The wizard men curing breast cancer

The US American charity Breast Cancer Research Foundation (BCRF) proudly lists its heroes, with profile pictures:

“We fund the best and brightest researchers in the world. Our nearly 275 grantees come from all disciplines of science and are given the creativity and intellectual freedom to pursue the most promising research. Each has an ultimate goal: to prevent and find a cure for breast cancer. Get to know our gamechangers.”

The pseudonymous image integrity sleuth Clare Francis specialises since many years on finding data manipualtion in cancer research, and now suggested I write about some of the scientists funded by BCRF. I think it is a good idea to honour these wizards of the Photoshop, the wise men whose cancer research brought them tremendous fame, money and power. But what did it objectively bring to cancer patients, like the many women suffering and dying of breast cancer? Will h-index and impact factor ever be truly able help them, or can we maybe place higher quality expectations on biomedical research?

Stuart Aaronson

At the BCRF website, the faces of the genius minds who help women suffering from breast cancer are arranged alphabetically. This is why it starts with Stuart Aaronson, founding chair and professor at Icahn Medical School at Mount Sinai, New York, which is hopefully not meant as a fair warning how exactly BCRF wishes to see breast cancer being treated: with Photoshop.

Aaronson namely has 20 papers flagged on PubPeer, of which 3 have been retracted, and 2 more received an expression of concern (see here). All co-authored with his protege, the Harvard professor and animal abuser Sam W Lee, who in turn boasts in total 5 retractions. Now you might say: Aaronson is just a victim of Lee’s naughtiness here? This paper from Aaronson lab for example has no Lee on it:

SK Mungamuri , RF Qiao , S Yao , JJ Manfredi , W Gu , SA Aaronson USP7 Enforces Heterochromatinization of p53 Target Promoters by Protecting SUV39H1 from MDM2-Mediated Degradation Cell Reports (2016) – doi: 10.1016/j.celrep.2016.02.049

It looks as if someone was cloning gel bands here, but Professor Aaronson was so busy curing cancer that he until now had no time to have a look at these 3 year old PubPeer concerns. Including this one:

A Bafico, G Liu , L Goldin , V Harris , SA Aaronson An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells Cancer Cell (2004) doi: 10.1016/j.ccr.2004.09.032 

Someone did not like the RT-PCR results in Figure 1B, and replaced the Wnt-6 signal with patches of empty background. Does Cancer Cell care? Are you serious? They love such stuff.

For his attitude to research integrity, Aaronson was awarded with “the Distinguished Service Medal from the U.S. Public Health Service, the AACR Award for Outstanding Achievement in Cancer Research, and the Paul Erhlich [sic!] Prize from Germany.”

Michael Andreeff

Next in this list and still under letter A is Michael Andreeff, a German-born professor at MD Anderson at Houston, Texas. Andreeff has 27 papers on PubPeer, but that is nothing special for an MD Anderson cancer researcher. The clinical institution seems to actively encourage data manipulation and readily takes measures against whistleblowers, in order to make even more money with impactful cancer research while avoiding scaring off mistrustful patients.

Andreeff’s papers are prone to duplications, but also this scientist is too busy curing cancer to bother. Like this here:

BZ Carter , M Milella , DC Altieri , M Andreeff Cytokine-regulated expression of survivin in myeloid leukemia Blood (2001) doi: 10.1182/blood.v97.9.2784

Loading controls are so unimportant that it is actually the due right of every important scientist to play with them in Photoshop. They are the doodle area of a paper, since apparently nobody minds what the scientists draw there. Certainly not the journal Blood, they don’t mind anything at all. Many of Andreeff’s PubPeer criticised papers were coauthored by another MD Anderson cancer wizard, Marina Konopleva. She is probably just as not responsible for the content of her papers as Andreeff is. Like this here:

X Ling , E Spaeth , Y Chen , Y Shi , W Zhang , W Schober , N Hail , M Konopleva , M Andreef The CXCR4 antagonist AMD3465 regulates oncogenic signaling and invasiveness in vitro and prevents breast cancer growth and metastasis in vivo PLoS ONE (2013) doi: 10.1371/journal.pone.0058426

It is not like the sins of the past are over. Quite the opposite, now even whole mice joined the Photoshop game apparently:

VL Battula , PM. Le , JC. Sun , K Nguyen , B Yuan , X Zhou , S Sonnylal , T McQueen , V Ruvolo , KA. Michel , X Ling , R Jacamo , E Shpall , Z Wang , A Rao , G Al-Atrash , M Konopleva , RE Davis , MA. Harrington , CW. Cahill , C Bueso-Ramos, M Andreeff AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth JCI Insight (2017)
doi: 10.1172/jci.insight.90036

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Still under A is Alan Ashworth, originally from England. You can read about his Photoshop achievements in my earlier article, this wizard of breast cancer research is definitely very dedicated to women’s issues. So much that he left ICR London and moved to UC San Francisco to do his BCRF-funded breast cancer research.

