Cont’d Hellinga Fall-Out (May 2008)
Ugh. Nature summarizes the continued (& spreading) negative repercussions of the retracted Dwyer et al. papers discussed here and throughout the scientific community. An excellent Nature feature article by Erika Check Hayden covers the entire saga in detail.
Earlier, our man-on-the-spot David added a nice summary of an article in the May 5, 2008 issue of Chemical & Engineering News, including a bit more insight from John Richard in Buffalo and Hellinga’s dismissive reply (thanks so much, David, for all your contributions).
Nature notes that Richard and his group “wasted seven months and tens of thousands of dollars failing to reproduce the results from Hellinga’s lab” and that Mary Dwyer’s scientific career is over before it started. The editors also observe the questionable rationale in Hellinga’s accusing her of scientific misconduct: “As Dwyer’s adviser, Hellinga was responsible for training her. If she made mistakes, they are ultimately his responsibility.”
And, Nature spreads the wealth by noting that Duke itself owes something to the scientific community, and indeed, one hopes they are not holding their breath and hoping this will blow over so Hellinga can get back to the business at hand: bringing in research dollars to the University.
Earlier discussion can be read first here (initial Science retraction and detailed comments on problems with the science involved) and then here (The Scientist blog coverage, Chemical & Engineering News synopsis, et al.).
BB said,
May 15, 2008 @ 8:53 am
In retrospect, Dwyer was warned by numerous folk that Hellinga wasn’t the best advisor. She was a lowly grad student at the time and so wasn’t in a position (she thought) to keep Hellinga from publishing. Hindsight is always 20/20; perhaps the cautionary lesson here is that the future Dwyers bring concerns about an advisor’s rush to publish to a chair, dean, or ombudsperson. And to be prepared to switch labs, unless one’s thesis committee can pressure the Hellinga advisors of this world (at some schools, they can).
I agree with Nature’s conclusion vis-a-vis Dwyer: her work was Hellinga’s responsibility. Kudos to her post-doc mentor for standing by her and giving her good advice. I think she’ll come through this fine in the end.
Probably the saddest fact is that similar things albeit less publicized often happen to lowly grad students and unpopular post-docs.
Noam Y. Harel said,
May 15, 2008 @ 9:03 am
I just caught up on this controversy through the Nature articles and your earlier blog thread.
Aside from all the shady ethics, what also deeply troubles me is the statement that Dr. Richard’s work leading to the retractions was done with “no discernable benefit to his own career”.
The lack of credit given to those who reproduce (or refute) others’ work directly leads to the perverse incentive to rush to publish work first, often with data that is shoddy at best, fraudulent at worst.
One way to improve these perverse incentives is to give more credit to those who reproduce or refute others’ findings. Though there will never be a perfect formula, we should strive/collaborate to come up with the best system possible to gauge an individual’s overall contribution to science.
You are all invited to collaborate on this project, tentatively named the Public Contribution Rating, at my wikispaces collaborative science site.
JSinger said,
May 15, 2008 @ 9:21 am
A few various points…
1) What struck me as odd was:
But Dwyer’s new adviser, Donald McDonnell, a professor of pharmacology and cancer biology, advised her not to meet Hellinga alone; he felt she should go with someone who could advocate on her behalf. McDonnell arranged a meeting later that week at which he, Dwyer and Hellinga were joined by two other faculty members from the biochemistry department.
Presumably, something was left out of the story before this. Normally, meetings with the old advisor don’t involve the postdoc coming in with an OJ-like defense team behind her. The rest of the department must have known she was getting ambushed even if she didn’t. (I give them credit for not reflexively backing the PI, although my cynical guess is that they don’t like Hellinga much.)
2) My favorite part was:
Some point to a Duke policy that states that if an allegation of misconduct is found to be “baseless and malicious or reckless, the matter will be dealt with in accordance with existing university policies and mechanisms”.
Sure, if there’s one thing Duke is known for, it’s sanctioning faculty and administrators who make wild accusations of misconduct against students! At least they didn’t make the whole biochemistry department sign a demeaning statement like the lax team had to.
3) On the plus side, the two-body problem seems to be getting adequately addressed! There’s, what, three pairs of spouses entangled in this?
4) re: In retrospect, Dwyer was warned by numerous folk that Hellinga wasn’t the best advisor. I always counterbalance these warnings to heed warnings by noting that I did the same thing she did, and it worked out very well for me. There are plenty of awful PIs out there, but there are plenty of gossipy, petty, vengeful grad students also.
5) Can’t WordPress get a freaking preview button? I’m holding my breath and hoping that I got all those tags right!
In defense of reviewers said,
May 16, 2008 @ 3:57 pm
Wow, Hellinga sure doesn’t help himself in that article. He basically takes no responsibility down to the bitter end and comes off looking like a huge jerk.
“Dwyer says that she raised her concerns with Hellinga at the time. But Hellinga says he does not feel he pushed Dwyer or anyone else to publish prematurely. “These things were talked through very carefully with all the people involved,” he says.”
In my opinion, Hellinga’s culpability really comes down to this: how much did he know about the variability (which didn’t end up in the final paper)? Whether or not he talked it through with his graduate students makes no difference - he’s the boss and should have held off on publishing until this issue was worked out.
“Asked whether he would have done anything differently in the NovoTIM experiments, Hellinga says, “I would like to not have the problem that we encountered.” When asked whether the lab moved too quickly, he says: “Given how we understood things to be at the time, no. Obviously if we had known things had gone wrong, we wouldn’t have moved forward with the speed we did.””
How could he say that he wouldn’t do anything differently unless he’s completely arrogant? If he was quoted correctly in this article, he should be banished from science.
noblesse d'epee said,
May 16, 2008 @ 11:06 pm
Hellinga is a crass embarrassment to Duke’s Biochemistry Department. His outrageous mistreatment of his student Mary Dwyer and his breathtakingly unethical approach to his recent retractions have confirmed what many here at Duke long knew: Prof. Hellinga is a malign influence upon the educational program to which he purports to contribute.
I fear that the widespread coverage of Hellinga’s sleaze will cause collateral damage to the reputation of Duke Biochemistry. The public should know that Hellinga’s behavior and science are not representative of our program. When faced with the choice between publishing questionable data and delaying publication in order to perform rigorous control experiments, the vast majority of our faculty, post-docs, and students choose the latter. There is no “culture of corruption” here. If anything is corrupted, it is Homme W. Hellinga. As is appropriate for rubbish, his exit from Duke Biochemistry should be rapid and unceremonious.
Despite his supremely arrogant aspirations, Hellinga may never be as famous as Charles Darwin. But all is not lost. Hellinga has furnished a superb case-study for research ethics courses the world over. That shall be his legacy.
Ph.D. Candidate, Duke Biochemistry
In the Know said,
May 18, 2008 @ 3:40 am
JSinger,
Your suspicion is correct - there are many PIs at Duke that don’t care for Homme, although after reading the article I don’t think you would have to be cynical to think that Homme had rubbed a number of people the wrong way. More famous than Darwin? I didn’t even know he was that arrogant.
I agree with you that the student population can be gossipy, but when ten of the PI’s first dozen graduate students quit grad school (as in Homme’s case) and the people WITHIN the lab are warning you not to join… I don’t think flags get any bigger, redder, and wavier. I would say this to any first year graduate students: if people outside the lab are warning you not to join while people within the lab are advocates of the PI, then think about it. But when the people within the lab are warning you not to join, run like hell.
George Smiley said,
May 20, 2008 @ 12:44 am
“In my opinion, Hellinga’s culpability really comes down to this: how much did he know about the variability (which didn’t end up in the final paper)?”
You understate Hellinga’s culpbability, and that of the referees. Consider the goal: to design a novel enzyme that mimics the activity of triosephosphate isomerase (TIM). TIM is, as all competent biochemists know, an enzyme with nearly perfect efficiency. TIM is also highly abundant in most cells, including E. coli, and WILL be a contaminant of any purification scheme. To produce your putative novoTIM, you will use E. coli. It is nearly a given that multiple separations will be required to separate your novoTIM from the real thing. How good does the separation have to be? If your novoTIM has 1/1000 the activity of the native enzyme - and you’d have to be very skilled AND very lucky to achieve this - 1% contamination by native enzyme would mean that 90% of the activity would be from the native enzyme. He surely knew this. Every competent protein biochemist in the wolrd knows this.
Yet Hellinga went to press with a single-step separation using a method known by every competent biochemist to be susceptible to significant contamination. No ion exchange. No gel filtration. No purification of novoTIM from cells genetically deleted for the endogenous enzyme. For this, Hellinga should be run out of the field on a rail. And this is not, of course, the only defect in a manuscript positively rancid with questionable details.
As for the referees who apparently did not consider this possibility, and demand more stringent biochemistry? They should take a break from refereeing papers and consider that if they had done their due diligence, they might have saved the career of a young woman whose prospects are now very much in question.
In defense of reviewers said,
May 22, 2008 @ 2:27 pm
George,
I disagree. The experiments in the original paper are well-controlled as described. There are many mutant proteins they made which exhibit no activity arguing against co-purification of endogenous activity. Furthermore the designed variant complements Tim- bacteria. In fact, this is why the explanation given in the retraction is unsatisfactory. Only later do we find out that there were red flags that weren’t included in the paper. Could data have been cherry-picked to make a case for the author’s conclusions? If so, this is fraud and should be punished. And this is what I believe happened. Hellinga thought he had a whale of a result on his hands and ignored the evidence against once he started envisioning all the accolades that would come.
