The Ballad of Claudio Hetz

There is a perfectly scientific theory that the Paris-residing German cancer researcher Guido Kroemer is somehow the centre of the biomedical data fudgery universe. Every questionable scientist seems to be somehow connected to Kroemer: Carlos Lopez-Otin, Didier Raoult, David Ojcius and Josef Penninger are his best friends, while Carlo Croce and Adriano Aguzzi awarded Kroemer a prize of €1 Million in 2019. Kroemer is even connected to Irina Stancheva, via her mentoring coauthor and his personal friend, Sir Adrian Bird. The main argument for this theory of Guidocentricity is that Kroemer never retracted a single paper or suffered any professional consequences despite his impressive PubPeer record of over 60 papers.

Let me now introduce to you another collaborator or maybe even a friend of Kroemer: Claudio Hetz. Hetz is an artist, a blues musician, but his performance artistry does not end there: he is also professor of neuroscience, his goal is to save the lives of sufferers of Parkinson’s, Alzheimer’s, Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases. And be not in doubt: Hetz succeeds, thanks to his creativity. And Photoshop.

A Chile native, Dr Hetz is a bigwig in his country and beyond. He runs, in his own words, “one of the most productive laboratories in Chile” at the University of Chile in Santiago (where he is Director of the Biomedical Neuroscience Institute), and is constantly in national news. In USA, Hetz progressed from adjunct professorship to faculty at the Buck Institute in California, where he is presently setting up a new franchise lab. The Chilean genius also is adjunct professor in Harvard and has 24 papers on PubPeer, none retracted.

Muy contentos de hacer pública la apertura de un laboratorio satélite en el Buck Institute en California para reforzar nuestros estudios sobre enfermedsdes cerebrales y el envejecimiento. https://t.co/q3VapDBgqv

— Claudio Hetz (@HetzLab) July 10, 2020

In 2016, on the occasion of his angling yet another big grant, Hetz was interviewed by the charity which supports him. He said:

“Patients affected with ALS now need to know that we are working for them, even though our current scientific efforts will benefit next generations. They can have the hope that we are doing our best effort to contribute to finding a possible cure for this disease, and that families suffering from loss of beloved ones and uncertainty about their future will count on powerful treatments to live a normal life. We feel completely motivated and convinced to dedicate our careers to fight ALS.“

You probably now want to see how Hetz finds his cures? He just knows what works, and bends reality to do his bidding. Just like Kroemer.

Like Kroemer, Hetz reached the supernatural status of a genius scientist where physical laws stopped applying. They can publish anything, and nobody will question it. Just last year, Hetz and Kroemer published a paper with mismatched raw data, simply because they can.

Sure, the raw data shows a completely different P-eIF2A result from the main figure. But then again, the pay-to-play pseudo-elite journal Nature Communications recently made their stance on research ethics by taking papers on eugenics or from zombie scientists like Kathrin Maedler and Maria Fousteri, despite past fraud findings. The Editor-in-Chief Elisa Di Raineri then blocked me on Twitter for slandering her valued paying customers. Why shouldn’t she accept such quality science from Kroemer and Hetz if they are paying $5500 for the service?

Hoy más que nunca se destaca la colaboración entre países en la investigación y busqueda de soluciones globales. Hace unas horas salió publicado un estudio de BNI conectando laboratorios en Suecia, Chile, Alemania, Estados Unidos y tres ciudades Francesas. https://t.co/uUPfeTs7aR pic.twitter.com/Y46la00xFr

— Claudio Hetz (@HetzLab) May 14, 2020

Now you know what you must do to publish in a Nature-themed journal. But not just there, here an older Kroemer and Hetz collaboration:

Cloned gel bands, it seems, and further analysis on Pubpeer strengthens the suspicion. These authors were deemed so important that also the rule “The journal does not permit citation of “Data not shown”” did not apply to them. Will there be a correction? While at it, maybe the publisher EMBO can gather courage to look into this paper by Hetz again:

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 

So far, only Figure 6D was corrected in 2017, the authors warned that “It is worth mentioning that the lysotracker signal was never significant in the non‐treated conditions“:

Maybe you notice that the image was not just accidentally copy-pasted, but shrunk and its red channel boosted. The falsification apparently did not affect the conclusions, you see, it was “never significant“. But what about Figure 6H, flagged in May 2020, what with its copy-pasted gel bands?