Lewis Cantley

Moving back to New York and on to another great man of cancer research, Lewis Cantley, director of the Cancer Center of Weill Cornell Medical College. Cantley has 25 papers on PubPeer, which visualise his contribution to the “Stand up to Cancer” initiative. A lot of PubPeer criticism is about gel splicing, which counter-critics explain was quasi-legal back then. Like this here:

SM Brachmann , CM Yballe , M Innocenti , JA Deane , DA Fruman , SM Thomas , LC Cantley Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement Molecular and Cellular Biology (2005) doi: 10.1128/mcb.25.7.2593-2606.2005

Apparently, there were times in biomedical sciences, where scientists assembled a Frankenstein picture of a gel in Photoshop from various bits and pieces, masked the splicing traces, and completed the figure with some “library” loading control they found somewhere in the drawer. Maybe that is why we haven’t moved much cancer therapy-wise in those decades, because of such attitude to research? Of course Cantley’s papers have other issues, too:

BM. Emerling , CH. Benes , G Poulogiannis , EL. Bell , K Courtney , H Liu , R Choo-Wing , G Bellinger , KS. Tsukazawa , V Brown , S Signoretti , SP. Soltoff , LC. Cantley Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients Proceedings of the National Academy of Sciences (2013) doi: 10.1073/pnas.1222435110   

How does this happen accidentally? Copy-paste image, shrink it slightly, change colour, all inadvertently and conclusions not affected? Here another example of an innocent mistake:

KA Lamia, OD Peroni , YB Kim , LE Rameh , BB Kahn , LC Cantley Increased insulin sensitivity and reduced adiposity in phosphatidylinositol 5-phosphate 4-kinase beta-/- mice Molecular and Cellular Biology (2004) doi: 10.1128/mcb.24.11.5080-5087.2004 

It seems, a band was somehow duplicated. The first author (now Scripps professor) Katja Lamia however dismissed the concerns with

“I can try to find the originals but I probably left them with the Cantley lab, who have since moved, so I doubt that they have been maintained (which I think is reasonable given the passage of more than a decade).“

Professor Cantley could not be arsed. Many of his criticised papers were done in collaboration with another genius of research integrity, the Harvard professor Ronald Kahn (mentioned here). Big men like these cannot be expected to adhere to basic research integrity, as they are busy curing diseases, in their own, mysterious way.

Andrew Dannenberg

Moving on to letter D we encounter a colleague of Cantley’s from Weill Cornell and an absolute star of Photoshop cancer research: Andrew Dannenberg. He now has 10 retractions because the no-nonsense Journal of Biological Chemistry (JBC) recently retracted 9 (NINE!) of his papers in one go. Dannenberg’s lawyer explained to Retraction Watch that their client had absolutely nothing to do with the experiments in the papers from his own lab. Weill Cornell added that they apparently see their professor as the actual whistleblower in this fraud affair. Of course there is more than the 9 retracted JBC papers, here some examples what else Dannenberg published as last author:

A Mohebati , JB Guttenplan , A Kochhar , ZL Zhao , W Kosinska , K Subbaramaiah , AJ Dannenberg Carnosol, a constituent of Zyflamend, inhibits aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and mutagenesis Cancer Prevention Research (2012) doi: 10.1158/1940-6207.capr-12-0002 

Sure, most problematic Dannenberg papers on PubPeer (there are 24 of them presently) have Kotha Subbaramaiah as coauthor, who is another Weill Cornell Professor deemed as whistleblower. But still, why was it OK for Dannenberg back then to claim full credit for his papers with Subbaramaiah in order to personally get very rich and very powerful, but when trouble arose he suddenly had absolutely nothing to do with these?

How about the following examples, in more papers in the same AACR journal, where Dannenberg just happens to be Senior Editor (so curb your enthusiasm about any possible retractions):

K Subbaramaiah , LR Howe , P Bhardwaj , B Du , C Gravaghi , RK Yantiss , XK Zhou , VA Blaho , T Hla , P Yang , L Kopelovich , CA Hudis , AJ Dannenberg Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland Cancer Prevention Research (2011)
doi: 10.1158/1940-6207.capr-10-0381 

Several western blot bands were apparently cloned and copy pasted in two simultaneously published papers. Genius, this will sure push medicine forward. It is not like the lab improved its ethics since, this appeared just in 2015 in same Cancer Prevention Research:

N Zhang , K Subbaramaiah , RK Yantiss , XK Zhou , Y Chin , R Benezra , AJ Dannenberg Id1 Deficiency Protects against Tumor Formation in Apc(Min/+) Mice but Not in a Mouse Model of Colitis-Associated Colon Cancer Cancer Prevention Research (2015) doi: 10.1158/1940-6207.capr-14-0411

Naturally, Dannenberg had nothing to do with all those bizarrely repetitive collages in the many papers from his own lab. Should the publisher AACR make any problems, he will maybe report those papers to Weill Cornell, as an experienced whistleblower.

