FundScience Blog

Notice is hereby given that ORI and the Assistant Secretary for Health have taken final action in the following case:

Rashanda Robertson, former Research Coordinator, Department of General Medicine, Emory University, engaged in research misconduct in research supported by grant K23HL077597. Specifically, the Respondent admitted that she fabricated enrollment forms to create enrollees who did not exist and falsified the data of some enrollees who did not exist to cover up the data fabrication. To create the fabricated enrollment forms, the Respondent:

• Identified patients who were eligible for the study based on their charge screens but who were considered ineligible after a face-to-face screen;
• Obtained patients’ names from the screening records and used the names to obtain the personal information (address and telephone numbers) on these patients from the site hospital’s pharmacy online system;
• Created a fabricated enrollment form for each of the non-existent enrollees; specifically, Respondent fabricated a participant’s name by using the name of a patient who had failed screening and then fabricated the date of enrollment by using the date of the patient’s screening failure; using this method, Respondent fabricated the participant names, personal information, and enrollment dates on twenty-eight (28) enrollment forms;
• Dispersed the fabricated enrollment forms among those enrollment forms, beginning around participant number 136 through 212;
• Falsified the numbering of the enrollment forms for some individuals who had actually been enrolled to disperse the fabricated enrollment forms among the authentic enrollment forms; Respondent falsified the status of some actual participants to include them in the intervention group, even though they had not actually received the intervention; Respondent falsified the data on both the enrollment form and the follow-up form for 16 participants between numbers 137 and 198;
• Respondent falsified data on the enrollment forms and follow-up forms for participant numbers 153 and 154 by changing their enrollment numbers.

ORI acknowledges that the Respondent was remorseful.

Fortunately, the K23 PI has been quite productive in terms of publications (per RePORTER Results tab) and has taken a new position with promotion … but no R01 or other mechanism funding as yet (though K23 was suspended/extended from Sept 2007 to June 2010, probably due to change in institution and misconduct investigation).

A three-fer again. The different terms used reflect the timing of the misconduct (scientific if the misconduct occurred before June 2005, research if after June 2005) due to a change in regulatory definitions.

Notice is hereby given that Zhong Bin Deng, former postdoctoral fellow at Medical College of Georgia, whose written and oral admissions and expressed remorse, engaged in scientific misconduct in research supported by grant P01AI42288 by falsifying research results reported in a paper published (and soon after retracted) in Nature Medicine. Specifically, in Figure 1(a), the Respondent falsified the Aire +/+ (thymus and liver) flow cytometry plots by substituting Aire +/- (thymus and liver) flow cytometry plots that were altered to disguise their origins and falsified the Aire -/- (bone marrow) flow cytometry plot by substituting the Aire +/- (bone marrow) flow cytometry plot, also altered to disguise its origin. In supplementary Figure 2, the Respondent also falsified flow cytometry plots.

Notice is hereby given that Nagendra S. Ningaraj, PhD, former Associate Professor of Neurological Surgery and Cancer Biology, Vanderbilt University School of Medicine engaged in scientific misconduct by falsifying MALDI-MS images and mass spectral tracings and associated text in Figure 21 reported in grant application U54CA119421 and by falsifying MALDI-MS images in a presentation during the American Association for Cancer Research meeting held on April 16-20, 2005, which cited support from grants R25CA92943 and P50CA098131. Respondent reversed the images for the control and minoxidil-treated brains; reported mass spectral tracings as having been obtained from brain tumors in Gleevec-treated mice that had been pretreated with minoxidil, while in fact they were pretreated with another potassium channel opener, NS1619, and Respondent falsely stated the minoxidil pretreatment caused an 8-fold increase in Gleevec delivery to brain tumors (compared to non-minoxidil pretreated tumors); and juxtaposed the reversed MALDI-MS images (obtained with mioxidil) with the mass spectral tracings (obtained with NS1619) in the same figure and failed to report that the images and spectra were actually obtained in totally different experiments, performed on different dates and with different K\+\ agonist pretreatments.

Notice is hereby given that Norma Couvertier, former Research Assistant II, APT Foundation, engaged in research misconduct in research supported by award R37DA015969 by falsifying and fabricating data that were reported on Participant Urine Monitoring and Breathalyzer Result Forms completed by the Respondent for 32 of the enrolled study participants in the computer Based Training in Cognitive Behavioral Therapy research study. A total of 253 alcohol breathalyzer results were recorded for the 32 participants as being 0.000 indicating no alcohol detected, rather than the code 999 used when no breathalyzer test was done. ORI also found that Ms. Couvetier, on 253 occasions, with 32 different study participants, falsified alcohol breathalyzer test results and knowingly and consistently entered a false negative test (indicated by 0.000) rather than identifying the result as a missing data collection (indicated by code 999). ORI acknowledges Ms. Couvetier’s verbal admissions and willingness to cooperate and assist during the APT Foundation’s investigation.

