Ariel Fernandez, an Argentine chemist (who claims to hold the fastest-awarded PhD from Yale) and the subject of institutional investigations at multiple universities, has corrected several papers recently. What makes the moves particularly unusual — and interesting — is the stated reason for the amendments: disclaiming any funding from the National Institutes of Health for the work.
Fernandez was the recipient in 2005 of a $275,880 award “Protein packing defects as functional markers and drug targets.” The following year he received $294,217, and in 2007, $284,461, for the same four-year project, if we’re reading the link correctly.
Fernandez, readers of this blog might recall, threatened us with legal action when we wrote last spring about an expression of concern regarding his 2011 paper in BMC Genomics, “Subfunctionalization reduces the fitness cost of gene duplication in humans by buffering dosage imbalances.” According to that notice:
After publication of this article (Fernandez et. al, BMC Genomics 2011, 12:604) it was brought to the Editors’ attention that the data generated by the first author, Ariel Fernandez, seemed anomalous. One of the author’s institutions found that the data were not reproducible from the described methods, but an investigation by the author’s other institution did not find the data or their interpretation suspicious. Given the conflicting conclusions of these investigations, the Editors advise the readers to interpret the data with due caution. We apologize to all affected parties.
Fernandez wrote an unusual rebuttal of sorts to the Expression of Concern on Academia.edu, which states:
My results in this paper were challenged. The challenger concealed his identity, his credentials and his employment. The paper was critically reviewed by a senior faculty member at the University of Chicago at the behest of BMC Genomics. The paper was found to stand on firm ground. The professor found the work to be correct and reproducible. Therefore, the paper will not be retracted and the record will not be corrected.
One of the new corrections involves a 2008 paper in PLoS Genetics, “Protein Under-Wrapping Causes Dosage Sensitivity and Decreases Gene Duplicability.” According to the article:
This research was supported by National Institutes of Health (NIH) grants to WHL and AF.
WHL is Wen-Hsiung Li, of the University of Chicago.
But the correction states:
The research of A. F. reported in this article was incorrectly stated to have been supported by the NIH grant R01 GM072614 entitled “Protein packing defects as functional markers and drug targets” (PI: Ariel Fernandez). The work is thematically unrelated to the grant. The author apologizes for the mistake.
That paper also has come under scrutiny at PubPeer, where a reader has questioned the validity of the data.
Fernandez also corrected a 2008 paper in Genome Biology, “Protein structure protection commits gene expression patterns”:
The research reported was incorrectly stated to have been supported by NIH grant R01 GM072614 “Protein packing defects as functional markers and drug targets” (NIGMS, PI: Ariel Fernandez). The work is thematically unrelated to the NIH grant and did not receive any NIH support. The author apologizes for the mistake. Ariel Fernandez
And he issued a two-fold correction of a paper in ACS Nano, “Bottom-Up Engineering of Peptide Cell Translocators Based on Environmentally Modulated Quadrupole Switches,” for the funding issue and a problem with one of the figures:
We have two changes to make to our article:
(1) The research reported was incorrectly stated to have been supported by NIH grant R01 GM072614 (NIGMS) entitled “Protein packing defects as functional markers and drug targets”. The work published in ACS Nano is thematically unrelated to the NIH grant and did not receive NIH support.
(2) In Figure 3b, the more informative quantitative analysis of cellular localization for peptide 1, (Arg)9, and TAT shown below should replace the original incompletely documented figure.
Now, we don’t work with NIH grants, but we’re wondering if it’s quite so simple to call a take-back on this sort of thing. After all, universities tend to have a keen interest in faculty grants, what with overhead, NSF, ORI and all.
Which makes this correction for “Rational Drug Redesign to Overcome Drug Resistance in Cancer Therapy: Imatinib Moving Target,” published in 2007 in Cancer Research, even more interesting:
In this article (Cancer Res. 2007;67:4028–33), which was published in the May 1, 2007 issue of Cancer Research(1), the authors wish to make a clarification in their grant support statement, which is appended below.