Finally, we don’t know what went on during the review process. Perhaps reviewers did request the things you mention (further purifications, etc), but because the data seemed so air-tight, these requests were considered unreasonable? This is not an unlikely scenario from my experience on both sides of the peer review system. I can easily see a reviewer making requests like the ones you describe and Hellinga responding that the data in the paper clearly shows that the activity is not from endogenous TIM (e.g. lack of activity in mutants and novoTIM complements a TIM- strain).
scotus said,
May 22, 2008 @ 3:31 pm
JSinger raises some important points.
Duke’s misconduct policy will definitely require that all parties respect the confidentiality of the process with possible penalties for not doing so almost certainly including dismissal so its notable that Dwyer has decided to speak out about her interactions with Hellinga that led to the misconduct investigation.
Duke’s policy will also have a provision that everything possible should be done to restore the repulation of an exonerated “respondant” (ie Dr Dwyer) so my suspicion is that she probably doesn’t feel as though this has been done to a sufficient extent and is taking the matter into her own hands.
Finally Duke’s misconduct policy will definitely have a provision to sanction individuals who make “Bad Faith” allegations of research misconduct. If Dr Hellinga accused Dr Dwyer of misconduct knowing that the charge was false then he would be guilty of making a bad faith allegation. Of course, looking objectively at whole mess I think its pretty obvious that being accused of a bad faith misconduct allegation is the least of Hellinga’s problems….
This whole episode could very easily turn into a science version of the Duke lacrosse case except that Hellinga will be playing both the Crystal Mangum AND Mike Nifong roles…
George Smiley said,
May 22, 2008 @ 9:08 pm
IDoR,
you make some excellent points. It’s clear that Hellinga’s conduct leading up to submission of the publications was a admixture of incompetence and dishonesty; in some respects the fractional contribution of each is irrelevant. He’s shown that his work, as the Nature editorial very nearly said, cannot be trusted, and that he does not deserve resources or attention, particularly at this moment when there are so many struggling scientists who are both competent and honest, if a bit less self-promoting.
Your points about the referees are well taken. Most importantly, no one here knows what went on in the Nature and JMB review processes, or if they do, they are not saying so. So we should be careful about criticising this process. Nevertheless, extraordinary claims require (or should require) extraordinary evidence, and I still find it shocking that the paper contains no statements dealing with the issue of contamination by native TIM. It is painfully evident now, and should have been evident all along, that this would be a major issue: TIM is, after all, a perfect enzyme. The paper as published contained elegant controls, but lacked obvious and simple ones.
Ultimately, of course, the question that we have to ask is to what extent we can give our colleagues the benefit of the doubt during the peer-review process. Unfortunately, the peer-review process does not proceed from a coherent or consistent set of assumptions about this, and referees often bury one manuscript in trivia while another sails through with fundamental and obvious flaws. I don’t think that anyone really knows how to fix this situation without putting an undue burden on the majority of good scientists.
whimple said,
May 22, 2008 @ 10:56 pm
Since the NIH awards grants to institutions, rather than to individuals, the NIH should investigate, and if it determines that its money was fraudulently wasted, should require Duke to repay the grants (out of whatever source of money Duke chooses). The NIH in theory holds all the cards here… I just don’t understand why the NIH continually throws in its hand to seemingly cater to the institutions’ every beck and whim.
scotus said,
May 23, 2008 @ 3:53 pm
Whimple-
The NIH requires institutions holding grants to adhere to their rules on responsible conduct of research which are ultimately governed by Federal Statutes. The misconduct investigation of Dr Dwyer and the now in my opinion inevitable investigation of Dr Hellinga are mandated by those rules. The institution, in this case Duke, has to conduct an investigation to establish if misconduct (ie deliberate fabrication or falisification of research results) occurred. Duke has to inform the NIH Office of Research Integrity (ORI) when the investigation is initiated, if it proceeds from an initial inquiry to a full blown investigation and at the end a complete report has to be submitted. The ORI would then make a decision about the validity of the conclusions drawn by the Duke investigation and determine any sanctions to be taken against Hellinga.
Duke could of course contemporaneously determine that Hellinga’s conduct is grounds for dismissal and pre-emptively fire him (or ask for his resignation) and give back his grants. This has actually happened in two recent high profile misconduct cases that also attracted a lot of popular science press attention (Luk Van Parijs- MIT and Elizabeth Goodwin- Wisconsin). However, the process can be interminably slow. Neither the Goodwin or Van Parijs cases appear to have been settled by the ORI yet even though the first of these is now almost 4 years old.
The good news is that once the process is started, it can’t just go away. The bad news is that it could take years to resolve.
In defense of reviewers said,
May 23, 2008 @ 8:00 pm
George,
Your statement, “Unfortunately, the peer-review process does not proceed from a coherent or consistent set of assumptions about this, and referees often bury one manuscript in trivia while another sails through with fundamental and obvious flaws.” succinctly describes what scientists probably find to be the most frustrating aspect of practicing science. Of course the big challenge is who decides what is a “trivial” vs. “fundamental” flaw? The editor is typically responsible for making these tough judgment calls and they have a very difficult job on their hands that isn’t getting any easier (more manuscripts, more complex science). Often the reputations of authors and reviewers come into play and this isn’t always a good thing (but shouldn’t be ignored either).
mark said,
May 25, 2008 @ 1:33 pm
I would bet that Hellinga used data from these papers to get NIH grants, if not his Pioneer award. Now that they are retracted, doesn’t he lose those grants?
Excellent point. And even so, the Great Zerhouni should consider whether Hellinga represents the sort of Pioneer he sought to promote through these awards. - writedit
Federale said,
May 27, 2008 @ 1:27 pm
Office of Research Integrity. Director is a Duke Alum. I’m sure a few phone calls inquiring why ORI has not decided to open an investigation wouldn’t hurt. Likewise, a phone call to NIH in the Office of the Director, as well as to the Office of the Secretary of Health & Human Services (HHS) might help.
Additionally, one could go for the jugular - the money. A call placed into the Office of Management and Budget (OMB) to their health division could be in order if someone felt there was a failure to comply in here..
Office Phone FAX
Office of the Director 240-453-8200 301-443-5351
Division of Investigative Oversight 240-453-8800 301-594-0043
Division of Education and Integrity 240-453-8400 301-443-5351
Assurance Program 240-453-8400 301-594-0042
Research Integrity Team/Office of the General Counsel 301-443-3466 301-594-0041
P R O F E S S I O N A L S T A F F
Office of the Director
Chris B. Pascal, Director, J.D. from Duke University
Division of Investigative Oversight
John E. Dahlberg, Director, Ph.D. in Virology from Purdue University
Nancy M. Davidian, Deputy Director, Ph.D. in Biochemistry from the University of North Carolina, Chapel Hill
Peter H. Abbrecht, Medical Expert, M.D. and Ph.D. in Chemical Engineering from the University of Michigan
Kay L. Fields, Scientist-Investigator, Ph.D. in Molecular Biology from the Massachusetts Institute of Technology
Susan Garfinkel, Scientist-Investigator, Ph.D. in Molecular Genetics from George Washington University
John W. Krueger, Scientist-Investigator, Ph.D. in Biomedical Engineering from Iowa State University
Linda D. Youngman, Scientist-Investigator, Ph.D. in Toxicology from Cornell University
Division of Education and Integrity
Sandra L. Titus, Director, Intramural Research Program, Ph.D. in Family Social Science from the University of Minnesota
Cynthia S. Ricard, Director, Extramural Research Program, Ph.D. in Biomedical Sciences from the Albany Medical College
Loc Nguyen-Khoa, Director, Online Education & Communication, Ph.D. candidate in Public Health at the University of Maryland
Robin Parker, Assurance Program Manager
Research Oversight Legal Team/Office of the General Counsel
Christian C. Mahler, Research Integrity Team Leader, J.D. from the University of Maryland
Jo An Rochez, Senior Attorney, J.D. from the University of Maryland
Alice Tayman, Senior Attorney, J.D. from the University of Maryland
postdoc said,
May 28, 2008 @ 10:30 am
I’m not sure I understand this. Duke has cleared Mary Dwyer of fraud, but her lab notebooks could not possibly be consistent with the published data.
In the Know said,
May 28, 2008 @ 3:06 pm
@ postdoc:
From the article (http://www.nature.com/news/2008/080514/full/453275a.html):
“By early 2004, Hellinga was ready to publish. On 29 March, he submitted a paper describing the NovoTIMs to Science, which accepted it on 6 May. The paper did not mention the variability Dwyer had noticed.”
The implication is that Dwyer didn’t write the paper, and amongst the piles of variable data, Hellinga cherry-picked the data that fit the model. You’ll notice a lack of reporting of statistical error in the original paper(http://www.sciencemag.org/cgi/content/full/sci;304/5679/1967).
Now we wait for a more in depth investigation to see if these inferences are true…
noblesse d'epee said,
May 28, 2008 @ 6:10 pm
Update from Duke Biochem.:
Prof. Hellinga has been telling his laboratory (and others) that Mary Dwyer is mentally unstable and that her data were artifacts of this state. This brilliant “defense” by Hellinga is not only weak, it is vile slander.
