Research integrity University Affairs

The Claudio Hetz Blues

"...Dr. Hetz seems rather to regret that he did not have better tools for editing the figures, so that the undeclared interventions would have gone unnoticed." - University of Chile investigative report.

The neuroscientist Claudio Hetz is now officially not just Chile’s top science genius, but also a national martyr saint. A research misconduct investigation (caused by my reporting from January 2021) absolved Hetz from all suspicions of fraud, because of course there was no intent.

The investigative report which the University of Chile released is however still damning: Hetz is accused of recklessness, negligence and overall a problematic attitude to research ethics, while some of his papers were not investigated at all, because Hetz was not a lead author or, most bizarrely, because the raw data was absent.

On 10 September 2021, the University of Chile in Santiago issued this press release, signed by the Vice-rector for Research and Development, Flavio Salazar Onfray:

“Regarding the substantive issue, the investigation establishes, as a first conclusion, that in the study of the antecedents, actions constituting scientific fraud were not detected, understood as a deliberate act of creating false data to support or demonstrate a certain scientific thesis . In this way, no publication has been retracted, maintaining the validity of its findings and conclusions.

Notwithstanding the foregoing, the committee detected some objectionable patterns of behavior that were at odds with scientific ethics, which were ratified in the report of the ethics commission of the Faculty of Medicine. In particular, these refer to manipulations not allowed, nor informed of figures published in some scientific works. See ethics report link

In this regard, the most important conclusions of the reports include:
1- That it has been documented in a certain way that Professor Hetz has engaged in behaviours that are classified as breaches in integrity of the scientific process, understood as an inexcusable abandonment of his duty of care in the performance as a professional of scientific research, Negligent acts and conducts and untidiness in the presentation of results, in particular those related to the figure presentations that suffered undue alterations and that were not correctly reported.
2- That the main responsibility for the anomalies detected falls on Dr. Hetz himself, as the corresponding author, without detriment to the specific responsibility that his subordinates and collaborators may have.
3- That these behaviors constitute an unacceptable behavior in the scientific process since they damage public trust, so they must be corrected immediately.”

I Google-translated the investigative report, which refers to several unpublished Annexes, including the list of papers analysed. The Advisory Committee started its work on 23 March 2021 and consisted of the Dean of the Faculty of Medicine Manuel Kukuljan, the Vice-Rector for Research and Development Flavio Salazar Onfray; the Legal Director of the Faculty of Medicine, Eduardo Díaz Silva; the president of the Ethics Commission of the Faculty of Medicine, Sergio Valenzuela Puchulu and the appointed members of the Committee, namely: 

  • Patricio Aceituno Gutiérrez, Emeritus Professor of the Faculty of Physical and Mathematical Sciences (FCFM) of the Universidad de Chile, former Academic Vice-Rector of the same university and former Dean of the FCFM, who acted as Coordinator of the Committee. 
  • María Inés Becker Contreras, Associate Professor of the Department of Chemical Engineering, Biotechnology and Materials of the FCFM – University of Chile, President of the Board of the Foundation Science and Technology for Development (FUCITED).
  • María Paz Marzolo Canales, Associate Professor, Department of Cellular and Molecular Biology, Faculty of Biological Sciences of the Pontifical Catholic University of Chile. 
  • Felipe Sierra Tirado, Member of the Executive Committee of the INSPIRE Program, Toulouse, France. Former Director of the Biology Division of the National Institute of Health, USA. 

“From its constitution, the Committee held a total of 13 weekly sessions, usually with the attendance of all its members. Initially, a total of 23 articles were selected for evaluation that were mentioned in the complaints against Dr. Hetz, published on 01/13/2021 in an article by Leonid Schneider on the For Better Science website (https://forbetterscience.com/2021/01/13/the-ballad-of-claudio-hetz/). Said complaints, which were reproduced in the national media, were based on observations and comments posted on the website PubPeer

In ANNEX 1, a list of the 23 articles initially selected by the Committee for analysis is presented, to which a correlative number was assigned for identification purposes in this report. From this set of articles, the Committee decided to evaluate only articles in which Dr. Hetz acted as the first author or corresponding author. This resulted in the selection of a sub-group of 18 articles.”

But from the report, it quickly became clear that the papers were numbered according to their listing in my article, plus 3 more discussed on PubPeer later, making it a total of 23. Here is the list I made, I could cross-check all listed papers with the investigative report listings, except numbers 21 and 23 which may be swapped in the Annex 4, but likely otherwise correct.

Fraud is apparently only when intent to deceive was unambiguously proven and no experiments were actually performed. In this regard, I agree with the Committee’s findings regarding Hetz, after all, he, his lab members and collaborators did many experiments, and Hetz probably very much sincerely believes that the Photoshopped results were more correct than the experimental reailty:

“Regarding the substantive issue that motivated the work of the Committee, it establishes that in the evaluation process that it carried out, no actions constituting scientific fraud were detected, understood as a deliberate act of creating false data to support or demonstrate a certain scientific thesis. However, the Committee detected some objectionable behavior patterns that were inconsistent with scientific ethics..”