The reported experimental findings validating the theoretical results in the article were obtained in compliance with the specific aims and collaborative agreements with Eli Lilly and Company recited in the NIH/National Institute of General Medical Sciences (NIGMS) grant R01-GM072614 (Ariel Fernandez, Principal Investigator).
So, just to keep score: Fernandez seems to be saying that he did the work in the Cancer Research paper using NIH money, but not the others — even though their titles so closely match that of the grant itself.
Fernandez in his CV claims to have received a total of $1.6 million from the NIH through the RO1. But he lists no other source of government funding (he does claim to be the recipient of “unrestricted research funds” from Lilly).
We haven’t done an exhaustive search of Fernandez’ bibliography, but we did find a couple of articles that cite the NIH grant. For example, in 2007 Fernandez published “Peptide translocators with engineered dehydration-prone hydrogen bonds” in the Journal of Chemical Physics, which stated:
The research of one of the authors (A.F.) is supported by NIH Grant No. R01-GM072614, by a grant from the John and Ann Doerr Fund for Computational Biomedicine (Program No. GC4R 2005), and by an unrestricted grant from Eli Lilly and Company.
And this 2007 paper, “An anticancer C-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic,” in the Journal of Clinical Investigation, on which he was first author, notes:
The research of A. Fernández was supported by NIH grant R01 GM072614 and by a grant from the Gulf Coast Center for Computational Cancer Research.
Fernandez hasn’t corrected the record when it comes to his 2006 application for a U.S. patent, for what he called “Methods and compositions related to wrapping of dehydrons:”
This invention was made with government support under R01 GM072614-01 awarded by National Institutes of Health. The government has certain rights in the invention. …
This application describes compounds designed using a novel technology in drug discovery and drug-based imaging/detection, i.e., the wrapping technology. This technology is based on identified singularities in the structure of soluble proteins. In contrast with drug-design approaches based on standard structural considerations, the packing of a protein, or more precisely, its dehydron pattern, may be used as a selectivity filter to design small-molecule inhibitors. The wrapping technology described herein is a novel form of rational design for avoiding side effects in drug therapy and sharpening the inhibitory impact of drugs on the oncokinome.
Embodiments of the invention are based on packing or wrapping defect not conserved across related proteins. Thus, the inventors introduce an additional technology, the wrapping technology, to target packing defects and turn molecular prototypes into therapeutic and diagnostic tools.
Finally, Fernandez has this doozy of a correction for a 2003 paper in PNAS, “Structural defects and the diagnosis of amyloidogenic propensity,”:
The undersigned authors note the following: “We wish to bring to your attention an issue regarding our PNAS publication referenced above. Although we cite our earlier PNAS publication (see ref. 23 therein), portions of the text and figures are similar to ref. 23 and were not properly attributed. Ref. 23 reports an experimental result, while the paper indicated above reports theoretical work. Nevertheless, in the examples below we should have provided a citation to ref. 23 as the source of the information.
“Fig. 2 was adapted from Fig. 1 in ref. 23. Fig. 5 was adapted from Fig. 2 in ref. 23.
“The following text in the section titled ‘Structure Wrapping and Molecular Disease’ on page 6447 of our text is similar to the text in the fifth paragraph of the “Results and Discussion” section on page 2392 in ref. 23:
Figs. 2 and 3 display the UWHBs for Hb β-subunit (pdb.1bz0, chain B) and human cellular prion protein (pdb.1qm0) (12–14). Within the natural interactive context of the Hb subunit, the UWHBs signal crucial binding regions (24): UWHBs (90, 94), (90, 95) are associated with the β-FG corner involved in the quaternary α1β2 interface; UWHB (5, 9) is adjacent to Glu-6 which in sickle cell anemia mutates to Val-6 and is located at the Val-6-(Phe-85, Leu-88) interface in the deoxyHbS fiber.“The following text in the section titled ‘Toward a Structural Diagnosis’ on page 6449 of our text is similar to the text beginning in the last paragraph on page 2392 in ref. 23:
The distribution of proteins according to their average extent of hydrogen bond wrapping and their spatial concentration of structural defects is shown in Fig. 5 (see also ref. 23). The sample of 2,811 PDB proteins is large enough to define a reliable abundance distribution with an inflection point at ρ = 6.20. The integration of the distribution over a ρ-interval gives the fraction of proteins whose ρ lies within that range. Of the 2,811 proteins examined, 2,572 have ρ > 6.20, and none of them is known to yield amyloid aggregation under physiological conditions entailing partial retention of structure. Strikingly, relatively few disease-related amyloidogenic proteins are known in the sparsely populated, underwrapped 3.5 < ρ < 6.20 range, with the cellular prion proteins located at the extreme of the spectrum (3.53 < ρ < 3.72)….
