Obituaries for explosive developments in cancer research

Join me in honouring the academic heritage of not one, but two dead great British cancer researchers.

In May 2023, the British biologist Mike Waterfield died, aged 82. Here is an obituary published by The Francis Crick Institute:

“We were very sorry to hear of the death earlier this month of Michael Waterfield, a key figure in the explosive developments in cancer research in the late twentieth century and a transformative influence at the Imperial Cancer Research Fund, precursor to the Francis Crick Institute’s co-founder and major funder, Cancer Research UK. […]

Mike left ICRF in 1986 to set up the Ludwig Institute for Cancer Research at University College London. […] e then drove forward the development of inhibitory drugs targeting this enzyme, first in collaboration with the pharmaceutical company Yamanuchi, then setting up the biotech company Piramed, together with Peter Parker and Paul Workman. […]

Mike wound up his lab in 2008, […] He leaves an enormous legacy, not just in the landscape of cancer therapies which he did so much to transform, but also in the training and promotion of the careers of so many leading scientists…”

You may have recognised the name of Waterfield’s business partner, Paul Workman, former President of the Institute of Cancer Research (ICR) London. Workman published lots of fake science.

In 2008, Waterfield and Workman sold their company Piramed to the pharma giant Roche for $ 160 million. That was the year when Waterfield retired, leaving many successful mentees at the helm of the British cancer research.

The obituary was written by Waterfield’s former PhD student and now Senior Group Leader at ICR London and The Crick professor, Julian Downward, who has a very serious PubPeer record of bad science.

After doing PhD with Waterfield, Downward continued his science training at MIT in USA with the cheater Bob Weinberg; with years, Downward established for himself a very impressive PubPeer record. On the occasion of the retraction of his Nature paper Kumar et al 2014, Downward explained in 2015 to Retraction Watch that, “Following a series of exhaustive London Research Institute (LRI) internal and external investigations, it was concluded” that he was an innocent victim of a fraud by his Indian mentee, Madhu S Kumar.

Downward is Fellow of various academies and Executive Chairman of the British Association for Cancer. Here is one paper of his:

Miguel Manuel Murillo , Santiago Zelenay , Emma Nye , Esther Castellano , Francois Lassailly , Gordon Stamp , Julian Downward RAS interaction with PI3K p110α is required for tumor-induced angiogenesis The Journal of clinical investigation (2014) doi: 10.1172/jci74134 

Now, a collaborative study by Downward and his visiting scientist, now Cancer Research UK officer David Hancock, with many big names of international cancer research on it:

Barbara Nicke , Julie Bastien , Sophia J. Khanna , Patricia H. Warne , Victoria Cowling , Simon J. Cook , Gordon Peters , Oona Delpuech , Almut Schulze , Katrien Berns , Jasper Mullenders , Roderick L. Beijersbergen , René Bernards , Trivadi S. Ganesan , Julian Downward, David C. Hancock Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells Molecular Cell (2005) doi: 10.1016/j.molcel.2005.10.038 

Those figures don’t look kosher at all, is this what Downward learned from Waterfield?

Also, the lessons learned from the Kumar retraction: zero. Bad science continues:

Mohamed Ismail, Stephen R. Martin , Roger George , Francesca Houghton , Geoff Kelly , Raphaël A. G. Chaleil , Panayiotis Anastasiou , Xinyue Wang , Nicola O’Reilly , Stefania Federico , Dhira Joshi , Hemavathi Nagaraj , Rachel Cooley , Ning Sze Hui , Miriam Molina-Arcas , David C. Hancock , Ali Tavassoli , Julian Downward Characterisation of a cyclic peptide that binds to the RAS binding domain of phosphoinositide 3-kinase p110α Scientific Reports (2023) doi: 10.1038/s41598-023-28756-0 

But then again, can anyone explain this Downward paper:

And here a rather recent paper by a certain Olivier Pardo, who has a number of papers on PubPeer and who, importantly, used to be Downward’s postdoc. Nowadays Pardo is now reader at Imperial College London, where he presumably was installed by the Imperial College professor Michael Seckl. Seckl in turn did his PhD at Waterfield’s Imperial Cancer Research Fund, quite possibly it was Waterfield who then installed his mentee as faculty member at Imperial. And yes, also Seckl has his own PubPeer record, often with Pardo.

