Toppling Giants in Stanford

The affair around the President of Stanford University, Marc Tessier-Lavigne, exploded and is all over the national media. I wrote about it before, in fact the evidence is 7 years old, and everyone knew of it. But out of the blue, the newspaper Stanford Daily started to report about the (growing) PubPeer evidence, and every other newspaper and TV followed suit. Now the Stanford University announced an investigation of their president’s research, and journal editors who deemed literature corrections unnecessary started to change their minds when prodded by journalists.

Urged by the image integrity sleuth Clare Francis, I decided to write about another Stanford giant, Thomas Rando. The man who cured muscular dystrophy and old age, the latter with “young blood”.

Note: the first part of this article has been mostly plagiarised from ealier Friday Shorts.

Marc Tessier-Lavigne, about to fall

Starting in 2015, Elisabeth Bik has been flagging and tweeting fake science in the papers of Stanford University’s President and influential neuroscientist Marc Tessier-Lavigne (MTL). At that time, there was a dozen of papers on PubPeer (now it’s almost 20), many with seriously fake figures. All these years, no journalist thought that was newsworthy. The authoritative journal editors, including of Science, remained silent, no watchdog barked about required retractions.

But suddenly, the proverbial faeces have hit the ventilator. Something happened, something clicked, and on 29 November 2022 Stanford Daily reported about the affair, even illustrates the article with pictures of fake data from MTL’s papers:

“The University acknowledged “issues” in the papers but downplayed Tessier-Lavigne’s role in the potential misconduct in a statement Monday night.

Spokesperson Dee Mostofi wrote Tessier-Lavigne “was not involved in any way in the generation or presentation of the panels that have been queried”in two of the papers, including the paper under review, which was published in The European Microbiology Organization (EMBO) Journal. Of the other two, the University wrote that the issues “do not affect the data, results or interpretation of the papers.”

As third author on the EMBO paper, “President Tessier-Lavigne was included solely to recognize his contribution in providing necessary reagents for the research by other authors,” the University wrote in its statement Monday night.#GiftAuthorship pic.twitter.com/tNQ87FSmiF

— Elisabeth Bik (@MicrobiomDigest) November 29, 2022

It seems, the image integrity sleuth Cheshire set off the chain reaction by writing to Stanford University Ethics and Compliance Helpline and to Stanford Daily (among other addressees) on 4 October 2022. The former acknowledged receipt, and the latter published the above bombshell article. And now US media is over it, all crying scoop.

If you ask me (please ask, nobody else does!), this is what happened. The Canada-born and trained president of Stanford is a very, very powerful man in US academia, but so are many others. These men are not necessarily all friends and wish the best for each other. My suspicion is that due to whatever multi-million dollar money pie MTL and other alpha males couldn’t share peacefully, someone phoned the Stanford Daily journalists and said: Now you can write about him. Which the journalists, sitting on the suppressed information for 7 years, then finally did. Right now, many among the US academics must be at each others’ throats, divided into two camps, for and against MTL (i.e., those who owe him their careers, and those who seek revenge for whatever they think MTL took from them).

As on cue, MTL’s loyal collaborators are now solemnly declaring that it was all their fault and MTL is entirely innocent. Like here:

Viola Maier , Christine Jolicoeur , Helen Rayburn , Noriko Takegahara , Atsushi Kumanogoh , Hitoshi Kikutani , Marc Tessier-Lavigne, Wolfgang Wurst, Roland H. Friedel Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development Molecular and Cellular Neuroscience (2011) doi: 10.1016/j.mcn.2010.11.005 

The Mount Sinai professor Roland Friedel blamed his first author, announced a correction, and added:

“I want to clarify that besides myself and the first author, no other co-authors were involved in experiments and data collection for Fig. 6. The co-authors Dr. Joliceur, Dr. Rayburn, Dr. Takegahara, Dr. Kumanagoh, Dr. Kikutani, Dr. Tessier-Lavigne, and Dr. Wurst have generated mouse lines and provided scientific advice for the studies of the paper, but were not involved in any way in data collection and figure preparation for this manuscript.“

Preventively, Stanford already decided that their president’s authorship on his papers was purely honorary. It also turned out, the editors at Science and Nature were (until Stanford Daily‘s reporting) not only not investigating, they even settled with the mighty MTL by not drawing any attention to the massive fraud in his papers. Total hush-hush was decided, not even corrections:

“According to the University’s statement, Tessier-Lavigne was made aware of several errors in his papers in late 2015, at the same time as he was being consideredfor the role of University president. “The same day in 2015 that President Tessier-Lavigne was alerted to the issues, he in turn alerted editors at the two journals about the three papers,” Mostofi wrote. She did not respond when asked how Tessier-Lavigne was alerted.