Oh I know, it’s merely a loading control, which was “never significant”, too! Don’t laugh, I wouldn’t be surprised if this is why there was no follow-up action from the journal till today.

Now I would like to show you a paper from the Hetz lab where the “raw” data (or what was passed off as raw data) has been apparently generated in Photoshop, to satisfy those petty journal requirements.

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 

The paper was corrected in 2018, to reassure the readers that “The authors declare no competing interests.” There is no need for this elite Nature family journal to correct anything else, as it seems.

Update: a reader informed me that one of this 2018 paper’s authors is Andres Couve Correa, professor at the University of Chile, who in December 2018 became Chile’s minister for research.

Felicitaciones a estos investigadores/as por este reconocimiento. Un ejemplo de cómo la mejor ciencia contribuye al bienestar de las personas y además se vincula con el desarrollo de políticas públicas en temas como escasez hídrica y cambio climático. pic.twitter.com/vvJrHCsyfv

— Andrés Couve Correa (@acouvecorrea) January 10, 2021

That mismatch in gel lane number was not a one-off. Such things happen when you accidentally mis-load your gel to obtain the desired result and then urgently need a nice equally loaded control (here, actin), which you pull out from your “loading control library” in a hurry and forget to at least count the gel lanes. Not that anyone noticed it during peer review. Or maybe they didn’t mind, remember: rules don’t apply to Hetz. So here another such situation:

Maybe Hetz likes to play practical jokes, because this lane number mismatch seems to be his signature prank. And academia loves it!

And now, some unhygienic insights into how sausages (aka research papers) are made:

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

The Supplemental data of that paper was stealthily modified right after Paul Brookes flagged the following issues on his now defunct Science Fraud website:

Do you see that the ATF4 gel is not cloned 1:1, but only two bands in it are identical? Seven years ago, Brookes commented on PubPeer:

“So this article was originally flagged on http://www.science-fraud.org, back in summer 2012.

Coincidentally (some might even say magically), on the exact same day that the supplemental data for this paper was modified, a commenter showed up at the site and left a comment claiming that the blog post was a lie, there was never any problem with the paper and they demanded the post be taken down. Perhaps not surprisingly, the commenter’s IP address mapped to Santiago Chile, where Dr. Hetz is based. How did this coincidence happen? Are we expected to believe that a random reader (not Dr. Hetz) just happened to read the newly modified article on the day it was released, then just happened to come to my website and write a flustered comment about how the claims being made were invalid?

This was all documented in a follow up post on the site, which was then sent to the journal, demanding an explanation for how exactly this “correction” had occurred without being logged on the journal’s pages or on PubMed. Needless to say, the journal offered a boilerplate “we’ll look into it” response, and that was that. Over a year later and no response, no update, and this simply wonderful paper is still out there with absolutely no acknowledgement whatsoever that the original version contained duplicated blots. Follow up emails to the journal using my real name have gone unanswered.

But hey, there’s nothing wrong right? Despite having 6 papers called out in public on my site as containing duplicated western blots and other apparent image fabrications, Dr. Hetz is doing great. His group has 7 post-doc’s, 12 grad’ students, 5 techs/admins, all supported by money from the ALS foundation, Michael J Fox Parkinson’s foundation, Alzheimer’s Association, the Christopher Reeve Foundation, and the Chilean government. The message here is clear – if you can persuade journals to make corrections without publicizing the fact, you can get ahead in science.“

Now, you might wonder what kind of a rotten crook of an editor would stealthily replace falsified figures, possibly to help a cheater sue his accuser for libel. The Editor-in-Chief of the Oxford University Press journal Human Molecular Genetics (HMG) is Dame Kay Davies of Oxford, who herself

• published fabricated data, including in her own HMG, and was exempt from investigation by her University of Oxford on the grounds the criticised papers were more than 3 years old;
• retaliated against a whistleblower who confidentially informed her of data manipulation in HMG, by reporting the whistleblower to their accused superior for due punishment, while refusing to do anything about that paper.