Pier Paolo Pandolfi

There are other BCRF funded researchers with PubPeer records, but I would rather let you meet the real stars, the greatest men of science. Hence, fast forward to P, as Pier Paolo Pandolfi, Italian-born head of the Cancer Center in Harvard and as big a bigwig as one can be in cancer research. The man is so important and well-connected, that cancer patients get miraculously cured when his Cell paper is waved at them. Well, it sure works on his mice, and this is maybe why Pandolfi has around 30 papers discussed on PubPeer. These are some of them:

S Zhong , P Salomoni , S Ronchetti , A Guo , D Ruggero , PP Pandolfi Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis The Journal of Experimental Medicine (2000) doi: 10.1084/jem.191.4.631

Someone inadvertently copy-pasted 3 bands, stretched them a bit, flipped them and stuck them onto another gel image. Happens daily. Another example of Harvard’s quality cancer research:

BS Carver , J Tran , A Gopalan , Z Chen , S Shaikh , A Carracedo , A Alimonti , C Nardella , S Varmeh , PT Scardino , C Cordon-Cardo , W Gerald , PP Pandolfi Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate Nature Genetics (2009) doi: 10.1038/ng.370

An image of a cell culture, copy-pasted and differently cropped by mistake of oversight to stand in for two different experiments. Not the only mistake in that paper. But the next case certainly cannot be important, because surely the respected National Academy of Sciences journal PNAS would have done something by now? Stop sniggering you all.

E. M. Rego , L.-Z. He , R. P. Warrell , Z.-G. Wang , P. P. Pandolfi Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins Proceedings of the National Academy of Sciences (2000) doi: 10.1073/pnas.180290497

How can the same cell reappear in different images of physically different experiments? This is how Harvard, world’s leading university, cures cancer. Remember Pandolfi’s papers next time you are supposed to show reverence for that place. Btw, that was a “communicated” paper, meaning a friendly NAS member submitted it without proper peer review, but on endorsement from other friends. Which is another reason for PNAS not to touch it, because so many important people will be embarrassed.

Robert “Bob” Weinberg

To conclude the parade, get ready to meet God. Robert Weinberg is director of the Ludwig Cancer Research Center at the Massachusetts Institute of Technology (MIT), another place which instils worshipping reverence in scientists around the world.

Weinberg is God of cancer research, and this means something in such a polytheistic religion as cancer research is. He is so important is that the only reason he has not received the Nobel Prize for curing cancer yet is because the Nobel would be a too small an award for his achievements. Weinberg is so respected by the scientific community that he is even allowed to submit manipulated data in his corrections.

Look at this, a seminal paper which proved where cancer really comes from. Turns out, it is a disease of the Photoshop:

A Rangarajan , SJ. Hong , A Gifford , RA. Weinberg Species- and cell type-specific requirements for cellular transformation Cancer Cell (2004) doi: 10.1016/j.ccr.2004.07.009  issn: 1535-6108 

Weinberg, in his infinite wisdom, agreed with Cancer Cell in 2013 to remove some figures because they contained duplicated western blot bands. The new western blot figures are Photoshop-assembled collages which still contain duplicated bits. Other issues in that paper were ignored completely, like this here on the right.

What Weinberg was actually doing, was testing Cell Press’s faith in his divinity. The elite journal passed the Abrahamian test by sacrificing research integrity, and can be now seen as the true disciple of Weinberg and MIT. The publisher’s reward will be more papers with Weinberg’s name.

To be fair: Weinberg had to retract 5 papers since that correction, including in the flagship journal Cell. 4 of them share same first author: Scott Valastyan, someone once so successful and now so toxic that no record of his current whereabouts is available on the internet. Did any of that dent Weinberg’s reputation? Not really. Here what looks like a minor case of inappropriate gel splicing, but the PubPeer comment cited at the end puts it into perspective.

SA Mani , J Yang , M Brooks , G Schwaninger , A Zhou , N Miura , JL Kutok , K Hartwell , AL Richardson , RA Weinberg Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers Proceedings of the National Academy of Sciences (2007) doi: 10.1073/pnas.0703900104

That PNAS paper was contributed by Weinberg himself, meaning he selected some friends as peer reviewers who did not mind the gel splicing. This was the PubPeer comment, already 5 years old:

“another one for the collection of Weinberg papers: https://pubpeer.com/search?q=Weinberg
and yes, splicing is widespread, everybody was/is/will be doing it, every paper was cited many times, why don’t we just accept it and move on. At the same time, a worryingly large proportion of studies (also and in particular in big journals) is not reproducible, so maybe these two developments are somehow connected.“

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