Medical Writing, Editing & Grantsmanship

Nothing to say here except thanks to DrugMonkey for the heads-up on spotting another case of misconduct causing extensive havoc in the scientific community – this time, Suresh Radhakrishnan, PhD, formerly at the Mayo Clinic Dept of Immunology. No word on whatever formal misconduct investigation may be in progress, but quite a list of affected articles, and some brief insight via the authors’ note to PLoS ONE:

An investigation by the Mayo Clinic has determined that one of the researchers in Professor Pease’s laboratory at the Mayo Clinic, Dr. Suresh Radhakrishnan, tampered with another investigator’s experiment with the intent to mislead toward the conclusion that the B7-DCXAb reagent has cell activating properties. Using blinded protocols, experiments were done to see if the results based on this reagent could be replicated. Specifically, the repeat experiments examined the activation of dendritic cells, activation of cytotoxic T cells, induction of tumor immunity, modulation of allergic responses, breaking tolerance in the RIP-OVA diabetes model, and the reprogramming of Th2 and T regulatory cells. In no case did these repeat studies reveal any evidence that the B7-DCXAb reagent had the previously reported activity. The authors of this paper therefore wish to retract this paper because of the inability to reproduce key aspects of the studies and hence the results in them cannot be considered reliable.

The note in PNAS gives the scope: “In the course of this re-examination, we were able to study all the antibodies used in the various phases of our work spanning the last 10 years. None of these antibodies appears to be active in any of our repeat assays. We do not believe something has happened recently to the reagent changing its potency.”

Retraction: Suresh Radhakrishnan, Esteban Celis, and Larry R. Pease, Proc Natl Acad Sci USA 2005;102:11438–11443

Retraction: Radhakrishnan S, Cabrera R, et al. (2009) PLoS ONE 4(4): e5373

Retraction: Suresh Radhakrishnan, Loc T. Nguyen, Bogoljub Ciric, et al., The Journal of Immunology, 2003, 170: 1830–1838

Retraction: Suresh Radhakrishnan, Koji Iijima, Takao Kobayashi, et al., The Journal of Immunology, 2004, 173: 1360–1365.

Retraction: Suresh Radhakrishnan, Loc T. Nguyen, Bogoljub Ciric, et al., The Journal of Immunology, 2007, 178: 1426–1432.

Retraction: Suresh Radhakrishnan, Karla R. Wiehagen, Vesna Pulko, et al., The Journal of Immunology, 2007, 178: 3583–3592.

Retraction: Suresh Radhakrishnan, Rosalyn Cabrera, Erin L. Schenk, et al., The Journal of Immunology, 2008, 181: 3137–3147.

Retraction: Suresh Radhakrishnan, Laura N. Arneson, Jadee L. Upshaw, et al., The Journal of Immunology, 2008, 181: 7863–7872.

He has other publications and patents that may have some issues as well. Stay tuned.

Update: A King County Superior Court Judge rejected Aprikyan’s request for a temporary injunction to stop the university from firing him. A trial on the case has been set for November.

Hot on the heels of one sensational misconduct case at U Wash, details have been made public about another since the research assistant professor (and UW table tennis coach) at the heart of the investigation, Andrew Aprikyan, has sued in court to save his job.

The Seattle Times reports on “some eye-opening revelations in the court documents — including Aprikyan’s own account that a technician working with him at one point wrote research notes on ‘approximately 30 paper towels,’ and the notes were never transcribed.” Clearly someone missed the seminar on maintaining a good lab notebook.

The case has dragged on 7 years, during which time Aprikyan has continued to publish, secure grant funding, and present his results. This year, UW President Mark Emmert intervened to say Aprikyan should be fired for academic misconduct.

But getting back to that long investigation (Duke watchers take note):

In 2003, when the journal “Blood” posted an Aprikyan paper on its website, another researcher noticed that something looked wrong: An image of a cell in one panel appeared to have been rotated 90 degrees and relabeled in another panel.

Aprikyan later withdrew the paper, which other researchers contributed to, noting that “errors in some of the digital images in the manuscript are under investigation.”

“We … extend our deepest apologies to the scientific community,” Aprikyan wrote on the “Blood” website.

In court papers, Aprikyan said it was a rival faculty member who turned him in after “I had refused to work with him on a research project.”