Dame Kay suffered exactly zero consequences for her perfectly upper class behaviour, because this is England and this is also how academia operates. The rules don’t apply to her also.

My First faculty meeting at the Buck Institute for research in Aging. And the First RO1 submitted!! Moving forward step by step. pic.twitter.com/AaNK2IEbi3

— Claudio Hetz (@HetzLab) November 13, 2020

Aside of Kroemer, Hetz has another friend in France. He coauthored several papers with the cancer researcher Eric Chevet from the INSERM institute in Rennes. Like Hetz, Chevet specialises on studying cellular stress of the endoplasmic reticulum (ER), he also has his own PubPeer record). Here one joint paper:

Now, a loading control from one gel was apparently flipped and shifted to stand in as loading control of another gel. I will help EMBO Press here: that loading control was probably “never significant” either. Now, a source told me that Chevet is not only best friends with Hetz, but was also was involved in the removal of his Rennes colleague, Patrick Legembre, after Legembre was accused of bullying and caught with manipulated data. My source finds this ironic.

Te invitamos a escuchar la entrevista en @InfinitaFM a nuestro investigador y director del @institutoBNI, @Hetzlab, donde explicó sobre el desarrollo de terapias génicas y la compra reciente de sus patentes. Mira la conversación completa en → https://t.co/lqNWf671ci#GeroChile pic.twitter.com/EdsodGRuTe

— GERO (@gerochile) November 27, 2020

Just so you don’t start blaming junior scientists for putting naughty stuff in Dr Hetz’ papers: much of his PubPeer record stems from the time when he was junior scientist himself. Like this, when Hetz did postdoc in the Dana Farber/Harvard lab of the late giant of cancer research, Stanley Korsmeyer.

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

There are duplicated gel bands and lots of splicing.

What does all that gel splicing mean? Oh, nothing serious, just some lanes showed wrong results and need to be replaced probably. And of course there is the signature panel with alternating lane number: anything between 7 and 11 lanes is correct, no peer reviewer would dare to object to a Korsmeyer paper.

Now, Korsmeyer died in 2005, this is why when the paper with its falsified data was published after his death, Hetz was the corresponding author. Not a nice thing to do to a dead person (but apparently common practice in academia, there are other examples on my site, read here and here). As it happened, Korsmeyer also trained another artist, Atan Gross from Israel (read here about this Weizmann Institute researcher).

The latest paper Hetz published with Korsmeyer was in 2012, seven years after the latter’s death. The following one appeared also post-mortem, it has a spliced gel and Hetz’s signature prank of mismatched gel lanes:

 

Here another work of art from the Korsmeyer period:

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

And guess what? Only the flow cytometry in Figure 5A was corrected (“This error does not change the interpretation of the results presented in this figure or any of the conclusions of the paper“), in 2012 after Paul Brookes flagged it on his now defunct site. Despite later PubPeer evidence above, in August 2020 Hetz insisted there were no other issues in that paper.

Going back in time, here is something from Hetz’ PhD period, recognised by the Chilean Society of Biochemistry and Molecular Biology with the Herman Neimeyer Medal, for him as the best PhD student in Biomedical Sciences of Chile in 2003. Who wants some flawed cytometry?

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

Another one, because many of my readers are PhD students who need to learn how to succeed in academia the proper way. Watch, children, and learn, so you don’t become failed scientists:

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

As graduate student, Hetz received Chilean fellowship funding to do his PhD abroad, in Switzerland. Once there, he obtained a Federal Swiss Confederation scholarship to do his PhD research at the Serono Pharmaceutical Research Institute in Geneva. This was where Hetz met his Chilean compatriot Cladio Soto, who is now professor at the University of Texas MacGovern Medical School. Soto of course is also Photoshop expert with his own PubPeer record. The collaboration was very productive, as you can see:

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 

These mismatched gel lanes again, what sense of humour. This also is quality science Made in Switzerland, by Hetz and Soto:

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 

More from the two Claudios, to round up. A fake immunohistochemistry image in Cell, a top-rank journal which could not give less of a toss, and a spliced gel while bullshitting the readers into believing they look at same protein blot re-probed:

#InfluyentesCNN | Claudio Hetz y las consecuencias de la pandemia del COVID-19: "Va a aumentar la carga de enfermedades que afectan al cerebro".

