Biotech Research integrity Smut Clyde

Richard Hill, the man even gels are afraid of

Get ready to meet Dr Richard Hill and his amazing jumping blots. Just don't stare, or you'll get hurt.

For those of you who started to miss Smut Clyde, he is back, with a whole travelling circus of fake western blots in tow. The central character here is the cancer researcher Richard Hill, a tough and rather physically intimidating English lad who used to sport a hairstyle popular among certain kind of football fans, and who looks at you from each photo as if he is about to headbutt you in the teeth. The photos don’t reveal what kind of boots Hill is wearing, but even from what we see it’s no wonder his western blots jumped through hoops backwards to do whatever Hill barked at them. Basically, it is good for Smut to be far, far away from Hill’s temper.

Dr Hill is namely tenured fellow at the University of Portsmouth in UK, where he took over a drug discovery unit on behalf of the retired professor Geoff Pilkington, and in this new role Hill continues to produce rigged science, which his university proudly pushes in press releases.

Update 25.10.2019: Hill was reported by two independent sources to have resigned from Portsmouth, as misconduct investigation began. See more below.

Got a problem with my science, mate?

Hill was recruited to Portsmouth from the Universidade do Algarve in Faro, Portugal, he still collaborates from his past colleague there, Patricia Madureira, who is also incidentally his wife. The family business might now urgently need a scapegoat to blame, any takers?

The dream couple. Photo source: University do Algarve

Just weeks ago, on 5 August 2019, University of Portsmouth issued this press release celebrating Hill’s allegedly successful test of a cancer drug which they now announce to bring into a clinical trial on humans. The trials were also announced by Hill in an interview with a brain cancer charity which funds his lab. Hill was asked “What’s been the biggest surprise to you as a result of your research?”, to which he mumbled something about “highly interactive patient networks, support groups“. Thanks to Smut Clyde, Hill will be getting his surprise now.

This is namely the blot-flipping science of Mihaljuk et al 2019 which the patients are to be treated with:

Photo source: University of Portsmouth

Before the stint in Portugal, Hill used to be a postdoc at the Dalhousie University in Canada, where his retired ex-boss Patrick Lee now fingers Hill in an email to me as the sole responsible for data irregularities in their common papers, and acknowledges to have reported the suspected research misconduct to the university’s authorities. Lee also wrote:

“I was informed of the issues raised in PubPeer several years ago and was both shocked and saddened by the evidence presented. I immediately contacted Dr. Hill and the journals involved, and felt that the fairest way to deal with this matter would be for Dr. Hill himself to provide his own defense/rebutal to these allegations, and let the journals decide on their acceptability. While some issues have since been resolved, others are still in the process of being sorted out. I was not aware of similar issues raised regarding his publications in Dr. Pilkington’s laboratory, until now. “

So we have two retired professors, and a bunch of soft journal editors. Mere pushover for Dr Hill. I will now hide behind the bushes also, and let Smut Clyde face the man now.


Dr Hill’s hilarious legerdemain, by Smut Clyde

Watch closely now, as I transform a Western blot of p21 protein blobs into a band of “Total p53”, and an Actin loading control into a different one, using only contrast enhancement and a horizontal flip! You’ll notice that at no time through the proceedings do my hands leave my wrists [Milligan 1972]. It is an unparalleled feat of prestidigitation, performed to great acclamation before the crowned heads of Europe, such as you will see nowhere else… unless you read decade-old cell biology journals, and particularly Hill et al (2008a) [1] and Hill et al (2008b) [2].

In total that Actin control band makes four appearances. It also illustrated Hill et al (2008c) [3], in a similar role. Then in 2013 the authors of [2] provided a Corrigendum to correct the excessive re-use of illustrations from [3], amending Figures 1, 4, 5 and 7 (which might not reach the threshold of what the RetractionWatch observers call a “mega-correction“, but is a “macro-correction” at the very least). The Actin band vanished from Figure 5A, but rose again in its fourth incarnation (truncated to three lanes and repurposed for a different set of conditions) within the new Fig 1D*.

Further displays of legerdemain await readers who care to examine the appropriate PubPeer threads… for instance, other concerns with the new Fig 1D*. I wrote this (as is the custom of my people) by strip-mining those threads and others, and by cherry-picking the low-hanging fruit in an unfortunate pile-up of metallurgical and horticultural metaphors, so it is not meant to be exhaustive. Admire, in passing, the similarities of three streaks of mRNA expression, from the ‘0-hour’ conditions of different experiments (after adjusting for lightness):

Some of the critiques of [2] involved Figures reused from [3] with different lanes or labels in the reuse, so they were preempted by the 2013 Corrigendum. Others were not.

