The Catholic University Leuven in Belgium is a haunted place. It is haunted not by a ghost, not by a vampire, but by a Zombie Scientist: Catherine Verfaillie, director of the Stem Cell Institute (SCIL) at the KU Leuven. Verfaillie’s infamous discovery was that of the alleged pluripotency of bone marrow cells, for which she was celebrated by everyone including the Catholic Church. Adult stem cells in the blood can create every tissue, exactly like the ethically problematic embryonic stem cells. The clinical potential for lab-grown organs was immediately obvious. Verfaillie became a star, Nobel Prize was all but sure. Now it’s time for exorcism, with the help of non other but Elisabeth Bik.
Even if her findings were debunked right after they appeared in Nature in 2002, the damage is still continuing. Clinical researchers used Verfaillie’s “discovery” as basis to test outrageously brain-dead and dangerous regenerative medicine ideas, where bone marrow cells are extracted form the patient and deployed to repair or even create organs. In particular, the surgeons Paolo Macchiarini and Martin Birchall applied bone marrow “stem cell” woo to test lab-grown tracheas on over 20 human guinea pigs. Almost every one of these patients died, but the experiments continue.
Verfaillie was even put on a stamp in her home county, so every Belgian had the opportunity to lick her behind. Despite the many data manipulations and the fact that her research was debunked long ago, Verfaillie was never found guilty of any research misconduct by her former employer, the University of Minnesota in USA. In fact, it seems Macchiarini’s & Birchall’s pioneering trachea transplant in 2008 might have saved her career: it namely proved that even if Verfaillie’s discovery of bone marrow pluripotency was based of falsified data, it was scientifically perfectly sound! Look, a whole trachea was grown in a lab to save the life of a young woman, just when Verfaillie was investigated for research misconduct. Only that that trachea transplant was the first big lie in a long string of lies, which left many patients dead. And there were and still are also many other bone marrow regmed enthusiasts, with their own countless victims. This carnage is the legacy of Verfaillie’s dishonest preclinical research.
She is still being paraded as Belgium’s greatest scientist and showered in funding cash: after the initial €5mn grant in 2011, Verfaillie became in 2015 project head of a €10 mn Consortium “Hepatic Microfluidic Bioreactor”, funded by the EU Commission, making artificial livers. In 2016, Verfaillie was part of the team awarded with €11.5 mn by EU to study Zika virus. Apparently, Verfaillie’s Photoshop skills are needed there. And in summer 2019, Verfaillie and her SCIL got €2.9 mn from Flanders Innovation and Entrepreneurship to collaboratate with a pharma company in designing therapies for myelin-related neurological diseases. There is truly nothing Photoshop cannot cure.
“Creating a windpipe out of the blue is certainly a major event,” says Verfaillie on the phone. “The evolution has been going fast in recent years. Techniques have been developed to make tissues by implanting stem cells on all kinds of constructs. But the effective applications are still rare. Apart from the windpipe and the bladder [reference to Anthony Atala’s bizarre experiment, -LS], which are both simple organs, I don’t see much coming yet. ”
The article went on to describe Verfaillie’s own stem cell research where she aimed to use her freshly awarded EU grant to treat “patients with gangrene in the lower leg”.
Just this year, in spring 2019, Verfaillie was recruited by the Belgian MEP Petra De Sutter (gynaecologist and stem cell enthusiast) as a list candidate for European Greens to the EU Parliament. On that occasion, the Belgian newspaper De Morgen celebrated again Verfaillie’s discovery of pluripotent bone marrow cells and declared:
“Verfaillie’s work was the basis of hundreds of publications and a Nobel Prize.”
Also this was not meant ironically – Verfaillie’s programme for the EU is research integrity, as she herself explained on De Sutter’s website:
“Only if there is room for independent research, with integrity and quality going hand in hand. Biomedical research funded by European public funds must serve the public interest in the first place“.
Incidentally, the biggest critic of Macchiarini’s and Birchall’s stem cell experiments was another KU Leuven professor: the surgeon Pierre Delaere, but he doesn’t get the publicity his genius colleague Verfaillie enjoys. KU Leuven eventually had Delaere silenced, maybe they wanted to divert attention from their own role in making the Macchiarini disaster possible.