The range of H-bond wrapping 3.5 < ρ < 4.6 of 20 sampled PDB membrane proteins has been included in Fig. 5 for comparison. As expected, such proteins do not have the stringent H-bond packing requirements of soluble proteins for their H bonds at the lipid interface. Thus, this comparison becomes suggestive in terms of elucidating the driving factor for aggregation in soluble proteins: Although the UWHB constitutes a structural defect in a soluble protein because of its vulnerability to water attack, it is not a structural defect in a membrane protein. The exposure of the polar amide and carbonyl of the unbound state to a nonpolar phase is thermodynamically unfavorable (22). The virtually identical ρ value for human prion and outer-membrane protein A (Fig. 5) is revealing in this regard.
Furthermore, all known amyloidogenic proteins that occur naturally in complexed form have sufficient H-bond wrapping within their respective complexes (ρ value near 6.2). Their amyloidogenic propensity appears only under conditions in which the protein is dissociated from the complex (compare Fig. 5). This finding is corroborated by the following computation. If an intramolecular hydrogen bond is underwrapped within the isolated protein molecule but located at an interface upon complexation, then to determine its extent of wrapping within the complex, we take into account the additional residues in the binding partner that lie within the desolvation domain of the intramolecular H bond. Thus, the uncomplexed or monomeric β2-microglobulin (pdb. 1i4f) (21) has ρ = 5.2, putting it in the purported amyloidogenic region. However, upon complexation within the MHC-I, its ρ increases to 6.22.“The original work on the diagnosis of amyloidogenic propensity was carried out in the summer of 2002 at Osaka University. We apologize for not alerting readers of the similarities between these two texts.”
Ariel Fernandez
R. Stephen Berry
If I was to be cynical, I’d say he’s doing this to try and protect himself from prosecution now that his shenanigans have been discovered…
I think that’s the only reasonable explanation.
perhaps he should have spent a little longer on his PhD, perhaps ethics and proper procedures in
scientific publishing and keeping your ego in check.
This is going to be fun!
just thinking: wtf?
I was right, it is fun. I just took a look at the paper being questioned on PubPeer: https://pubpeer.com/publications/18208334
Odd patterns are emerging in the data. There may be more to find.
Obviously the key fact is that if NIH didn’t fund a paper then the ORI cannot investigate it. And its validity or otherwise cannot be taken into consideration by the NIH or ORI.
Also, I think everyone here will agree that those who graduate especially early from a Ph.D. program do so because the department wants them out, not because they are Very Good.
ORI is a waste of taxpayer money without subpoena power and should be defunded, purged of
the existing donothing check cashers, and replaced with an agency outside PHS with subpoena
power and non MD PhD types who can actually do the job
There is such an agency outside NIH with subpoena powers. We call them “the police”. The problem is it is hard to get them interested in claims of academic misconduct. You know, what with murders and stuff going on.
The question is: How much money should be taken away from research in order to pursue misconduct through the courts? It would be extremely expensive, and would certainly fail.
not quite on the second assumption. In Brazil departments get extra “points” for graduating students as fast as possible, thus this is encouraged. Many professors try to get popular by graduating their students as soon as they can, whatever means employed. And usually these students are led to believe they are Really Good, so that they do not complain about not having had more time to learn (e.g. about Ethics).
