Lawyering-up Research integrity

Dr. Ignarro has suffered stigma, and was denied at least two interviews on television

"The presence of such articles online have severely affected Dr. Louis J. Ignarro’s public reputation, and his personal life. Dr. Ignarro disputes any accusations of wrongdoing. There was no fabrication of data, although there was a mistaken duplication of data which occurred due to error. None of the data was false." -J.L. Perez, Esq.

The right way to breathe during the coronavirus pandemic

Inhale through your nose and exhale through your mouth. It’s not just something you do in yoga class – breathing this way actually provides a powerful medical benefit that can help the body fight viral infections.

The reason is that your nasal cavities produce the molecule nitric oxide, which chemists abbreviate NO, that increases blood flow through the lungs and boosts oxygen levels in the blood. Breathing in through the nose delivers NO directly into the lungs, where it helps fight coronavirus infection by blocking the replication of the coronavirus in the lungs. But many people who exercise or engage in yoga also receive the benefits of inhaling through the nose instead of the mouth. The higher oxygen saturation of the blood can make one feel more refreshed and provides greater endurance.

I am one of three pharmacologists who won the Nobel Prize in 1998 for discovering how nitric oxide is produced in the body and how it works. […]

The author of this ingenious COVID-19 solution, published in June 2020 on The Conversation, is the 79 year-old Nobel Prize winner Louis J. Ignarro, emeritus professor of the University of California Los Angeles, and incessant peddler of Herbalife diet supplements (paid $15 mn by 2012 alone) as well as of POM Wonderful pomegranate juice (income unclear, but POM owners payrolled their academics very wonderfully).

But now I think Dr Ignarro is hyperventilating, and it might be my fault.

Ignarro, with his Nobel vehicle, as he arrived to 2018 Lindau Nobel meeting.

Some days ago, a message reached me via my site’s contact form. It came from the lawyer J.L. Perez, based in Florida, US and specialising on criminal law and “reputation protection”. This was the message:

Dear For Better Science,

I am reaching out to you on behalf of Dr. Louis J. Ignarro to address his concerns regarding the article found on the following link on your website:

https://forbetterscience.com/2018/08/27/fake-data-and-real-pomegranate-juice-in-nobelist-lois-ignarros-papers/

We are requesting that the above link be taken offline, as a courtesy to my client. As an attorney, I fully acknowledge your First Amendment right to publish news content and legal information. Accordingly, I am making this request on his behalf on the basis of professional ethics and voluntary courtesy.The presence of such articles online have severely affected Dr. Louis J. Ignarro’s public reputation, and his personal life.

Dr. Ignarro disputes any accusations of wrongdoing. There was no fabrication of data, although there was a mistaken duplication of data which occurred due to error. None of the data was false. Unfortunately, in this internet saturated age, the continued presence of negative content online can cast an undeserved shadow over worthy individuals and endeavors. Dr. Ignarro has suffered stigma by the online presence of the above cited article, and was denied at least two interviews on television after the links were discovered by the media. I would respectfully suggest that whatever the initial informational purpose of this report, it now only serves to cast a cloud over Dr. Ignarro.

Accordingly, I kindly and respectfully request that the above cited report be taken offline as a courtesy to Dr. Louis J. Ignarro. Please feel free to contact me should you wish to discuss the matter. We look forward to your prompt response.

Sincerely,
/S/J.L. Perez, Esq.

Now, the online presence of this J L Perez Esquire is not really awe-inspiring: the owner is such a cheapskate he uses the gratis website service provided by Weebly (hence the domain “appealsfla.weebly.com“, the lawyer’s officially listed contact email address is a Gmail one. I therefore replied and requested proof that JL Perez is really representing the multimillionaire and Nobel Prize winner Professor Louis Ignarro, of whose amazing cancer research Smut Clyde and yours truly had the honour to report about two years ago, in August 2018.