Mostofi wrote that Tessier-Lavigne voluntarily submitted corrections to Science that were not published. The University and Tessier-Lavigne did not explain why the corrections were not published, and The Daily has requested copies of the proposed corrections.”

Elke Stein , Yimin Zou , M Poo , Marc Tessier-Lavigne Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation Science (2001) doi: 10.1126/science.1059391 

Regarding a fraudulent Science paper with just two authors (the other one being MTL’s cheating protege Elke Stein), Stanford, when pushed, now declared that it was the journal or the publisher who faked the data:

“The University wrote that “The origin of the tiling and of the partial overlaps is unknown but may have occurred during transfer of images to the journal.””

On 29 November 2022, the elite university reluctantly announced to start an investigation. On 2 December 2022, Stanford Daily brought a follow -up that even more papers were found to be problematic, thanks to PubPeer commenters, especially Elisabeth Bik. Like this beautiful Cell paper by the Stanford’s President and his dear protege Elke Stein:

Kyonsoo Hong , Lindsay Hinck , Makoto Nishiyama , Mu-ming Poo , Marc Tessier-Lavigne , Elke Stein A Ligand-Gated Association between Cytoplasmic Domains of UNC5 and DCC Family Receptors Converts Netrin-Induced Growth Cone Attraction to Repulsion Cell (1999) doi: 10.1016/s0092-8674(00)80804-1

Now, Stein is truly a very special character. Having done such great science under MTL back at Howard Hughes Medical Institute, University of California San Francisco, she became associate professor at Yale, where it seems she must have quietly left around 10 years ago. Stein founded several businesses, like “Scientific Advising and Consulting” (est 2013, “Set up a research lab in Molecular Oncology at Stanford University“, “Felicitas-Gaia Foundation” (est 2008, “Bioethic and Outreach as well as Science Awareness“), and “Scientists against peer sabotage”, est 1990 and described on LinkedIn as:

“Scientist against peer sabotage and corruptive activities in biomedical research. The goal is to preserve research material, data and respect research accomplishments of Scientists (and their privacy) that are/ were funded by federal and private foundations or special donations.”

Eventually the failed entrepreneur Stein returned to Tessier-Lavigne and is recorded as “visiting faculty scholar” in Stanford, where she declares to have “Identified a Biomaker for Infantile Autism” and that “non-fat/ low-fat milk is good for you!“. She is also writing a book titled “How to make your child autistic” (“What parents and the Society need to do to prevent that their children become autistic.”) Her other research topics at Stanford are “Why is it bad to work in retail when being educated, white, single and female“, and

“Investigation of the causes that triggered the traumatic increase in autism spectrum disorders especially since implementation of ACA. Protecting the future of the next generation of Dickenson, Einstein, Michelangelo and Tesla.”

If you wonder why MTL was allowed to give this failed scientist a faculty job in Stanford, despite her being a paranoid loony and despite everyone knowing of her data fudging skills, well, if you do insist on asking, I can only widely speculate here that maybe, just maybe Elke and MTL are, or used to be, really, really close friends. Friends with certain kind of benefits even?

On 5 December 2022, Stanford Daily brought this scoop about the new Stanford investigation:

“Felix Baker, the only trustee who was appointed to the committee with a bioscience background, will no longer be a member of the committee. This comes after The Daily discovered that Baker’s investment firm, co-founded by him and his brother, maintains an $18 million stake in Denali Therapeutics, a biotechnology company co-founded by Tessier-Lavigne. Now serving on its board of directors and as a scientific advisor, Tessier-Lavigne maintains more than $50 million of stock in Denali.