The graph above is an interesting representation of data.
Maybe learning about the value of error bars on graphs would have been useful for the high flyer in question. Forgive my ignorance but that graph without error bars is unfathomable.
Does anyone do similar work and can comment on the quantitative analysis that was performed?
“Many professors try to get popular by graduating their students as soon as they can”
I am aware that such things occur outside of the US. However, in the US, and particularly in biology departments, it can take a long time to finish a degree. I left my department without my degree after 7.5 years.
Thanks this is really interesting information from another place. In Brazil if one is refused to get a degree, it generates a huge problem to that department, so no-one expects someone to fail graduating. This is also a problem as anyone who stays until the end of the graduation period will be given a degree unless they, e.g. kill someone at the department.
Time to completion for degrees depends on the field a lot more in the USA, from what I have seen. (I got my phd in 4.5 years– but, it’s in chemistry, not biology.)
Whereas other nations do seem to want to “rush” their students out of the university and into good STEM jobs (can’t say I blame them). In the US, many phd students are not starting with a 2 year Master’s (like they do in Europe), just a 4 year Bachelor’s; so that might explain some of it. I think if you added on the time it took to get a Master’s, many time-to-degree outcomes might start to even out a bit between different countries.
Absolutely. If the papers do not present (anymore) NIH-funded work then “El Gran Hombre” is, allegedly, immune from ORI investigation of his allegedly dubious results. How amazing, that such an intellectual powerhouse – perhaps the most brilliant man on the planet itself – could mistakenly attribute the source of his research support. Several times. One might think that in terms of intellectual achievement accurate funding attribution is a half-step above successfully spelling one’s name. But perhaps we fail to see the brilliance: with that pesky NIH out of the picture, perhaps he can now rake in millions!
Or perhaps not. I would be curious to learn about the verbal gymnastics utilized by Eli Lilly and Company and the other private funding sources to express their confidence in “El Gran Hombre” and his work. After all, what basis could there possibly be for any funding organization/company to be seriously concerned about the validity of work coming from a Giant Among Men who repeatedly misidentifies their funding source(s)? And is repeatedly targeted for investigation? And repeatedly needs to correct his published work? I also wonder how confident they can possibly be in the likelihood that any of the money funneled to “El Gran Hombre” will ever translate into meaningful/reliable/clinically-approved/profitable vehicles.
On what baisis could he possibly threaten a lawsuit?
John Searles
The PubPeer investigation has just gone nuclear. Someone has presented data plots that are really quite astonishing.
Now that the US government is up again, the NIH Reporter website is useful. That is important, because it tells which papers Fernandez claimed credit for as results of the NIH Grants. (Pretty much same data as EnGrant, but official).
0) Click on that link.
1) Put in Fernandex Ariel for PI
2) Click on Submit Query at bottom. That gives you “no results” and some choices.
3) Click on “Search all fiscal years”
Voila: 4 grants: 5 R01 GM072614 01A1 through 04, 2005, 2006, 2007, 2008.
4) For each of the 4 years:
a) Click on GM072614, which gives that description.
b) CLICK on RESULTS.
A brief look finds 2 of the papers he disavowed as having anything to do with the NIH:
04 Protein structure protection commits gene expression patterns. 2008 paper in Genome Biology
04 Bottom-up engineering of peptide cell translocators based on environmentally modulated quadrupole switches. ACS nano. 2008 Jan; 2 (1) :61-8
Now, that might a problem, because he claimed credit from NIH for work that he later said wasn’t.
I had to research this sort of thing a while back when writing this, where 2 researchers did all sorts of work that had nothing to do with their grants, and then claimed them, either on Acknowledgements or in reports to funders, including NIH.
