The original sins of Leonard Guarente

Leonard Guarente is a Novartis professor at MIT in Boston, USA. He is carrier of many awards and academy memberships. His anti-aging research brings enormous money from public and especially private investors, especially to his own businesses which he set up with his former mentee David Sinclair, now a Harvard professor.

Despite past retractions and embarrassing corrections, MIT announced not to investigate Guarente because… the evidence is on PubPeer, and hence inadmissible.

Which now helps us understand why MIT previously found their disgraced “mTORman” David Sabatini innocent of research misconduct, having sacked him for sexual harassment. Sabatini now sues MIT and the whistleblower, his lawsuit is supported in part by the MIT’s failure to investigate his science.

But this article is about a different MIT giant, Guarente. I wrote about his mentee and business partner Sinclair before, on the occasion of the latter’s genius proposal to cure COVID-19 with anti-aging supplements; also Guarente was mentioned. The two men must be filthily rich, and not even from their already hefty salaries at elite university.

Guarente is founder of the anti-aging start-up Elysium Health, which sells NAD+ supplements patented by Sinclair. It has EIGHT Nobel Prize laureates on board, which is proof enough that we shouldn’t consider Nobelists as role models for anything including science. Naturally, also Guarente’s MIT colleague and Colossal Wanker George Church is board member of Elysium, simply because this unextinctable eugenicist sticks his snout in every trough with anti-aging money.

Guarente’s and Sinclair’s previous financial masterpiece was the company Sirtis, which was set up by the latter to market the magic substance resveratrol as anti-aging supplement. Resveratrol is normally a natural plant substance very popular with scientists and media, because it is present as trace element in (among many other things) red wine, which makes for excellent marketing.

Guess who I am #10. Descended from 🇮🇹, I am a rebel scientist who quit 🚬 in 3rd grade, then used a simple organism to figure out how genes are regulated, and how gene regulation regulates lifespan. 🍻#longevity #lifespanbook pic.twitter.com/IsQOFaeIxH

— David Sinclair (@davidasinclair) May 24, 2019

Resveratrol in a pill would make you young and on top cure all possible diseases like diabetes and even cancer via the (never confirmed, but often postulated) process of activation of SIRT enzymes, or sirtuins. These are NAD-dependent deacetylases of various proteins involved in cancer and cellular senescence, which led Sinclair and Guarente to another commercial idea, namely that of NAD+ as SIRT1 activator, marketable as dietary supplement.

In 2008, Sinclair sold Sirtis to the pharma giant GlaxoSmithKline (GSK) for $700 million, which made him and Guarente very, very rich. GSK however soon regretted the purchase and in 2010 abandoned the SIRT research. The snag was hit long before any pharmacological efficiency could be tested in vivo, namely with achieving any significant bio-availability of resveratrol. It is not clear if the lead product SRT501 ever delivered anything. On top of that, one of Sirtris’ original founders, Christoph Westphal, had to resign when GSK found out he was selling same SRT501 supplements via his own private company. Sirtis then tried its luck with alternative supplements (SRT2104 and SRT1720) but that led nowhere either (there were rumours of toxicity), so GSK pulled the plug completely.

These days Elysium sells NAD+ supplements, a monthly supply for $60 a bottle. The company is being presently sued by its competitor ChromaDex over proprietary rights for these NAD+ products. ChromaDex product is cheaper, $40 for a monthly supply bottle, maybe that’s because they don’t have any Nobelists or Church on scientific advisory board.

Guarente had to retract papers and issue embarrassing corrections in the past. More recently, the pseudonymous sleuth Claire Francis decided to have another look at his papers and found more evidence of fudged data. However, only in older studies – after all, Guarente is certainly not stupid and learned from his past trouble. The PubPeer record is here, and even if the papers are old, it is serious enough to open a research misconduct investigation. Except it won’t happen, by official decree from MIT, as you will soon learn.