I eventually received these documents:

In the above letter, the lawyer appeals to my “professional ethics” and requests that the evidence (which has been originally published on PubPeer) is deleted or that at least Ignarro’s name is redacted. But I am confused. How am I supposed to remove Ignarro’s name from his own peer-reviewed publications, even if it was “mistaken duplication of data which occurred due to error“?

I for one, would never dispute that “None of the data was false“. I merely dispute what the Nobel Prize winner defines as “data”. The Photoshop duplications had probably their right purpose, this is exactly why Dr Ignarro is perfectly happy to continue being associated with these papers. Please have a look for yourself.

Many of these problematic studies on PubPeer (presently 28) were done by Ignarro in collaboration with the Italian immunologist Claudio Napoli, professor at the University of Campania in Naples (Napoli in Italian). Personally, I would have expected Ignarro to blame his past associate Napoli of Napoli for everything, admit having accepted gift authorships without contributing to or properly reading that Napoletan trickster’s papers, but no, Ignarro’s lawyer defends the Photoshop fabrications instead.

Now I am disappointed at not being proposed at least a small bribe (e.g., May Griffith offered me €400 for two articles). The Porsche enthusiast who made many millions with Herbalife and POM Wonderful alone asks me to do it for free as a “voluntary courtesy”. Instead, I wish to use the occasion to present some new findings in the Nobelist’s papers which probably also occurred due to error.

We shall start with a PNAS paper which Napoli and Ignarro already corrected.

F De Nigris , V Crudele , A Giovane , A Casamassimi , A Giordano , HJ Garban , F Cacciatore , F Pentimalli , DC Marquez-Garban , A Petrillo , L Cito , L Sommese , A Fiore , M Petrillo , A Siani , A Barbieri , C Arra , F Rengo , T Hayashi , M Al-Omran , LJ Ignarro, C Napoli CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy Proceedings of the National Academy of Sciences (2010) doi: 10.1073/pnas.1008256107

Like all the other joint PNAS papers below, that one was originally “Contributed by Louis J. Ignarro“, a PNAS specific track reserved to National Academy of Sciences (NAS) members which means that the paper was not independently peer reviewed. Ignarro was elected to NAS in 1999, right after his Nobel Prize, and he immediately used the opportunity to smuggle some rather horrible Photoshop fabrications he co-authored with Napoli. Many artefactual or fabricated papers were published in this way, by other dishonest scientists. The PNAS journal usually does not even bother to correct these fakeries, as not to embarrass the prestigious Academy members. In fact, 3 more Ignarro-Napoli coproductions in PNAS are left to fester in peace. This is what that De Nigris et al 2010 paper contained:

Fig 5A

Fig S3 “The PCR results obtained with VEGFB, VEGFD and GAPDH transcripts appear to be the same (modulo different exposures and vertical stretching). At least, they share identical scratches and defects.”

On 25 March 2019, a correction was issued:

The authors wish to note the following: “Concerns about the presentation of data in some of the figures in our paper were brought to our attention. During the process of data checking by international ALCOA parameters, we detected mistakes during figure preparation of some in vitro results in Figs. 3B and 5 A and C and Fig. S3. We have been able to find many original autoradiographs to confirm the results reported in our paper. We apologize for the inconvenience for these honest errors, which, importantly, do not affect the main results of the study.

Well, “original autoradiographs to confirm the results” is not the same thing as original autoradiographs to behind the results presented in the original figures, mind you. A certain Hoya camphorifolia asked:

Could the authors explain the honest errors whereby the original autoradiographs came to be replaced with the confections seen above, when the paper was first published?

But anyway, Elisabeth Bik noticed that the authors and PNAS forgot something, in Figure 1B. The image integrity expert wrote on PubPeer:

Red boxes: Panels b (SaOS mouse group after treatment with 100 nM of T22 peptide) and c (shYY1 mouse group) appear to look very similar. This appears not just to be a simple duplication. Of note the aspect ratio is different, and a white line visible at the top in b) is not visible in c) because it appears to be covered with a green box.

