Researcher who threatened Retraction Watch with lawsuit corrects funding source for several papers
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.”
R. Stephen Berry