Standard playbook of academia.
Don't want to confirm #misconduct by those in power?
Simple. Appoint his/her friends to "investigate the matter."https://t.co/SDfmqJaNka
🙏@tab_delete @MicrobiomDigest #AcademicTwitter #ConflictsofInterest pic.twitter.com/aXuYmoklOV

— Dr. Nancy Olivieri (@DrNancyOlivieri) December 5, 2022

On 6 December 2022, Stanford Daily informed that MTL issued a public statement:

“The statement, also released to the Tessier-Lavigne lab website, said that he is in communication with Science and Cell to “determine the appropriate next steps” about new concerns raised regarding the papers on which he is the lead author. Tessier-Lavigne added that, in the papers he co-authored, the “specific images that are being queried are from collaborators’ laboratories.”

However, Tessier-Lavigne wrote, “I want to be clear that I have never submitted a paper without firmly believing that the data were correct and accurately presented. I also want to be clear that I take responsibility for any concerns that arise with respect to any work with which I have been involved.””

Tessier-Lavigne’s PubPeer record now stands at almost 20 papers. Of course there will be no retractions, but everyone involved will want a shower after approving corrections for all that fraud. MTL will probably soon resign and leave Stanford and maybe even USA completely. Back to Canada? Into retirement?

But it is not MTL alone who is the problem. Look at this new discovery by Elisabeth Bik (and do note the second author!):

Yuru Liu , Elke Stein , Timothy Oliver , Yong Li , William J Brunken , Manuel Koch , Marc Tessier-Lavigne, Brigid L.M Hogan Novel Role for Netrins in Regulating Epithelial Behavior during Lung Branching Morphogenesis Current Biology (2004) doi: 10.1016/j.cub.2004.05.020 

I can’t even fathom why MTL’s protege Elke Stein (or whoever faked all this), with MTL smiling on. Maybe the images are stolen from someone else’s published papers and original labels had to be erased. In any case, this is massive fraud.

Guess how the last author reacted? Brigid Hogan, 79 year old retired professor at Duke University and Fellow of the Royal Society in UK, wrote this on PubPeer:

“I agree that the highlighted areas do appear to have some similarities. However, this must be by chance, reflecting in part the repetitive nature of the process of branching morphogenesis and the structure of the embryonic lung .[…] Importantly, there would have been no motivation whatsoever for us to deliberately duplicate the small regions highlighted since they do not affect the interpretation of the data.“

This denial of the obvious is just mind-boggling. Is Hogan suffering from old age dementia? Is she rather cunningly pulling our leg, and we don’t get her fine English humour? She is not replying to mine or anyone’s emails.

In any case, Hogan is covering up fraud. As MTL and his Stanford did and still do.

"had the research been conducted at SLAC I imagine we would already be processing MTL’s paperwork for dismissal for cause": criticism within University grows as committee investigating Stanford president hires lawyers. My latest @StanfordDaily:https://t.co/M3heRs6NSQ

— Theo Baker (@tab_delete) December 8, 2022

MTL is untenable now, even if Stanford predictably finds him innocent. Most likely he will resign soon and move somewhere far away. Maybe back to Canada. Maybe he will return to pharma industry (he used to be senior vice-president at Genentech). Most likely he will take Elke Stein with him. Maybe he will just retire and spend time playing golf or whatever it is rich people do.

Stanford previously elegantly got rid of a cheating scientist by sending him off to Oxford. Amato Giaccia (14 papers on PubPeer) can now produce crap cancer research in England, all possible because Stanford found absolutely no research misconduct in the phony cancer cures Giaccia published and monetised with his cheating then-postdoc Janine Erler (now professor in Denmark).

Tom Rando’s skeletons in the closet

Thomas Rando is a giant of stem cell and anti–aging research. In Stanford, he is listed as the founding director of the Muscular Dystrophy Association Clinic, director of The Glenn Laboratories for the Biology of Aging, deputy director of Stanford Center on Longevity, plus chief of neurology and of several other things. In 2021, Rando was appointed by University of California Los Angeles as director of the Broad Center of Regenerative Medicine and Stem Cell Research. Of course he also has his own start-up, Fountain Therapeutics, which is in anti-aging business, and he of course also sits on the boards of other anti-aging companies.

A press release by Fountain from October 2022 (about some Swiss award Rando just got) refers to the Stanford affiliations in past tense though, probably he is in the process of moving his lab from San Francisco to Los Angeles.

