which are identical, consist of two 
panels purported to be TUNEL data showing sham operated controls (panel 
a) and the effect of transient ischemia for 30 minutes (panel b). 
However, these data are identical to Figure 10, p. 32, in NIH 
application K08 HL03881-01, reported a control and the effect of 
nontransient ischemia, i.e., 20 hours of ischemia followed by 24 hours 
of reperfusion.
    (9) Falsified data in Figure 14 on p. 27 in NIH grant application 
R01 HL66230-01A1, as representing a gel electrophoresis data from an in 
vivo experiment on rat myocardial ischemia.
    However, the same data was represented as Figure 3, p. 23, of the 
application (and also as in Figure 1, J. Cell. Mol. Cardiol. 33:2007-
2014, 2001), as results from a study of embryonic chick heart cell 
cultures for the effect of preconditioning on opioid receptors. 
Furthermore, Dr. Yao falsified the stated size of the fragments in the 
DNA marker ladder by altering the position of the molecular weight 
markers in Figure 14.
    (10) Falsified Figure 3, p. 27, in 1 R01 HL67416-01, a DNA-
laddering gel electrophoresis experiment, showing that apoptosis in 
cardiocyte cultures is significantly increased by staurosporin and by 
12 hours of simulated ischemia.
    The same data was shown in Figure 1, p. 26, in application HL03881-
07 showing that apoptosis is significantly increased by 10 [mu]M NE and 
by 15 nM TNF-[].
    The research misconduct was significant because Dr. Yao's research 
involved the fundamental mechanisms for cardiac cell injury and 
pathogenesis after a heart attack. The falsified data were significant 
to reviewers' opinions on funding because they were advanced as 
preliminary results showing successful new experiments extending his 
experimental model to adult rat hearts.
    Dr. Yao has entered into a Voluntary Exclusion Agreement in which 
he has voluntarily agreed:
    (1) To exclude himself from any contracting or subcontracting with 
any agency of the United States Government

[[Page 57241]]

and from eligibility for, or involvement in, nonprocurement 
transactions (e.g., grants and cooperative agreements) of the United 
States Government as defined in 45 CFR part 76 (Debarment Regulations) 
for a period of five (5) years, beginning on August 20, 2002;
    (2) 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 five (5) years, beginning on August 20, 2002; and
    (3) to submit a letter to the Journal of Molecular and Cellular 
Cardiology requesting retraction of Figure 1 in the article by Hui Liu, 
et al., J. Mol. Cell. Cardiol. 33:2001-2014, 2001, within 30 days of 
notification of this action. This requirement will be noted on the 
ALERT System until Dr. Yao sends a copy of the retraction letter to 
ORI.

FOR FURTHER INFORMATION CONTACT: Director, Division of Investigative 
Oversight, Office of Research Integrity, 5515 Security Lane, Suite 700, 
Rockville, MD 20852, (301) 443-5330.

Chris B. Pascal,
Director, Office of Research Integrity.
[FR Doc. 02-22794 Filed 9-6-02; 8:45 am]
BILLING CODE 4150-31-P