But this overtly narrow definition of research fraud would absolve everyone who doesn’t voluntarily admit to outright fraud, except of the customers of Chinese paper mills. Maybe.

Because even those can be excused if the papermill customers credibly assure to have trusted those “external companies” who provided the “data”. Basically, this definition means Diederik Stapel, ex-professor of psychology and author of the bestselling book “How I intentionally faked everything out of thin air”, must be the only research fraudster in the history of science then.

Let us dig into Hetz’s investigative report, which I analyse and illustrate.

“Regarding the conclusions reached by the Committee after evaluating the selected articles, it is necessary to point out first that not all the observations or questions published in PubPeer were validated by the Committee, because in some cases the originals were not available due to the time that had elapsed. , which was recorded in the reports that were written on each article. Such is the case of observations referring to articles N ° 14 (Figure 1B and 6B and C), N ° 16 (Figure 5A), N ° 1 (Supplementary Figure 5C); N ° 22 (Figure 3A, 5C and supplementary 3).”

So here are the papers which somehow are declared to be free of research misconduct because their raw data is AWOL.

#14: Claudio Hetz, Milene Russelakis-Carneiro, Sébastien Wälchli, Sonia Carboni, Elisabeth Vial-Knecht, Kinsey Maundrell, Joaquín Castilla, Claudio Soto The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity Journal of Neuroscience (2005) doi: 10.1523/jneurosci.4090-04.2005

Raw data unavailable: not investigated
Raw data unavailable: not investigated

Also not investigated, under the excuse of unavailable raw data, despite being utterly fake, were these blots:

#16 Claudio Hetz, Joaquín Castilla, Claudio Soto Perturbation of endoplasmic reticulum homeostasis facilitates prion replication Journal of Biological Chemistry (2007) doi: 10.1074/jbc.m611909200

Now, how can a paper featuring Guido Kroemer ever be fake, right? Perish the thought!

#1 Estefanie Dufey, José Manuel Bravo-San Pedro, Cristian Eggers, Matías González-Quiroz, Hery Urra, Alfredo I. Sagredo, Denisse Sepulveda, Philippe Pihán, Amado Carreras-Sureda, Younis Hazari, Eduardo A. Sagredo, Daniela Gutierrez, Cristian Valls, Alexandra Papaioannou, Diego Acosta-Alvear, Gisela Campos, Pedro M. Domingos, Rémy Pedeux, Eric Chevet, Alejandra Alvarez, Patricio Godoy, Peter Walter, Alvaro Glavic, Guido Kroemer, Claudio Hetz Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response Nature Communications (2020) doi: 10.1038/s41467-020-15694-y

PubPeer comment: “Supplemental Fig. 1C: Blot doesn’t match with the raw data.”

Hetz admitted the figure was wrong and replaced it:

He then explained: “Importantly, the biological conclusion of the experiment is not altered by this mistake.”

Really? His P-eIF2a result is now quite different of what it originally was made to look like, and now scientifically utterly unconvincing, which was probably the very reason the figure was tuned in the first place. And yet the Committee swallowed Hetz’ bullshit, because “the originals were not available due to the time that had elapsed.

Really? The paper is from 2020! It was just some months old when the investigation began, and a principal investigator’s failure to store raw data for at least 10 years can be research misconduct in itself, especially when concerns about data integrity are raised.

Similar thing happened here:

#22 Soledad Matus, Estefanía Lopez , Vicente Valenzuela , Melissa Nassif, Claudio Hetz Functional contribution of the transcription factor ATF4 to the pathogenesis of amyotrophic lateral sclerosis PLoS ONE (2013) doi: 10.1371/journal.pone.0066672

Hetz explained on PubPeer, that the first author (now a group leader herself) is to be blamed for everything (“These experiments were performed by the first author Dr. Soledad Matus (postdoctoral fellow at that time) with a research assistant” and that yes, those are indeed Franken-figures:

Notice that not all western blots were loaded in the same order or do not contain the same number of animals. The whole experiment involved running two blots to analyze the full panel of animals. We apologize for these omissions in the legends. Regrettably, when we review this data, we realized that there was a mistake in selecting the loading control bands, and they only corresponded for one animal group. However, because the loading control between this group was similar, the conclusions of the experiments are not altered by this mistake.

So the 7 year old paper was not investigated because “the originals were not available due to the time that had elapsed.” Are you confused? Well, Hetz stated:

For comments on figure 4B, the bands were indeed spliced together, obtained from the same film, and this was not stated in the figure legend. A few years ago, the computer of Dr. Matus was stolen, and we lost many of the backup information of this article. We were able to recover independent experiments from the backups of a research assistant showing virtually the same result.

The Stolen Laptop Excuse(TM)! Must be those same criminals who stole Oona Lönnstedt’s and Tony Turner’s laptops in Sweden! Meh, Olivier Voinnet‘s excuse of a lab flood at CNRS Strasbourg was at least more convincing (a pipe supplying the rooftop greenhouse indeed once burst on the 4th floor, while Voinnet’s lab was on the 2nd, but the excuse worked).

