The Crooks of CRUK

If you are a British cancer researcher, chances are you will be applying to the charity Cancer Research UK (CRUK) for funding. Here a tip how you can succeed getting that money British people donate to cancer research: be open about having published some fraud, and you will receive a conspirational nod.

Don’t believe me? The University of Manchester-based immunologist Silvia Bulfone-Paus receives CRUK funding despite past massive misconduct findings and forced resignation as institute director in Germany, after 13 retractions (read more here). More recently, CRUK announced to have no inclination whatsoever to investigate the accusations of bullying and research misconduct in the Manchester CRUK institute of Richard Marais.

CRUK Chief Scientist Karen Vousden never replied to the cries for help posted as comments under my article, but as I demonstrate below, she has good reasons to be disinterested in this affair. Both Vousden and Marais are mentees of the late Chris Marshall, a legend of British cancer research. Marshall’s lab was at ICR London; this CRUK-funded cancer research centre has its own issues with research integrity and bullying, but what with ICR’s past and present leadership (Alan Ashworth and Paul Workman) being part of the problem, you can’t expect much.

Richard Marais: “Feel the power”

Regarding the Marais affair in Manchester (a deleted press release, overruled misconduct findings and cancelled retractions, all because the accused former Marais postdoc Romina Girotti lawyered-up), complaints like this were posted in the comment section on my site:

“I had the misfortune to work with Richard Marais who has literally made my life hell. He was insecure in the extreme, to the point that anyone who managed to do their job well, who had friends in work or generally just got on with people, became the subject of his vitriol. […] I was denigrated and humiliated constantly, when eventually, I made a bullying/harassment case to HR. My story was swept under the carpet because he was the director of the Institute“.

Or this comment:

“for so many years, we have been cordial to a man who used every chance to humiliate us in public and to block our careers. We are and we were ashamed to describe the details of what we witnessed and tried hard to forget. When so many former Marais alumni posted in this blog what Richard Marais has done to them, we had to confront our cowardice. As others, we felt that nobody would care about our pain and suffer, likely as an effect of the many times we were told, especially by Richard, that we were nobody.”

Richard Marais always happy to see himself #FaceOff @CRUK_MI #AACR19 pic.twitter.com/hcLcRwzdnb

— Science and Innovation at Cancer Research UK (@CRUKresearch) April 1, 2019

Here a comment from a clinician:

“Richard Marais can push his lab members to suffer whatever is necessary to make his own way. Richard Marais can ask his postdocs to sit on his chair “to feel the power”. Richard Marais can call his postdocs “bodies” (on their back) because they are only occupying space in his lab and “not producing”. […] Richard Marais’ hate towards clinicians is ridiculous and he enjoys making their life miserable in his lab“.

Marais really does not sound like a nice person:

“Marais has made a career out of bullying his trainees, establishing fear as a policy in his lab, making students and postdocs cry and humiliating them. He used to brag about it and nobody dared to stop him. Human resources staff were accomplices of it. He also bragged about his expensive life and frequent first class flights and felt good by asking British Airways staff “do you know who I am?”. Truly pathetic. He enjoyed having tearful students presenting 2h-straight presentations at lab retreats with their voice broken. As a ‘good bye’ from his lab people were given the last instruction: you cannot work in melanoma and your ideas belong to me. “

How exactly is it good for science to usurp a research field as you own private fiefdom and to ban others from working on melanoma? How exactly is this beneficial for patients and their families, whose charity funds Marais’ research and his gigantic salary? Yet this suppression of science is apparently exactly what Marais is free to do:

“He pushes junior PIs to not do research projects that might have competing interests with his lab. A former CRUK MI PI was asked to change his research focus to lung cancer and stop any melanoma work because it was competing with him.”

Bullying and research misconduct often go hand in hand. How else do you sanction lab members who refuse to produce the results you want to see as PI? Marais was described as “a total bully which let his postdocs to fight like gladiators to publish first (likely at the cost of quality)”.

In this regard, see this CRUK insider comment, about Marais and his CRUK Manchester colleague (and ex-wife) Caroline Springer:

“Caroline Springer selectively deletes data she does not like at lab meetings. Richard Marais approves this. Staff members can’t argue against her decisions. […] Filing a complaint puts our job in jeopardy. Caroline also runs her lab in a suspicious manner, hiding information for a part of her group and viceversa. She selects the experiments she wants to present in papers and meetings at Wellcome Trust and hides how many negatives there were. This has been ongoing for several years.”