This is consistent with a pattern that has long been recognized by graduate students in Duke Biochem: Hellinga is widely known to instigate whispering campaigns against other students who have left his lab. In each case, he has questioned students’ intelligence, sanity, and general mental well-being. Interestingly, Hellinga’s wife (and collaborator) Prof. Lorena Beese has consistently employed the same modus operandi to discredit her own graduate and rotation students — always behind their backs. Such behavior is a particularly despicable, if disingenuous, method by which a PI may “cover” for his atrocious mentoring and/or misconduct. Why do this pair of professors get away with this? Does having large grants and high profile publications really excuse all other wrongdoings in the eyes of the scientific community? Do Hellinga’s colleagues and superiors have insufficient conscience and decency to demand of him some modicum of responsibility?
If academia tolerates this sort of behavior by so-called “educators,” I want no further part of it.
Trevor said,
May 28, 2008 @ 9:46 pm
Noblesse d’epee:
Please, please, please don’t paint us all as with the same brush. The vast majority of us would not, could not, do not tolerate such behavior. It is reprehensible that at least some in the Duke biochemistry department apparently do.
I am left wondering why Hellinga is not under investigation - the system is currently failing. It has not as yet failed, but it is coming close.
postdoc said,
May 28, 2008 @ 11:49 pm
Noblesse d’epee:
You obviously have a personal problem with HH, therefore your claims about this matter lack credibility.
postdoc said,
May 29, 2008 @ 12:16 am
In the know:
So, basically, she was a victim? Please. It is very hard to accept that a first author of two major papers that are not backed by her lab notebooks can be declared innocent of misconduct.
A grad student in that kind situation does not have to confront her superviser in person. She could have gone to the dean of students or the dean of research and asked for help.
Trevor said,
May 29, 2008 @ 7:52 am
Postdoc:
Are you actually there in the Duke biochem department? Have you ever been put in a situation similar to that of Dwyer? Have you met HH? I think you are misjudging just how difficult it would be for a student to dispute an advisor such as Hellinga (I have met him). Yes, she could (and probably should) have taken her concerns to a higher authority, and yes, she shares some culpability for not doing so. However, it is very easy for us to pass that judgement. We weren’t there and most of us, I wager, have never been personally involved in a situation such as this.
noblesse d'epee said,
May 29, 2008 @ 8:34 am
@ Postdoc:
Were one to survey my graduate student colleauges in the Duke Biochem. Dept., I think that one would find that my claims are indeed credible. Since we’re talking anonymously on the internet, I fear that you will just have to take my word for it.
It is true, as is clear from my posts, that I detest Hellinga (HH). From my vantage point, I think that any decent, concientious scientist might feel similarly. Do my opinions invalidate what I have observed and experienced? Only if one assumes that my bias causes me to fabricate such observations. I’ll leave the fabrication to HH.
David said,
May 29, 2008 @ 11:38 am
In response to Postdoc.,
First, the Biochemistry Department at Duke is within the Medical School. The difference between departments in Medical Schools and Arts and Sciences Colleges is striking from my experiences in both types of departments. The power structure and focus on students is far different than in an Arts & Sciences Department where teaching and students are a major focus.
Second, while I do not know HH at all, I know four people who have left his lab - unhappily. One is now successfully self-employed. The other three left unhappily only to find success in other labs. The claim that a disproportionate number of his grad. students left his lab and/or science seems to be true.
Third, as for what the student should have done, why don’t we reference another case that has been mentioned - where the students did report alleged misconduct. This is the UW-Madison case of Prof. Elizabeth Goodwin. see http://www.uwalumni.com/home/worms.aspx
The 7 students/employees banded together. In the end, all but one student left Wisconsin, careers in shambles. As bad as that seemed, it could have been worse. The administration in the UW Ag School was very supportive of the students. All of them seemed to genuinely like Goodwin and had a good relationship with her before they went to the administration. Still there were reports of a whisper campaign behind their backs.
Contrast the UW circumstances to the Duke circumstances. Is it realistic to expect solitary Mary Dwyer to oppose HH by going up the Medical School Administrative ladder? I can be certain that her career would be in shambles AND she would be unemployed.
Here is an idea. Anyone who attends one of those mandatory ethics training sessions should be introduced to an administrator entrusted with the well-being of students/postdocs. If such a relationship were cultivated before problems arose, perhaps problems could be caught earlier. It takes unrealistic bravery to send a career in shambles without a safety net.
In the end, Mary Dwyer was cleared by a committee of HH’s peers. Would that have happened without the forced retractions and scrutiny of the scientific community?
Trevor said,
May 29, 2008 @ 12:37 pm
David wrote:
Here is an idea. Anyone who attends one of those mandatory ethics training sessions should be introduced to an administrator entrusted with the well-being of students/postdocs. If such a relationship were cultivated before problems arose, perhaps problems could be caught earlier. It takes unrealistic bravery to send a career in shambles without a safety net.
Many institutions have ombudsmen who have the responsibility you described. Unfortunately they are often anonymous administrators who have little or no contact with their constituents, and also little or no experience in science.
In addition to an all-purpose ombudsperson, every institution should have a Research Integrity Officer for just this reason (neutral, confidential sounding board/reporting official for scientific misconduct concerns), but their (unpaid) role is often downplayed, possibly because they too are busy trying to do their own work, get grant funding, write papers, train students, etc. Plus, different institutions give them different degrees of power/authority. - writedit
In defense of reviewers said,
May 29, 2008 @ 2:46 pm
Postdoc writes:
“A grad student in that kind situation does not have to confront her superviser in person. She could have gone to the dean of students or the dean of research and asked for help.”
It’s not the student’s responsibility to do this. Students should have avenues for such situations, but if they don’t take advantage of them, it doesn’t mean they’re responsible. The advisor is ultimately responsible for deciding when and what to publish. If Dwyer had kept the variability from Hellinga then she would be at fault, however this is not the case (from what I understand). Instead Hellinga was made aware of this and still decided to publish and thus is completely responsible and should be punished appropriately.
In the Know said,
May 29, 2008 @ 4:54 pm
@ postdoc:
I was there, heard the progress talks, met the people involved, and knew several of the people who left the lab previously. You can maintain your suspicions, but from what you have written you don’t know the players involved. The reason I even started posting to this forum was to offer an inside view of this situation, since I had seen knee-jerk “blame the lead author” reactions from several of my colleagues. Ultimately, however, I’m hoping that my views here and your suspitions are all rendered meaningless by a published report of an in-depth investigation of the situation.
another postdoc said,
May 30, 2008 @ 12:18 am
@postdoc,
There is no reason for her or anyone in her position to believe that their personal interests would be served by speaking to someone about their advisor, especially given that they have no good reason to have much trust in the people whom you mention. There is a huge asymmetry of power between a grad student and a tenured professor, and I think most grad students in such situations are acutely aware of this asymmetry. Why should one trust a bunch of people who have consistently looked the other way when the advisor behaved like a jerk ?
A tenured professor can get away with anything short of a criminal act, and not be really penalized for it, and it is not in the interests of others in the dept or the administration to go after one of their colleagues. It is on the other hand a lot easier to let the student out to dry. Also, given that there is no public investigation by Duke into Mr. Hellinga’s actions (he has after all openly slandered his former student who has been exonerated, and not acknowledged any wrongdoing) even at this stage, she probably did the sensible thing by not going to anyone else in the administration.
postdoc said,
May 30, 2008 @ 2:20 am
I’m in COAS, and indeed, as another poster said, students and teaching are taken seriously. Perhaps I’m naive, but I still think that a dean or a department chairperson can be trusted to offer good advice and not to spread the word in cases of conflict with one’s adviser. Sure beats being complicit in scientific fraud.
In the Know said,
May 30, 2008 @ 2:01 pm
In this particular situation, the department chair (at the time) did not have a reputation of confidentiality, and taking this type of situation to a Dean when your PI is the darling of the Medical Center and has a reputation for ruthless retaliation takes some serious faith.
For others following this drama, I think the lesson is to not allow yourself to be cornered in this manner. If a PI has this type of reputation, don’t join the lab. If you are in the lab before you see these issues, then quietly leave the lab and tell someone in power if you know you can trust them. Graduate students often have the mistaken idea that changing labs will come at a high price in terms of time, and that other PIs will never take them, when in truth this often isn’t the case.
In defense of reviewers said,
May 31, 2008 @ 3:45 pm
Postdoc writes, “Perhaps I’m naive, but I still think that a dean or a department chairperson can be trusted to offer good advice and not to spread the word in cases of conflict with one’s adviser.”
That is a naive assessment of the situation. Who knows what any individual might do, but deans and department chairs definitely have conflicting interests in these situations. Look at Hellinga’s case. He had brought tons of money into the department and was supposedly on a steep upward trajectory. There’s no question that a chair or dean would want this to go away. Now they might do the right thing anyway, but the motivations for saving the PI vs. the grad student are definitely there. So to just assume that the administration is going to do the right thing in cases like this is simply a matter of not thinking it through.
postdoc said,
June 1, 2008 @ 9:31 pm
In defense of reviewers:
You’re forgetting the context. HH already had a unsavory reputation in the department. Let’s further assume that MD was respected by her colleagues and the faculty members. In such conditions an astute administrator should realize that the accusing student is telling the truth and that something has to be done to avoid a scandal.
