[Federal Register Volume 74, Number 14 (Friday, January 23, 2009)]
[Notices]
[Pages 4201-4202]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-1453]


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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:
    Luk Van Parijs, PhD, Harvard Medical School, Brigham and Women's 
Hospital, California Institute of Technology, and Massachusetts 
Institute of Technology: Based on the reports of separate 
investigations conducted by Harvard Medical School (HMS)/Brigham and 
Women's Hospital (BWH), California Institute of Technology (CalTech), 
and Massachusetts Institute of Technology (MIT) and additional analysis 
conducted by the Office of Research Integrity (ORI) in its oversight 
review, the U.S. Public Health Service (PHS) found that Dr. Luk Van 
Parijs, former Graduate Student, Department of Pathology, HMS, former 
Research Fellow and Instructor of Pathology, BWH, former Postdoctoral 
Fellow, Department of Biology, CalTech, and former Associate Professor, 
Department of Biology, Center for Cancer Research, MIT, engaged in 
scientific misconduct in research supported by National Institute of 
Allergy and Infectious Diseases (NIAID), National Institutes of Health 
(NIH), grants U19 AI56900, R21 AI49897, R01 AI42100, P01 AI35297, R37 
AI25022, R01 AI32531, National Cancer Institute, NIH, grant R01 
CA51462, and National Institute of Environmental Health Sciences 
(NIEHS), NIH, grant P30 ES02109, and National Institute of General 
Medical Sciences (NIGMS), NIH, grant R01 GM57931.
    PHS found that Respondent engaged in scientific misconduct by 
including false data in NIAID, NIH, grant applications R01 AI54519-
01A1, R01 AI54973-01, and R01 AI54973-01A1, NCI, NIH, grant application 
2P30 CA14051-34, and National Institute of Diabetes and Digestive and 
Kidney Diseases (NIDDK), NIH, grant application R21 DK69277-01.
    Specifically, PHS found that Respondent engaged in scientific 
misconduct by including false data in seven published papers, three 
submitted papers (with two earlier versions submitted for one of 
these), one submitted book chapter, and multiple presentations as 
follows:
    1. While at HMS/BWH, Dr. Luk Van Parijs falsified the expression of 
IFN-[gamma] and KJ-126 in flow cytometry dot plots for the immunized, 
naive, tolerized and tolerized + IL-12 experimental groups in Figure 4, 
JEM 186:1119-1128, 1997, by using the same non-stained cell population 
in the lower left quadrant to falsely represent CD4+ T cells negative 
for IFN-[gamma] and KJ-126 in each experimental group.
    2. That Dr. Luk Van Parijs falsified the expression of different 
proteins in flow cytometry dot plots in Figure 1, Immunity, 8:265-274, 
1998, in Figure 1C, Immunity, 11:281-288, September 1999, and in Figure 
5, Immunity 11:763-770, December 1999, by using portions of the same 
dot plot to represent different cell populations expressing different 
proteins. Specifically:
    a. While at HMS/BWH, Dr. Van Parijs used portions of the same dot 
plot to represent T cell populations expressing the 3A9 T cell receptor 
and CD4+ (top panel) or CD8+ (bottom panel) in 3A9+ (wild type), in 
3A9/lpr (Fas<SUP>-</SUP>), or in 3A9/gld (FasL<SUP>-</SUP>) transgenic 
mice in Figure 1, Immunity 1998, where:
    i. The CD4/3A9 dot plots for the 3A9+ and 3A9/gld transgenic mice 
were the same, and the 3A9+ dot plot was a subset of the 3A9/lpr dot 
plot;
    ii. The CD8/3A9 dot plots for the 3A9+ and 3A9/lpr transgenic mice 
were the same in the lower left and lower right quadrants, and the 3A9/
gld dot plot was a subset of the wild type dot plot
    b. While at CalTech, Dr. Van Parijs used portions of the same dot 
plot to represent the expression of hIL-2R[beta] and GFP in T cells 
infected with WT or [Delta]355+8F IL-2R mutant in Figure 1C, Immunity, 
September 1999, where the [Delta]355+8F dot plot was a subset of the WT 
dot plot
    c. While at CalTech, Dr. Van Parijs used portions of the same dot 
plot to represent the expression of B220 and IgM in infected (GFP+) and 
not infected (GFP-) spleen cells isolated from reconstituted mice in 
Figure 5, Immunity, December 1999, where the Infected (GFP+) dot plot 
for control mice was a subset of the Not Infected (GFP<SUP>-</SUP>) dot 
plot for FLIP mice.
    3. While at MIT, Dr. Luk Van Parijs falsely claimed in the text of 
RNA Interference Technology (Cambridge University Press, July 2004) and 
in Figure 2 of Nature Genetics 33:401-406 (2003) that experiments 
depicting the functional silencing of genes in hematopoietic stem cells 
(HSCs) and in non-cycling dendritic cells by lentiviral-mediated RNAi 
were performed, when they were not. Specifically, in Nature Genetics:
    a. Figure 2b falsely showed the transduction of bone marrow-derived 
dendritic cells infected with pLL3.7 Bim by flow cytometry, and 
knockdown of Bim expression by Western blot
    b. Figure 2d falsely showed the efficiency of pLL3.7 CD8 lentiviral 
infection in HSCs by flow cytometry for GFP expression (left panel), 
and falsely showed stable gene expression in progeny by flow cytometry 
for GFP expression in spleen cells from chimeras derived from infected 
HSCs (right panel)
    c. Figure 2e falsely showed the reduction of CD8+ T cells in spleen 
cells from chimeras derived from pLL3.7 CD8 infected HSCs (right panel) 
and controls (left panel).
    4. While at MIT, Dr. Luk Van Parijs falsified figures in grant 
applications submitted to the National Institutes of Health (NIH), a 
presentation in 2003, and Figure 6A, Immunity 19:243-255 (2003), by 
falsely claiming that the image in the figure represented an 
immunoprecipitation assay for Ras-GTP and a Western blot for total Ras 
protein, when it actually represented a Western blot for Bcl-2 and 
[beta]-actin in T cells, previously published as Figure 5C, J. 
Immunol., 168:597-603 (2002).
    Dr. Van Parijs also admitted to falsification or fabrication of 
data in multiple submitted manuscripts, grant applications submitted to 
NIH, and presentations as follows.
    5. While at MIT, Dr. Luk Van Parijs admitted that in multiple 
presentations and submitted manuscripts in 2004, he falsely claimed 
that the bifunctional lentiviral vectors, U6-shRNA-rat insulin promoter 
(RIP)-Myc had been made, when they had not, and that transgenic mice 
carrying these lentiviral vectors with shRNA silencing Bim or Pten 
proteins in pancreatic cells showed accelerated tumorigenesis and 
death.
    6. While at MIT, Dr. Luk Van Parijs admitted that in multiple 
presentations in 2003 and 2004 and in grant application R21 DK69277-01 
submitted to NIH in 2003, he falsely claimed that the number of CD8+ T 
cells and the incidence of diabetes was reduced by silencing CD8 
expression with the pLL3.7 CD8 lentivirus in non-obese diabetic (NOD) 
transgenic mice, when the NOD transgenic mice data did not exist.
    7. While at MIT, Dr. Luk Van Parijs admitted that in multiple 
presentations,