The fourth correction (for Cancer Res.) is odd, but I think it is also an attempt to disclaim NIH funding. The original article acknowledged NIH funding, so what is being corrected or clarified? The correction states that some results were “obtained in compliance with the specific aims and collaborative agreements with Eli Lilly and Company recited in [Fernandez’s NIH grant]” That does not actually say that any work was funded by NIH. I think he is trying to claim that, even though the work was mentioned in the grant application, it was not supported by NIH funds.
The CV he has posted raises many doubts on this academician’s “achievements”…
Rats, sinking ship, jumping, are the words that spring to my tired mind this Friday afternoon. Weird – I cannot see why.
This guy reminds me of Billy Crystal’s character Fernando – he looks mahvelous!
http://www.dailymotion.com/video/x2cu7f_billy-crystal-marvelous_music
Steve Berry got caught up in this mess??
He has co-authored 13 articles with Fernandez:
http://www.ncbi.nlm.nih.gov/pubmed/?term=Berry+RS+Fernandez+A
Two of these came after their retraction for duplicate publication. An earlier paper of theirs had a correction that pointed out overlap with a previous publication and unreferenced reuse of figures.
Do you know him?
Steve Berry has, I mean (I meant this as a reply to Eli Rabbett).
From Wikipedia, comments section: “According to the Collegium Basilea (Swiss Institute for Advanced Study) website at Academia.edu, Dr. Ariel Fernandez is currently an Honorary Faculty Member who works at this institution. The letter of appointment signed by the president of Collegium Basilea can be downloaded from the website: http://colbas.academia.edu/ArielFernandez”
What I have to state (as a Swiss researcher who had never heard of this institute): This “Collegium Basilea (Swiss Institute for Advanced Study)” is an obvious bogus thing. It is basically a virtual “institute” with no buildings and staff. The address given on its webpage is a private house where you can find a Chinese restaurant, a car spare-parts dealer, some funny companies and flats of private persons.
According to the web-page (http://www.colbas.org/) it has “no residential accommodation”, but it encourages intellectual exchange between members… and you can become a member by applying to the president – and paying an annual subscription.
The president is a Mr Jeremy Ramsden who apparently is a true scientist, but has a rather similarly colorful CV and unclear affiliation situation like A. Fernandez. You can try to find out where or what he really is by googling, but I gave up after some time.
So I think this tells anybody who wants to know what kind of “institute” that is. Everybody can join and it has no scientific credibility at all. However, the web-site is full of claims of other bogus institutes and organizations (which can only be reached by the e-mail: [email protected]….
It should not be so difficult to find out the validity of the results from the Plos paper or the BMC paper. Most of the results are calculated from the PDB or other structural data from the Protein Data Bank. If the calculation equations are clear, it should not be difficult to reproduce these results if they are valid. I don’t understand why the author from https://pubpeer.com/publications/18208334 simply plots the data points without acutally calculting them from the source. I would like to see a more thorough investigation into these concerned results since the work from Ariel is actually very interesting regardless of his personality/whatever gossips.
One of his institutions investigated the BMC paper and concluded that the results could not be reproduced. Suspicious patterns have been revealed.
Thank you! This is not good news and alarming, please also see his paper coauthored with Michael Lynch:
Fernández A, Lynch M. 2011. Non-adaptive origins of interactome complexity. Nature 474:502–505.
In the supplementary information and methods of the main article, there are detailed equations to calculate all those data points for figures with plots to support the paper’s main hypothesis. It is no easy job to reproduce these results from those equations. Independent trained Physicists/Biochemists are needed to reproduce them. Some of his prominent coauthors are not trained Physicists/Biochemists, most are Geneticists, for example, Michael Lynch and Wen-Hsiung Li. Maybe that is one of the major concerns that when scientists collaborate on large scale interdisciplinary projects (e.g., how do you validate the results of your coauthors?).
Because these papers basically talk about similar ideas from Ariel, a through investigation of all his major papers is required to find out the validity of the results.
For that Nature paper, Fernandez has provided a tutorial because of “the need to address the difficulties encountered by some readers who tried to reproduce and interpret the raw data”:
http://tinyurl.com/po6uskv
It tells us that “The sizeable Supplementary Information provided with the original publication proved insufficient to address the unfathomable hurdles that some readers encounter.”
