Prominent heart researcher dismissed by Ontario university; colleagues appeal

Earlier this month, Morris Karmazyn, an award-winning cardiovascular researcher who’s published hundreds of papers, was called into a meeting with the office of faculty relations at the University of Western Ontario, and terminated.

The reason? A series of image problems in some of his papers, raised by a former member of his lab. When Karmazyn, Canada Research Chair in Experimental Cardiology, was told it was a case of “misconduct,” he was floored:

If I would have committed misconduct, I probably wouldn’t have felt so badly. I would have felt I deserved it. But I have never in my life committed misconduct…It’s a horrible injustice.

In response, Karmazyn’s former lab manager has launched a petition to have him reinstated, and the University of Western Ontario Faculty Association has filed a grievance on his behalf, arguing his termination violates administrative procedure.

The saga was prompted by Bo Li, who in 2012 moved to Ontario, Canada to complete her postdoc in Karmazyn’s lab. Two years later, she became a whistleblower.

A letter to Li from Vice President of Research John Capone dated October 11 lists seven instances of image issues, including duplication and “inappropriate reproduction of images.” It concludes:

The University determined that Dr. Karmazyn was in breach of the expectations of MAPP 7.0 and the Tri-Agency Framework: Responsible Conduct of Research, with respect to the duplication of images of cardiac myocytes across multiple journal articles, and in the reporting of southern blots and western blots, in that he failed to properly oversee the accuracy of the work of lead authors operating under his purview.

As a result, disciplinary measures have been taken.

A petition filed October 9 by Karmazyn’s former lab manager, Tracey Gan, outlines those disciplinary measures:

Professor Morris Karmazyn has been dismissed on October 6, 2016 by the University of Western Ontario followed by the immediate closure of his laboratory. All his lab personnel were demanded to submit their UWO ID and lab keys and have been escorted to leave the lab by taxi.

We contacted multiple administrators at the University of Western Ontario, and were referred to the communications office. A spokesperson told us:

The university has initiated a disciplinary process with regards to [Karmazyn]. And as a result, he has appealed that, so it’s now in an appeals phase of that process. So we are not in a position to comment until that process is complete.

Karmazyn is a well-known expert in the field of cardiac hypertrophy and failure; one of his 1988 papers has been cited more than 400 times, according to Clarivate Analytics’ Web of Science, formerly part of Thomson Reuters. He has been the recipient of numerous awards, including the Suresh Gupta Award for Excellence in Cardiovascular Sciences.

He has received numerous grants from the Heart and Stroke Foundation, as well as millions of dollars in federal funding from the Canadian Institutes of Health Research (CIHR).

On October 7, Ann Bigelow, the president of the University of Western Ontario Faculty Association, filed a grievance on behalf of Karmazyn, arguing that:

The Collective Agreement and the relevant portions of MAPP are clear that in order for a finding of scientific misconduct to be made, there must be a finding of dishonest purpose and an intent to mislead or reckless disregard for the intent to mislead. No such findings were made by the Investigation Panel in its report. Without such a finding, the termination of Professor Karmazyn’s employment (or any discipline) constitutes a breach of the Collective Agreement. Additionally, the termination of Professor Karmazyn’s employment, a Member with no disciplinary history, constitutes a breach of the Collective Agreement related to progressive discipline.

Bigelow told us the Faculty Association was unable to comment further.

In her petition, Gan argues that the problems identified in the papers were all honest mistakes:

It is certainly remorseful that some errors in figures were identified in various publications. however these are minor in nature and have no bearing whatsoever on the study results.  These represent only a tiny fraction of the thousands of the subfigures in his 217 publications. In addition, from the search of PubMed, it is clear that there are numerous corrections due to human error in many publications including those which have appeared in the highest ranking journals. During the investigation, all of the leading authors with primary responsibility for the articles in question admitted to their honest mistakes and all the original and the collected images/western blots/data are available for the corrections for the publications. More importantly, all the data are repeatable.

She adds that none of the mistakes were Karmazyn’s fault (and underlined one section):

Neither I nor my colleagues are aware of a single incident in which the senior author of a publication is disciplined for errors committed by a co-author.  This is unheard of either in Canada or anywhere in the world.

The Investigation Report makes no findings against Professor Karmazyn with respect to falsification, dishonest purpose or intent to mislead and these errors were not even known to Professor Karmazyn or in fact any of the authors until the investigation was initiated. The termination of Professor Karmazyn’s employment is a grave injustice.

We reached out to some of the first authors of the papers in question. We’ve heard from Sabzali Jabadov, now at the University of Puerto Rico, and first author of “Anti-hypertrophic effect of NHE-1 inhibition involves GSK-3β-dependent attenuation of mitochondrial dysfunction,” published in 2009 by the Journal of Molecular and Cellular Cardiology, now cited 31 times:

I worked in Dr. Karmazyn laboratory in 2003-2008, and all original data from my studies was stored in the laboratory. I have not seen the investigative report of UWO regarding Dr. Karmazyn’s case. Last year, I received from Dr. Karmazyn an email regarding to the same western blot image that was given as a loading control in Figure 3B and Figure 3C in the paper by Javadov et al, J Mol Cell Cardiol, 2009; 46:998-1007 (https://www.ncbi.nlm.nih.gov/pubmed/19318234).

I replied that I admit to making a technical mistake that could occur during assembly of representative western blots for Fig.3C.

Again, I confirm that I admitted to making an honest mistake in the aforementioned paper.