Hetz is the master of victim-playing, and the investigators noticed and resented it:

“However, it is the corresponding author who must assume the greatest share of responsibility in ensuring the quality and scientific rigour of the articles that are published. 

Multiple evidences compiled during the course of the investigative work of the Committee, lead it to conclude that in his role as corresponding author, Dr. Hetz is not able to fully assume the responsibility that corresponds to him in the errors reported. On the one hand, in the responses and disclaimers submitted to PubPeer and to the journals where the articles in question were published, the Committee noted a tendency to identify by name the collaborators responsible for the experiments or authors of the experiments. questioned figures. Such is the case of its responses to the questions in articles N ° 1, 3, 4, 5, 6, 20, 21 and 23.”

The problem was that the Committee refused to investigate those papers where Hetz was neither first nor last author. To the very least, they could have contacted the institutions of his collaborators. For all we know, they might even informed their Chilean colleagues that the coauthors are blaming Hetz’ lab for having contributed those figures? Not entirely impossible.

#23 Sebastian A Barrientos, Nicolas W Martinez , Soonmoon Yoo , Juan S Jara , Sebastian Zamorano, Claudio Hetz, Jeffery L Twiss, Jaime Alvarez, Felipe A Court Axonal degeneration is mediated by the mitochondrial permeability transition pore The Journal of neuroscience (2011) doi: 10.1523/jneurosci.4065-10.2011

Supplemental Figure 1
Fig 1G

Falsifications like these don’t happen by accident. Hetz’ collaborator at the Universidad Mayor (also in Santiago, Chile), Felipe Court, declared on PubPeer:

We have reviewed the images and we agree there are involuntary errors in Figure 1 and Supplementary Figure 1 of our paper. Together with the authors of the paper we have identified the source of these errors. […] We will contact the editor of Journal of Neuroscience for this error and our response in PubPeer to ask for next steps. These unintentional errors do not change in any way the conclusion of our paper.

And this is how the case was closed. If anyone at Universidad Mayor ever pressures Court how the figures got manipulated so involuntarily, don’t be surprised if he blames Hetz, while Hetz has been apparently blaming him. And nobody investigates anything.

Who rigged the figure in the next paper? Someone else, case closed!

Mathieu Nivon, Loïc Fort, Pascale Muller, Emma Richet, Stéphanie Simon, Baptiste Guey, Maëlenn Fournier, André-Patrick Arrigo, Claudio Hetz, Julie D. Atkin, Carole Kretz-Remy NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation Molecular Biology of the Cell (2016) doi: 10.1091/mbc.e15-12-0835

And here? Why was that gel faked in Photoshop? Does not matter.

Rodrigo Herrera-Molina, Renato Frischknecht, Horacio Maldonado, Constanze I. Seidenbecher, Eckart D. Gundelfinger, Claudio Hetz, María De La Luz Aylwin, Pascal Schneider, Andrew F. G. Quest, Lisette Leyton Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1 PLoS ONE (2012) doi: 10.1371/journal.pone.0034295

In research integrity, it should matter less who faked the figure down in the lab, but rather who up there in the PI’s office doesn’t mind the fakery and covers it up. I know someone! Even the Committee had its suspicions:

“The Committee considers that, with this action, it negatively marks the scientific record of the aforementioned persons. Without them having the opportunity to defend themselves or express their version, Dr. Hetz dilutes a responsibility that mainly concerns him as corresponding author onto doctoral students, post-doctoral researchers and research assistants.

This behavior was also noted in the letter that Dr. Hetz sent to the Committee in response to specific inquiries. It includes explanations that tend to dilute the appropriate responsibility. Examples “…the type of errors is common and was made by multiple researchers over time.” It is obvious that the following sentence refers to others, not to himself: “… the inability to detect this type of errors… they have to do with untidiness, human errors where the researcher already loses the ability to see the error (the memory images) or does not have optimal training in “how” tests should be done. “. And this sentence referring to the obligation to declare the “splicing”: “…unfortunately several researchers ignored this requirement”.

Hetz was basically bullshitting his investigators, they even tried to fight back:

On the other hand, the Committee records in this report that it considered some of the answers or explanations provided by Dr. Hetz to be unsatisfactory, considering them incomplete, insufficient and in some cases confusing. These situations occurred in relation to the articles mentioned below, and whose reports are presented in ANNEX 4. 

  • Partially satisfactory clarification for the Committee as to why the image of the blot sent to clarify Figure 1A of article N ° 8 has little resolution and, in this same article, without clarification of the difference in the number of lanes in Figure 3A.” 

#8 Claudio Hetz, Paula Bernasconi, Jill Fisher, Ann-Hwee Lee, Michael C Bassik, Bruno Antonsson, Gabriel S Brandt, Neal N Iwakoshi, Anna Schinzel, Laurie H Glimcher , Stanley J Korsmeyer Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha Science (2006) doi: 10.1126/science.1123480

Figure 1A: Hetz provided alleged raw data to refute the accusation of band duplication, but the “raw data” simply doesn’t match.
Suppl Fig 2B
Gel lanes were copy-pasted in Suppl Fig 2B to change an undesired result, as raw data posted by Hetz proves. PubPeer comment: “Fig. S2B: -p-JNK is very different between conditions when you compare time 0h. This was not shown in the published Figure (in red). -Why there’s no JNK in the raw data? Were they performed with the same samples?
Suppl Fig 3A
Suppl Fig 2A
Suppl Fig 5E

That paper of Hetz’ should have been retracted in shame. But we are talking about that journal Science here, so it won’t be, also given whose legacy a retraction would taint.