Yakinthi Chrisochoidou, Rajat Roy , Pooyeh Farahmand, Guadalupe Gonzalez , Jennifer Doig , Lukas Krasny , Ella F. Rimmer, Anne E Willis, Marion MacFarlane , Paul H. Huang , Neil O. Carragher, Alison F. Munro , Daniel J. Murphy , Kirill Veselkov , Michael J. Seckl, Miriam F. Moffatt, William O. C. Cookson , Olivier E. Pardo Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells Cell Death & Disease (2023) doi: 10.1038/s41419-023-06240-x 

Among the authors above is also Anne E Willis, Director of the MRC Toxicology Unit at the University of Cambridge, who prominently featured here:

As it happens, Seckl did PhD at UCLA in USA with Enrique Rozengurt, who has his own worrisome PubPeer record. Here is Seckl with Pardo, reusing data from Seckl’s paper with a former postdoc of Waterfield’s: a certain Alexandre Arcaro, who until a few years ago used to be group leader at the University of Bern in Switzerland. It is not clear why Arcaro disappeared in Bern (his PubPeer record is very bad, but when did that ever matter in academia?), or where he works now.

• Anna Wojtalla , Barbara Fischer, Nataliya Kotelevets , Francesco A. Mauri , Jens Sobek , Hubert Rehrauer , Carlos Wotzkow , Mario P. Tschan , Michael J. Seckl, Uwe Zangemeister-Wittke, Alexandre Arcaro Targeting the phosphoinositide 3-kinase p110-α isoform impairs cell proliferation, survival, and tumor growth in small cell lung cancer Clinical cancer research (2013) doi: 10.1158/1078-0432.ccr-12-1138 
• Ewa Rupniewska , Rajat Roy , Francesco A. Mauri , Xinxue Liu , Maciej Kaliszczak , Guido Bellezza , Lucio Cagini , Mattia Barbareschi , Stefano Ferrero , Anna M. Tommasi , Eric Aboagye , Michael J. Seckl , Olivier E. Pardo Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors Oncotarget (2018) doi: 10.18632/oncotarget.25213

The older paper in Clinical cancer research received a correction on 17 February 2025:

“In the original version of this article (1), the SCLC-positive image in Fig. 1A did not coincide with the SCLC-positive 200× image, and the Western blots used to represent Total Akt, S6, and beta-actin in Fig. 2C were misaligned with the lane labels. The figure panels in the authors’ original manuscript did not contain these errors; the errors were introduced when the authors submitted subsequent revisions to the journal.”

Here is a lovely study by Waterfield and his mentees Seckl and Arcaro:

Alexandre Arcaro, Umme K. Khanzada , Bart Vanhaesebroeck , Teresa D. Tetley , Michael D. Waterfield , Michael J. Seckl Two distinct phosphoinositide 3-kinases mediate polypeptide growth factor-stimulated PKB activation The EMBO Journal (2002) doi: 10.1093/emboj/cdf512 

That other paper, in Cell Signalling, is authored by Seckl and Arcaro (plus the Edinburgh professor Margaret Frame, who has a problematic PubPeer record of her own):

Alexandre Arcaro, Muriel Aubert , Maria E. Espinosa Del Hierro , Umme K. Khanzada , Smaragda Angelidou , Teresa D. Tetley, Anne G. Bittermann , Margaret C. Frame, Michael J. Seckl Critical role for lipid raft-associated Src kinases in activation of PI3K-Akt signalling Cellular Signalling (2007) doi: 10.1016/j.cellsig.2006.12.003 

On this set of papers, which were published in parallel, and share same data for different experiments, we have Pardo, Downward, Seckl, and Arcaro:

• Olivier E. Pardo , Alexandre Arcaro , Giovanni Salerno , Selina Raguz , Julian Downward , Michael J. Seckl Fibroblast growth factor-2 induces translational regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway: correlation with resistance to etoposide-induced apoptosis Journal of Biological Chemistry (2002) doi: 10.1074/jbc.m109006200 
• Olivier E Pardo , Alexandre Arcaro , Giovanni Salerno , Teresa D Tetley , Taras Valovka , Ivan Gout , Michael J Seckl Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells Oncogene (2001) doi: 10.1038/sj.onc.1204994 

The JBC paper was retracted in 2015, with the only note of “This article has been withdrawn by the authors.” The Oncogene paper received an Erratum in December 2014:

“Most of these errors concern duplication of small amounts of negative control data that appeared in the Oncogene manuscript and that were reused in the J Biol Chem paper without proper attribution to the original publication in Oncogene. […] We have therefore repeated these experiments and presented the replacement figures to J Biol Chem. Importantly, the results confirm our original findings. Moreover, none of the errors have any impact on the interpretation of the data or conclusions presented in our original Oncogene manuscript.”