Will PNAS issue another correction? Or will they retract this Photoshop orgy? Don’t be silly, Nobel Prize winner Dr Ignarro and his lawyer explained it to you already.

Before we move on to more image irregularities, here is some self-plagiarism, or double publishing. Ignarro and Napoli published the same review paper twice, in two different journals. That was spotted by Clare Francis, and confirmed by the detailed analysis using the gratis Similarity Texter tool. But hey, both reviews are published by Springer so there is no copyright-infringement. Each paper costs roughly €40 to read.

Louis J Ignarro, Claudio Napoli “Novel Features of Nitric Oxide, Endothelial Nitric Oxide Synthase, and Atherosclerosis” Curr Diab Rep . 2005 Feb;5(1):17-23. doi: 10.1007/s11892-005-0062-8.

Louis J Ignarro, Claudio Napoli “Novel Features of Nitric Oxide, Endothelial Nitric Oxide Synthase, and AtherosclerosisCurr Atheroscler Rep. 2004 Jul;6(4):281-7. doi: 10.1007/s11883-004-0059-9.

It is not just the title. The two papers are literally identical, most instances missed by Similarity Texter are merely words broken in-line during type-setting, e.g “evi-dence” vs “evidence”.

Similarity Texter analysis (Ignarro 2004 left, Ignarro 2005 right). Colour-coded are identical text sections.

Between submissions, the text was however slightly modified. E.g., “production of reactive oxygen species (ROS)“. became “production of ROS“, “CHD patients” became “patients with CHD“. Surely that shifty Napoletan Napoli did it all behind the Nobelist’s honest back? Nope. Both papers were submitted by Ignarro as the sole corresponding author.

Here more Napoli-Ignarro shenanigans, these were known before, but Smut Clyde couldn’t bothered to list them all. Neither can I, so here some examples. The journals, including PNAS, don’t really care either.

Sica et al Cell Cycle 2006 and Napoli et al Nat Clin Cardiovasc Med 2008
De Nigris et al PNAS 2005 and De Nigris et al PNAS 2003. The latter paper was corrected in 2004 to note that Ignarro patented relevant health supplements and works for Herbalife.
Bucci et al PNAS 2005 No Napoli here, but the paper is still from Naples. Contributed by Ignarro.

In 2008, the then-EiC of PNAS Randy Sheckman issued an (so far unresolved) expression of concern for 3 Stefano Fiorucci papers, including Fiorucci et al 2002 (with Ignarro as last author):

The editors wish to note that a reader has raised questions about the apparent duplication in the use of certain figures in the foregoing articles. We have been informed by the University of Perugia, Italy, of an ongoing review conducted by an inquiry committee at the university. We are awaiting the findings of the committee to determine the appropriate next steps.

And yet, even a shameless Photoshop bandit like Napoli cannot be blamed for everything. Not even other Italians, except, well, Ignarro himself, whose parents were Italian immigrants from… Naples.

Daigo Sumi, Toshio Hayashi, Hisako Matsui-Hirai, Aaron T. Jacobs, Louis J. Ignarro , Akihisa Iguchi 17β-Estradiol inhibits NADPH oxidase activity through the regulation of p47phox mRNA and protein expression in THP-1 cells Biochimica et Biophysica Acta (BBA) – Molecular Cell Research (2003) doi: 10.1016/s0167-4889(03)00026-0

Also here, Bik spotted something very unusual:

Figure 4. In the blot area where the p47phox band runs, a blank area with straight lines and sharp transitions appears to be visible, as if a grey rectangle has been placed over bands in the area. Could the authors please comment? Maybe there was a smudge they tried to cover up?

Or maybe the authors didn’t like the upper bands and compelled them to hide behind a gray bar. The next paper creatively reused western blots.