In defense of reviewers said,
June 2, 2008 @ 1:00 am
Postdoc,
I don’t really know what you’re arguing anymore. We now need to assume that the grad student is well-respected and the administrator is astute? Can’t we just agree that contacting the administration is not an obvious course of action in this situation, what you were stating earlier in the discussion?
And speaking of context, in this case Dwyer was concerned about variability but her mentor was telling her that it was nothing out of the ordinary (from the Nature article). I could easily see her second-guessing any decision to make an issue out of it.
noblesse d'epee said,
June 2, 2008 @ 5:24 pm
A “Former Hellinga Graduate Student” posted recently in one of the older, inactive portions of this thread (see below). What he/she says is interesting. I suspect that an investigation of HH would not suffer from a shortage of testimony.
Former Hellinga Graduate Student said,
May 30, 2008 @ 11:30 pm · Edit
Federale said:”Office of Research Integrity. Director is a Duke Alum. I’m sure a few phone calls inquiring why ORI has not decided to open an investigation wouldn’t hurt. Likewise, a phone call to NIH in the Office of the Director, as well as to the Office of the Secretary of Health & Human Services (HHS) might help.”
This sounds great, and as a former graduate student in Hellinga lab at the time the designs were made I could testify (and so could other former lab members) about many wrongdoings on Homme’s part that were not just unethical and unprofessional, but just plain wrong from a human perspective. He treated his students as some data collecting monkeys, who were supposed to train themselves to be able to collect the vast amount of groundbreaking data in the first place. And those multi million dollar grants received for which absolutely no work had been done in the lab. Ever. And why would science fiction type research proposals be funded and never worked on? Without any preliminary experimental work? I wonder how much those phone calls could change the reality. ( Forgive my cynicism, but its all about money he brought in.)
writedit said,
June 3, 2008 @ 9:21 pm
A few thoughts on all this finally …
First, there won’t be a “published report of an in-depth investigation of the situation.” Maybe, in a few years (as was noted earlier by scotus), ORI will publish their summary findings. Of course, ORI needs to hear from Duke about this first, but I’m sure they have. We just won’t hear about it nightly on the 6 o’clock news.
Second, as evidenced by the fear of tenured professors and senior researchers to speak out against something that is very public & very obviously not right (see local article describing the lengths faculty are going to protect themselves), it probably is too much to think a grad student would feel comfortable going to administration officials whose salaries are paid off the indirects from her “mentor’s” grants. Hellinga is a cash cow, plain and simple.
However, the research conduct and compliance arm should be completely (reporting lines & budget support) independent of any other branch of research development to avoid any such conflict of interest (this is how they structure things here at Baby It’s Cold Outside anyway so the engine driving the research train is not the one to put on the brakes). Unfortunately, I can’t quite figure out, going through the Duke Research links, who manages their conduct & compliance issues.
Third, for concerns about grant funding being misused in any way, anonymous tips can be submitted to the US DHHS Office of the Inspector General Hotline (and rewards are paid based on savings to the federal government).
scotus said,
June 4, 2008 @ 3:20 pm
It’s been well established that PHS/NIH grants are not “contracts” to conduct the research proposed. If Hellinga had support from other agencies such as the Department of Defense, Department of Veterans Affairs or private sources it is likely that some sort of a contractual obligation to attempt the funded research could be invoked. However, when it comes to NIH grants, only egregious misuse of funds for purposes unrelated to scientific research would be grounds for a complaint. Of course, were a misconduct investigation to find that Hellinga obtained funds on the basis of fraudulent research and/or used the funds for fraudulent research then the implications for him and Duke are clear as established by the Poehlman case (which was of course a lot more egregious than the alleged Hellinga misconduct).
The other point I wanted to make is that all of the suggestions that Hellinga will be protected by Duke because of all the funding he attracts are way off the mark. In the scale of things Hellinga’s support may be high on an individual basis but it’s a tiny portion of all the PHS research support at DUMC. Duke will not jeopardize this by doing anything that could be seen to be complicit with Hellinga’s alleged misconduct.
Some “creative tension” between mentors and their trainees is an inevitable part of the academic research “circle of life”. I have had an NIH funded lab for 15 years (I’m negotiating the 4th renewal of my R01 now). I’m not as “successful” as Hellinga by any stretch but I have learnt from experience and mistakes that if I do not maintain an open, trusting and respectful relationship with the people who work with me in the lab the fundamental equilibrium of the research process is disrupted. It sounds as though Hellinga had been sailing close to the wind for a while. Research misconduct is such an emotive issue that I really can’t see an easy exit strategy.
My prediction is that Hellinga will end up moving to the private sector later and that it will take another 3-4 years before ORI publishes anything about the case.
noblesse d'epee said,
June 4, 2008 @ 4:58 pm
Scotus said:
“Duke will not jeopardize this by doing anything that could be seen to be complicit with Hellinga’s alleged misconduct.”
Perhaps. But DUMC, early in its misconduct investigation, “lost” the laboratory notebook recording Mary Dwyer’s work on the Novo-TIMS. Fortunately, Dwyer made *NOTARIZED* copies of the relevant notebook. These copies were apparently used to mount a successful defense against Hellinga’s charges. If this unusual precaution had not been taken, the outcome of the investigation would have hinged upon Hellinga’s word vs. Mary’s. If Duke isn’t complicit in Hellinga’s misconduct, it is doing a superb job of pretending to be. Of course, we must remember that Duke is run by the ham-handed crowd who brilliantly managed the lacrosse fiasco, so we cannot assume malfeasance when gross incompetence would suffice.
I should point out the my information about the lost notebook is well-vetted. This, among other sordid details, will continue to bubble to the surface as this disaster continues to lurch into the open.
scotus said,
June 4, 2008 @ 5:28 pm
It would be standard procedure for copies of the research records to be made at the time when they were submitted to the panel conducting the intiial investigation. Don’t forget that according to the ORI misconduct regulations failure to produce these records by Drs Hellinga or Dwyer would constitute misconduct (see below). One thing that I don’t understand is that if Dwyer had already left Hellinga’s lab then the original lab records should have stayed there and not been in her posession at the time the investigation was initiated. If she held on to these records that might be significant and suggest she knew they might become a focus of attention in the future. Does anyone know anything about this?
I am sure that the relevant administrators at DUMC are doing their best to handle this in a fair way that respects the confidentiality of the process. I am also sure Hellinga has retained counsel who are pressurising Duke not to do anything to harm Hellinga’s reputation until they reach a decision. I can’t believe that Duke are not now investigating Hellinga but I expect his lawyers are doing their best to make sure the process is super confidential, particularly in light of Dr Dwyers decision to talk publically about it through the science press.
If there was an attempt to protect Hellinga by tampering with the records whoever instigated it was both reckless and stupid. In the end the reputation of the institution is what matters. There are plenty of decent investigators at Duke doing worthwhile highly regarded research. The $100s of millions of research funding they bring in each year are much more important than the money it appears as though Hellinga has scammed out of the NIH for his “research”.
Q: Is the destruction, absence of, or the respondent’s failure to provide research records adequately documenting the research that is the subject of an allegation of research misconduct evidence of research misconduct?
A: Yes, if the institution or HHS establishes by a preponderance of the evidence that: (1) the respondent intentionally, knowingly, or recklessly had research records and destroyed them, had the opportunity to maintain the records but did not do so, or maintained the records and failed to produce them in a timely manner; and (2) the respondent’s conduct constitutes a significant departure from accepted practices of the relevant research community. Section 93.106(b)(1).
In defense of reviewers said,
June 4, 2008 @ 6:40 pm
Scotus, thanks for your well-written posts (and good luck on your renewal). I have one nit to pick. You state, “failure to produce these records by Drs Hellinga or Dwyer would constitute misconduct” but the quote you supply does not support such a strong assertion. First, the question says that not supplying these records could be “evidence of research misconduct”. Second, the answer states that additional things (that could be very difficult) must be proven in addition to failing to supply the records, in order for this to constitute misconduct.
However, I think you hit the nail on the head:
“My prediction is that Hellinga will end up moving to the private sector later and that it will take another 3-4 years before ORI publishes anything about the case.”
In the Know said,
June 4, 2008 @ 7:15 pm
It is my understanding that Mary copied the notebooks before she left the lab in anticipation of future troubles, but I don’t know for sure. Since she was/is still working at Duke, she may have simply gone back to the lab early in the drama and photocopied them then.
I have also heard that Duke lost the notebooks, but from another pretty reliable source I heard that the notebooks are not (and never had been) lost, and are being securely held by the Med School administration. It is hard to beleive, given the “impact factor” of the issue, that someone would be negligent enough to loose the notebooks, or stupid enough to ‘misplace’ them on purpose.
For the more experienced commentators on here:
Wouldn’t, at least in this case, the manuscript drafts and editing communications between Mary and Homme be the most revealing? Assuming that these communications occurred through e-mail, couldn’t the school pull communications between the two from department servers? Certainly if we were talking about a company, e-mail communications would be fair game. With a university, however, I don’t know if e-mails can be pulled without a search warrant, or if the university/department would even maintain records that are several years old.
scotus said,
June 4, 2008 @ 9:46 pm
IDOR- You are right. Inability to produce the data would not automatically result in a finding of misconduct.