In my earlier article about Sinclair’s bad science, I mentioned this paper:

Abhirup Das , George X. Huang , Michael S. Bonkowski , Alban Longchamp , Catherine Li , Michael B. Schultz , Lynn-Jee Kim , Brenna Osborne , Sanket Joshi , Yuancheng Lu , Jose Humberto Treviño-Villarreal , Myung-Jin Kang , Tzong-tyng Hung , Brendan Lee , Eric O. Williams , Masaki Igarashi , James R. Mitchell , Lindsay E. Wu, Nigel Turner , Zolt Arany, Leonard Guarente, David A. Sinclair Impairment of an Endothelial NAD-HS Signaling Network Is a Reversible Cause of Vascular Aging Cell (2018) doi: 10.1016/j.cell.2018.02.008 

In 2018, Sinclair announced on PubPeer to issue a Correction, which appeared in February 2019 and fixed Figure 2C and 2D, while adding:

“In addition to these two figures, the authors wish to clarify that one of the corresponding authors, Leonard Guarente, is a founder of Elysium Health. In the Declaration of Interests section of the original version of the paper, he was listed as an advisor of the company.”

Sinclair however declared to have no financial involvement with Elysium, only with “Metro International Biotech, Jumpstart Fertility, Life Biosciences, and Liberty Biosecurity and D.A.S. to EdenRoc Sciences, ArcBio, Segterra, Animal Biosciences, Senolytic Therapeutics, Spotlight Biosciences, Continuum Biosciences”. Here is another joint paper by Sinclair and Guarente, it also has the cancer research bigwig Bill Hahn on it:

Ron Firestein , Gil Blander , Shaday Michan , Philipp Oberdoerffer , Shuji Ogino , Jennifer Campbell , Anupama Bhimavarapu , Sandra Luikenhuis , Rafael De Cabo , Charles Fuchs , William C. Hahn , Leonard P. Guarente , David A. Sinclair The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth PLoS ONE (2008) doi: 10.1371/journal.pone.0002020 

This is basically how sirtuins do their anti-aging magic. Instead of fudging data, why not just photoshopping your own mug to look young, saves work?

Here is a beautiful old forgery from Guarente’s lab, newly found:

Xiaoling Li , Songwen Zhang , Gil Blander , Jeanette G Tse , Monty Krieger , Leonard Guarente SIRT1 deacetylates and positively regulates the nuclear receptor LXR Molecular Cell (2007) doi: 10.1016/j.molcel.2007.07.032 

It wasn’t enough to clone a gel lane five times, they digitally altered it in one case to prove their skills. Maybe the Cell Press editors demanded more sophistication in Photoshop fraud?

A decade ago, Guarente stood in the middle of a huge research fraud scandal and came out totally unscathed. His then-postdoc Gizem Donmez falsified a number of high profile papers which won her a professorship at the Tufts University and a very prestigious award from the Ellison Foundation (incidentally, its board member then was Guarente). When University of Rochester researcher and whistleblower Paul Brookes exposed Donmez’ Photoshop activities in 2012, she hired a star lawyer to threaten Brookes. Worth noting: the same lawyer previously won the David Baltimore and Thereza Imanishi-Kari case, which set the USA on course of accepting research fraud:

At the journal Cell, then led by the fraud-fetishist Emilie Marcus, nobody initially gave a toss, the editor tasked with telling Brookes to get lost was Sri Devi Narasimhan, Guarente’s scientific “grandchild”, i.e. a mentee of his mentee Heidi Tissenbaum.

Eventually, Donmez’s fraud proved too much to cover up, two papers were retracted, and she was sacked by Tufts. She returned to Turkey, as faculty member of the Adnan Menderes University. It seems MIT decreed Guarente officially had absolutely nothing at all to do with his own last author’s papers retracted for fraud.

This was the retracted Cell paper:

Gizem Donmez , Diana Wang , Dena E. Cohen , Leonard Guarente SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10 Cell (2010) doi: 10.1016/j.cell.2010.06.020

 

But Guarente stood by Dönmez and together they declared in 2014 in the Retraction notice (highlights mine):

“It has come to our attention that several figures in the paper contain images in which gel lanes were spliced together without appropriate indication. There are also instances of image duplication. We believe that these errors do not affect the conclusions of experiments in the paper. Moreover, the finding that SIRT1 upregulates the ADAM 10 α-secretase in neurons was reported by Theendakara et al. (Theendakara, V., et al. [2013]. Proc. Natl. Acad. Sci. USA 110, 18303–18308), and the more detailed finding that SIRT1 and RARβ cooperate in neurons to activate ADAM 10 has also recently been reported by Lee et al. (Lee, H.R., et al. [2014]. J. Neurosci. Res. Published online June 5, 2014. http://dx.doi.org/10.1002/jnr23421), thereby supporting our main conclusions. However, the level of care in figure preparation in Donmez et al. falls well below the standard that we expect, and we are therefore retracting the paper.”

