FINDINGS OF SCIENTIFIC MISCONDUCT NIH GUIDE, Volume 25, Number 22, July 5, 1996 P.T. 34 Keywords: Ethics/Values in Science & Technol Grants Administration/Policy+ Department of Health and Human Services Notice is hereby given that the Office of Research Integrity (ORI) has made final findings of scientific misconduct in the following cases: Robert J. Altman, M.D., University of California at San Francisco (UCSF): Based on an investigation conducted by the institution as well as information obtained by ORI during its oversight review, ORI found that Robert J. Altman, M.D., Research Fellow, Department of Obstetrics, Gynecology, and Reproductive Sciences, UCSF, committed scientific misconduct by fabricating and falsifying data in research supported by two National Institutes of Health grants. Specifically, Dr. Altman fabricated an experiment related to an ovarian cell line injected intraperitoneally into 12 nude mice. The resulting data were reported in (1) a manuscript in page proof entitled "Inhibiting vascular endothelial growth factor arrests growth of ovarian cancer in an intraperitoneal model" (Journal of the National Cancer Institute); (2) a manuscript entitled "Vascular endothelial growth factor is essential for human ovarian carcinoma growth in vivo," submitted to the Journal of Clinical Investigation (JCI manuscript); and (3) a published abstract entitled "Vascular endothelial growth factor is essential for ovarian cancer growth in vivo" (Society for Gynecologic Investigation, abstract #079). Further, in the JCI manuscript, Dr. Altman (1) falsified the number of subjects with ovarian tumors from whom he obtained sections of tissue for examination of the expression of vascular endothelial growth factor (VEGF) purportedly by both in situ hybridization and immunohistochemistry, and (2) falsely reported that VEGF expression was examined by in situ hybridization and immunohistochemistry in papillary serous- (n=7) and mucinous- (n=5) cystadenocarcinomas, when the number of surgical cases involving papillary serous tumors was four and the number of mucinous tumors was zero. Dr. Altman examined VEGF expression in only three papillary serous tumor specimens, one specimen both in situ and by immunohistochemistry and the remaining two solely by immunohistochemistry. Dr. Altman has entered into a Voluntary Exclusion Agreement with ORI in which he has voluntarily agreed, for the three year period beginning June 11, 1996, to exclude himself from: (1) any contracting or subcontracting with any agency of the United States Government and from eligibility for, or involvement in, nonprocurement transactions (e.g., grants and cooperative agreements) of the United States Government as defined in 45 C.F.R. Part 76 (Debarment Regulations), and (2) serving in any advisory capacity to the Public Health Service (PHS), including but not limited to service on any PHS advisory committee, board, and/or peer review committee, or as a consultant. The above voluntary exclusion shall not apply to Dr. Altman's future training or practice of clinical medicine whether as a medical student, resident, fellow, or licensed practitioner, as the case may be, unless that practice involves research or research training. Vipin Kumar, Ph.D., California Institute of Technology: Based upon a report forwarded to the Office of Research Integrity (ORI) by the California Institute of Technology (C.I.T.) dated January 10, 1991, as well as information obtained by ORI during its oversight review, ORI found that Vipin Kumar, Ph.D., formerly a scientist at C.I.T., engaged in scientific misconduct in biomedical research supported by Public Health Service (PHS) funds. Specifically, ORI found that Dr. Kumar committed scientific misconduct by falsifying and/or fabricating Figures 2a and 2b in a scientific paper published in the Journal of Experimental Medicine, 170:2183-2188 (1989) (JEM paper). ORI accepted the C.I.T. conclusion that Dr. Kumar ~freely admitted~ that he mislabeled the lanes in Figures 2a and 2b, which are labeled to indicate they represent the results of research from different DNA samples when in fact a number of lanes are duplicates. Although Dr. Kumar denies that he intended to deceive anyone, C.I.T. concluded in its Report that the "deliberate presentation of duplications of one experiment which are labeled to indicate they came from separate DNA samples deceives the reader as to the real source of the DNA in the experiment, where the central point of the experiment is the similarity of results among different sources." ORI also accepted the C.I.T. conclusion that Dr. Kumar presented Figure 2c of the JEM paper "in a very misleading fashion." The central observation of the JEM paper is that both alleles of the alpha chain of the T-cell receptor gene are frequently rearranged. This conclusion was based, in part, on Figure 2c, which C.I.T. found had been labeled in a misleading fashion that led the reader to believe that the heavy band at the top of the blot was an 8kb restriction fragment (i.e., representing an internal control) rather than undigested material that failed to enter the gel. Examination of the original film indicates that there was no evidence that the second alpha-chain rearranges in mature T-cells. Thus, ORI further accepted the C.I.T. conclusion that Figure 2 was intentionally falsified and/or fabricated and that, as a result, "one of the main scientific results of this paper was not substantiated by the original data." In addition, ORI found that Dr. Kumar committed scientific misconduct by falsifying and/or fabricating Figure 5b of a manuscript that was submitted for publication to the journal Cell (Cell manuscript), but was later withdrawn. ORI accepted the C.I.T. conclusion that lanes 6, 7 and 8 of Figure 5b are the same as lanes 11, 12 and 13, respectively, even though they are labeled as being from different samples. ORI also accepted the C.I.T. conclusion that Dr. Kumar made a number of other materially misleading statements in the Cell manuscript that were not supported by the primary data. For example, C.I.T. concluded that Dr. Kumar made a number of materially misleading statements about the age of mice and the timing of the injection of peptides into these mice in a paper published in the Proceedings of the National Academy of Sciences, 87:1337-1341 (1990) (PNAS paper). This information is material because induction of the disease studied (i.e., allergic encephalomyelitis) is dependent upon the age of the mice. Based upon the findings of scientific misconduct in the C.I.T. Report, the JEM and PNAS papers were retracted prior to ORI's findings in this case. ORI and Dr. Kumar agreed to resolve the case through a negotiated settlement and limited voluntary exclusion agreement (Agreement), which the parties agreed shall not be construed as an admission of liability or wrongdoing on the part of the Dr. Kumar. Dr. Kumar plans to submit a letter to ORI in which he summarizes his response to ORI's findings. Dr. Kumar has agreed to exclude himself voluntarily from serving in any advisory capacity to the PHS, including service on any PHS advisory committee, board, and/or peer review committee, or as a consultant for a period of three years. Dr. Kumar has also agreed to exclude himself voluntarily, for a period of 18 months from any contracting or subcontracting with any agency of the United States Government and from eligibility for, or involvement in, nonprocurement transactions (e.g., grants and cooperative agreements) of the United States Government. However, this provision will not apply to a currently pending PHS grant application involving Dr. Kumar. In addition, any institution that uses Dr. Kumar in any capacity on PHS supported research must concurrently submit a plan for supervision of Dr. Kumar's duties, designed to ensure the scientific integrity of Dr. Kumar's research, for a period of three years. Similarly, any institution employing Dr. Kumar must submit, in conjunction with each application for PHS funds or report of PHS funded research in which Dr. Kumar is involved, a certification that the data provided by Dr. Kumar are based on actual experiments or are otherwise legitimately derived and that the data, procedures and methodology are accurately reported in the application or research report, for a period of three (3) years. INQUIRIES For further information, contact: Director, Division of Research Investigations Office of Research Integrity 5515 Security Lane, Suite 700 Rockville, MD 20852 Telephone: (301) 443-5330 .
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