I was trying to make the point that “losing” the data in mid investigation would not terminate the process and would therefore not be a particularly sensible or effective strategy for some unknown Duke operative to protect Hellinga for the purpose of retaining his research funding as some others here have suggested.
scotus said,
June 5, 2008 @ 1:55 pm
ITK-
Good points. Email is discoverable and its very likely that these emails could be obtained by the investigators. At most universities, the computer system belongs to the university and the resonable expectation of privacy can be usurped when matters that potentially contravene the universities rules and regulations are involved. If Hellinga and Dwyer did communicate by email I wouldn’t be surprised if Dwyer didn’t share these and drafts of the manuscripts with the investigators. In any case, at this stage the issue of these communications seems moot. Dwyer has been exonerated and, as I explained above, it is very unlikely that anyone at Duke will confirm Hellinga is under investigation although I cannot imagine he isn’t. If the investigation has started just about anything is fair game which could include forensic analysis of his computers to examine drafts of the papers. I am sure Duke will have some CSI fanboy IT people who would be only too happy to look into this.
My Chair, Division Chief and VP for research will not communicate with me by email about certain “sensitive” matters like hiring, promotion, space, research resources for exactly the reason that they don’t want an electronic paper trail.
Federale said,
June 6, 2008 @ 4:24 pm
There seem to be a number of individuals leaving comments on here who really need to hear the following:
1 - If you feel you have information that is pertinent to this case, and you feel you have a duty to provide it (ie familiar with the players, discussions, data, witnessed acts, analysis of other potential misconduct acts, analysis of other papers that are suspect) you should say something to one of the following appropriate authorities. Contacting these groups (which constitute a number of funding agencies for the laboratory of the person involved) and the appropriate other actors who have a stake would constitute a fulfillment of a duty-bound obligation to scientific integrity.
a, Office of Inspector General at HHS
b. Office of Inspector General at DoD
c. Office of the Director of DARPA
d. Office of Research Integrity at HHS
e. Editorial Staff at any Journal with a suspect publication
You can contact any of these places and outright demand confidentiality. They take these matters very seriously, as any issues that are brought to them and not followed up on is a black eye for them too. It’s their job and they are professionals. Do not be afraid to contact these groups, keep good records of when you contacted them, whom you spoke to, and what you provided. Also, consider how effectively you control your own disclosure that you’ve spoken to any of these groups. Controlling your own personal release of information and knowing who you’ve said things to can go a long way in killing/preventing whispering campaigns and protect you from retaliation.
Likewise, should it become known that you’ve contacted authorities about something, and should you be retaliated against in any way; the individuals who retaliate are in for a world of hurt. Universities, and the Federal Government come down on people with an iron fist for retaliating and the penalties in all aspects are steep, sweeping, and lasting.
2. It is expected and accepted that Duke has a financial interest in this matter. It is expected and accepted that the administration of Duke University Health System has a managerial interest in this matter. If you feel that you have substantive issues relating to managerial or financial impacts of this case, directly contacting them is a duty-bound thing to do. Appropriate contacts include.
a. Biochemistry Dept. Chair Kenneth Kreuzer
b. School of Medicine Dean Nancy Andrews
c. DUHS Chancellor Victor Dzau
e DUHS Dean Gordon Williams
3. For graduate student concerns over the power dynamics within a medical center teaching institution, avenues exist within the medical center as well as the university proper. Important contacts include
a. Graduate Student Affairs Deans Tomalei Vess, Jacqueline Looney
b. DUHS Vice Dean for Research Sally Kornbluth
c. Dean of the Graduate School at Duke, Jo Rae Wright
It is my distinct hope that all those who have been hurt by these events can find a way to positiively contribute to such things never happening again. In the end many will regret their severity in complicated situations like these. Few people ever regret their compassion in situations like this. Do the right thing, for the right reasons, and find it within yourself to muster up the courage to speak up when you need to without fear.
whimple said,
June 6, 2008 @ 10:21 pm
I completely disagree. If you are a grad student and you know something, you should *SHUT UP ABOUT IT* and get on with your life. There is no upside to you to coming forward. There is a significant downside to coming forward. I can guarantee that if you get involved, you will be attacked, and nothing “Federale” ever does for you (if anything) will make up for (at a minimum) this distraction to your career.
There’s nothing left to know. Hellinga published bogus science. His grad student is exonerated. There’s no one else to blame. Duke should fire him, end of story.
Trevor said,
June 7, 2008 @ 7:46 am
I completely disagree. If you are a grad student and you know something, you should *SHUT UP ABOUT IT* and get on with your life. There is no upside to you to coming forward. There is a significant downside to coming forward. I can guarantee that if you get involved, you will be attacked, and nothing “Federale” ever does for you (if anything) will make up for (at a minimum) this distraction to your career.
Unfortunately whimple is right. I would like to think we had developed our institutions in ways where all was open and accountable, and people pointing out wrongdoing would be lauded as heroes, but we have not. Anyone know of a single case where there was a happy ending for the whistleblower? Not just in academia, but anywhere?
Having said that, I do firmly believe that academia is more open and accountable than most of society. We should all keep in mind that sordid affairs such as this really are very rare occurrences. Not much comfort to those directly involved, but hopefully encouraging to those who have been turned off academia by this.
John Richard said,
June 7, 2008 @ 4:00 pm
Courage can only be shown in situations where one’s actions carry an element of risk. Risks are weighed and one acts in one’s own best interests. The penalty for playing it safe is the knowledge that one has acted in a cowardly manner, and this is a penalty that some are reluctant to pay. A person comfortable with their cowardice might make the argument that there is “no upside in coming forward”, but most will understand this to be specious. The reward for “doing the right thing” is simply to have done what one thinks needs to be done.
I do not consider this sordid occurrence to be a rare one. What is rare is the very public and vigorous effort being made to keep its full sordidness hidden. At present, I see no reason for Duke to fire Homme Hellinga.
scotus said,
June 7, 2008 @ 11:25 pm
As a tenured professor, firing Hellinga would require a lengthy process that would not be initiated until after any misconduct investigation had concluded. Unless Hellinga admits to misconduct I don’t see this happening. What I do think will happen is that Hellinga will quietly move on, perhaps back to Europe but more likely into the private sector where venture capitalists will see some of his more fanciful protein design projects as “high-risk high-gain” investments. All we scientists have are our reputations. Irrespective of the eventual outcome, this episode has established that Hellinga is either dishonest or a terrible scientist or both. Neither scenario is compatible with Hellinga’s continued ability to operate in academia, sustain research funding and publish high profile papers, all of which are regulated by peer review conducted by individuals who would reasonably regard his future work with skepticism.
With regards to the issue of weighing the potential harm of speaking out against one’s duty to do the right thing when faced with evidence of research misconduct thing I agree with Dr Richard that this is essentially an issue of character and conscience. Science is a strange business because as practitioners we both compete with and depend on each other. Hellinga’s efforts in the area of TIM design were built on the work of other scientists, including Dr Richard, who identified the gene, determined its function, solve the protein structure, defined the catalytic mechanism and so on. Being a scientist means honoring and building on the work of our predecessors and contemporaries. The fundamental harm to everyone of deliberately introducing false information into the scientific record is something that anyone who spends their time designing, conducting and interpreting experiments should be able to easily comprehend.
Hear, hear. So well said. Thank you, scotus. And Dr. Richard’s eloquent commentary on courage as well. - writedit
noblesse d'epee said,
June 8, 2008 @ 12:34 pm
Federale, Trevor, Whiple, John Richard, Scotus,
As I have mentioned in a previous post, I am a graduate student in Duke. Biochem. While I have not worked under the supervision of Hellinga, I am familiar with several colleagues who have. Long interaction with these students has convinced me of the high probability, through multiple lines of evidence, that Hellinga has committed gross violations of commonly accepted scientific ethics, if not perpetrated outright fraud. I should note that this alleged (mis)behavior is not limited to the novo-TIM work.
For the past several months, a letter has sat, unsigned, on my desk at home. In it, I summarize the troubling accounts of the research wrongdoings described to me by primary witnesses. I then provide the names of these individuals, urging investigators to contact them. Some of these (former) Hellinga lab members have told me that they fear to initiate contact with investigators, but will provide information if asked and/or compelled to do so.
I am faced with some dilemmas. First, I have never worked for Hellinga, so the appropriateness of urging an investigation based on my second-hand knowledge, however accurate, may be questioned. Second, my detestation of Hellinga and his wife is well-known (I was the subject of a whispering campaign by the latter), so one may argue that my involvement is merely “sour grapes.” Despite my admitted bias against Hellinga, I have tried to keep my mind open to ways by which accounts of his alleged misconduct may be explained by non-controversial mistakes and misunderstandings. The more that I have learned, the more I feel that serious allegations against Hellinga would be supported by primary testimony, and therefore ought to be investigated. When considering whether to facilitate such testimony, I arrive at my third dilemma, namely, the “outing” of witnesses who I consider friends, and who have expressed to me their desire to quietly pursue their careers as far away as possible from Hellinga and his scandals.
I am left with the following choices:
1. Leave my letter unsent, hoping that investigators will interview former Hellinga lab members without my prompting (by no means an unlikely outcome, but surely much delayed).