One unrelated commenter said something similar:

“I’ve sat at their joint Springer/Marais lab meetings thinking they are the worst scientists I’ve ever met. Not only they cherry pick the data they want, they force their staff to “decrease” the IC50 of a shitty LOX compounds orders of magnitude within a week time so they can reach their ‘milestones’ for Wellcome Trust. As if you could do magic. No research integrity at all.“

Seeing Prof Caroline Springer, from our @ddu_crukmi, at the #CRUKWoI event made us feel very proud! The Women of Influence initiative is a great way to encourage more #WomenInSTEM. Thanks to all these amazing #WomeninScience for being part of it! We want to see more of this! https://t.co/4T2lUeKv0h

— CRUK Manchester Institute (@CRUK_MI) July 4, 2019

This criticism by former lab member goes into a different direction:

“Neither Richard Marais nor Caroline Springer have truly supported women in science. Quite the opposite, they have both banned them from working in similar research fields. It is ironic that Richard is an invited speaker of Women in Science Conferences“.

The Athena SWAN (Scientific Women’s Academic Network) award is just an undeserved trophy for Marais, as other CRUK Manchester commenter confirms and adds:

“His post docs get yelled at routinely, they cry in the bathroom, they are afraid to speak of truth and live in fear of Richard’s fury.
The fact is, CRUK MI has lost too many good staff since Richard took the directorship. I have had conversations with the leavers where they confessed that they can not work for such a director anymore without self loathing. […] Occasionally, people were brave enough to make official complains regarding Richard’s bullying […], but HR (directly managed by Richard) never responded.”

It gets worse:

“I have witnessed terrible scenes: women crying because of their public humiliation in front of their lab mates, Richard Marais enjoying seeing them crying while thinking they are weak. Those were tears of frustration and impotence. […] While Lab meetings were bad, private meetings could be worse because there were no witnesses. […] Fear has fueled our silence. Fear to lose our jobs, to be excluded from conferences, to not publish again, to not get funding for our research. […]
Note: Take this description and multiply by 3, that is the accurate description of Caroline Springer“.

There are more comments, in same vein: bullying, harassment, lab members reduced to tears, alumni banned from working on melanoma, unreliable preclinical and clinical research. CRUK informed me that they forwarded the issue to University of Manchester, obviously on assumption that the university will continue doing the same as they did before: nothing. Maybe this comment will with time grow into something which will make the crooks of CRUK stop and think:

“I am writing as someone who has raised over £5,000 for Cancer Research UK in sponsored runs in the last 10 years. I lost my wife to breast cancer in 2014. Another fundraiser passed on the link to your blog to me. I am deeply upset about these accusations against the professors in Manchester. If any of them are true I feel very betrayed.”

Another CRUK fundraiser demanded their £10k back: “I’ll give it to somewhere deserving“.

Karen Vousden: lifelong learning of data integrity

As it is common with the rotten fishes, they stink from the head down. Marais is one example, but let’s move one floor higher, to the top executive offices. Meet the official Chief Scientist of CRUK, Karen Vousden, internationally influential p53-oncosuppressor protein researcher, formerly director of the CRUK Beatson Institute in Glasgow and now at The Crick in London, and her exciting PubPeer record.

Professor Karen Vousden became our chief scientist in 2016, after a 30-year career at the forefront of cancer research. She’s oversees our scientific research programme: https://t.co/QT6Thbqwgx #WomeninScience pic.twitter.com/A8liYIhUtB

— Cancer Research UK (@CR_UK) February 11, 2018

The PubPeer evidence is rather old, but being a busy scientist and CRUK exec, Professor Vousden has yet to find time to address the concerns. Let us start with this vintage p53 paper from the Vousden lab.

M Ashcroft, MHG Kubbutat, KH Vousden Regulation of p53 function and stability by phosphorylation Molecular and Cellular Biology (1999) doi: 10.1128/mcb.19.3.1751 

All three lane pairs are same, as background pattern makes evident. That assay and the entire paper should have been disposed as radioactive waste, yet it was never even corrected.

The first author Margaret Ashcroft is now professor in Cambridge. Many Vousden lab alumni moved on to become today’s science elites. In the greater scheme of things, what do some fabricated gels matter?

p53 induces cell cycle arrest via protein p21, and this of course was studied by the Vousden lab in detail. Another vintage classic:

S Bates, KM Ryan, AC Phillips, KH Vousden Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression Oncogene (1998) doi: 10.1038/sj.onc.1202104 

Apparently, some flow cytometry files got accidentally duplicated. Yet the green/blue labelled ones are not identical. They seem to derive from the same FACS measurement file, but re-gated. Something unlikely to happen by a mistake of oversight, indeed such manipulations are much present in the papers of the unashamed data manipulator Giorgio Zauli.