So far we have looked at a remarkable trilogy from the Department of Microbiology and Immunology at Dalhousie University, Halifax (a city best-known for exploding, a century ago). By the time of Hill et al (2013) [4] the group had acquired second affiliations with the University of Algarve (on the south coast of Portugal), while following the same policy: repurposing protein bands from Western blots into new ones as evidence that experiments had indeed occurred. Often the bands were flipped vertically or horizontally, which had the unintended side-effect of making the re-use less apparent.

Now in electrophoresis commentary, one school of thought holds that loading controls are no big deal, because researchers can be confident that their cell-lysate preparations reliably contain the same total amount of protein. So it is fine if they do not bother with controls in an experiment, and fake them later while preparing a Figure (to grudgingly assuage the Third Reviewer’s unreasonable demands), cutting out the necessary number of lanes from any old source, like strips of wallpaper. Like this:

It is harder to be complaisant when the conjuring trick of inversion turns one protein into another.

Skipping a few years brings us to Hill et al (2017) [5]. By now Professor Lee had retired and the Dalhousie team had dispersed… or at any rate, relocated to University of Algarve. The proteinaceous transformations continued, reaching new heights of exuberance. The authors display an open-minded acceptance or even permissiveness towards their slices of gel: if one chooses to identify as AKT or β-actin rather than FOX03a why stand in its way?

TRIB2, I’d like to introduce you to pSER253-FOX03a… but I see you’ve already met.

The number of pairs of duplicated bands in Figure 2(c) (the doubling variously concealed by rescaling, darkening or horizontal flips) exhausts the number of colors available to show their kinship.

Figure 4(e) is intimidating in its scale but at least one dup triplication emerges from its murky depths.

The innovation in [5] is the provision of Supplementary Information files containing raw data – the original Western Blot gels (full-size and un-retouched) from which the in-text illustrations came as cleaned-up excerpts. Alas, these raw-data files are lower-resolution than those image files in the text. More to the point, they mirror the in-text duplications.

The charitable impulse when one finds an image repeated in a paper to illustrate different results is to think “Someone accidentally chose the wrong panel while assembling a complex Figure”, but this “carelessness” interpretation is not an option when ‘raw gels’ have been created by flipping and selectively cropping an original, and changing the labels on the lanes.

By 2019, regular first author Richard Hill had found a permanent post as Senior Research Fellow at Portsmouth University, so I think of these last two papers as the Portsmouth Diptych: Mihajluk et al (2019) [6] and Howarth et al (2019) [7]. They are linked by an Actin loading band, serving to equalise overall protein concentration across different sets of conditions in independent studies of two wholly-different proteins. Is there nothing that a horizontal flip can’t accomplish?

image-1565187919298

Dr Hill’s photographs on the Portsmouth University website are chosen to convey a sense of concentration and brooding intensity. I am left wondering whether one of the Midwich Cuckoos survived the explosive denouement of that novel and went on to a successful career in cell-biology research.

[6] and [7] are subdued in comparison with [5] but one still finds blotty duplicates working double-time to illustrate different experiments. Again, the duplications are paralleled by the fabrication of flipped, selectively-cropped “original unretouched gels” in the Supplementary Data files, so they are unlikely to be accidental. [7] is of special interest because there the fabrication was in the service of a patent application for a new class of anti-cancer drugs, filed by “Opal Oncology Ltd.” (a company founded by co-author Morley).

[Thx Melipona Capixaba]

To compensate for that lack of exuberance, I violated chronological sequence and left the best until last. Prepare yourself for Hill et al (2011) [8]. In fact we saw its Figure 1A already, as the lower half of a comparison with [4], but the majority of the linkages are internal. They are completely over-the-top, with splicing within bands on top of the insouciant recycling.

‘Condylocarpon Amazonicum’ commended the Supplementary Data file to the readers’ attention. It is a Blot Bacchanalia.

Protein bands cavort and caper, tumbling and swapping faces like figures in the marginalia of medieval manuscripts, or like the unleashed familiars in ‘The Downfall of Hermogenes‘.