Instead of fixing what they started, KU Leuven prefers to hold image integrity events (like this one on 12 December 2019), where Verfaillie most definitely never be mentioned. As my distant, unsolicited and unwelcome contribution, I asked the famous image Integrity sleuth Elisabeth Bik to have a look at Verfaillie’s papers. Bik kindly agreed, below are some of her discoveries, more is on Pubpeer.
This was the disastrous Nature paper which set in motion the deadly bone marrow quackery worldwide:
Y Jiang, BN Jahagirdar, RL Reinhardt, RE Schwartz, CD Keene, XR Ortiz-Gonzalez, M Reyes, T Lenvik, T Lund, M Blackstad, Ji Du, S Aldrich, A Lisberg, WC Low, DA Largaespada, CM Verfaillie Pluripotency of mesenchymal stem cells derived from adult marrow Nature (2002) – doi: 10.1038/nature00870
“In summary the following errors were found and corrected:
- In Figure 1b, the IgG isotype control tracings for several of the plots (n=5) differ by 1 log in fluorescence intensity; a new version of Figure 1b are provided but for a different set of MAPC cells
- in the original Fig. 1b, the plot for MHC I was a duplication of the FACS plot for Mac-1
- In the legend to Fig. 1b, the superscripts ‘k’ in MHC II (I-Ak) and MHC I (H- 2Kk) should be ‘b’.
- In the Methods under ‘Differentiation culture and analysis’, the concentration of 109 M dexamethasone should be 0.05 mM.
- In the Supplementary Information, the sequence of the primers rex-1 and oct-4 were incorrect; correct sequences are provided.
However, what the Correction does not address is that six of the panels in Figures 1b and S1b from this Nature paper are also shown in a second paper by the same group, i.e. Yuehua Jiang et al. Experimental Hematology 30 (2002) 896–904, DOI: 10.1016/s0301-472x(02)00869-x. See: https://pubpeer.com/publications/9F0F20DFB792B0606731DB6E20C3CE Although this Nature paper was published before the Exp Hem paper, the Exp Hem manuscript was submitted and accepted earlier than the Nature paper.
The six panels duplicated between the two papers represent different MAPC cell lines, as can be learned from the Erratum belonging to the Exp Hematology paper, found at: https://www.exphem.org/article/S0301-472X(06)00305-5/abstract. “
And then Bik found another new problem, somehow ignored in that mega-corrected Nature paper. It is the same image, but showing different mice (control vs chimeric) and different antibody stainings, with the green signal removed in one case. In order to produce some result Verfaillie needed to prove her ground-breaking discovery:
Also Figure 6m shows traces of Photoshop manipulation: the repetitive patterns suggest an undesired feature was retouched:
That 2002 Nature opus was suspicious from the very beginning. Nobody could reproduce Verfaillie’s results, while she prevented her peers from accessing the allegedly pluripotent bone cells which only her lab was able to extract from mice.
Maybe that Nature paper should be retracted after all? Especially considering how much damage it still keeps doing? Or will Verfaillie and Macchiarini eventually share a joint Nobel Prize?
In March 2009, Verfaillie had the following infamous retraction, initiated by the University of Minnesota in October 2008. This 2001 Blood paper was the precursor to Nature‘s pluripotency claims and served to establish bone marrow cells as a magic source to grow all organs.
M Reyes, T Lund, T Lenvik, D Aguiar, L Koodie, CM Verfaillie Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells Blood (2001) doi: 10.1182/blood.v98.9.2615
The retraction notice was unspecific, just saying:
“Based upon the conclusions of the investigation by the University of Minnesota and Blood, the paper was found to contain duplications and other irregularities in multiple figures.”
“Lead author Catherine Verfaillie, now director of the Stem Cell Institute at the Catholic University of Leuven in Belgium, was cleared of academic misconduct but blamed for insufficient oversight. That suggests the blame rests with the only other scientist under investigation, Verfaillie’s graduate student Morayma Reyes, now at the University of Washington. However, the findings regarding Reyes cannot be released because of privacy laws. Reyes says that she made “honest unintentional errors”.