The UW appointed a committee, composed of three scientists, to investigate Aprikyan’s work. Under UW rules, such investigations are supposed to take 90 days. But the committee got at least 16 extensions as the investigation dragged on. It worked for three years, eventually issuing a report of more than 450 pages.

It took another year for Paul Ramsey, dean of the UW School of Medicine, to review the reports and issue his own findings. Ramsey concluded that Aprikyan had falsified seven figures and tables in two research papers, and that his actions amounted to academic misconduct.

Then things took a turn. Ramsey and Provost Phyllis Wise asked a faculty panel — which included professors of English, Scandinavian studies and several other disciplines — to decide whether Aprikyan should be fired. Aprikyan, in turn, asked the panel to reconsider the entire case against him.

Over the objections of UW administrators, a law professor decided the faculty panel could reconsider the case. Two years later, the panel concluded, in a 70-page report, that while there was plenty of evidence of sloppy methods and erroneous results, there was no evidence Aprikyan had deliberately falsified his work.

Earlier this year, Emmert made his own ruling: The second panel had no authority to review the first committee’s findings. Emmert wrote that he, therefore, accepted those initial findings — that Aprikyan had committed scientific misconduct — and concluded the researcher should be fired.

Whoa … 3 scientists devoted 3 years to preparing a 450-p report about 7 falsified figures & tables in 2 papers?

Wonder what will be left for ORI to say when they finally issue their report.

And then some …

“Specifically, ORI made 15 findings of misconduct in science based on evidence that Dr. Brodie knowingly and intentionally fabricated and falsified data reported in 9 PHS grant applications and progress reports and several published papers, manuscripts, and PowerPoint presentations.”

Oof. Note the multiple mechanisms (3 P01s, 4 R01s, 1 U01, and 1 R01 converted to a U01) and funding institutes (NICHD, NIAID, NIDCR, NHLBHI). And Dr. Brodie, a research assistant professor (i.e., non-tenure track) fought them every step of the way it seems. Without further ado …

Notice is hereby given that on March 18, 2010, the DHHS Debarring Official, on behalf of the Secretary of HHS, issued a final notice of debarment based on the misconduct in science findings of the ORI in the following case:

Based on the findings in an investigation report by the University of Washington and additional analysis conducted by ORI in its oversight review, ORI found that Scott J. Brodie, DVM, PhD, former Research Assistant Professor, Department of Laboratory Medicine, and Director of the UW Retrovirology Pathogenesis Laboratory, committed misconduct in science (scientific misconduct) in research supported by or reported in the following US PHS grant applications:

1 P01HD40540
5 P01HD40540
1 P01AI057005
1 R01DE014149
2 U01AI41535
1 R01HL072631
1 R01(U01)AI054334
1 R01DE014827
1 R01 AI051954

The 15 findings [of misconduct in science] are as follows:

1. Respondent knowingly and intentionally falsified a figure that was presented in manuscripts submitted to the Journal of Experimental Medicine and the Journal of Virology and in several PowerPoint presentations that purported to represent rectal mucosal leukocytes in some instances and lymph nodes in other instances.

2. Respondent knowingly and intentionally falsified portions of a three-paneled figure included in several manuscript submissions, PowerPoint presentations, and grant applications.

3. Respondent knowingly and intentionally falsified a figure included as Figure 1N in American Journal of Pathology 54:1453-1464, 1999, three NIH grant applications, and several PowerPoint presentations.

4. Respondent knowingly and intentionally falsified a figure that was published as an insert within Figure 1K in American Journal of Pathology 54:1453, 1999 and included the figure in a number of NIH grant applications.

5. Respondent knowingly and intentionally falsified a figure representing a panel of four green fluorescent cells and included it as a figure in several grant applications claiming that each cell had been subjected to different treatments when three of the cells came from a single image.

6. Respondent knowingly and intentionally falsified an image included as Figure 5A in a paper published in the Journal of Clinical Investigations 105:1407, 2000 and submitted to various journals and included in different grant applications.

7. Respondent knowingly and intentionally falsified a figure appearing as Figure 3.III.A, inset, in a manuscript submitted to Science entitled “A persistent reservoir of HIV-1 in pulmonary macrophages’ and as figures in various grant applications and PowerPoint presentations.