How this Western Walpurgisnacht was ever accepted for publication is anyone’s guess. Perhaps Dr Hill used his Cuckoo mind-control powers on the Oncotarget editors and peer-reviewers.

[8] could serve as an educational resource for would-be contributors to PubPeer, to train them gradually in spotting blot manipulations or repurposing, for the shenanigans are not well-concealed and there is nothing too challenging for the untrained eye. Proving in passing that whatever its detractors might say, Oncotarget can play a useful role in the scientific literature.

SOURCES (frequent names in bold)
 

[1] Richard Hill, Michael D. Bodzak , Patrick W.K. Blough , Patrick W.K. Lee 

p53 Binding to the p21 promoter is dependent on the nature of DNA damage.

Cell cycle (2008) doi: 10.4161/cc.7.16.6440 PubPeer here.

[2] Richard Hill , Andrew M. Leidal , Patricia A. Madureira , Laura D. Gillis , David M. Waisman , Arthur Chiu , Patrick W.K. Lee

Chromium-mediated apoptosis: involvement of DNA-dependent protein kinase (DNA-PK) and differential induction of p53 target genes.

DNA Repair (2008) doi: 10.1016/j.dnarep.2008.05.007 Pubpeer here.

[3] Richard Hill , Andrew M. Leidal , Patricia A. Madureira , Laura D. Gillis , Haley K. Cochrane , David. M. Waisman , Arthur Chiu , Patrick W.K. Lee

Hypersensitivity to chromium-induced DNA damage correlates with constitutive deregulation of upstream p53 kinases in p21−/− HCT116 colon cancer cells.

DNA Repair (2008) doi: 10.1016/j.dnarep.2007.10.001 PubPeer here.

[4] R Hill, M Rabb, P A Madureira, D Clements, S A Gujar, D M Waisman, C A Giacomantonio, P W K Lee

Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy.

Cell Death and Disease (2013) doi: 10.1038/cddis.2013.307 PubPeer here.

[5] Richard Hill, Patricia A. Madureira, Bibiana Ferreira, Inês Baptista, Susana Machado, Laura Colaço, Marta Dos Santos, Ningshu Liu, Ana Dopazo, Selma Ugurel, Angyal Adrienn, Endre Kiss-Toth, Murat Isbilen, Ali O. Gure, Wolfgang Link

TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT.

Nature Communications (2017) DOI:10.1038/ncomms14687 PubPeer here.

[6] K. Mihajluk , C. Simms , M. Reay , P.A. Madureira , A. Howarth , P. Murray , S. Nasser , C.A. Duckworth , D.M. Pritchard , G.J. Pilkington , R. Hill 

IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas.

Cancer Letters (2019) doi: 10.1016/j.canlet.2019.05.028 PubPeer here.

[7] Alison Howarth , Claire Simms , Nitesh Kerai , Olivia Allen , Karina Mihajluk , Patricia A. Madureira , Giannis Sokratous , Simon Cragg , Sang Y. Lee , Andy D. Morley , Ashkan Keyoumars , Paul A. Cox , Geoffrey J. Pilkington , Richard Hill

DIVERSet JAG Compounds Inhibit Topoisomerase II and Are Effective Against Adult and Pediatric High-Grade Gliomas.

Translational Oncology (2019) doi: 10.1016/j.tranon.2019.07.007 PubPeer here.

[8] Richard Hill, Patricia A. Madureira, David M Waisman, Patrick W.K. Lee

DNA-PKCS binding to p53 on the p21WAF1/CIP1 promoter blocks transcription resulting in cell death.

Oncotarget (2011) doi: 10.18632/oncotarget.378 PubPeer here.


Update 24.08.2019

On 23.08.2019, Geoff Pilkington finally replied, saying he has been away on vacation without internet access. He immediately announced an investigation. I was also informed that Adrian Parry, Executive Director of Corporate Governance at Portsmouth University, wrote in an email today:

…we have instigated an investigation. The investigation will be taken forward in accordance with the University’s “Procedure for the Investigation of Allegations of Misconduct in Research”. A copy of this document can be found at: http://policies.docstore.port.ac.uk/policy-023.pdf?_ga=2.1109553.1837825534.1566309627-64763708.1535967744

Update 10.09.2019

A Screening Panel was assembled at University of Portsmouth to investigate the Hill case. The panel Chair Karen Ball, Head of School of Pharmacy and Biomedical Sciences, even invited “Ms Francis” to give evidence in person. I tried to alert Ball and the other two panel members, Jerome Swinny and Matt Guille, that this “Clare Francis” is a pseudonym, not the British novelist, just as this Karen Ball isn’t. To no avail.