The last author, the Harvard professor Stanley Korsmeyer, died even before that fraudulent paper was published. You can see this parade of fraudulent figures as an act of grave-pissing, not uncommon in academia (e.g., here and here).

  • Committee was not satisfied with the explanation why it did not show original gels, although PlosOne accepted it (Figure 3A of article N ° 5). In this same work, the Committee was not satisfied because it did not indicate what each lane corresponds to, Supplementary Figure 2C. 

# 5 Mauricio Torres, Karen Castillo, Ricardo Armisén, Andrés Stutzin, Claudio Soto, Claudio Hetz Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress PLoS ONE (2010) doi: 10.1371/journal.pone.0015658

Hetz on PubPeer: “The problem was generated during the generation of new versions of the paper since initial figures were correct as indicated here (took 7 years to publish the data).” Note he chose not to show the original gels for the Grp blots.

So PLOS One editors didn’t know that the original gels were in reality unavailable, while they accepted a correction (not published yet though).

  • Committee considers partial answer of problem related to Figure 6D of article N ° 3 (same image in control and experimental cells), in the same article there is no explanation about band inversion in a gel, Figure 6B.

#3 Karen Castillo, Diego Rojas-Rivera, Fernanda Lisbona, Benjamín Caballero, Melissa Nassif, Felipe A Court, Sebastian Schuck, Consuelo Ibar, Peter Walter, Jimena Sierralta, Alvaro Glavic, Claudio Hetz BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response The EMBO Journal (2011) doi: 10.1038/emboj.2011.318  

2017 correction: “Figure 6D was assembled by directly pasting cropped sections of the original images, after adjustment of individual channel levels. A zoom of the dBI-1EY03662 NT panel was placed in the Control NT panel, duplicating the image by mistake. It is worth mentioning that the lysotracker signal was never significant in the non-treated conditions.” It always was though, that’s the point of controls.
Fig 6D.

Figure 6B contains an utterly fraudulent gel. Any paper containing something like this must be retracted as utterly untrustworthy.

It seems however , the EMBO Journal is about to retract just the offending Figure 6B:

Dr. Hetz has carried out various actions to solve the problems detected in the preparation and presentation of the figures of his experimental results in various publications under his authorship, the corrections he proposed to the journals where they were published have been mostly accepted. An exception was an issue that was published on PubPeer and with which the Committee agreed, which concerns Figure 6B of article No. 3. After a long exchange by Dr. Hetz with the editors of the journal, it decided to retract said figure.

Some papers were done by Hetz as a fellowship-funded graduate student at the Serono Pharmaceutical Research Institute in Geneva, Switzerland, supervised by their senior scientist and Hetz’ Chilean compatriot, Claudio Soto (now professor at the University of Texas MacGovern Medical School). Soto has 11 papers on PubPeer, 5 of them without Hetz as co-author and still very fake, some (Barria et al PLOS Pathogens 2009 and Castilla et al Nature Medicine 2005) were embarrassingly corrected. So the Committee understood that consulting with a dishonest character like Soto would not be helpful:

  • The Committee did not have access to explanatory Figures on those questioned in article N ° 13 in which on 01/25/2021 Dr. Hetz sent Power Point to EMBO J (corresponding author Dr. Claudio Soto). Unlike the situations in articles N ° 11 and N ° 12, where Dr. Hetz is also the first author, in this case the Committee decided not to consult Dr. Soto, after considering the explanations provided by Dr. Hetz . 

#13 Claudio Hetz, Milene Russelakis-Carneiro, Kinsey Maundrell, Joaquin Castilla, Claudio Soto Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein The EMBO Journal (2003) doi: 10.1093/emboj/cdg537 

Correction 15.09.2021:

The journal was informed of potential image aberrations in Fig 7A. The authors claim that the loading control in the originally published figure corresponded to a replicate experiment as many Western blots were run in parallel with the same samples to measure levels of ER stress markers. The control panel in Fig 7A is herewith retracted and replaced with the author-supplied loading control of the experiment shown in Fig 7A.

The journal noted that Fig 3 and Appendix Figure 3 were duplicated and that the legend to Appendix Figure 3 did not match the displayed figure. The authors recovered the quantification data for Appendix Figure 3, but not the scanned blots. The authors state that they no longer have access to the laboratory books or primary data and that they cannot definitively say which image was analysed. The authors withdraw Appendix Figure 3.

The authors also acknowledge that there are undeclared splice sites in Fig 3, but that they could not locate the source data.

The source data for Fig 7A are available with this corrigendum notice.