Arcaro as you can imagine has a very serious PubPeer record. Here a paper of his with a Swiss bigwig Michael Grotzer, Medical Director of the University Children’s Hospital Zurich:

Danielle Boller , Kathrin T Doepfner , Angela De Laurentiis , Ana S Guerreiro , Marin Marinov , Tarek Shalaby , Paul Depledge , Anthony Robson , Nahid Saghir , Masahiko Hayakawa , Hiroyuki Kaizawa , Tomonobu Koizumi , Takahide Ohishi , Sarah Fattet , Olivier Delattre , Anelia Schweri-Olac , Katrin Höland , Michael A Grotzer, Karl Frei , Olivier Spertini, Michael D Waterfield, Alexandre Arcaro Targeting PI3KC2β impairs proliferation and survival in acute leukemia, brain tumours and neuroendocrine tumours Anticancer Research (2012) 32 (8) 3015-3027;

Guess what Arcaro, Waterfield, Grotzer and their many coauthors did. They just republished that paper, in the same journal, as Boller et al 2022, and they kept the recycled blot!

Grotzer has more bad papers with Arcaro. Like this:

Deborah Castelletti , Giulio Fiaschetti , Valeria Di Dato , Urs Ziegler , Candy Kumps , Katleen De Preter , Massimo Zollo , Frank Speleman , Tarek Shalaby , Daniela De Martino , Thorsten Berg , Angelika Eggert , Alexandre Arcaro , Michael A. Grotzer The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors Molecular Cancer Therapeutics (2010) doi: 10.1158/1535-7163.mct-10-0539 

This, by the same Swiss team, was corrected:

G Fiaschetti , D Castelletti , S Zoller , A Schramm , C Schroeder , M Nagaishi , D Stearns , M Mittelbronn , A Eggert , F Westermann , H Ohgaki , T Shalaby , M Pruschy , A Arcaro , M A Grotzer Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma Oncogene (2011) doi: 10.1038/onc.2011.10 

There is of course more forged science by Arcaro and Waterfield. Here they are with a certain German superstar named Axel Ullrich, after whom a whole medal and a lecture was named, courtesy of the Max Planck Institute in Dortmund (read March 2024 Shorts). Ullrich has 3 retractions and a worrisome PubPeer record.

Alexandre Arcaro , Marketa J. Zvelebil , Christian Wallasch , Axel Ullrich , Michael D. Waterfield , Jan Domin Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors Molecular and Cellular Biology (2000) doi: 10.1128/mcb.20.11.3817-3830.2000 

Here is Arcaro with Pardo and their Italian collaborators:

Angela De Laurentiis , Olivier E. Pardo , Andrea Palamidessi , Shaun P. Jackson , Simone M. Schoenwaelder , Ernst Reichmann , Giorgio Scita , Alexandre Arcaro The catalytic class I(A) PI3K isoforms play divergent roles in breast cancer cell migration Cellular Signalling (2011) doi: 10.1016/j.cellsig.2010.10.021 

The penultimate author from IFOM-IEO in Milan, Italy, is Giorgio Scita, he featured in this article:

Another bad paper, with Scita and three academic generations: grandpa Waterfield, his offsprings Arcaro and Downward and Downward’s offspring Pardo.

Roy M. Katso, Olivier E. Pardo , Andrea Palamidessi, Clemens M. Franz, Marin Marinov , Angela De Laurentiis , Julian Downward, Giorgio Scita, Anne J. Ridley, Michael D. Waterfield , Alexandre Arcaro Phosphoinositide 3-Kinase C2beta regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms Molecular Biology of the Cell (2006) doi: 10.1091/mbc.e05-11-1083 

The first author Roy Katso went on to work for pharma industry and died in 2018, aged 47. The coauthor Anne Ridley, now professor at the University of Bristol, began her PI career at Waterfield Ludwig Cancer Institute. She also has a problematic PubPeer record, including a retraction with the infamous Sam W Lee.

In memoriam of John Timms

Here is a paper of Ridley’s with Waterfield and a former postdoc of Waterfield’s: John Timms, who made it to associate professor at UCL, but then died in January 2021, aged only 51.

Hong-Lin Chan , Hsiu-Chuan Chou , MaCarmen Duran , Jana Gruenewald , Michael D. Waterfield , Anne Ridley, John F. Timms Major role of epidermal growth factor receptor and Src kinases in promoting oxidative stress-dependent loss of adhesion and apoptosis in epithelial cells Journal of Biological Chemistry (2010) doi: 10.1074/jbc.m109.047027

The data in Fig 1A was reused from the paper Huang et al 2010 by Hsiu-Chuan Chou and Hong-Lin Chan, but without the British coauthors.

