Amato Giaccia: too big to fall

The Danish cancer researcher and entrepreneur Janine Erler retracted her 14 year old Nature paper. It was the product of her postdoctoral studies at Stanford University, USA, which catapulted her stellar career in academia and business. I presented Erler’s story in my previous article in 2018, together with the evidence of excessive data manipulation in the 2006 Nature publication.

The retraction of Erler et al Nature 2006 on 18 March 2020 was a major surprise. Stanford namely officially closed the case and told everyone who kept complaining to get lost. Maybe Nature really began a new research integrity policy? In this particular case, the claims of a lysil oxydase (LOX) inhibitors to being a cure for cancer never went anywhere in clinical trials. Labs whose LOX research allegedly supports Erler’s results, like labs of Richard Marais and Caroline Springer, stand accused of bad scientific practices themselves. In short, it very may be that the entire billion-dollar-heavy LOX field was a cancerous hoax.

To put things into the correct perspective, the ultimate US authority on research integrity, Retraction Watch, now brought an article about Erler’s Nature retraction. Stanford is mentioned only once in passing and, most notably: Erler’s former mentor and the paper’s last author Amato Giaccia is not mentioned even once. As if he has absolutely nothing to do with any of that unfortunate cock-up.

That is a pity, because Giaccia’s lab published a number of problematic papers without Erler’s contribution. Clare Francis, who posted some evidence years ago on PubPeer, kindly agreed to have yet another look. It seems, Giaccia is simultaneously very famous and revered cancer researcher, but also a somewhat bad principal investigator, of the kind who lets his lab members publish fake data and does nothing to fix the literature. The main conclusions, that everyone made a nice academic career and earned a lot of money (especially Giaccia himself), do remain unaffected indeed, so there. Only right that the Watchdogs of Retraction Watch decided not to burden their readers’ gentle brains with any mention of this Italian cancer researcher.

Giaccia has since left Stanford and joined another highly prestigious institution, the University of Oxford in UK, where he now heads the MRC Oxford Institute for Radiation Oncology. Which is the absolutely right place to seek shelter with when you are caught on rigged science. At Oxford, data manipulation is never investigated if the paper is older than 3 years and/or if the author is very important (see Oxford’s statement on the case of Dame Kay Davies).

We are pleased to announce that Professor Amato Giaccia has been appointed as Director of the MRC Oxford Institute for Radiation Oncology (OIRO): https://t.co/JGc7qUpTSe @The_OIRO pic.twitter.com/HRsrO1KuyM

— Medical Research Council (@The_MRC) January 24, 2019

The MRC issued in January 2019 a press release celebrating Giaccia’s appointment:

“Amato is a fantastic catch for the Oxford oncology community and we are delighted he has chosen to join us from Stanford. He has already made his presence felt having hit the ground running and we look forward to him taking the Institute to the next level.”

It is a challenge to take Oxford’s Photoshop output to the next level, but Giaccia is definitely the right man for that. Let’s have a look what his Stanford lab delivered under his guidance. As starter, a collaborative paper with the Oxford MRC Institute for Radiation Oncology, published 10 years before Giaccia become its director:

Z Bencokova , MR Kaufmann , IM Pires , PS Lecane , AJ Giaccia , EM Hammond ATM activation and signaling under hypoxic conditions Molecular and Cellular Biology (2009) doi: 10.1128/mcb.01301-08

Incidentally, the last author and Oxford professor Esther Hammond is a former Giaccia mentee, she did postdoc in his Stanford lab. The PubPeer evidence is festering for already 3 years. Yet these two Oxford professors have better things to do, like getting hold of more of your tax and charity money for quality cancer research.

You probably started to pity poor Dr Hammond for becoming victim of someone else’s naughtiness? That is from her own first author paper as Giaccia’s postdoc:

Another Giaccia classic, 20 years old, Clare Francis even spotted a dog’s face there, twice:

H L Maecker, C Koumenis, A J Giaccia p53 promotes selection for Fas-mediated apoptotic resistance Cancer Research (2000) Aug 15;60(16):4638-44.

Cloned gel lanes? Woof woof to that. Here is a vintage one, by now 22 years old and same age as many of my readers. A cloned and mirrored gel band:

Zundel W, Giaccia A. Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress. Genes & Development (1998) DOI: 10.1101/gad.12.13.1941

If you liked that, here is another original Zundel for you:

Zundel W, Swiersz LM, Giaccia A. Caveolin 1-mediated regulation of receptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide.Molecular and Cellular Biology (2000) DOI: 10.1128/mcb.20.5.1507-1514.2000

Pretty, isn’t it? That Wayne Zundel apparently was really determined to make a career in academia. He had several stints as department head at University of Louissville and Oregon Health & Sciences University, until he opened his own consultancy business in 2011. Is this the kind of scientific method Zundel now consults about? Will Zundel be invited to Oxford Radiation Oncology to show the tricks to young aspiring graduate students and postdocs there? One more:

W Zundel , C Schindler , D Haas-Kogan , A Koong , F Kaper , E Chen , A R Gottschalk , H E Ryan , R S Johnson , A B Jefferson , D Stokoe , AJ Giaccia Loss of PTEN facilitates HIF-1-mediated gene expression Genes & Development (2000) Feb 15;14(4):391-6.