The authors apologize for these errors and agree with this corrigendum; no response could be obtained from MR-C.

The Figures 3 and Suppl Figure 3 are indeed identical, but the paper’s text speaks of statistical analysis, but of what actually if there was just one experiment after all? Each gel band quantified 3 times? The correction does seem to openly admit this.

Yes, this is a problem. Caspase-12 is 55kDa, and tubulin is 50kDa. Close, but not identical, so the bands can’t run exactly same.

The following paper of Hetz’ with Soto was deemed outside of Committee’s scope. The figure is just too fraudulent.

Joaquín Castilla, Paula Saá, Claudio Hetz, Claudio Soto In vitro generation of infectious scrapie prions Cell (2005) doi: 10.1016/j.cell.2005.02.011

These were the two papers briefly mentioned above.

#11 Claudio Hetz, María Rosa Bono, Luis Felipe Barros, Rosalba Lagos Microcin E492, a channel-forming bacteriocin from Klebsiella pneumoniae, induces apoptosis in some human cell lines Proceedings of the National Academy of Sciences (2002) doi: 10.1073/pnas.052709699

The report stated:

…an explanation was requested of undeclared interventions in figures of articles N ° 11 and N ° 12 that were reported on PubPeer and confirmed by the Committee, which until then had not been explained. These two papers were published in 2002 and correspond to investigations carried out under the supervision of Dr. Rosalba Lagos (article No. 11) and Dr. Andrew Quest (article No. 12) who participated as corresponding authors. The Committee first consulted with Dr. Lagos and Dr. Quest (see letters in ANNEX 2, pages 2 and 9). Both responded indicating they did not have an explanation for the interventions mentioned, noting that the responsibility for the preparation of the figures had been Dr. Hetz.”

Rosalba Lagos is Hetz’ colleague at the University of Chile and also a member of Chilean Academy of Sciences. Let’s see if she will request a retraction of that paper:

referring to Figure 1A of article No. 11, Dr. Hetz insists in the response sent to the Committee in not acknowledging the existence of an undeclared manipulation of the same, which explains the fact that Figures 1A and 1D are more similar to each other than expected in the most significant section of the x-axis. This situation observed in PubPeer and verified by the Committee led Dr. Rosalba Lagos, corresponding author of the article, to modify her initial judgment, being convinced that there was an undeclared intervention of the figure, which forces her to send a response to the journal where the article was published (see their response in ANNEX 3, page 51).

Andrew Quest is another Chilean researcher, this is the aforementioned paper Number 12, and it’s very fake:

#12 Claudio A Hetz, Martin Hunn, Patricio Rojas, Vicente Torres, Lisette Leyton, Andrew F G Quest Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase Journal of Cell Science (2002) doi: 10.1242/jcs.00153

Fig 4D
Fig 4E
Fig 4A
Fig 9A

Well, did you know that all that image fudging in Photoshop actually PROVES how REPRODUCIBLE Hetz’s research results are? The report mentions: “Regarding the query about an undeclared intervention in Figure 3E of article 12, Dr. Hetz answers the following:

“… that several cells from different photos were put together in one image in order to show more cells in the figure and give a vision general of the reproducibility of the phenomenon”,….”I do not consider this assembly to be a problem. It was not indicated in the legend because I did not consider it necessary.” “

Oh, and Hetz is sorry his Photoshop forgeries were “not very elegant”: “Regarding the intervention not declared in Fig. 9A of article 12, Dr. Hetz provided the following explanation in his response to the Committee:

“…cells were removed from the image to highlight the morphologies that were to be shown. For this, pieces of background were copied and pasted on top. “…”Given my little knowledge in digital image processing at that time, the way of hiding the cells that we did not want to show was not very elegant“. “There was no error or manipulation.”

This following quote from the report is amazing, I highlight the last sentence:

“These explanations caused great surprise among the members of the Committee, because the interventions described were adopted without consulting and obtaining the approval of the corresponding author of the article, with the consequent damage to their reputation and that of the remaining co-authors once they were discovered.

More relevant still, with nearly 20 years having passed since the publication of the two articles, Dr. Hetz shows a total lack of self-criticism regarding the actions that then and now violate the basic ethical principles in a scientific publication. Furthermore, with the latter explanation, Dr. Hetz seems rather to regret that he did not have better tools for editing the figures, so that the undeclared interventions would have gone unnoticed. 

If this behavior is not research misconduct, what is? No, seriously, what else does one have to do to qualify?

Hetz, who otherwise blames his junior lab members, was in the case of his old papers an inexperienced victim of his youthful innocence:

In Dr. Hetz’s reply letter, no explanation is given for the undeclared manipulation in Figure 2A of article N ° 11 and in Figure 4A of article 12. Regarding the first case, his explanation concludes as follows:

Sincerely, I have meditated a lot trying to think what happened and I have no explanation, there must be a reason that at that time for a student of “undergraduate training” with little experience seemed correct. I think there must have been a logical reason that I don’t know”.

Regarding the second case, he answered the following:

Unfortunately, I do not have an explanation of why there is this coincidence of points on the right, and at what stage of the figure assembly this happened since there are no backups.”, “… this manipulation I think is explained by lack of experience and neatness in the figure assembly in that early stage of development as a student”.