Thanks! I will follow that tutorial, and to see how far I can get to reproduce some of his results.
Good luck.
I mean that simultaneously as sincere encouragement and dismay at the prospects that you will be able to reproduce the results. I predict that you will be told that your difficulties are “unfathomable” before it’s over.
Please do keep us informed, here or on PuPeer.
Don’t waste your time. The calculation in the tutorial doesn’t even match the methods described in the paper. I am willing to bet serious cash that nobody can reproduce that data.
I agree, but would like to see somebody try and report on what happens.
Yet another strange Correction concerning funding has appeared for one of Fernandez’ papers:
http://www.jci.org/articles/view/73378
The original paper acknowledged his NIH grant (among other funding sources). The correction adds this:
“The experimental findings reported in Figure 5 validating the theoretical results in the paper were obtained in compliance with the aims and collaborative agreements with Eli Lilly and Co. specified in the NIH/NIGMS grant R01GM072614 (A. Fernandez, principal investigator).”
What is going on here? Should we be scrutinizing Figure 5?
He published 23 papers in his first year as an asst prof .. amazing!
http://www.as.miami.edu/chemistry/history/umchem/UMCHEM%201991%20apr.pdf
I also heard he is a great scholar in many other respects, including the ability to translate Russian into English!
I am not sure whether you are sincerely praising Fernandez or being sarcastic. Needless to say, the usual concern about quality vs. quantity is amplified in this case due to his several recent questionable papers.
Russian? Doveryai, no proveryai, I suppose. Well, maybe not doveryai any more.
This reminds me of an old joke in my field: no matter what amazing thing you come up with, somebody probably published it in Russian first. Usually this happens by accident.
I remain puzzled as to what you’re trying to tell us about Fernandez. You seem to be quite familiar with him, since you referred us to a 22-year-old department newsletter item about him. What’s the scoop?
It’s more fun this way.
His book must be amazing. Four people gave it five star reviews within days of release, even before they could probably even read it! Of course, Ana Beaven is his friend who runs a restaurant in Houston, and Sean Sessel is his former student, so maybe they had advance copies. None of them has submitted a review before or since, so they must have been really moved by his incredible book!
http://www.amazon.com/Transformative-Concepts-Drug-Design-Wrapping/dp/3642117910
Yes, his sockpuppetry is artless, but let’s not give him any clues about how to improve. But what about his scientific claims? And what does this all have to do with Hindu mythology?
Hindu mythology? I was thinking more Greek or Roman. He takes awfully nice pictures, don’t you think?
Don’t you think this whole discussion becomes a little childish?
There’s one thing to expose scientific misconduct for the better of the community – bullying of people for behavior which one does not agree with is another thing.
Don’t be silly. You can’t bully a man as great and powerful as A.F. He’s a genius – he doesn’t even care about what normal people say, and nor should he, because he operates on a higher intellectual and moral plane, where normal rules of, say, data manipulation, simply don’t apply.
This is not bullying. Nobody is personally harassing him or posting malicious gossip. Moreover, nobody has made a single accusation against him, even if you might imagine differently based on your personal interpretation of what was said. People are within their rights to post opinions, riddles and sarcasm. If you don’t find it entertaining or illuminating, then don’t read it.
There are two more, both handled with a single “Addendum” in Drug Discovery Today: http://www.sciencedirect.com/science/article/pii/S1359644613003103
It says this:
“The reported experimental findings validating the theoretical results in the paper were obtained in compliance with the specific aims and collaborative agreements with Eli Lilly and Co. recited in the NIH/NIGMS grant R01GM072614 (Ariel Fernandez, PI).”
That’s a total of 7 papers with such corrections.
Why would anyone do this unless ORI was going after them? If that is the case, it makes him look more guilty in my opinion to make all these corrections. I just cannot imagine anyone could mistake the funding source on seven different articles, so something is pretty fishy about the whole situation.