Verfaillie again fingered Reyes, even for the papers where Reyes was not coauthor, and declared herself a victim:
“The University indeed concluded that another individual working in my lab committed academic misconduct by improperly manipulating western blots in the Blood paper. Although the University Panel did not conclude that the conclusions of the paper are invalid, it has requested that the Blood paper be retracted.
The University concluded that allegations against me personally were not substantiated, and that I was not responsible for the alleged manipulations. Nevertheless, I am extremely sorry about this, as I was the senior author on the paper and did not notice the problems with these figures. The University’s statement also concluded that I did not provide sufficient oversight and mentoring. I do not agree with the University’s conclusion with regard to the question of oversight and mentoring.
I am committed to honesty in the pursuit of science. The methods that were followed in my lab at the time of the research in question were, and still are, common practice in the scientific community.”
Verfaillie is actually right. Data forgery is indeed common practice in the scientific community, and this was exactly what many regenerative medicine researchers do, while building on Verfaillie’s work.
Faced with a cryptic retraction notice, Bik performed a “Post mortem analysis” of that Blood paper, and found fake western blots and some Flaw Cytometry:
Another Verfaillie paper was retracted in same year 2009, there is no Reyes on it:
J Lin, Feng, Y Hamajima, M Komori, TC Burns, S Fukudome, J Anderson, D Wang , CM Verfaillie, WC Low Directed differentiation of mouse cochlear neural progenitors in vitro AJP Cell Physiology (2009) doi: 10.1152/ajpcell.00324.2008
The notice went:
“This article has been retracted by APS on the grounds that aspects of the data presented have now been shown to be unreliable.”
As Bik discovered, something was very, very wrong with Figure 3B. Who was responsible for that sickening parade of copy-pasted bands? Surely not the Belgian genius scientist Verfaillie? I mean, they just tried to use stem cell technology to cure deafness, and surely the Photoshop means justify the goal, right?
Bik also analysed this 2002 paper by Verfaillie, corrected in November 2008 for some unspecified errors with certain figures. The University of Minnesota decided there was definitely no research misconduct there, just some “problematic images”. The paper claimed to have discovered that bone marrow cells can generate vascular endothelium, a scientifically very shaky claim which had to be substantiated by some Flaw Cytometry:
M Reyes, A Dudek, B Jahagirdar, L Koodie, PH Marker, CM Verfaillie Origin of endothelial progenitors in human postnatal bone marrow Journal of Clinical Investigation (2002) doi: 10.1172/jci200214327
Another two corrections of a figure shared between two papers were explained by Bik here:
Y. Jiang , R. C. H. Zhao, C. M. Verfaillie Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity Proceedings of the National Academy of Sciences (2000) – doi: 10.1073/pnas.190104497
That paper was corrected in April 2009, where the authors declared to have “inadvertently inserted the Western blot from a different experiment (Western blot for Cdk2, following immunoprecipitation of Cdk2 from a different experiment), instead of the correct Western blot for Cdk4, following immunoprecipitation of Cdk4 for the study described in Fig. 3“
Y Jiang, F Prosper, CM Verfaillie Opposing effects of engagement of integrins and stimulation of cytokine receptors on cell cycle progression of normal human hematopoietic progenitors Blood (2000) doi: 10.1182/blood.v95.3.846.003k31_846_854
It turned out that neither the cdk4 blot in PNAS not cdk2 blot in Blood ever existed as presented. The authors provided replacement for both, and were made to clearly indicate previously underhand gel splicing:
“a validated Cdk2-IP/WB gel was located and has now been used to replace the row in question. In addition, black lines have been added to the row showing the IP + WB for cyclin E and the row showing the kinase assay, per Blood’s current policies, to indicate that blank lanes were spliced out. The authors removed the quantification under the lanes and revised the figure legend…”
The PNAS paper contained another issue, which was reported by some whistleblower(s) to New Scientist, but which evaded correction. Bik highlights it now on PubPeer, with “blue boxes marking similarity between de Cdk2 panel in Figure 5A and the p27KIP panel, if one of the two panels is rotated 180 degrees and stretched a bit“.