One really wonders if Hetz himself believes the drivel he told the Committee. Maybe he does, this is what narcissism does to people.

“The Committee found both responses unsatisfactory for two reasons. Firstly, because as a student, the interventions in the two figures had to be consulted with the corresponding authors of the respective articles and reported in the captions of both figures and, secondly, because it reveals a complete absence of self-criticism in the face of obvious ethics failures that the aforementioned manipulations show in the presentation of experimental results. “

More forgivable sins of Hetz’ innocent youth:

#10 Claudio Hetz, Pierre-Alain Vitte, Agnes Bombrun, Tatiana K. Rostovtseva, Sylvie Montessuit, Agnes Hiver, Matthias K. Schwarz, Dennis J. Church, Stanley J. Korsmeyer, Jean-Claude Martinou, Bruno Antonsson Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia Journal of Biological Chemistry (2005) doi: 10.1074/jbc.m505843200

Fig 4G

Hetz explained that none of that research misconduct altered the conclusions.

“On the other hand, Dr. Hetz effectively recognizes some of the manipulations reported in PubPeer and confirmed by the Committee through specialized support in image management. In one of them (Figure 5C of article N ° 10) he justifies the intervention as follows:

Later, for aesthetic reasons, more cells from other photos of the same condition were added so as not to have empty spaces that generated asymmetries. This was not necessary, but showing more cells produced a more robust result. “…”This inclusion of cells does not alter the conclusions of the experiment. It was not mentioned in the legend because it was not deemed necessary. ”

Honest scientists don’t splice gel lanes, they redo the experiment. Also this helps reproducibility. There is no reason to stealthily create Franken-gels, unless the desired results won’t manifest otherwise.

“The Committee considers that this was always a recommended practice of transparency in the presentation of results, for which it considers that not having applied it in articles published when it was already mandatory constitutes a serious offense. Such is the case of articles 20, Supplementary Figures S1b and S4 F and H (year 2009); 13, Figure 6B and 6D (year 2011); 22, Figure 4B (year 2013) 

Fernanda Lisbona, Diego Rojas-Rivera, Peter Thielen, Sebastian Zamorano, Derrick Todd, Fabio Martinon, Alvaro Glavic, Christina Kress, Jonathan H. Lin, Peter Walter, John C. Reed, Laurie H. Glimcher, Claudio Hetz BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha Molecular Cell (2009) doi: 10.1016/j.molcel.2009.02.017 

Btw, Hetz’s co-author here is John C Reed, Global Head of Research & Development at Sanofi, whose own PubPeer record is actually much more impressive than that of Hetz. Yes, Sanofi, the Big Pharma which probably has more money than whole of Chile.

Regarding this paper, and #13 and #22 above, the Committee concluded:

“The situations described reveal an enormous carelessness and lack of rigor in the presentation of results. This malpractice had already been pointed out in the conclusions of another instance evaluating articles published by Dr. Hetz that the Ethics Commission of the Faculty of Medicine organized in 2012. Thus, in a letter addressed to the President of said Commission, Dr. Juan Olate from the University of Concepción pointed out:

However, there is a significant degree of negligence in the processing of the experimental data published in these high-impact journals, where the errors committed are highlighted with greater force and questioned, putting into question of judgment the veracity of the experimental work and trajectory of a renowned scientist like Dr. Claudio Hetz”.

For his part, in a report prepared by Dr. Luis Valladares of INTA on questioned articles by Dr. Hetz, and referring to an abnormally high frequency of errors that he described as unintentional, he concluded: “… the lack of neatness can be inferred of Dr. Claudio Hetz in his scientific articles”. 

Negligence, really? How do they even know the spliced lanes of those Franken-gels are really what Hetz’ labels say they are? In all these 3 papers the raw data was not available, and the papers are not that old.

But then again:

The Committee reiterates its opinion that, although Dr. Hetz must fully assume his main responsibility for the errors or sloppiness reported in publications where he participated as the corresponding author, this responsibility is also shared with the co-authors, as well as with the journals that published them. In this regard, a significant portion of the anomalous situations reported could have been avoided if the journals, through the peer reviewers and editorial teams, had done their job well, detecting obvious errors in a timely manner.

It’s like defending the thief by blaming the shop for failing to employ qualified detectives. Note that the Committee doesn’t blame the journals for refusing to retract those fraudulent papers, but instead commends them for issuing corrections and declaring conclusions not affected. Kind of contradictory, no?

And this, finally:

“Regarding the work carried out by PubPeer, the Committee regrets the anonymous nature of the comments and complaints published there, which favours the occurrence of persecutory actions and the publication of unfounded complaints, some of which were detected during the work process. of this Committee. However, as long as untidy and not very rigorous behavior persists, both in the preparation of articles and in the review processes carried out by the journals where they are published and, as long as situations that conflict with ethics continue to occur in the process of publication of scientific research results, the Committee considers that their existence is a contribution to the development of a reliable science.