Hence quick, before Rando leaves, let’s give Stanford another project to investigate (hahah, they won’t) . Let’s start with a vintage Rando.

Now, one might protest, it’s an old paper, gel splicing was allowed back then! Well, the vertical splice between the 3rd and 4th lane is actually not really OK, even in 1999 this was deemed poor science. And the horizontal splice in the lanes 1 and 2 is nothing but outright fraud. Note this splice is very well hidden, quality work done in early version of Adobe Photoshop almost quarter a century ago.

But I have something even better by this member of Rando lab of many years, Marie-Helene Disatnik!

Marie-Hélène Disatnik , Stéphane C Boutet , Wilfred Pacio , Annie Y. Chan , Lindsey B. Ross , Christine H. Lee , Thomas A. Rando The bi-directional translocation of MARCKS between membrane and cytosol regulates integrin-mediated muscle cell spreading Journal of Cell Science (2004) doi: 10.1242/jcs.01309 

I guess because the second paper Disatnik et al 2022 was published in the same journal it is not a copyright infringement and hence OK, right? Does it matter that the earlier paper has its own fudged gel?

Marie-Hélène Disatnik , Stéphane C Boutet , Christine H. Lee , Daria Mochly-Rosen , Thomas A. Rando Sequential activation of individual PKC isozymes in integrin-mediated muscle cell spreading: a role for MARCKS in an integrin signaling pathway Journal of Cell Science (2002) doi: 10.1242/jcs.115.10.2151 

Another paper from Rando’s lab, again with Disatnik and more fake gels:

Stéphane C. Boutet , Marie-Hélène Disatnik , Lauren S. Chan , Kevin Iori , Thomas A. Rando Regulation of Pax3 by proteasomal degradation of monoubiquitinated protein in skeletal muscle progenitors Cell (2007) doi: 10.1016/j.cell.2007.05.044

Again with Disatnik (or Dziesietnik), who according to her LinkedIn profile retired as Senior Research Scientist in Stanford in 2016:

Gayle M. Smythe , Joshua C. Eby , Marie-Helene Disatnik , Thomas A. Rando A caveolin-3 mutant that causes limb girdle muscular dystrophy type 1C disrupts Src localization and activity and induces apoptosis in skeletal myotubes Journal of Cell Science (2003) doi: 10.1242/jcs.00806 

This kind of irregular gel splicing was never OK, figures like these are scientifically worthless, if not worse. I once blogged about it here:

20 years ago, Rando presented a cure for muscular dystrophy, with his patented method of gene therapy:

Carmen Bertoni , Catherine Lau , Thomas A Rando Restoration of dystrophin expression in mdx muscle cells by chimeraplast-mediated exon skipping Human Molecular Genetics (2003) doi: 10.1093/hmg/ddg133 

There is a reason why the data needed to be forged. This chimeraplast technology doesn’t work, as Science reported in 2002, a year before Rando’s paper was published (hattip to a PubPeer user):

“Most researchers who tried chimeraplasty failed from the beginning. Science spoke to researchers from over 30 laboratories that had tried the RDOs and failed to produce evidence that they could target and correct dysfunctional genes, either in vitro or in vivo. Researchers at biotech companies such as Epoch Biosciences, Isis Pharmaceuticals, Millennium Pharmaceuticals, and Lexicon Genetics all failed to get chimeraplasty to work in their labs. Experienced gene-targeting researchers at MIT’s Whitehead Institute, NIH (including in Blaese’s own laboratory), Maine’s Jackson Laboratory, and Sweden’s Karolinska Institute also saw no effects. Even members of Kimeragen’s own scientific advisory panel, such as Baylor’s John Wilson, tried it and failed. “Under our conditions,” Wilson says, “we found no correction above background.””

And as for the journal where that fraudulent paper was published: expect exactly zero action. The chief editor of Human Molecular Genetics, the Oxford professor and Dame Commander of the British Empire Kay Davies, is a science cheater herself (incidently also in the field of muscular dystrophy), and a dangerous bully who enjoys defending even the worst research fraudsters and ratting out whistleblowers:

The second author of that paper, Catherine Lau, became Professor of Clinical Medicine at UC San Francisco. The first author Carmen Bertoni now works as Scientific Review Officer at NIH, meaning, the person who published that massive forgery now evaluates your grant proposals and reports. She decides if your science is good or not. How does this make you feel?