This was the other retracted paper:

Gizem Donmez , Anirudh Arun , Chee-Yeun Chung , Pamela J McLean , Susan Lindquist , Leonard Guarente SIRT1 protects against α-synuclein aggregation by activating molecular chaperones Journal of Neuroscience (2012) doi: 10.1523/jneurosci.3442-11.2012

The Retraction notice from 2016 was short, at least it had no claims of unaffected conclusions:

“It was brought to our attention that the Donmez et al., 2012 paper has numerous examples of unindicated splicing of gel lanes and of duplications and inversions of gel images. The prevalence of these occurrences is unacceptable and compels us to retract the paper. We offer our most sincere apologies to readers.”

Note that there is no reference to any institutional investigations at MIT. Likely because there weren’t any. Tufts wouldn’t be able to investigate, since the raw data was with Guarente, but it is rather clear that Tufts, and certainly not MIT, pushed for retractions of Dönmez’s fraudulent papers.

Basically, Guarente was never investigated, despite his public defence of Dönmez’s fraud. And there was more. Here another joint effort of this duo which was solved with correction, the last author Gillian Bates is presently research centre director and faculty dean at UCL, London.

Anna Bobrowska , Gizem Donmez , Andreas Weiss , Leonard Guarente, Gillian Bates SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of Huntington’s disease phenotypes in vivo PLoS ONE (2012) doi: 10.1371/journal.pone.0034805

The PLOS One mega-correction from 2021 admitted that Figures 5A,B,C,E and F were falsified. Also the Figures 1C, 1E, 2A, 2C, S2C and S3A were in need of fixing. The results section had to be re-written.

This wasn’t the first PLOS mega-correction for Guarente. This one was faked long before Dönmez even joined his lab:

The original PubPeer evidence consisted only of the forged Figure 7A, yet the Mega-Correction from 2015 addressed many other falsifications:

“The correct control for the original Fig 7A could not be located; this panel has therefore been removed after a careful assessment and investigation determined that the result for which original Fig 7A was cited is supported elsewhere in this article, and that removal of this panel does not affect the conclusions of the paper.

We have also taken this opportunity to provide new versions of several figures (Figs 4, 5, 6, 7) in which gel/blot splices and a non-linear level adjustment were made but were not previously indicated or declared, or to replace incorrectly spliced gels/blots with the un-spliced originals. We also take the opportunity to correct two errors in the legend to Fig 6, first to remove a redundant and incorrect sentence, and second to address incorrect description of p values.”

Because the new figures rendered the previous scientific claims untenable, the text in the results section was changed also here. Meaning, Guarente’s conclusions about SIRT1 once again went tits up. You might ask, why didn’t PLOS retract these two papers then? Well, these mega-corrections were the most they could do under immense pressure from MIT seeking to defend Guarente and to prevent further retractions.

Already in 2004, Guarente had to correct a Nature paper right after its publication:

Frédéric Picard , Martin Kurtev , Namjin Chung , Acharawan Topark-Ngarm , Thanaset Senawong , Rita Machado De Oliveira , Mark Leid , Michael W. McBurney , Leonard Guarente Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma Nature (2004) doi: 10.1038/nature02583

In reality of course, that figure was intentionally faked. But this SIRT1 supplement dieting study earned Guarente many millions of dollars, not just in research grants, but for his anti-aging businesses Sirtis and Elysium Health. So yes, the conclusions that it was all a scam remain unaffected.

With this parallel-published SIRT1 study (cited over 1600 times), there wasn’t even a correction because it’s Cell:

Maria Carla Motta , Nullin Divecha , Madeleine Lemieux , Christopher Kamel , Delin Chen , Wei Gu , Yvette Bultsma , Michael McBurney , Leonard Guarente Mammalian SIRT1 represses forkhead transcription factors Cell (2004) doi: 10.1016/s0092-8674(04)00126-6 

Those gels were forged, authors spliced (or just copy-pasted) gel bands where they didn’t like the real results. One co-author is a certain Wei Gu of Columbia University. He was trained in data forgery by the American bigwig of cancer research Robert Roeder, and Gu’s PubPeer record recently grew thanks to Claire Francis’s investigations (due to his common name, searchable here and here).