The blog post title and the news conveyed come from Nature, which “obtained documents from a source at ONR that relate to the debarment” of Rusi Taleyarkhan at Purdue University, who in 2002 reported in Science that nuclear fusion reactions could be triggered by firing sound waves into deuterated acetone – a claim that has never been independently verified. But let me back up.

This complicated and colorful case began in 2006 and was tracked throughout 2007-2008 by Science and Nature. The NYT reported on Congressional involvement, which Nature followed with interest. An earlier post here tracks a long, heated exchange among Taleyarkhan, Purdue, the House Oversight Committee, et al., with more dogged coverage by Nature.

It took Purdue four investigations to find Taleyarkhan guilty of misconduct (citing work from his own lab as ‘independent’ confirmation of his findings and adding the name of a student to a publication when they had not contributed to the research), strip him of his endowed professorship, and limit his role in mentoring students in July 2008. Taleyarkhan ultimately lost his appeal, but this did not stop him from receiving an award from the NSF (ended in Aug 2009).

It seems, however, this will not happen again:

The ONR, which had funded part of Taleyarkhan’s research, has now reviewed Purdue’s investigation. Its conclusions state that Taleyarkhan’s misconduct was “so severe as to merit debarment” from federal funding. Although the ruling was made in May, when the debarment came into effect, no public announcement was made.

Myers Vasquez, a spokesman for the US Navy, says that Taleyarkhan’s name has now been added to the ‘Excluded Parties List’ that government agencies are required to check before making awards.

His bubble has finally burst.

Update: Links to the Höcker PNAS abstract and paper are now functional, and The Scientist has posted the full text of comments submitted by Hellinga and Looger (links to their statements posted below among the comments).

Whispers that more of Homme Hellinga’s landmark work could not be replicated began last summer as part of our lengthy discussion of the retraction of Hellinga’s 2004 Science paper (here and earlier here) and then his 2007 JMB paper … and his accusation of misconduct laid against his grad student Mary Dwyer. More recently, observers close to the situation had advised us to watch PNAS for an interesting report on the matter.

Whereas Science was mum on the whole debacle when their article was retracted, Nature has taken a proactive analytic approach to the possibility that Hellinga’s 2003 Nature article (and a 2004 PNAS paper) may need to be retracted based on a report entitledComputational design of ligand binding is not a solved problem in PNAS by Schreier et al. … announced even in advance of e-publication by Nature News.

According to Nature News,

Now Birte Höcker, a former postdoctoral fellow of Hellinga’s, and her team at the Max Planck Institute for Developmental Biology in Tübingen, Germany, have assembled and analysed five of the designed proteins that seemed to work best5. She found that all five were very unstable, and one was too unstable to analyse further.

The group then examined the structure of one of the proteins using crystallography and found that its binding pocket was similar to that predicted by Dezymer — but that it did not bind its intended ligand, which was serotonin. And using three methods to detect the changes in stability, heat and shape that normally occur when proteins bind their ligands, the team found no evidence that the designed proteins were binding their intended ligands.

“All together, our combined analysis of the binding properties of the designs indicates that no specific binding of the target ligands to the respective designs occurs,” Höcker’s team reports.

Hellinga’s lab is studying her re-analysis.

Höcker speculates that she obtained different results from Hellinga because she used different methods to test binding. Her methods included direct measurements of binding, such as isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. Hellinga used an indirect method: he designed the proteins so that they included a fluorophore that emitted a signal when the proteins changed shape, which his team interpreted as an indicator that the proteins had bound their ligands. But Höcker says the assay might have given a false-positive signal if the ligand or the solvent in which it was dissolved interacted with the fluorophore.

Hellinga says if his studies of low concentrations of proteins find that they do not bind their ligands, then he will accept Höcker’s explanation: “If these studies also show that our original interpretations are in error, we deeply regret that our reports of these designed receptors do not live up to closer scrutiny,” he wrote.

More deep regret. Other scientists interviewed considered various angles as to why the results might be so different – but all agreed the controversy needs to be resolved and soon. While one former Hellinga postdoc and Nature article coauthor stands by at least one of the proteins reported, the lead author – a former grad student and co-author on the retracted Science article – is not surprised that his findings have been called into question.

“I am not terribly surprised by [Höcker's] results,” Looger wrote to Nature, adding that he had begun to think “that the designed proteins did not work very well, due to several lines of data” collected in Hellinga’s and other labs.