2. Send my letter, signed, and risk hurting the careers of my friends and myself. No company is likely to hire someone known to be a “trouble-maker,” even if for a good cause. I should note that academic jobs will not be pursued by any of us; we’ve had quite enough of academia, and consider the pursuit of money to be more practical than academia’s pursuit of ego.
3. Send my letter, unsigned, thereby protecting myself but potentially harming my friends. Effective, but cowardly. If Homme’s lawyers start harassing the witnesses, I know that neither they nor I have the resources to retain counsel of adequate quality to prevent their lives from being picked apart in an attempt to scare them into silence. We can’t count on support from our program’s faculty, which has shown itself to be remarkably spineless in the face of Homme and his supporters in the DUMC administration.
At the same time, I am keenly aware of my responsibility to my nominal profession, and to the millions of taxpayers who have not had the opportunities which I have been afforded, but by whose hard-earned wages my education and research have been so generously funded.
I would send my letter, which I think is the “right” course of action, but only if I could find a mechanism by which to protect those whose interview it urges. I have no shortage of courage with regard to my own future, as I’ve concluded that life is too short to abet, through silence, wrongdoing on the scale of Hellinga’s. However, I am hesitant to act with the assumption that my friends and colleagues share this opinion.
Given what I have told you, what course of action would you suggest?
David said,
June 8, 2008 @ 2:13 pm
noblesse d’epee,
It seems that these primary sources to which you refer are not comfortable sending their own individual letters (to your knowledge). I do not think it would be fair to them to name them in a letter to Duke without their permission. If these primary sources merely desire a intermediary with Duke, there are better choices than a “graduate student in Duke. Biochem.” Three clearly trustworthy and informed choices named in the Nature article are Dr. John Richard, Dr. Jack Kirsch, and Dr. Donald McDonnell. If the above post is indeed from Dr. John Richard [it is indeed - writedit], he seems an excellent choice. It is a shame that no Duke Biochemistry faculty have been mentioned in any reports, but if you know of one, he or she would also be a better choice than you.
whimple said,
June 8, 2008 @ 5:33 pm
Obviously, my advice is to let go of your hate, and get on with your life, and not send the letter. Dr. John Richard advocates courage, but the measure of the courage of a graduate student in Hellinga’s own department is not necessarily similar to the courage of a tenured full professor at an institution in a completely different part of the country. In any event, your hearsay evidence is of no legal value.
I wonder if there are going to be parallels in the Hellinga case to the fallout of the well-documented case of Steven Leadon down the road at UNC-CH a few years back. Beth Ruggiero, a graduate student in Leadon’s lab, spoke up and finally managed to bring an end to years of extensive scientific fraud. I wonder what she’s up to these days.
noblesse d’epee said,
June 8, 2008 @ 5:55 pm
I agree that Prof. Richard would be a good person to contact. Unfortunately, it is true that no Duke Biochem. professor seems willing to publicly demand, as a colleague ought, accountability from HH. Why are they so afraid of offending him? In contrast to most employees, tenured professors have extraordinary autonomy. However, the price of not having a “boss” is the expectation that these professionals will, in effect, informally regulate their colleagues. This just isn’t happening when it is needed most. Secure in their jobs and their status, Homme’s colleagues have a responsibility to demand, loudly and publicly if neccessary, that he explain himself in a satisfactory manner. If he can’t, they are morally obliged to request that he consider resigning from their company. Ideally, graduate students should have no role in this controversy, but if no one else will . . . .
John Richard said,
June 9, 2008 @ 1:02 am
noblesse d’epee
I see you as a spectator, and don’t think that you would be happy with the result of sending your letter. I will not become directly involved in matters about which I know very little and I think you should be talking with someone at Duke. However, if there really is no one there you trust, then I am willing to discuss with you what I think your options might be.
science_first said,
June 9, 2008 @ 3:02 am
noblesse d’epee writes:
“ I should note that this alleged (mis)behavior is not limited to the novo-TIM work.”
There is no risk for you or your friends (and many benefits for those interested in the scientific implications of this scandal) in being explicit about what other results/publications we should double check. Let science speak for itself after that.
In defense of reviewers said,
June 9, 2008 @ 2:47 pm
I don’t have any inside information, but it isn’t much of a leap to wonder about the following work which has the identical set of authors to those of the retracted Science paper:
Dwyer MA, Looger LL, Hellinga HW., “Computational design of a Zn2+ receptor that controls bacterial gene expression.” (2003) PNAS, 100, 11255
Looger LL, Dwyer MA, Smith JJ, Hellinga HW., “Computational design of receptor and sensor proteins with novel functions.” (2003) Nature, 423, 185
The Nature paper really concerns me because it is more complex and much more difficult to verify than the enzyme design paper (thanks to Dr. Richard for taking care of that one).
David said,
June 9, 2008 @ 3:41 pm
Another problematic paper that has been whispered about is:
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4955-60.
Conversion of a maltose receptor into a zinc biosensor by computational design.
Marvin JS, Hellinga HW.
Another group published a follow-up:
J Mol Biol. 2005 Dec 9;354(4):829-40. Epub 2005 Oct 28.
Structural studies of an engineered zinc biosensor reveal an unanticipated mode of zinc binding. Telmer PG, Shilton BH.
The Telmer and Shilton paper states that the goal of Hellinga’s work was to “produce an MBP molecule in which Zn2+ binding was accompanied by a conformational change from open to closed. Thus, two of the Zn2+-binding residues were introduced onto the N-terminal domain of MBP, and the other two on the C-terminal domain; in this way, full tetrahedral coordination of Zn2+ could only be achieved when the protein was in the closed conformation.”
However Telmer and Shilton “were surprised to find that binding of Zn2+ to the engineered MBP molecule does not result in domain closure. Rather, Zn2+ is bound in an unexpected manner by residues on the N-terminal domain alone. Furthermore, the engineered metal coordination site can bind Cu2+ and Ni2+, although in a slightly different manner than Zn2+. The plasticity of the engineered Zn2+-binding site results in unexpected metal coordination that is accompanied by only a subtle conformational change from the fully open form of the protein.”
Telmer and Shilton’s data proves that the assumptions and molecular modeling by Hellinga are probably not correct. It is not obvious how zinc-binding results in a fluorescence response without formation of a closed complex. At least the mutant MBP binds zinc, but no else has confirmed the zinc-dependent fluorescence change. In light of the retractions, someone really ought to check on this.
Trevor said,
June 9, 2008 @ 8:09 pm
John Richard wrote:
Courage can only be shown in situations where one’s actions carry an element of risk. Risks are weighed and one acts in one’s own best interests. The penalty for playing it safe is the knowledge that one has acted in a cowardly manner, and this is a penalty that some are reluctant to pay. A person comfortable with their cowardice might make the argument that there is “no upside in coming forward”, but most will understand this to be specious. The reward for “doing the right thing” is simply to have done what one thinks needs to be done.
I do not consider this sordid occurrence to be a rare one. What is rare is the very public and vigorous effort being made to keep its full sordidness hidden. At present, I see no reason for Duke to fire Homme Hellinga.
Dr. Richard, in principle I fully agree with you. I have the greatest admiration for the efforts you have made in this matter. However, I stand by my opinion that there is little or nothing for a graduate student to gain, and everything to lose, in speaking up in a Department where the faculty are apparently not willing to say anything. Should there be even just the one faculty member in that Department willing to stand up for what is right, then my opinion would be quite the opposite.
I also disagree with you when you say such affairs are not rare. Yes, “data massaging” is unfortunately commonplace, but fabrication of data in a high-profile publication coupled with abuse of multiple students, such as has been alleged by some in this case? I truly doubt that. Note that I said “alleged” - I am not in a position to adequately judge either the science or the tales of abuse.
I do agree with you that there is no reason for Duke to fire Hellinga at this point in time. Whether or not that is necessary can only be determined after a full and open investigation.
John Richard said,
June 9, 2008 @ 9:05 pm
There are no good options for a student confronted by unethical behavior by his/her research adviser. My advice to someone in this situation would be simply to try and find a better position elsewhere. Now, if this situation is repeated over and over again in the same lab, then it is likely that some sort of breaking point will eventually be reached.
I am under the impression that some of the contributors to this blog want very badly to tell their stories to someone. I expect that these people understand they are free to walk away and say nothing, but they still want to tell their stories. They stand to lose a lot by coming forward. On the other hand, in doing nothing they may become so embittered at their own weakness, and cynical about the way science is done as to have to find another career. It may be that they simply have no good options in struggling to find their way out of a bad situation. This is very depressing to think about.
There is sordid, more sordid and most sordid. I know of many cases of academic misconduct that I would consider to be sordid. They are not rare. If this is something else entirely, then I expect that people will eventually come forward.
ruggizzle said,
June 9, 2008 @ 10:16 pm
A friend of mine at Duke just told me about this ongoing story, and asked if I was interested in posting something here since unfortunately I’m somewhat qualified to comment on issues of alleged scientific misconduct.
(whimple said,
June 8, 2008 @ 5:33 pm
“I wonder if there are going to be parallels in the Hellinga case to the fallout of the well-documented case of Steven Leadon down the road at UNC-CH a few years back. Beth Ruggiero, a graduate student in Leadon’s lab, spoke up and finally managed to bring an end to years of extensive scientific fraud. I wonder what she’s up to these days.” )
Well, I’m actually the aforementioned former grad student. It’s weird to see my name here, since I tried to stay out of the spotlight but did agree to one interview once the frenzy had died down. But if putting my two-cents in helps out, or just adds to a worthwhile discussion, I’d be happy to share my experience. I had intended to read all the posts and a maybe a couple of the articles before commenting, but haven’t had a chance to get through them all. But already there are several things here that seem familiar to my experience, even though many of the details are different.