I wrote about Gu and Roeder before:

For example, look at this Nature paper by Gu with his New York colleague Ariel Shiloh, professor at the Albert Einstein College of Medicine:

Jianyuan Luo , Fei Su , Delin Chen , Ariel Shiloh , Wei Gu Deacetylation of p53 modulates its effect on cell growth and apoptosis Nature (2000) doi: 10.1038/35042612 

You see the insolence. And here we have Gu and Shiloh, accompanied by same Gu-trained fraudsters Jianyuan Luo and Delin Chen, on another Cell paper from Guarente’s lab. It was cited over 2600 times, and it’s completely fake:

Jianyuan Luo, Anatoly Y. Nikolaev , Shin-ichiro Imai, Delin Chen , Fei Su , Ariel Shiloh , Leonard Guarente , Wei Gu Negative control of p53 by Sir2alpha promotes cell survival under stress Cell (2001) doi: 10.1016/s0092-8674(01)00524-4 

What co-authors Guarente had there! Also, Gu’s russia-born PhD student Anatoly Nikolaev , who is now PI at Cleveland Clinic, in between went on to work at Genentech under Marc Tessier-Lavigne, today’s president of Stanford University. As it came out very recently (thanks to student newspaper Stanford Daily), Nikolaev faked data in a 2009 Nature paper and other studies at Genentech, and Tessier-Lavigne knew and covered it up.

Bad scientists are attracted to each other, they cooperate to defraud the public and to parasitise science, and they breed by installing their own academic progeny in high academic positions. Made possible by total failure of elite institutions to act on fraudulent science.

On 11 March 2023, Claire Francis wrote to MIT, reporting problematic data by Guarente and two other MIT bigwigs of cancer research who featured on For Better Science before, Robert Weinberg and Tyler Jacks.

On 11 April 2023, the sleuth received this “Personal & Confidential” reply from Maria Zuber, Vice President for Research at MIT. She was also the person who investigated Sabatini following my notification and found nothing wrong with his research:

“Dear Claire,
I am writing in response to your March 11, 2023 email to MIT’s President which was forwarded to the Office of the Vice President for Research (OVPR) with the subject line “Problematic data Tyler Jacks, Leonard Guarente and Robert Weinberg.” The email contained three links to a list of publications on PubPeer by Professors Tyler Jacks, Leonard Guarente and Robert Weinberg, respectively.
As MIT’s Vice President for Research (VPR), I am responsible for initiating and overseeing the review of allegations of possible misconduct in research conducted by members of the MIT community under Policies and Procedures § 10.1 (the “MIT Policy”). Under the MIT Policy, “Research Misconduct” is defined to include “Fabrication, Falsification, or Plagiarism in Research Activities at MIT or Deliberate Interference. It does not include honest error or differences of opinion.” These terms are further defined in the MIT Policy.
While I appreciate you bringing your concerns to MIT’s attention, your March 11th email with links to a list of publications by the named MIT professors with a subject line of “problematic data” does not provide sufficient specificity for MIT to assess whether the MIT Policy applies, and if so, who the appropriate respondents may be. Without specific and credible allegations of research misconduct, MIT is unable to take any action. If there are specific issues with the publications referred to in your email that you have reason to believe may constitute research misconduct, I ask that you supplement your March 11th email with additional, detailed information as to each publication in order for MIT to assess what action may be appropriate.
MIT is committed to reviewing all good faith allegations of specific instances of possible misconduct in research conducted by members of the MIT community to protect the integrity of scholarship and research. MIT’s receipt and review of allegations of possible research misconduct are treated as highly confidential. My office does not intend to disclose its receipt and assessment of this issue to anyone else except as I determine may be necessary. If we do not hear from you
by Thursday, April 20, 2023 with additional information to substantiate possible concerns of research misconduct, MIT will close its consideration of this matter.”

Basically, Zuber stated that PubPeer evidence as such is inadmissible. Claire Francis was invited to submit a full report, which was expected not only to explain in detail each allegation, but also to prove who the responsible forger may have been. The sleuth was given one week to deliver this full report. Which MIT would reject anyway, declaring all those to be “honest error or differences of opinion.”

MIT did not reply to my email. Neither did Guarente.

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