8. Respondent knowingly and intentionally falsified multiple versions of a figure depicting green and red fluorescent cells used as Figures 3.III.H and I in a manuscript submitted to Science, as Figures 6C and 6D of grant application 1 R01 DE14827-01, as Figures C.2.1 1H and C.2.11I of grant application 1 R01 HL072631-01, and in PowerPoint presentations.

9. Respondent knowingly and intentionally falsified a figure, labeled as Figure 9E in grant application 1 R01 DE014827-01 and in various other grant applications and PowerPoint presentations.

10. Respondent knowingly and intentionally falsified the bottom half of Figure C.2.5 of grant application 1 R01 HL072631-01 by using the same image twice, labeling it once as being treated for 2 hours with lipopolysaccharide (LPS) and the second as being treated for 12 hours with LPS. Respondent also used a second image twice, labeling it once as “no LPS’ and the second time as “24 hours with LPS.’

11. Respondent knowingly and intentionally falsified a figure that purports to represent viral decay in rectal mucosa and included the figure as a slide in two PowerPoint presentations and three NIH grant applications.

12. Respondent knowingly and intentionally falsified: (a) A histopathology figure that was described in a paper published in the Journal of Infectious Diseases 83:1466, 2001, as inguinal lymph nodes from an untreated AIDS patient using in situ PCR to show the presence of HIV-1 cells when it was actually from a tissue expressing the neomycin marker; (b) the gel images resembling Figures 2A and C, which Respondent claimed to be based on lymph node cells, although he reported the gel images elsewhere to represent results from rectal tissue; and (c) various versions of these blots that Respondent reported elsewhere and labeled differently with respect to the copy numbers detected and as detecting DNA in some instance and RNA in others.

13. Respondent knowingly and intentionally falsified Figures 2DI and 2DII included in a paper published in the Journal of Leukocyte Biology 68:351-359, 2000.

14. Respondent knowingly and intentionally falsified Figure 4, Panels A and B, in grant application 1 R01 DE014827-01 by manipulating the source images.

15. Respondent knowingly and intentionally falsified a number of figures and made false statements in the text of grant application 1 R01 AI051954-01 submitted jointly with a colleague by relabeling figures based on research carried out with HIV-1 or HIV-2 and identifying the figures and text as research conducted with ovine lentivirus (OvLV).

ORI issued a charge letter enumerating the above findings of misconduct in science and proposing HHS administrative actions. Dr. Brodie subsequently requested a hearing before an Administrative Law Judge (ALJ) of the Departmental Appeals Board to dispute these findings. In January 2009, the ALJ issued a ruling holding that there were no triable issues challenging ORI’s findings that there were materially false statements, images, and other data in the relevant publications, presentations, and grant applications. However, the ALJ held that Dr. Brodie raised triable issues about his intent to commit scientific misconduct and the reasonableness of the proposed debarment of 7 years.

On January 12, 2010, the ALJ issued a recommended decision to the HHS Assistant Secretary for Health granting summary disposition to ORI. The ALJ also stated that Dr. Brodie committed scientific misconduct on multiple occasions and that its extent amply justified debarment for a period of 7 years.

On February 1, 2010, Dr. Brodie submitted a letter to the HHS Debarring Official with attachments to request that the ALJ’s recommended decision be rejected as a whole. On February 26, 2010, Dr. Brodie submitted a letter requesting the opportunity to meet with the HHS Debarring Official to orally present the reasons supporting his request that the ALJ’s recommended decision be rejected. However, the HHS Debarring Official determined that Dr. Brodie had been afforded an opportunity to contest ORI’s findings of scientific misconduct … Given the findings of facts in this case, the HHS Debarring Official determined that the issues in his presentation in opposition to the ALJ’s recommended decision did not raise a genuine dispute over facts material to the recommended debarment.

Accordingly, the HHS Debarring Official also denied Dr. Brodie’s request to make an oral presentation and issued a notice of debarment to begin on March 18, 2010, and end on March 17, 2017.

On March 23, 2010, Dr. Brodie submitted a letter requesting a postponement of the effective date of the debarment. This request was denied by the Debarring Official on April 6, 2010.

Thus, the misconduct in science findings set forth above became effective, and the following administrative actions have been implemented for a period of 7 years, beginning on March 18, 2010.

I wonder if ORI began to think 7 years wasn’t enough …