It’s been several years since I came forward regarding my (former) PI’s misconduct. It was between my 5th and 6th year of grad school, and I had to start over in a new lab with a new project (yes, that totally sucked) but was able to finish about 2 1/2 years later (that didn’t suck as much). There’s a whole long, sad, infuriating story about all the fabricated data, what was being fabricated and how it was done, and how long it had been going on. You can Google my former PI (mentioned above). Most of the articles are accurate, although some of it is crap, especially most of the quotes from one very skilled liar.
My decision to come forward was not made lightly and it took a very long time for me to decide what to do. There’s no way to know how things will turn out if you turn someone in, but for me it got to a point where I really had no other choice. The investigation dragged out for several years (long after I had completed my role as a witness) and there were many retracted papers, and probably millions of NIH dollars wasted on the primary research as well as the follow-up studies by other labs.
I’ve read a lot of stories about whistleblowers, especially those in science, and it seems that their outcomes vary widely. Some of them didn’t turn out well at all and those students or postdocs involved have left science altogether. I guess things for me turned out fairly well, except for those years I lost in grad school. To be honest, part of what kept me motivated to finish my Ph.D. was the “screw you” factor (as in, “screw you, I got my Ph.D. anyway you big liar!” ).
After finally getting my Ph.D., I did 3 years as a postdoc in the lab I had moved to. Now I’ve changed directions somewhat and am training to become board certified in medical genetics, learning how to make clinical diagnoses of patients with suspected inherited diseases. If I pass the boards I’ll become certified to run a diagnostic genetics lab. It’s probably not a coincidence that one of the things I really like about this area is that clinical labs are highly regulated and subject to random audits of all their records and laboratory procedures.
Regarding misconductees (a.k.a. lying liars who lie):
Unfortunately, the fact is liars can be found in every profession, even in science. “Career-liars” seem to share a lot in common in how well they lie, how they try to cover things up and defer the blame to others, how long they can go on lying before being found out, and how they’ll almost never admit they did anything wrong (so don’t hold your breath!). Please note that I’m not claiming to know if anyone in this current case is lying or not.
If you’re curious about what happens to “known” misconductees:
You can go to the Office of Research Integrity website and read the “Case Summaries.” (http://ori.dhhs.gov/misconduct/cases/). (ORI is a division of Health and Human Services, and HHS is in charge of NIH.) It can be infuriating to read about these people, but it’s also satisfying to see them busted and usually barred from NIH funding for some period of time. And they remain on the Federal Register forever! (not that most people check the federal register, but anyway… ) The ORI case summaries are pretty matter of fact and “sans drama” but you might Google the people mentioned to find out more.
Someone asked why ORI hadn’t initiated an investigation into the Duke matter:
Generally an institution conducts an investigation first, and if the institution receives PHS (NIH) funding, then once they’ve reached a conclusion in the investigation they’ll refer it to ORI for review. ORI then makes an independent finding and a decision on any disbarment from future NIH funding. Throughout the process there are multiple opportunities for the accused person to appeal any finding and then it has to be reviewed independently all over again. For various legal reasons, an institution is usually not allowed to comment on an ongoing investigation and/or whether they’ve referred it to ORI. Apparently a whistleblower can also report the misconduct directly to ORI, but I don’t think that happens very much. Either way, someone (a person or an institution) has to make an allegation to ORI before they can look into it.
Regarding the possible outcomes for whistleblowers:
There’s an interesting report from a study at Research Triangle Institute, posted on the ORI web site, on “Consequences of Whistleblowing for the Whistleblower in Misconduct in Science Cases”. Some of their findings may seem like common sense once you finish reading them, but there’s actually data to go along with it (ori.dhhs.gov/documents/consequences.pdf ). I’d recommend it to anyone who is considering blowing the whistle and wants some objective information on how things can turn out for whistleblowers.
Well, this comment has become MUCH longer than I’d planned, so I’ll stop commenting for now… hope you find some of the info helpful.
Trevor Creamer said,
June 9, 2008 @ 10:20 pm
John Richard wrote:
I am under the impression that some of the contributors to this blog want very badly to tell their stories to someone. I expect that these people understand they are free to walk away and say nothing, but they still want to tell their stories. They stand to lose a lot by coming forward. On the other hand, in doing nothing they may become so embittered at their own weakness, and cynical about the way science is done as to have to find another career. It may be that they simply have no good options in struggling to find their way out of a bad situation. This is very depressing to think about.
Indeed, it is clear some of the contributors to this blog do have stories to tell, need to tell them, and have already become embittered. Very depressing.
Perhaps even more depressing is the extent to which the system is broken. Dr. Richard, when this story first broke a good friend emailed me excitedly about how “this is science working!” Yes, your contributions show how science should work, but this whole affair has demonstrated quite clearly that aspects of academic science are well and truly broken. The graduate students involved are caught in a situation with no good options. Hence our conflicting opinions (Trevor = Trevor Creamer).
But you are right of course. We should all strive to do the right thing.
Trevor Creamer said,
June 9, 2008 @ 10:29 pm
Ruggizzle, I’m glad to see myself proven wrong re the fate of whistleblowers. Good luck with the boards and may you have a long and fruitful career in medical genetics!
whimple said,
June 9, 2008 @ 11:38 pm
Ruggizzle, fascinating account. Thanks so much for sharing your first-hand experiences with us. I know several PhD’s that have either finished or are partway through medical genetics training. This is a field with a very promising future and I wish you all the best.
justaguy said,
June 10, 2008 @ 7:16 am
Yes, the Telmer and Shildon JMB paper calls into question the interpretation by Marvin and Hellinga in PNAS, but there is no indication of fraud or even sloppiness. Shildon agrees that Hellinga’s conclusions — based on the data at hand — were quite reasonable.
Any further papers to consider?
scotus said,
June 10, 2008 @ 2:06 pm
Rugizzle-
Kudos for your persistence. As Dr Richard put it, you should take pride in having done the right thing. I’m also pleased to hear that your career is progressing.
N d’E-
Allegations of misconduct by proxy are not really appropriate. As I’ve noted elsewhere, I cannot imagine that Duke is as rotten as some of the posters here seem to think. Duke is clearly aware of the unresolved issues from the Science paper (inadequacy of the retraction, incongruous kinetic parameters for the engineered enzymes and the implausible complementation experiments). I suggest waiting to see how this all plays out. There is no statute of limitations on research misconduct.
Quick question. Lets accept that your observations of widespread Hellinga misconduct are genuine. Surely Hellinga’s students have dissertation research committees that can at least police his activities to some extent. What’s going on here? Does he just load up these committees with colleagues that won’t challenge his behavior? Perhaps Dr Mcdonnell needs to be on every Hellinga graduate student committee from now on?
John Richard-
Could you provide some insight into how the Science retraction was handled? Did you consider asking them to publish your data as a “technical comment” which presumably would have been reviewed and could have then required Hellinga to provide a more complete response to some of the more disturbing aspects of the Dwyer paper. Who required Hellinga to provide any explanation for the retraction at all?
In defense of reviewers said,
June 10, 2008 @ 2:18 pm
justaguy writes “Shildon agrees that Hellinga’s conclusions — based on the data at hand — were quite reasonable.”
Based on the data at the time the enzyme design paper’s conclusions were quite reasonable. The question about many of Hellinga’s papers is could the “data at hand” be flawed as it was in that paper. The two papers that I pointed out earlier in the comments are obvious ones to be suspicious of.
Trevor Creamer said,
June 10, 2008 @ 2:30 pm
A couple of people here have mentioned Hellinga publications that may or may not be suspect. I’m certainly not leaping to Hellinga’s defense here, but I will say I do not think this forum should be used to try to divine which publications might contain fabricated data. Or to hold some kind of de facto trial. We have all been frustrated by Duke’s apparent unwillingness to hold an investigation. However, as Ruggizzle has recently pointed out, any university embarking upon such an investigation is likely to keep very quiet about it. In an earlier post I had bemoaned the “fact” that Duke wasn’t doing anything. That was a lack of thought on my part. Simply put, we don’t actually know for a fact that Duke is not investigating Hellinga. Despite Dr. Richard’s data and all the subsequent speculation, we also don’t know for a fact that Hellinga did fabricate or cherry-pick data. The only thing that is clear is that he has acted abominably towards Mary Dwyer (at least according to the Nature report) and perhaps to other members of his laboratory.
I have stated that I believe that academic science is in part broken. I do believe that. I also believe that we need to allow other parts of the system a chance to prove they are not broken.
noblesse d’epee said,
June 10, 2008 @ 3:37 pm
Scotus said:
“Surely Hellinga’s students have dissertation research committees that can at least police his activities to some extent. What’s going on here? Does he just load up these committees with colleagues that won’t challenge his behavior?”