It was very wise of University of Minnesota not to have screened Verfaillie’s papers properly (presumably they just acted on the concrete evidence of a long-sacked whistleblower). This is namely the kind of science with which Verfaillie’s career as director of the Stem Cell Institute at University of Minnesota took off:
R C Zhao, R S McIvor, J D Griffin, C M Verfaillie Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors methotrexate-resistant and CML progenitors functionally normal and nontumorigenic in vivo Blood (1997) 15;90(12):4687-98
Would you like to know how Minnesota professor Verfaillie announced to cure leukaemia? Hold on to your seat.
This is a truly some cock-sure handiwork of data forgery, a wanton debauchery of gel band cloning, probably done with scissors and glue, years before Photoshop became the standard tool. If only Verfaillie’s science was exposed back then, over 20 years ago – that disastrous Nature paper would not have happened.
The following flow cytometry duplication does not seem like an innocent mistake of oversight anymore:
V Roy, CM Verfaillie Expression and function of cell adhesion molecules on fetal liver, cord blood and bone marrow hematopoietic progenitors: implications for anatomical localization and developmental stage specific regulation of hematopoiesis Experimental Hematology (1999) -doi: 10.1016/s0301-472x(98)00031-9
The next case does not look like a mistake at all. Even if once might accidentally reuse a flow cytometry plot, how can one accidentally calculate slightly different numbers from it? Unless, that was done intentionally, to make the two plots look different:
CED Lamming, L Augustin, M Blackstad, TC Lund, RP Hebbel, CM Verfaillie Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis Journal of Clinical Investigation (2003)
Update 6.12.2019. Bik now found another Verfaillie coauthored paper with serious issues. This time, the authors appealed to kidney failure patients on dialysis: a regenerative medicine cure is possible, with just a little bit of Photoshop.
S Gupta, C Verfaillie, D Chmielewski, Y Kim, ME Rosenberg A role for extrarenal cells in the regeneration following acute renal failure Kidney international (2002) doi: 10.1111/j.1523-1755.2002.kid569.x
The Verfaillie scandal exploded in around mid 2000s, it included misconduct investigations by University of Minnesota, and ended with two retractions and some embarrassing corrections. In the middle of that, Verfaillie moved back to Belgium in 2005. By 2010, everyone moved on, the scientific community forgave Verfaillie and showered her and her SCIL with public funding. But the shenanigans continued, as Bik now uncovered.
MB Sahin, RE Schwartz, SM Buckley, Y Heremans, L Chase, WS Hu, CM Verfaillie Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver Liver Transplantation (2008) doi: 10.1002/lt.21380
Maybe the rat liver was “unmanipulated”, but the data in this paper is a different story. It definitely does not look like an accident or mistake of oversight. Same field of cells was rotated and cropped in two different ways to stand in for two different antibody stainings. And it happened already at KU Leuven, after the scandal in Minnesota.
This collaborative paper was also made with Verfaillie’s KU Leuven affiliation:
M Luo, Z Liu, H Hao, T Lu, M Chen, M Lei, CM Verfaillie, Z Liu High glucose facilitates cell cycle arrest of rat bone marrow multipotent adult progenitor cells through transforming growth factor-β1 and extracellular signal-regulated kinase 1/2 signalling without changing Oct4 expression Clinical and Experimental Pharmacology and Physiology (2012) doi: 10.1111/j.1440-1681.2012.05747.x
There are even worse collaborative Photoshop jobs, with Verfaillie’s name on them: Kwan et al 2006, Lu et al 2010, or this Verfaillie co-production with the Radboud University Nijmegen Medical Centre in Netherlands, Huls et al 2010:
Actually that Photoshop art is too fancy for Verfaillie’s lab. Her KU Leuven lab issued in 2013 this simple and traditional image fabrication, the good old shifted picture motif:
Y Li, K Eggermont, V Vanslembrouck, CM Verfaillie NKX2-1 activation by SMAD2 signaling after definitive endoderm differentiation in human embryonic stem cell Stem Cells and Development (2013) doi: 10.1089/scd.2012.0620
The most recent Verfaillie paper Bik reported on PubPeer is this, from 2014. So far, “just” one cloned gel band.