The evidence is 3 years old, nothing has happened since. Worth noting that the first author and former Vousden mentee Stewart Bates became a senior executive scientist at GlaxoSmithKline. A similar thing happened in another Vousden paper, with Bates as coauthor:

AC Phillips, S Bates, KM Ryan, K Helin, KH Vousden Induction of DNA synthesis and apoptosis are separable functions of E2F-1 Genes & Development (1997) doi: 10.1101/gad.11.14.1853 

Also here same flow cytometry sample was apprently re-gated by software, and wham, one experimental sample became two utterly different ones. It is worth mentioning who another coauthor on that Vousden lab is: Kristian Helin, then at IEO in Milan, where he published a number of papers now discussed on PubPeer. You can read about Helin’s stellar and more recently less stellar career in cancer research here. You know, birds of a feather flock together.

In this vein, Vousden demonstrated her attitude to gel splicing and loading controls in this paper contributed with the US star cancer researcher Arnold Levine (who also doesn’t care much how his papers get made):

MH Kubbutat, RL Ludwig, AJ Levine, KH Vousden Analysis of the degradation function of Mdm2 Cell growth & differentiation: AACR (1999) Vol. 10, 87-92

The last lanes on the Mdm and p53 gels is spliced on. But there is no splicing on the loading control GFP. That last lane is very important, it namely shows that for that last sample (a certain deletion mutant Mdm protein), highlighted bands are much weaker or much stronger than with the wildtype or other mutants. But how do we know if that last sample is unadulterated, since it is spliced on and the loading control comes from a separate gel?

There are other examples of problematic gel splicing in Vousden papers, eg this Blagosklonny et al Carcinogenesis 2001. The practice was never actually accepted, after all this is exactly why good scientists load their samples on same gel, and check that same gel for equal loading: to be able to compare the signals properly. But some scientists already already “know” the result, you know.

Another star US collaborator one should have been careful with is Pier Paolo Pandolfi (here his PubPeer record).

R Bernardi, PP Scaglioni, S Bergmann, HF Horn, KH Vousden, PP Pandolfi PML regulates p53 stability by sequestering Mdm2 to the nucleolus Nature cell biology (2004) doi: 10.1038/ncb1147

An accident? Can one really confuse PML protein image with that of p53, and then crop it? In this case, Vousden is the p53 expert, the experiment might have been made in her Beatson lab.

Just when Vousden was moving from Glasgow to The Crick in London, she published this paper with her Beatson Institute colleagues:

P Lee, AK Hock, KH Vousden, EC Cheung p53- and p73-independent activation of TIGAR expression in vivo Cell Death and Disease (2015) doi: 10.1038/cddis.2015.205 

The last three bands of the TIGAR and CDK4 gels share many common features and artefacts to manifest the suspicion that they show the same signal. It is not clear if they are different film exposures of same western blot, or digitally processed duplications. In any case, it is not clear how that could have happened by chance or mistake.

Maybe Vousden is just unlucky with who she works with. In 1989, she published a paper in The Lancet, which was immediately retracted by her two coauthors John Tidy and Paul Farrell, for being irreproducible. However, Vousden’s name is not on the retraction notice, she just stayed out of it:

Now one could think: well, the sins of youth. The Vousden lab surely matured and does only the bestest and the most reliable of sciences now. Although it does seem Professor Vousden still has very little understanding of the concept of data integrity. This paper Labuschagne et al Cell Metabolism 2019 was published just 2 months ago:

A PubPeer commenter Plukenetia Lehmanniana jumped to Vousden’s defence:

“Would it be nice to also see the Ponceau staining? Certainly. Is there any reason to believe that this is anything other than a well-done experiment? In my opinion, no. “

My reply “no reason at all” with a hyperlink to Vousden’s PubPeer record did not pass moderation. It is namely unscientific and slanderous.

– absence of scientific content (e.g. "Life is so special you can never understand how it works")
– absence of supporting information (e.g. marked-up image when image manipulation is suggested); help the reader
– compression artefacts are not accepted

— PubPeer (@PubPeer) August 18, 2019

Now here is an idea: maybe certain CRUK top scientists would be more useful volunteering in CRUK charity shops?

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