Often, these committees don’t have membership whose expertise extends to key types of experimental work undertaken in a project. For instance, a committee heavy on bioinformaticists is rarely in a position to look critically at data arising from enzymological experiments. I do know that in the case of one Hellinga graduate student, a faculty member with a specific experimental expertise strongly suggested the completion of essential controls, and saw his/her input dismissed by Hellinga. The issue was never pursued, as the expert professor was not in a political position to insist that his/her concerns be acted upon. The outcome has been regrettable.
ruggizzle said,
June 10, 2008 @ 5:10 pm
Quoting Scotus,
“N d’E-
Allegations of misconduct by proxy are not really appropriate.”
I completely agree that there’s no point in making an accusation you can’t back up with proof. This can be very frustrating for people who really believe there’s something fishy going on but don’t have proof. Still, the bottom line is that you either MUST either have tangible proof or be a direct witness (and preferably have other witnesses to back you up) to the misconduct. The best situation is to have tangible proof AND multiple witnesses. Remember, too, that just because someone is a complete asshole doesn’t mean they are lying, and just because someone seems like a great person and everyone likes him and you get along well with him it doesn’t mean he’s not a pathological liar. Again, I’m not referring to anyone in particular, just something to keep in mind.
Even if know in your heart of hearts that someone is doing something wrong, without hard evidence there’s no point in making any formal claims of misconduct. Nothing is likely to come of it, and it may just end up reflecting badly on you because it will seem that you don’t comprehend or respect the process that requires tangible evidence.
Liars suck! That’s just a fact of life. But it’s better to wait for someone who has direct proof, and if you personally know anyone who does have proof, please encourage them to consider coming forward in whatever manner they feel comfortable with. If they’re just not ready or too scared or whatever, I guarantee you will be unsuccessful in trying to force them into blowing the whistle. Perhaps you can try gently steering them in that direction, but ultimately it’s a very personal decision. Either way, be as supportive as you can - it is quite a traumatic experience to see this stuff going on first hand, and especially to become a whistleblower.
P.S. Ditto on the comment that this site needs an Edit option!! I inadvertently had several smiley faces on my last post
(that’s an intentional frowny face)
noblesse d’epee said,
June 10, 2008 @ 6:10 pm
IDoR,, scotus, Trevor, whimple, John Richard, ruggizzle, et al.,
Thanks for your input, and for the time that you have spent in its thoughtful composition. I’ve concluded that the direct witnesses of Hellinga’s misconduct will have to come forward on their own accord — I’ve done everything that I can to convince them to do so. But, as Prof. Richard so nicely states, “a person comfortable with their cowardice might make the argument that there is ‘no upside in coming forward.’”
I should point out that there are a few Hellinga papers about which I am deeply suspicious, but my mention of these papers may cause the readers of this blog to speculate regarding the identity of my “primary sources.” I will leave it to former members of the Hellinga lab to speak about their scientific misgivings. You should trust, however, that my concerns as an imformed “bystander,” are not fabricated, not exaggerated.
Will Duke make a good-faith effort to investigate Hellinga? I doubt it. I’ve directly observed plenty of evidence that DUMC is unethical to its core. Perhaps all “teaching” med. centers are. If I do post-doctoral work, it will be in an Arts and Sciences program. There are just too many conflicts of interest in medical center settings. The cost of these conflicts tends to be the well-being, both personal and academic, of the graduate students and post-docs upon whose labors these medical centers build their research reputations.
Mary Dwyer will never really find justice, nor will the many others who Homme Hellinga (and others like him) have buried, screwed over, driven from the science they once loved.
John Richard said,
June 10, 2008 @ 11:30 pm
Scotus -
Science sets a time limit after the initial publication date for submission of Technical Comments - perhaps six months. In any case, technical would not have been the appropriate word for my comments. None of Hellinga’s mutations introduced any TIM activity into ribose binding protein. All of the experiments designed to demonstrate a viable design strategy, or that wildtype and novo-TIM were different proteins were wrong for reasons known only to Homme Hellinga and Mary Dwyer.
After having convinced ourselves that the protein we expressed had no TIM activity, we decided to sequence the plasmid Hellinga sent us, only to find that it coded for a protein that had a sequence different from NovoTIM. At that point we decided to cut our losses and write Hellinga.
I am unhappy about the way Science handled the retraction, but am too tired to write a narrative account. The initial publication of the retraction was delayed for perhaps two months while the coauthors worked to find wording that they all could agree upon. I asked to see an advance copy of the retraction, but Science never responded. I sent my letter to Science a couple of days after publication of the retraction, but only learned from Jack Kirsch that the letter had been published electronically many weeks later. Oh well.
scotus said,
June 11, 2008 @ 8:40 am
John-
The revelation that Hellinga sent you plasmids that didn’t encode the actual Novo-TIM proteins described in the paper is frankly mind-boggling. Since you weren’t able to observe any activity I suppose we can rule out the obvious possibility that this was an attempt by Hellinga et al to “cover their tracks” by sending you plasmids that might encode, for example, catalytically crippled variants of wild type TIM. Do we even know that the Novo-TIM constructs described in the paper actually exist?
To the disillusioned young people posting here-
Have any of you read Allegra Goodman’s book “Intuition”. It’s not a great (or factually correct) account of the trajectory of a research misconduct investigation but what it does do well is to capture the sense of bitterness and resentment that “underlings” can feel when working for a “successful” investigator. A month or so ago after something disappointing happened, my wife said to me something to the effect that “we got into science because we loved the sense of purpose that working carefully on important problems provides but she wished someone had told her that research is actually an advertising and public relations job”. I thought about this some and realized that I used to feel like she does but part of my own “growing up” is that I now understand that science isn’t all about high profile publications, NIH directors awards and prizes at all. The reality is that a lot of what we do is about frustration, disappointments, difficulties and imperfection. A lot of the time it’s like climbing a big ladder only to find you put the ladder up against the wrong wall. At the same time, if you work carefully and critically, doing things the right way as Dr Richard put it becomes its own reward. If you keep your eyes open and, yes, have a little luck, you’ll get to see and find out things that nobody knew before you. You can make an everlasting contribution to the body of human knowledge. You can make some of the best friends you’ll have in your life and eventually you can pass along your skills and knowhow to the next generation of scientists. And that’s pretty cool.
whimple said,
June 11, 2008 @ 9:48 am
The revelation that Hellinga sent you plasmids that didn’t encode the actual Novo-TIM proteins described in the paper is frankly mind-boggling.
Not really; this kind of thing happens innocently all the time. I have found it easily worthwhile to have the inserts of all plasmids we receive from other labs sequenced at the time of arrival, regardless of how trusted the source of the plasmid is. Trust me on this, it’s worth doing this.
Trevor Creamer said,
June 11, 2008 @ 1:04 pm
Whimple wrote:
Not really; this kind of thing happens innocently all the time. I have found it easily worthwhile to have the inserts of all plasmids we receive from other labs sequenced at the time of arrival, regardless of how trusted the source of the plasmid is. Trust me on this, it’s worth doing this.
I would second that. We recently received a plasmid for a heterodimeric protein. Upon sequencing we found the two encoded subunits were from different isoforms! I’m not sure how that happened, but sequencing certainly saved us a lot of time and money.
scotus said,
June 11, 2008 @ 1:52 pm
Yes, its easy to screw up and send people the wrong things although one might expect that a lab like Hellingas that must make a lot of constructs and has a lot of resources would have a pretty foolproof inventory system in place to avoid this from happening. All you need is a freezer, some boxes, some software and someone with basic attention to detail to curate everything.
Its pretty clear from the sequence of events that led Dr Richard to get his hands on the Novo TIM plasmids that, for reasons that are now obvious, Hellinga appeared resistant to providing them in the first place. Given the scrutiny that he must have known was going to be applied to these reagents it still seems mind boggling to me that Hellinga didn’t take extra care to make sure that the correct constructs were provided.
Having said that, last week we sequenced an expression construct provided by a collaborator and found that it was not only made using a different splice variant of the relevant gene but also in a different variety of the vector he thought it was in….However in this case the construct worked as advertised and a re-examination of the provider’s lab records essentially ratified our findings.
In defense of reviewers said,
June 11, 2008 @ 5:45 pm
“she wished someone had told her that research is actually an advertising and public relations job”
I find it amusing that so many scientists neglect to realize this is a big part of the job. I guess we start from this belief that we throw an idea out into the system and it rattles around with other ideas and the best one wins. But of course that’s hardly the case - even the best ideas need to be properly “sold” (presented in well-written papers, clear talks, etc.). While it’s offensive to see a sales job when there’s no meat to back it up, we have to realize that a big part of an effective scientist’s role is a cheerleader for the models that they’ve constructed based on their observations. Failing to do this can make all your hard work end up in the dust-bin of science.
John Richard said,
June 11, 2008 @ 9:24 pm
All
We were/are novices at protein expression, and did not think to sequence these plasmids. It is an inexpensive precaution, but in this case probably would not have saved us any time. When I received the plasmid for E Coli NovoTIM I imagined that it held a position of honor in the Hellinga lab as the point of departure for the design of even better catalysts. I have since learned that Hellinga was telling people that EColi Novo TIM was thermally unstable (Figure 4A of the Science paper). Hence the application of his design strategy to produce a second NovoTIM from a RBP present in a thermostable bacteria. This led to a second publication and retraction. Note that wildtype TIM is a robust enzyme.
anom_01 said,
June 11, 2008 @ 11:56 pm
John Richard wrote:
“After having convinced ourselves that the protein we expressed ha