EN VIVO ➡️https://t.co/dUAL1sPmRK pic.twitter.com/97rH8EoE5U

— CNN Chile (@CNNChile) November 1, 2020

The fact that neither Hetz nor Kroemer ever retracted paper while bagging one cash award and grant after another, should give you, dear reader, pause to ponder what the hell are you doing in science, taking away resources from productive geniuses like these two. You parasite.

Update 13.01.2020

Reader alerted me to a statement Hetz published on his own lab website (referencing papers up to 2018, pdf generated on 11 August 2020). There, Hetz addresses the PubPeer evidence for each paper, and explains that gel splicing and band copy-pasting was “a normal practice 10 years ago” and everything else was either “unintentional errors” or false alarms for which no correction is needed. The editors at Nature Cell Biology, EMBO Press, PNAS, Society of Neuroscience, and of course also HMG accepted his explanations, Hetz even posts their emails. He also mentions:

“For full transparence we also requested an ethic investigation to the Faculty of Medicine. An inter-institutional commission was generated with no-conflict of interest, and concluded that errors when existed where [sic!] unintentional.”

It seems, that investigation by the university of Chile took place in 2017, possibly with the outcome that the raw data deposition and review mandate began in June 2017, because Hetz writes on his lab site:

“In addition, since 2017 as part of this policy all lab books are revised once a moth and all image splicing and statistical analysis and number of replicates are indicated in figure legends.”

Here some screenshots from Hetz’ August 2020 statement:

Update 15.01.2021

I now commented on the above PDF, the concerns remain. Please download the file, my own comments are in red.

Hetz’ institute issued yesterday a statement in support of its director as reaction to this article, and referencing earlier reporting by Paul Brookes. The great man himself will soon reply on PubPeer.

A translation is available here.

Vía WhatsApp compartieron un comunicado desde el laboratorio de Claudio Hetz esta mañana 👇 pic.twitter.com/07sUpLPAzl

— Carla Hernández (@Carla_H_S) January 15, 2021

Update 18.01.2021

Regarding this case, the University of Chile issued a press release today:

“The university must be able to guarantee that the information that emanates from it is transparent, objective and truthful, so that the Rectorate will implement an independent investigative commission of the highest scientific and academic level, which provides guarantees of transparency and objectivity in order to verify, clarify, and propose the necessary measures to prevent any potential laxity or lack of scientific rigour in this case.”

Update 19.01.2021

Another university press release from same day announced about the investigative commission:

“The group must be made up of academic researchers, internal and external to the University, with the required technical skills and working completely independently.”

More Hetz’ co-authored papers were criticised on PubPeer:

Update 20.01.2021.

Another paper flagged on PubPeer, and what coathor Dr Hetz had there! None other but Sanofi’s R&D Head John C Reed, who has an impressive record of problematic papers from his startup past.

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 

Update 15.09.2021

Hetz was found guilty of what sounds like research misconduct by gross negligence. No fraud was found though because no intent could be determined.

Es increíble @latercera publique un titular como este, considerando que la definición que usó el comité científico revisor para definir "fraude científico" es extremadamente acotada, y no se condice con el quehacer científico a nivel internacional. (1/n)https://t.co/Ysf6LiP5TR

— Néstor Espinoza (@nespinozap) September 10, 2021

Here the university’s press release:

“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.”

It links to the investigative report which mentions interesting things. First, the investigation was set up specifically because of my article, and second: Hetz is constantly berated for being evasive, and for failing to show any concept of guilt for the data manipulations he admits to have committed as first author, while blaming his lab members and collaborators for manipulations in his later papers.

Click to access informe-final-comite-asesor.pdf

This is my favourite quote:

“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.”

Indeed, he has much better tools now, so you won’t catch him again.

Finalmente, si bien concuerdo con el comité que la forma en la que se compilaron estas críticas no es la mejor (https://t.co/eFP3im8ez8), creo la conclusión del comité mismo es evidencia de que no parece existir una mejor.

Eso es lo más triste de todo. (11/n)

— Néstor Espinoza (@nespinozap) September 10, 2021

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