Well bloody thank you for forgiving us all. Can you tell us what the “unfounded complaints” were, pray?

I guess those must this:

#4 Hery Urra , Daniel R. Henriquez, José Cánovas, David Villarroel-Campos, Amado Carreras-Sureda, Eduardo Pulgar, Emiliano Molina, Younis M. Hazari, Celia M. Limia, Sebastián Alvarez-Rojas, Ricardo Figueroa, Rene L. Vidal, Diego A. Rodriguez, Claudia A. Rivera, Felipe A. Court, Andrés Couve, Ling Qi, Eric Chevet, Ryoko Akai, Takao Iwawaki, Miguel L. Concha, Álvaro Glavic, Christian Gonzalez-Billault, Claudio Hetz IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A Nature Cell Biology (2018) doi:10.1038/s41556-018-0141-0

Supplementary Fig. S3D

It was the complaint of Figure S3D which the Committee decided was unfounded, because Hetz reassured it showed a stripped gel membrane, hence the identical background, and because the journal accepted his explanation based on a picture he posted on PubPeer. Yet did the Committee ask Hetz to present the original X-ray film or the file from the gel documentation machine? It doesn’t seem they did, maybe the co-authorship of Andrés Couve, Chile’s Minister for Research and Education discouraged them from investigating this 2018 paper?

Here another “unfounded” accusation:

#6 Rene L. Vidal, Alicia Figueroa, Felipe A. Court, Peter Thielen, Claudia Molina, Craig Wirth, Benjamin Caballero, Roberta Kiffin, Juan Segura-Aguilar, Ana Maria Cuervo, Laurie H. Glimcher, Claudio Hetz Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy Human Molecular Genetics (2012) doi: 10.1093/hmg/dds040

PubPeer commenter: “Supplementary Figure 4A and D are more related than not.
In both figures ATF4/shCTR lanes are identical but the two attached lanes to the right are different. In 4D, the splice is clearly visible
. In the Hsp90 lanes, three of the four bands are the same. They are bands 2-4 in part A, and the bands 1-3 in part D.

Hetz first tried to claim the bands were not identical by posting a different HSP90 gel as “raw data”. He then announced a second correction (after the first stealth correction, read here). I am sure Hetz will be accommodated, that journal Human Molecular Genetics and its hilariously dishonest editor-in-chief Dame Kay Davies specialise on helping research cheaters with stealth corrections and cracking down on whistleblowers. Maybe this is why the Committee assumed the evidence of data manipulation to be “unfounded”?

All allegations against Hetz’ collaborator Guido Kroemer are of course unfounded, the man never retracted a single paper (out of SEVENTY on PubPeer).

Melissa Nassif , Vicente Valenzuela , Diego Rojas-Rivera , René Vidal , Soledad Matus , Karen Castillo , Yerko Fuentealba , Guido Kroemer, Beth Levine, Claudio Hetz Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis Autophagy (2014) doi: 10.4161/auto.28784

PubPeer commenter: “Figure 7B and 7C – more similar than expected (Looks like it is the same original picture with different magnification).

Hetz admitted a duplication, blamed “the first author of the paper Dr Melissa Nassif who performed the experiments“, declared “this error does not alter the biological conclusions“, and issued a correction for two figures, where for some reason the SOD1 blots were removed. Unfounded allegations, you see.

The scientific community has forgiven Hetz, he is again speaking at conferences and teaching early career researchers how to do science properly.

Hetz’ punishment now is that he is asked not to get caught again:

“Finally, the Committee appreciates the eight measures that Dr. Hetz has resolved to adopt in his laboratory to prevent the situations that motivated the Committee’s work. In particular, the decision to reduce the number of researchers in your laboratory by 30% is a sign that from now on the emphasis will be on the quality and thoroughness of what is published. However, among the measures proposed by Dr. Hetz, the Committee misses effective measures to ensure supervision and strict compliance with the highest ethical standard in the work carried out by each of the members of the laboratory. Regarding compliance with this measure, as with the others committed by Dr. Hetz, the Committee suggests the installation of a specific supervisory body, ideally external to his laboratory, in order to ensure compliance. “

I would love to know more about that lab downsizing. Which lab members were removed, why, and where are they now?

Enough of boring investigative reports. After Hetz was absolved of being slandered by me, he was interviewed by proper science journalists. And in that newspaper interview Hetz speaks about me. I am crying.

“Of the site that made the complaint, Hetz says that he had heard of him from other colleagues in the United States, because he has dedicated himself to attacking very important people in the field of science, including scientists who have won the Nobel Prize. In his opinion, it is a platform that seeks to satire science, due to the type of communication and language it uses. In no case is it science journalism. From the note that talked about his work, he learned from social networks and because colleagues from his laboratory told him.

“When I read it, it was a feeling of anger and injustice. A very malicious story was generated, it showed an intentionality in the errors ”. Today he prefers not to refer to either the site or the author. It simply does not consider it valid in the questioning exercise it claims to do with science. For that, says Hetz, there are established protocols and anonymous complaints, it is important to occupy institutional and formal mechanisms that exist in the journals and not to use offence and discredit.”