Here another badly fudged gel by Bertoni, in same garbage journal edited by that toxic dame Davies:

Carmen Bertoni , Glenn E. Morris , Thomas A. Rando Strand bias in oligonucleotide-mediated dystrophin gene editing Human Molecular Genetics (2005) doi: 10.1093/hmg/ddi020

And another one:

Carmen Bertoni , Arjun Rustagi , Thomas A Rando Enhanced gene repair mediated by methyl-CpG-modified single-stranded oligonucleotides Nucleic acids research (2009) doi: 10.1093/nar/gkp757 

Rando is however famous not for his cures for muscular dystrophy, but for his young blood scam business, based on parabiosis experiments of suturing mice together. The idea is to produce preclinical science in order to get rich by rejuvenating rich old gits with the blood of young donors, or, even more patentable, with some magic factor from their young blood. Read here:

In 2021, the ASBMB magazine wrote about the young blood hype:

“First, a group led by Amy Wagers and Irv Weissman used parabiotic mice to track the fate and movement of blood stem cells. That research wasn’t focused on aging, but their method captured the imagination of two other Stanford scientists who studied longevity, Irina and Michael Conboy — a wife-and-husband duo working in the lab of Thomas Rando at the time. They learned the method from Wagers and went on to show that young blood could rejuvenate tissue-specific stem cells that had grown sluggish with age. By uniting the circulatory systems of young and old mice, the Conboys restored youthful molecular signatures in the aged animals and reactivated the regenerative capacity of various organs, including muscle and liver.”

Amy Wagers‘ is a huge story of research fraud on its own (read a quick take here), she is Harvard’s embarrassment now. But the Conboys, now at Berkeley, learned to splice gels in Rando’s lab, after all this gets you the right results!

Irina M. Conboy , Michael J. Conboy , Gayle M. Smythe , Thomas A. Rando Notch-mediated restoration of regenerative potential to aged muscle Science (2003) doi: 10.1126/science.1087573 

Speaking of blood rejuvenation: of course Rando is board member of Alkahest, a “young blood” start-up founded by his Swiss-born lab neighbour Tony Wyss-Coray, another Stanford bigwig who also published dodgy science (discussed here). Rando recruited Wyss-Coray to Stanford in 2002, and right away they started to suture mice together, applauded by all the science groupies, pardon expert journalists, like here in Guardian.

Congrats Tom Rando & @wysscoray @StanfordMed who showed old mice that exercise are better at repairing muscles than non-exercisers & that injecting blood from one to the other confers benefits via stem cell cyclin D1 💪@NatMetabolism #fitness #Longevity https://t.co/5Q1ei89Pbg

— David Sinclair (@davidasinclair) April 21, 2020

Let’s end with Rando’s collaborative paper:

Y Liu , M Adachi , S Zhao , M Hareyama , A C Koong , Dan Luo , T A Rando , K Imai , Y Shinomura Preventing oxidative stress: a new role for XBP1 Cell Death and Differentiation (2009) doi: 10.1038/cdd.2009.14 

Those are old papers of course, and the newer ones do not show any forged gels. But this doesn’t mean that the science in Rando’s lab (or Tessier-Lavigne’s, or Wyss-Coray’s, or Amati’s) got any more reliable. These people wouldn’t have made it to where they are if they weren’t cunning and creative in ways which are not necessarily scientific. Only newbies, backwards hillbillies, and utter idiots are still caught with Photoshopped figures in their recent papers these days. Like certain professors at Temple University.

Rando did not reply to my emails. I kind of understand, he is a kind of god, what does he care about the old stuff on PubPeer. But then again, also Stanford’s President Tessier-Lavigne didn’t give a toss, but eventually the old fraud caught up with him.

It’s time to pull off these grand white men of science off their pedestals. If you stop and think what they actually, purely objectively, achieved for science and medicine, what actual advances for knowledge, society and the patients their oh-so-celebrated biomedical research actually delivered… Well, they sure got rich and famous themselves, but otherwise?

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