We also heard from Asad Zeidan, now at the American University of Beirut. He confirmed that he made some “honest mistakes” in “Prevention of RhoA activation and cofilin-mediated actin polymerization mediates the antihypertrophic effect of adenosine receptor agonists in angiotensin II- and endothelin-1-treated cardiomyocytes,” published in 2014 by Molecular and Cellular Biochemistry, and cited five times.

We reached Karmazyn at home, who told us that he tried to repeat the experiments that were flagged by the university:

As soon as I found out these errors were there, I requested the lab to repeat every single one of those experiments. Every single one – without exception – was repeatable…From a science perspective, there was nothing to worry about…All the quantitative data were correct. It’s just that people make mixups when they are putting together figures.

Gan confirmed Karmazyn’s account to us:

The errors that were identified are simply that, errors.  This happens among the best of scientists.  Dr Karmazyn does not work in the lab and he has limited computer skills.  Once he became aware of these problems he requested that all experiments in question be completely repeated, to ensure that the results are vaild.  Every single experiment was completely reproducible.  We have all this data.

The errors were fixable problems of mislabeling, for instance, Karmazyn argued — not a matter of misconduct:

To be told this is misconduct because of a few errors? Oh my goodness…Anyone with a type of a reasonable mind would see this is not misconduct. Also, how can you hold a senior author responsible for errors the first author committed?

But Li presented a different picture to Retraction Watch:

The work environment was very “toxic” in Dr. Karmazyn’s lab. To be honest, I didn’t feel I was working in a research lab. It was rather like a place where people did business affairs without a bottom line for morals. For Dr. Karmazyn, everything is good if the lab can make papers published and obtain money from funding agencies. The lab does not follow any basic principles in [conducting] scientific research…When the experiments did not work as they expected, the only thing trainees would get was Dr. Karmazyn’s expression of dissatisfaction at lab meetings. Furthermore, as trainees we were not allowed to talk to people outside the lab regarding problems we encountered. According to them it’s too bad for the lab’s reputation.

Li, who now works at an insurance company, explained what led her to bring her concerns to the administration in 2014:

While I was trying to culture neonatal rat cardiomyocytes in Dr. Karmazyn’s laboratory using his lab protocol, I found that cardiomyocyte purity was very poor. Cardiomyocyte purity is commonly tested by staining with myosin heavy chain, a cardiac specific marker. Only 20% positive cardiomyocytes were found in the total cultured cell preparation. Before I pointed out this problem in Dr. Karmazyn’s lab in November 2013, the purity of cultured cardiomyocytes had apparently never been tested…Having observed lots of irregularities in the lab, I became concerned about aspects of their published work. By reviewing their previously published papers, I found problems with data that involved replication and manipulation of images in at least 11 papers. That’s why I brought my research misconduct allegation to Western University in September 2014 and contacted the journals involved and CIHR in December 2014.

Li said Karmazyn didn’t renew her contract in 2015.

Karmazyn vehemently denied all of Li’s accusations:

I’ve been in this business long enough to know not all experiments work. My attitude has always been that if experiments don’t work, let’s figure out why they didn’t work, and move on.

He added that it was mainly Li’s experiments that didn’t work, and he tried to provide her with resources and help to improve her skills. But he didn’t see enough improvements, and that’s why he didn’t renew her contract. As to Li’s allegation she was told not to discuss problems outside the lab, Karmazyn told us that was restricted to lab members’ personal lives, such as illnesses that affected their schedules.

I certainly made the statement in lab meetings not to discuss personal matters….we didn’t have any problems. The lab ran so smoothly.

We have not found any previous retractions for Karmazyn, although some of his papers have been discussed on PubPeer. We have found one correction for “Endothelial Nitric Oxide Synthase Promotes Bone Marrow Stromal Cell Migration to the Ischemic Myocardium via Upregulation of Stromal Cell-Derived Factor-1α,” a 2009 paper in Stem Cells on which he is listed as the second to last author, noting one image was created by merging two others.

Here is a list of the other papers mentioned in the letter to Li:

• Estrogen exerts concentration-dependent pro-and anti-hypertrophic effects on adult cultured ventricular myocytes. Role of NHE-1 in estrogen-induced hypertrophy, Journal of Molecular and Cellular Cardiology. Published in 2009, cited 23 times.
• An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1, Journal of Molecular and Cellular Cardiology. Published in 2006, cited 63 times.
• Increased endothelin-1 and endothelin receptor expression in myocytes of ischemic and reperfused rat hearts and ventricular myocytes exposed to ischemic conditions and its inhibition by nitric oxide generation, Canadian Journal of Physiology and Pharmacology. Published in 2003, cited 18 times.
• Ouabain increases iNOS-dependent nitric oxide generation which contributes to the hypertrophic effect of the glycoside: possible role of peroxynitrite formation, Molecular and Cellular Biochemistry. Published in 2012, cited three times.

David Eisner at the University of Manchester, editor of the Journal of Molecular and Cellular Cardiology, told us:

The Editors of The Journal of Molecular and Cellular Cardiology (JMCC) were contacted in 2014 by a complainant about papers published by Dr Karmazyn.  I began an investigation of these papers .  We were then contacted by the Vice-President for Research of the author’s institution and informed that an institutional investigation was underway.  In those circumstances, I agreed to wait until that investigation was concluded and that any subsequent action by JMCC would take the findings of that investigation into account.   JMCC has not yet received the report.  When received, it and our own investigation will determine the action to take.

We have contacted the other journals listed in the letter to Li, and will update if more respond.

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