… In retrospect, Looger says in his opinion that “more attention [should] have been drawn to the aggregation and instability of the proteins, and how that might give rise to artefacts.”

Indeed, Hockner became concerned about questions raised and their impact on her own work:

Höcker says that she had a “good relationship” with Hellinga, and had discussed crystallizing the designed proteins with Hellinga while she was still at Duke. “Since I never heard of the outcome [of the crystallization trials], and the program Dezymer, which I myself was using, was under question, it became more and more important for me to know what it was good at and what not,” she says.

Höcker says her results also have broader importance for the protein-design field. “I think that we need to focus again on binding in order to improve receptor design,” she says, “as well as enzyme design”.

Nature alludes to findings from researchers at the University of Western Ontario (Telmer & Shilton), as does Perplexed Periplasmic in a comment in the prior Hellinga discussion on this blog.

Nature: Another group has analysed the structure of a different set of engineered proteins described by Hellinga in a 2001 PNAS paper6, and found that the proteins behaved differently than Hellinga predicted they would7. The designed proteins did bind their intended ligand, a zinc ion, but did not adopt the ‘closed’ state normally associated with binding.

Perplexed Periplasmic: There has been an attempt to reproduce this [Telmer & Shilton, cited by Nature above]. It is described in a poster published on the internet from a group at Imperial College. Unfortunately it’s not clear if this was ever published elsewhere in any peer-reviewed forum.

And what of the misconduct investigation at Duke?

Hellinga wrote to Nature in July 2008 indicating that Duke had, at his request, opened an enquiry into his own actions in connection with the events surrounding last year’s retractions8. [there was also a grad student petition requesting an investigation] Duke declined to answer questions about the status of the enquiry. [insiders suggest nothing is happening, though one would not expect publicized activity in such an investigation]

Other scientists said that the new developments should spur Duke to complete its analysis of both the previous retractions and the current developments. “I think it should be brought to a conclusion fairly quickly because the scientific community is perplexed by the contradictory results both from this and Richard’s analysis,” says Kirsch.

The Scientist offers their take on the whole matter as well.

As I mentioned earlier, ORI has ventured into the blogosphere, and a few recent posts caught my attention, such as the Meaning of RCR by John Galland, PhD, Director pf the Division of Education & Integrity. He concludes with a list of objectives for RCR training:

(a) Protect animal subjects, human participants, research personnel, and the environment
(b) Be honest and transparent, not deceptive (e.g., falsifying, fabricating, or plagiarizing data or deceitful attribution of authorship)
(c) Be fair by not introducing unwanted bias into research results, conclusions, or inferences (e.g., conflicts of interest and commitment, sloppiness)
(d) Be benevolent, not be malicious (e.g., thievery of ideas, unfair criticism during peer review for personal gain; exploitive of others)
(e) Be open to creativity and innovation
(f) Protect the public trust

I like (e) conceptually but cannot for the life of me imagine how typical RCR training would achieve this … hopefully not during lectures about falsification and fabrication.

Today I spotted a new post of personal interest on the Integration of RCR Education and Bioethics Education. Specifically, the question is posed,

What educational programs, what research environment can be fostered, at our institutions to help researchers with such decisions [e.g., fabricate data to secure grant funding needed to sustain research program & staff], or better yet, to help them never have to make such decisions?

Regular visitors will know that I monitor studies and analyses of procedural and distributive justice in the context of the research environment, such as the work of Brian Martinson, Melissa Anderson, et al.. Nice to see ORI giving a little thought to the research environment itself (and its administration) as a means for preventing misbehavior and worse. In discussing grant funding policy here at MWEG, some have suggested that institutions be required to pay the major portion of researcher salaries (hard money), and this would certainly be one way to foster a much more pleasant environment that would likewise be more conducive to the responsible conduct of research. If you have other suggestions, I am quite sure Dr. Galland would appreciate such comments on his blog.

Little late getting this up, October deadlines and all …

Notice is hereby given that ORI and the Assistant Secretary for Health have taken final action in the following case:

Based on the findings of an investigation report by the Universidad Central Del Caribe and additional analysis and information obtained by ORI during its oversight review, ORI found that Jennifer N. Arriaga, former Research Assistant in a clinical trial project entitled Brief Strategic Family Therapy for Adolescent Drug Abusers, engaged in research misconduct in research funded by U10 DA13720.

Specifically, ORI found that Ms. Arriaga knowingly and intentionally engaged in research misconduct by fabricating 17 interviews and falsifying 10 subject incentive receipts in the trial. The interview record consisted of Timeline Follow Back information, confidentiality self-report forms, and urine drug test results.