Science elites like Hetz think only they can only be judged by their own kind. And their own kind is above all criticism, exactly because they are science elites. Especially if they won a Nobel Prize. Well, even Gregg Semenza and Louis Ignarro got in trouble over falsified data.


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6 comments on “The Claudio Hetz Blues

  1. It is somewhat of a philosophical question: if a “scientist” truly believes that manipulating images in Photoshop is part of the scientific method, is it truly fraud?

    In some sense, it is reminiscent of the story of The Grad Student Who Never Said “No”. Brian Wansink seemed to honestly not understand the problem with p-hacking. So is it really fraud then, or extreme incompetence?

    I used to think that nobody could really think image manipulations acceptable, but I’m no longer sure of that. Many so-called scientist seem not to understand even the basic facts of how experiments are supposed to relate to reality.

    In my opinion, the question of whether there was intentional fraud or not is not really relevant from the point of view of science (it might be when it comes to repaying grants etc.). Papers like these should be retracted, and the responsible authors removed from their positions working as scientists. Even if what happened was “only” incompetence and sloppiness, it is so extreme that no results associated to this researcher could ever be considered reliable.

    Liked by 1 person

    • Fraudsters always existed in science. However, academia has now reached a point (of no return?) where fraudsters are (often) tolerated and (sometimes) rewarded. It is a sad state of affairs, but junior scientists and graduate students are trained how to spin data for the purpose of landing grants and high impact publications, rather than being truthful. In many universities, they go through mandatory mock study sections, publishing in high impact journals workshops, career advices webinars, bureaucracy-navigating skills seminars, etc…This process is religiously enforced by an authoritarian administration with the following subliminal message ; science is nothing else but a business. If scientific research is not exclusively about truth, anything is permitted.

      Like

  2. “Even if what happened was “only” incompetence and sloppiness, it is so extreme that no results associated to this researcher could ever be considered reliable.”
    These frauds allow some researchers to create company … such as Thabor Therapeutics created on the discovery of Chevet and colleagues… so why they have to change anything ?
    https://pubpeer.com/publications/C246FEC9AAB300E7C7144338AC779D

    Like

  3. “Regarding the substantive issue, the investigation establishes, as a first conclusion, that in the study of the antecedents, actions constituting scientific fraud were not detected, understood as a deliberate act of creating false data to support or demonstrate a certain scientific thesis . In this way, no publication has been retracted, maintaining the validity of its findings and conclusions.”

    There’s the problem, right at the beginning of the review report.

    Translation: If we don’t catch you doing what we consider to constitute totally making up fake shit, then everything you say is absolutely valid.

    In the end, hackers like Hetz are judged not by their superiors but by their peers. It’s clear that anyone in his field who has functioning brain cells doesn’t believe his crap. Eventually some of them will end up on a grant panel or a manuscript review and justice will be done. It will also be done by those with sufficient discernment not to cite this mishmash. Those who decide to employ such charlatans, give them grant funding and base companies on fantasies are not doing their due diligence, and deserve the worst punishments possible. As for Hetz, he seems to be little more than a stumbling fool.

    Like

  4. There’s a deep psychological phenomena underlying most of these cases of meteoric careers and young researchers that believed their own tales. At some point the tale becomes more fun than the science. It becomes addictive, and needs to keep being fed. Seen it too many times.

    Like

  5. Diego Ortiz in Interferencia, 18/09/2021
    https://interferencia.cl/articulos/ministro-de-ciencia-es-coautor-de-uno-comite-encontro-graves-faltas-la-integridad-de
    How then is it explained that there is no fraud if Hetz himself, according to the report, acknowledges manipulating images? Leonid Schneider, the biologist who initially denounced through an extensive article the multiple irregularities committed by Hetz – and, by extension, Couve in one of the studies where he is a co-author – provides an explanation. [..]

    “It is impossible to prove that these manipulations were a deliberate act to defraud, since for that he would have to admit it. You cannot demonstrate that intention except with a confession, you can only prove that there are errors and manipulation ”, he explains in conversation with INTERFERENCIA.

    According to Schneider, the report is devastating, and many of the complaints he made are verified, although there were others that the committee of specialists could not even review. At the beginning of the document, the commission acknowledges that “not all the observations or questions were validated by the Committee, because in some cases the originals were not available due to the time that had elapsed.[..]
    Schneider, meanwhile, as a connoisseur of Hetz’s successful career, is not convinced. “He is a very intelligent scientist with a long career, and for the same reason I do not think it could be errors,” he says.

    Also Elisabeth Bik is quoted:
    “I find that Hetz’s explanations [of Schneider’s complaints and the anonymous ones inPubPeer] are not convincing, ”he said. On Couve, Bik said that “it would seem to be an unfortunate co-authorship for him”, since the main problem in terms of scientific integrity is not the current minister, but Hetz, who at the time of the interview registered 27 questioned investigations.

    After analyzing three of these complaints, Bik concluded that in at least three different investigations there are suggestions that there was “intention to deceive”, “photo duplication” and “possible use o fPhotoshop”.

    Like

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