Prof Amato Giaccia from @The_OIRO and Prof Laurence Zitvogel from @GustaveRoussy will deliver their plenary sessions during the last day of #NCRI2019. Join us for 3 days packed full of learning in Glasgow this November 👉 https://t.co/ZvsmscBA70 pic.twitter.com/uuXREak0rk

— NCRI Partnership (@NCRI_partners) August 27, 2019

Here a collaborative study featuring Giaccia and other Stanford colleagues. The first author Barbara Bedogni now runs a lab at the University of Miami:

Bedogni B, Warneke JA, Nickoloff BJ, Giaccia AJ, Powell MB. Notch1 is an effector of Akt and hypoxia in melanoma development. J Clin Invest (2008) DOI: 10.1172/JCI36157

As you see, it is not always just duplications, but also many spliced gels. A legend goes around in biomedicine that it was once “legal” until 2008 to stealthily splice lanes, in order to bullshit readers into believing they were looking at an intact gel, truthfully probed for equal loading. Luckily, Giaccia published that spliced paper just in 2008, and then another one in Cancer Cell, which is nice because at Cell Press nobody cares about data manipulation anyway.

S Turcotte , DA. Chan , PD. Sutphin , MP. Hay , WA. Denny , AJ. Giaccia A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy Cancer Cell (2008) doi: 10.1016/j.ccr.2008.06.004

What exactly is the scientific message of this collage? Not much remains standing, except to wonder why authors resorted to such tricks. But it helped Sandra Turcotte become professor at the Atlantic Cancer Research Institute in Canada. Sure, 2008, the mythical deadline, state of limitations etc. But this Giaccia paper is from 2014:

EB. Rankin, KC. Fuh, L Castellini, K Viswanathan, EC. Finger, AN. Diep, EL. LaGory, MS. Kariolis, A Chan, D Lindgren, H Axelson, YR. Miao, AJ. Krieg, AJ. Giaccia Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET Proceedings of the National Academy of Sciences (2014) doi: 10.1073/pnas.1404848111

Now, it again may look like nothing, but two things are clear: The 3rd lane of the AXL western blot was digitally spliced in, and the entire analysis lacks a proper loading control. The reason why PNAS has done absolutely nothing about that so far is the fact that Giaccia is such a bigwig that you simply must trust him on his word. The paper was incidentally editorially handled by Tony Hunter, star of the Salk Institute who is also too big to bother about what he actually published.

Now I would like to introduce to you another Giaccia alumnus: Cullen Taniguchi, now head of Radiation oncology at MD Anderson. In the world of cancer research, where data manipulation is boringly normal, MD Anderson stands apart because of their apparent institutional policy to actively recruit dishonest scientists. The only people MD Anderson does crack down upon in research fraud cases, are the whistleblowers. Here is what Taniguchi published with Giaccia:

CM Taniguchi, YR Miao, AN Diep, C Wu, EB Rankin, TF Atwood, L Xing, AJ Giaccia PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2 Science Translational Medicine (2014) doi: 10.1126/scitranslmed.3008523

Not convinced about these two bands? Have a look at another paper by Taniguchi which qualified him for the MD Anderson faculty job:

CM Taniguchi , EC Finger , AJ Krieg , C Wu , AN Diep , EL LaGory , K Wei , LM McGinnis , J Yuan , CJ Kuo , AJ Giaccia Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes Nature Medicine (2013) doi: 10.1038/nm.3294

Still thinking about innocent oversight as possible explanation? Taniguchi is the middle one on this 3-author paper, the last one being the Harvard star scientist C Ronald Kahn, another American giant who can’t be bothered to apply a minimum of research integrity to his groundbreaking biomedical research. The paper Entingh et al 2003 has been retracted by the no-nonsense Journal of Biological Chemistry:

For Retraction Watch, Kahn explained that the results of the retracted study were perfectly reproducible, while Taniguchi surprised everyone that he actually contributed no research data whatsoever to that paper. Probably like with the other 6 papers with Kahn, flagged on Pubpeer for data manipulation. Which might be even true, Taniguchi likely only contributed some artwork instead. Like this Taniguchi et al Mol Cell Biol 2007:

Scientist titans like Kahn and Giaccia are the reason why USA is the scientific world leader, followed by United Kingdom. But China is catching up.

Dr. Amato Giaccia of @StanfordMed at this year's induction ceremony! Welcome to the NAM, Dr. Giaccia! pic.twitter.com/x5SkujlR9w

— National Academy of Medicine (@theNAMedicine) November 8, 2016

Update 20.04.2020

Oxford University Registrar Gillian Aitken predictably refused outright a research misconduct investigation, just as she did in a different case (that of Kay Davies). I received this reply:

“I have considered whether the matter should be reviewed under the University’s Code of practice and procedure on academic integrity in research, and have concluded that as the papers were published before Professor Giaccia was employed by the University, and more than three years ago, the University’s Code is not engaged.
I have therefore decided that no further investigation is required by the University of Oxford, and I consider this matter closed.“

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