[[Page 4202]]

submitted manuscripts, and grant applications submitted to NIH in 2004, 
he falsely claimed that transgenic mice had been generated with the 
mono-functional lentiviral vectors with c-Myc, Ras or Akt under the 
control of the CD4 promoter, when they had not, and that transgenic 
mice had been generated with the bi-functional lentiviral vectors with 
CD4-c-Myc, Ras or Akt- and U6-shRNAs targeting luciferase, Bcl-2, or 
Bim proteins, when they had not. The effect of these misrepresentations 
was the reported false conclusion that a cytokine-stimulated proto-
oncogene network regulated CD4+ T-cell survival and responses to 
foreign and self antigens.
    8. While at MIT, Dr. Luk Van Parijs admitted that in presentations 
and submitted manuscripts in 2004, he falsely claimed that mice 
injected with plasmids carrying shRNAs for Bcl-2, Akt1 and Akt2, 
complexed to polyethylene imine (PEI) showed a significant reduction in 
c-myc-induced tumor growth, when the experiments had not been done.
    9. While at MIT, Dr. Luk Van Parijs admitted that in presentations 
in 2004, he falsely claimed that shRNAs designed using algorithms 
developed in 2004 were more effective to silence target genes than the 
shRNAs designed with algorithms in 2002.
    10. While at MIT, Dr. Luk Van Parijs admitted that in multiple 
presentations, submitted manuscripts, a grant application submitted to 
NIH, and in the text of Current Opinions in Molec. Therapeutics, 6:136, 
2004, he falsely claimed that an in vivo RNAi screen was developed to 
identify genes in cytokine and apoptosis pathways that accelerated or 
suppressed Myc-induced tumorigenesis in lethally irradiated mice, by 
using bi-functional lentiviral vectors that expressed c-Myc under 
control of the CMV enhancer-[beta]-actin promoter (CAG) and U6-driven 
shRNAs designed to silence 168 selected genes, when the experiments had 
not been done.
    11. While at MIT, Dr. Luk Van Parijs admitted that in a submitted 
manuscript in 2004 and a grant application submitted to NIH in 2003, he 
falsely claimed that with the use of retroviral vectors with Bim and 
activated Ras, Akt or Myc, he showed that the IL-2-stimulated 
activation of proto-oncogene pathways functioned to promote the 
survival of T cells following antigen encounter by regulating Bim and 
Bcl-2 pathways, when the experiments that were performed were 
inconclusive.
    Dr. Van Parijs has entered into a Voluntary Exclusion Agreement in 
which he has voluntarily agreed, for a period of five (5) years, 
beginning on December 22, 2008:
    (1) to exclude himself 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 
referred to as ``covered transactions'' pursuant to HHS' Implementation 
(2 CFR Part 376 et seq.) of OMB Guidelines to Agencies on Government 
wide Debarment and Suspension (2 CFR, Part 180); and
    (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 FURTHER INFORMATION CONTACT: Director, Division of Investigative 
Oversight, Office of Research Integrity, 1101 Wootton Parkway, Suite 
750, Rockville, MD 20852, (240) 453-8800.

    Dated: January 14, 2009.
Chris B. Pascal,
Director, Office of Research Integrity.
 [FR Doc. E9-1453 Filed 1-22-09; 8:45 am]
BILLING CODE 4150-31-P