Min Zheng, Seul‐Ki Kim, Yeonsoo Joe, Sung Hoon Back, Hong R. Cho, Hong Pyo Kim, Louis J. Ignarro, Hun‐Taeg Chung Sensing endoplasmic reticulum stress by protein kinase RNA‐like endoplasmic reticulum kinase promotes adaptive mitochondrial DNA biogenesis and cell survival via heme oxygenase‐1/carbon monoxide activity The FASEB Journal (2012) doi: 10.1096/fj.11-199604

The nuclear and cytosolic bands for Nrf2 + PERK-/- are the same, modulo a horizontal reflection.

The last author Hun Taeg Chung eventually replied, blaming a postdoc:

It has been too long since my post-docs, who performed the Nrf2 translocation blot for Figure 2E, left my lab. I think he has had a problem during the arrangement of many blots. Therefore, we tried to do the same experiments under same conditions to confirm the results.

Unsurprisingly, the results from 7 years ago were perfectly confirmed and no correction is necessary. Next example:

Karuppaiyah Selvendiran , Anna Bratasz , Liyue Tong , Louis J. Ignarro , Periannan Kuppusamy NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and modulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts Cell Cycle (2008) doi: 10.4161/cc.7.1.5103

The lanes are labeled quite differently.

If you want more, please go back to PubPeer or read Smut Clyde’s article which JL Perez, Esq has asked For Better Science to delete.

Update 16.10.2020

In more positive news, Professor Ignarro has been appointed Honorary President and founding member of Italian Scientists Association“, a society which aims to provide

“the definition and dissemination of high standards of integrity in scientific research with constant reference to gender balance. […] Each of us, in his own area of ​​expertise, knows the errors, sometimes gross, that are made every day. Just to give some examples, it is enough to recall the climatic and environmental emergency, the disinformation campaign on the usefulness of vaccines or the instrumental contrast between different generations also through the false thesis that the retirement of the elderly favours the recruitment of young people.”

While you might be laughing at the bit about research integrity and the errors Ignarro et al has made, only 2 out of 10 founding members are female, and also the overwhelming majority (73 out of 92) of regular members have members. I can’t be bothered to check these gentlemen’s age, but I suspect there to be many old farts concerned about young people, some even female, going for their extremely comfortable and influential faculty thrones.


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15 comments on “Dr. Ignarro has suffered stigma, and was denied at least two interviews on television

  1. Smut Clyde

    Harumph. The offending piece is cross-posted on my own blog. What do I have to do to hear from lawyers?

    Liked by 1 person

  2. Patricia Murray

    It is very disappointing to see how high profile individuals, including several Nobel laureates, are bringing their research fields, and even science itself into disrepute. These individuals have been well rewarded already, so very sad to see them engaging in pseudoscience and quackery for the sake of £$€ that they can’t possibly need.

    Like

    • Not true. Certainly any kind of faculty member whose ego has been inflated with a Nobel Prize can rationalize a need for more money: they need more money to buy their own island in the Caribbean Sea in which to retire on.

      Like

  3. His publications have “severely affected Dr. Louis J. Ignarro’s public reputation”.
    His publications are readily observable.

    Like

  4. https://retractionwatch.com/2018/11/08/judge-dismisses-most-of-carlo-croces-libel-case-against-the-new-york-times/

    “Dr. Croce contends that not all papers on which his name is listed were the product of research either conducted by him or under his supervision. But the Court believes that an ordinary reader would credit such a paper, on which Dr. Croce willingly allowed his name to appear as a co-author, to him.”

    Like

  5. Dr. Ignarro has several times been obliged to merely chuckle while heading to the bank. Puleeees!

    Like

  6. In one of his Porsches, of course.

    Like

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  10. what is the point of your existence? what are you offering? How do you make what you are attacking better?

    Like

    • Maybe a better question to ask is why this kind of stuff is happening to Louis? What did he do to get this response? Actions have consequences. Sincerely, a failed scientist.

      Like

    • Dear gold:

      First, criticism is not an attack.
      Second, by criticizing bad behavior perhaps you’ll get less bad behavior in the future… just like training a dog.
      Third, point 1 and 2 are obvious.

      Like

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