K Vanuytsel, Q Cai, N Nair, S Khurana, S Shetty, JR Vermeesch, L Ordovas, CM Verfaillie FANCA knockout in human embryonic stem cells causes a severe growth disadvantage Stem Cell Research (2014) doi: 10.1016/j.scr.2014.07.005
Verfaillie is 62 now, presumably KU Leuven would like her to retire in piece soon, and close the chapter. But of course Verfaillie will not leave her SCIL institute to some Tom, Dick or Harry when she retires. She namely installed Maurillo Sampaolesi as her second-in-command at SCIL. And Sampaolesi has extensive Photoshop experience, as his PubPeer record certifies. Look at this for example, Cassano et al PLOS One 2008, published by Sampaolesi’s new lab at SCIL:
This is why Sampaolesi is the perfect successor for Verfaillie: he published in all the big journals, with the help of some Photoshop. The example of the disassembled Figure 2B in Sampaolesi et al Science 2003 shows his skills:
The elite journal Science did exactly nothing about that, not a thing. In a different case, the Journal of Cellular Biology accepted a forged correction from Sampaolesi and Cossu, for Galvez et al 2006. Look at the PubPeer discussion, and the illustration on the right.
Would you like to know why the journals behaved so meekly? Sampaolesi’s mentor and last author Giulio Cossu was namely investigated and whitewashed by his then-employer UCL in 2013, including for this paper. Cossu paid back his gratitude by lead-authoring in 2017 a white paper in The Lancet, where he, together with the UCL trachea transplanters Martin Birchall and Paolo De Coppi declared that Macchiarini’s technology works while calling for more human experimenting.
Full circle for the magic bone marrow of Catherine Verfaillie.
The article was updated on 6.12.2019
A reader pointed me to these papers:
M Delforge , MA. Boogaerts , PB. McGlave , CM. Verfaillie BCR/ABL− CD34+HLA-DR−Progenitor Cells in Early Chronic Phase, But Not in More Advanced Phases, of Chronic Myelogenous Leukemia Are Polyclonal Blood (1999) doi: 10.1182/blood.v93.1.284
In another case, it seems the publisher BioMedCentral (BMC, owned by Springer Nature) issued a silent correction:
F Ulloa-Montoya , BL Kidder , KA Pauwelyn , G Chase , A Luttun , A Crabbe , M Geraerts , AA Sharov , Y Piao , MSH Ko , WS Hu , CM Verfaillie Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity Genome Biology (2007) doi: 10.1186/gb-2007-8-8-r163
The duplication is clearly present in the version initially deposited by the publisher BMC at NCBI PMC (PubMed). However, the online version at BMC itself shows a different plot for the sample mClone-3 CD44. No correction was announced.
Meanwhile, KU Leuven opened a misconduct investigation into Verfaillie affair. The research integrity manager Inge Lerouge offered to keep me updated, provided I sign a legally binding Non-Disclosure Agreement (NDA) which would prevent me from reporting, sharing or discussing any of that information for all eternity. Lerouge explained:
“both the respondent and the notifying party are subject to strict confidentiality and this obligation remains applicable after the closure of the entire CRI procedure and even after eventual public statements by the KU Leuven about it (see sub 4).
- The possibility exists that the Rector (or his delegate) decides to make a public statement, he being, according to article 9 of the CRI Procedure, the only person responsible for external communication about CRI cases. Although we cannot at this stage predict the future nor guarantee that such public statements will be made, we can agree that, if they are, you will be duly alerted. The information included in public statements by the Rector is by its nature not covered by confidentiality obligations.“
I refused to sign the NDA, since it would allow KU Leuven to control my reporting with legal threats.
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