Update 25.10.2019

Two independent sources confirmed to me that Hill has resigned from his position at Portsmouth University.

In other developments, Hill issued a corrigendum for Mihajluk et al Cancer Letters 2019, which goes like this:

Source: PubPeer

“In the article above, we, the authors, discovered that a single microscopy panel was inadvertently placed in Figure 1f, using the SEBTA-023 panel twice instead of the SEBTA-003 representative image. We discovered that an actin western blot loading control data associated with Figure 3a was also incorrectly placed in Figure 5i. We retrieved the original actin western blot data linked to Figure 5i and corrected this error.

Neither correction alter the conclusions of the original paper; however, we sincerely apologize for any confusion that this may have caused.”

Thing is, the corrected Figure 5i does not match the raw data authors provided in same paper, as criticised on PubPeer:

It also appears Hill only pretended to have issued the Corrigendum in agreement with his coauthors. Geoff Pilkington, the penultimate author, informed me:

“I am not involved with any independent enquiry process although I have requested that such process should be carried with all haste as I think it is in the best interests of everyone that this matter is dealt with honestly and expediently. 
Moreover, I have not communicated with Richard on this matter, nor have I seen him since my return from New Zealand.”

Update 28.10.2019

Maybe it was too early to pity Pilkington as a hapless and clueless victim of a dishonest successor. Turned out, Pilkington was not honest himself, on 25 October he told me a fib about not having known of the correction. Which lets one wonder how trustworthy all his other statements are.

Manfred Schwab, EiC of Cancer Letters and emeritus professor at DKFZ, Heidelberg, wrote to me today in regard to the disputed correction:

“thanks for pointing out to us the possible problems with this manuscript. It is our policy to contact the corresponding author for comment. After this, we will take the necssary actions. In cases of obvious scientific misconduct we have a zero-tolerance policy.

[…] Geoff Pilkington did send an email confirming that he approves of the changes on the 29th of August.”


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14 comments on “Richard Hill, the man even gels are afraid of

  1. “Hill was recruited to Portsmouth from the Universidade do Algarve in Faro, Portugal, he still collaborates from his past colleague there, Patricia Madureira.”

    Patricia Madureira sans Richard Hill.

    http://www.bloodjournal.org/content/117/15/4095?sso-checked=true
    Regulation of S100A10 by the PML-RAR-α oncoprotein
    Paul A. O’Connell, Patricia A. Madureira, Jason N. Berman, Robert S. Liwski and David M. Waisman
    Blood 2011 117:4095-4105; doi: https://doi.org/10.1182/blood-2010-07-298851
    https://pubpeer.com/publications/17E011389206C424054093E0CB6098

    Figure 5A.

    Like

  2. Just got a rejection from a journal and the main reason was lack of a full mechanistic explanation why our cancer drug works very efficient in PDX models. When you see all the junk science published in the very same journals, you get a bit frustrated. I really hope it will go down Hill!

    Like

    • Well, there is always the possibility that he move to Hollywood and he and Jason Stratham are the bad guys in the next Die Hard movie sequel. In America there is always a chance one can reinvent himself….

      Like

  3. I do not like judge people based on their look. But on professional ground, these blots warrant retractions. Even less overwhelming irregularities can pull down a paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133963/.

    Like

    • Smut Clyde

      A good point. Leonid Schneider can vouch for the fact that my own personal appearance and choices of clothing are not designed to inspire anyone with confidence or trust,

      Liked by 1 person

  4. Smut Clyde

    C. Amazonicum continues to have fun with the Supplementary Figures from the 2011 Oncotarget paper, even if the result looks like an explosion in an arrow factory.

    Like

  5. Crikey mate: Halifax (NS) is renowned for a great many other things, including nearby lighthouses, the Tattoo, and exceptional evolutionary microbiology. And anyway, rampant rebuilding has wiped out far more old buildings downtown than the explosion managed to. But yeah, egregious stuff abounding.

    Like

  6. Richard Hill announces retraction of Oncotarget. 2011 Dec;2(12):1094-108 on Pubpeer

    See: https://pubpeer.com/publications/8A3553A6E3588DA79EC450A57E1CE5#29

    Like

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