Again, Timms and Waterfield, with Ridley:

• Ma Carmen Durán, Francisco Vega , Gema Moreno‐Bueno , Ma Jesus Artiga , Lydia Sanchez , Jose Palacios , Anne Ridley , John F. Timms Characterisation of tumoral markers correlated with ErbB2 (HER2/Neu) overexpression and metastasis in breast cancer PROTEOMICS (2008) doi: 10.1002/prca.200780020
• S L White , S Gharbi , M F Bertani , H-L Chan , M D Waterfield , J F Timms Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression British Journal of Cancer (2004) doi: 10.1038/sj.bjc.6601458 

Data from Proteomics paper appeared in another study by Timms:

Jenny Worthington , Mariana Bertani , Hong-Lin Chan , Bertran Gerrits , John F Timms Transcriptional profiling of ErbB signalling in mammary luminal epithelial cells–interplay of ErbB and IGF1 signalling through IGFBP3 regulation BMC Cancer (2010) doi: 10.1186/1471-2407-10-490 

The BMC Cancer paper in turn reused data from an older study by Timms and Waterfield:

Another problematic Timms paper, but without Waterfield:

Marjo De Graauw , Ine Tijdens , Rainer Cramer , Steve Corless , John F. Timms, Bob Van De Water Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis Journal of Biological Chemistry (2005)
doi: 10.1074/jbc.m412708200 

The UCL obituary for Timms mentioned:

“John Timms who was Associate Professor of Cancer Proteomics at the Elizabeth Garrett Anderson Institute for Women’s Health (IfWH) was an outstanding scientist in the pioneering development and application of proteomic technologies in cancer research. John gained his DPhil from Oxford University in 1995 going on to a Leukemia Society of America Fellowship in Prof Benjamin Neel’s laboratory at Harvard Medical School. He returned to the UK in 1999 as a postdoctoral research fellow with Prof Mike Waterfield at the UCL Ludwig Institute for Cancer Research and in 2002 he became an Assistant Member of the Ludwig, leading a successful cancer proteomics research group.”

The UCL announcement also linked to Timm’s obituary written by “Prof Martin Widschwendter, personal friend and John’s previous Head of Department”:

“Simply put, John was a shining beacon in the world of academia, a world that at times can be uncompromising and difficult to negotiate.”

The aforementioned Benjamin G. Neel is now Director of the Perlmutter Cancer Center at NYU Langone Health, he once reportedly kicked out Sam W Lee from Beth Israel Deaconess Medical Center (BIDMC) and had him moved to the very periphery of Harvard Medical School. It is not clear whether that was because Lee being fraudster who also tortured animals, or because of Lee’s antisemitism.

But here is a paper by Timms and Neel:

Neel published quite a lot of bad science, with some very problematic people, including Robert Weinberg, as I discussed in August 2023 Shorts. One such coauthor of Neel was Weinberg’s postdoc Julian Downward. Yet Neel saw no problem with those spliced gels:

Shairaz Baksh , Stella Tommasi , Sarah Fenton , Victor C. Yu , L. Miguel Martins , Gerd P. Pfeifer , Farida Latif , Julian Downward, Benjamin G. Neel The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death Molecular Cell (2005) doi: 10.1016/j.molcel.2005.05.010 

Moving on. here is Waterfield with the UCL professor Parmijit Jat, who did his PhD in 1982 at the Imperial Cancer Research Fund, and who has a worrisome PubPeer record of his own:

Silvia Benvenuti , Rainer Cramer , Christopher C. Quinn , Jim Bruce , Marketa Zvelebil , Steven Corless , Jacquelyn Bond , Alice Yang , Susan Hockfield , Alma L. Burlingame , Michael D. Waterfield , Parmjit S. Jat Differential proteome analysis of replicative senescence in rat embryo fibroblasts Molecular & cellular proteomics (2002) doi: 10.1074/mcp.m100028-mcp200 

And here is Jat with Downward, the last author is UCL professor Nicholas Wood, who collaborated with awful people like Frédéric Checler and, well, see if you recognise some very big fish here. The duplication was corrected soon after the publication:

Alison Wood-Kaczmar , Sonia Gandhi , Zhi Yao , Andrey Y Abramov , Andrey S Y Abramov , Erik A Miljan , Gregory Keen , Lee Stanyer , Iain Hargreaves , Kristina Klupsch , Emma Deas , Julian Downward , Louise Mansfield , Parmjit Jat , Joanne Taylor , Simon Heales , Michael R Duchen , David Latchman , Sarah J Tabrizi , Nicholas W Wood PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons PLOS One (2008) doi: 10.1371/journal.pone.0002455 

What surprise, the billionaire heir and Master of Birkbeck David Latchman was on board!

Here is Jat with some very toxic people from ICR London, Christopher Lord and his mentor Alan Ashworth, who until his escape to California used to be President of ICR and thus the predecessor of Waterfield’s business partner Workman:

Emilie Rovillain , Louise Mansfield , Christopher J Lord , Alan Ashworth, Parmjit S Jat An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence BMC Genomics (2011) doi: 10.1186/1471-2164-12-355

Read about Ashworth and Lord here:

Concluding, whatever Waterfield’s own scientific achievements were, as a mentor and business partner he damaged science by installing and promoting all the wrong people. Including Timms, who is also dead now.

But you know what Max Planck said.

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