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Case Summary - Steven A. Leadon

[Federal Register: June 8, 2006 (Volume 71, Number 110)]
[Notices]
[Page 33308-33309]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08jn06-61]

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Office of the Secretary

Findings of Scientific Misconduct

ACTION: Notice.

SUMMARY: Notice is hereby given that the Office of Research Integrity (ORJ) and the Assistant Secretary for Health have taken final action in the following case:

Steven Anthony Leadon, Ph.D., University of North Carolina: Based on the report of an investigation conducted by the University of North Carolina (UNC) at Chapel Hill and additional analysis conducted by ORI in its oversight review, the U.S. Public Health Service (PHS) found that Steven Anthony Leadon, Ph.D., former Professor of Radiation Oncology, Department of Radiology, School of Medicine, UNC, engaged in scientific misconduct while supported by National Cancer Institute (NCI), National Institutes of Health (NIH), grant R01 CA40453-09 to 15.

Specifically, PHS found that Dr. Leadon engaged in scientific misconduct by falsifying DNA samples and constructing falsified figures for experiments done in his laboratory to support claimed findings of defects in a DNA repair process that involved rapid repair of DNA damage in the transcribed strand of active genes, included in four grant applications and in eight publications and one published manuscript, which were included as an Appendix to the Voluntary Exclusion Agreement entered into by Dr. Leadon and are as follows:

Figures 1, 2, and 3 in the article by Gowen, L.C., Avrutskaya, A.V., Latour, A.M., Koller, B.H., & Leadon, S.A. ``BRCA1 Required for Transcription-Coupled Repair of Oxidative DNA Damage.'' Science 281:1009-1012, 1998. In grant application 2 R01 CA40453-14 (p. 9), this article was used as justification for proposed research on BRCA1 and related proteins that may be required for transcription-coupled DNA repair of oxidative DNA damage. Data from the research reported in this paper was also used as preliminary data (Figure 2, p. 16) to support proposed experiments on BRCA1.

Figures 1A, 2A, and 3 in the article by Leadon, S.A. & Avrutskaya, A. ``Differential Involvement of the Human Mismatch Repair Proteins, hMLH1 and hMSH2 in Transcription-coupled Repair.'' Cancer Research 57:3784-3791, 1997.

Figures 1 and 3 in the article by Leadon, S.A. & Avrutskaya, A.V. ``Requirement for DNA Mismatch Repair Proteins in the Transcription Coupled Repair of Thymine Glycols in Saccharomyces Cerevisiae.'' Mutation Research 407:177-187, 1998.

Figures 7B and 7C in the article by Cressman, V.L., Backlund, D.C., Avrutskaya, A.V., Leadon, S.A., & Koller, B.H. ``Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1- deficient mice.'' Molecular and Cellular Biology 19:7061-7075, 1999.

Figures 1 A-D, 3A, 3C, ajd 3D and graphs in the unpublished manuscript by Rauscher, F. J. III, Jensen, D.E., Patel, G., Fredericks, W.J., Schultz, D.C., Proctor, M., Sekido, Y., Minna, J., Chernova, T.A., Wilkinson, K.D., Avrutskaya, A.V., & Leadon, S.A. ``BRCA1-associated ubiquitin hydrolase required for transcription-coupled repair of oxidative DNA damage.'' Submitted to Science on May 16, 2001. In figure 4 in grant application 2 R01 CA40453-14 (pp. 17-18), data from this unpublished manuscript was used regarding BAP1 defects in TCR.

Figure 1A and 3A in the article by Cooper, P.K., Nouspikel, T., Clarkson, S.g., and Leadon, S.A., ``Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G,'' Science 275: 990-993, 1997. In NIH grant application R01 CA40453-10A1, some of the same data for XPG or XP-G/CS cells from this Science article were included by Dr. Leadon as graphs (Figures 4 and 5, pp. 25-27) before the Science paper was published.

Figure 1C, 2A and 2B in the article by LePage, F., Kwoh, E.E., Avrutskaya, A., Gentil, A., Leadon, S.A., Sarasin, A., & Cooper, P.K. ``Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome.'' Cell 101:159-171, 2000. Figure 7 in grant application 1 R01 CA092390-01.

Figures 1 and 2 and Table 1 in the article by Leadon, S.A., Barbee, S.L., & Dunn, A.B. ``The yeast RAD2, but not RAD1, gene is involved in the transcription-coupled repair of thymine glycols.'' Mutation Research 337:169-178, 1995.

Figure 6 in the article Nouspikel, T., Lalle, P., Leadon, S.A., Cooper, P.K., & Clarkson, S.g. ``A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: Implications for a second XPG function,'' Proc. Nat. Acad. Sci. USA 94, 3116-3121, 1997.

Dr. Leadon's position is that he did not engage in scientific misconduct. His position is that a systematic error was introduced into the experiments in question and he recognizes that it could have influenced or accounted for the results. Dr. Leadon states that he has entered into a Voluntary Exclusion Agreement (Agreement) because he cannot sustain the significant financial burden of a legal proceeding to resolve the disagreements between his position and that of HHS. By entering into this Agreement, Dr. Leadon has voluntarily agreed:

(1) To exclude himself from knowingly contracting or subcontracting with any agency of the United States Government and from eligibility or knowing involvement in nonprocurement programs of the United States Government referred to as ``covered transactions'' as defined in the debarment regulations at 45 CFR Part 76 for a period of five (5) years, beginning on May 10, 2006;

(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 consultant for a period of five (5) years, beginning on May 10, 2006; and

(3) To submit letters of retraction to the editors of the journals listed below within ten (10) business days from the effective date of this Agreement, stating as follows:

(A) ``I have recently had the opportunity to review some of the raw data used for this paper in the above-referenced publication, and it is clear that the data as reported in this paper cannot be relied upon. Therefore, I request that you retract this paper.'' A letter using only the aforementioned language in this subsection will be sent to Mutation Research to retract the following paper: Leadon, S.A., Barbee, S.L., & Dunn, A.B. ``The yeast RAD2, but not RAD1, gene is involved in the transcription-coupled repair of thymine glycols.'' Mutation Research 337:169-178, 1995.

(B) ``I have recently had the opportunity to review some of the raw data used for Figure 6 in this paper in the above-referenced publication, and it is clear that the data as reported in this figure cannot be relied upon. Therefore, I request that you retract Figure 6 of this paper.'' A letter using only the aforementioned language in this subsection will be sent to Proceedings of National Academy of Sciences concerning the following article: Nouspikel, T., Lalle, P., Leadon, S.A., Cooper, P.K., & Clarkson, S.G. ``A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: Implications for a second XPG function.'' Proceedings of the National Academy of Sciences 94:3116-3121, 1997.

(C) ``I have recently had the opportunity to review some of the raw data used for Figures 7B and 7C in this paper in the above-referenced publication, and it is clear that the data as reported in these figures cannot be relied upon. Therefore, I request that you retract Figure 7B and 7C of this paper.'' A letter using only the aforementioned language in this subsection will be sent to Molecular and Cellular Biology concerning the following article: Cressman, V.L., Backlund, D.C., Avrutskaya, A.V., Leadon, S.A., & Koller, B.H. ``Growth retardation, DNA repair defects, and lack of spermatogensis in BRCA1-deficient mice.'' Molecular and Cellular Biology 19:7061- 7075, 1999.

FOR FURTHER INFORMATION CONTACT:

Director, Division of Investigative Oversight

Office of Research Integrity

1101 Wootton Parkway, Suite 750

Rockville, MD 20852

(240) 453-8800.

Chris B. Pascal,
Director, Office of Research Integrity.