Clare Francis, Data Fabrication, Data Falsification, Defamation, Defamation lawsuit, Due process, Expression of concern, Federal law, First Amendment to US Constitution, Misconduct, Paul S. Thaler, Reputation Damage, Research Integrity, Research misconduct, Retraction Watch, Scientific Integrity, Scientific Misconduct, Scientific publication, Social Media

Scientific Journals: Are Expressions of Concern Illegal?

PAUL S. THALER is Managing Partner at Cohen Seglias Pallas Greenhall & Furman PC, a law firm with offices in Washington, D.C. One of his main areas of practice is scientific misconduct. He has successfully defended clients accused of research misconduct, becoming a towering figure in this aspect of civil litigation. In addition, his firm provides a peerless level of sophistication in Title IX matters. Paul S. Thaler has been admitted to the Bar in Washington, DC and Maryland.

In regards to scientists enduring misconduct accusations, Paul S. Thaler made the following enlightening remark:

The first thing to remember is that the federal regulations, as well as the internal policies of most institutions, protect the confidentiality of respondents in research misconduct matters.  Thus, as a matter of federal law, institutions are prohibited from disclosing the identity of an accused scientist, except on a “need to know” basis, for example, to a member of the investigation committee, unless and until a finding of research misconduct is made.  These proceedings are not public as court is in criminal and civil disputes.  It is more comparable to proceedings against other professionals, such as lawyers, who are governed by their licensing organization.  Privacy in these matters is critically important as there is no public need to, or right to know, about professionals simply accused of wrongdoing.  What the public has a right to know about is a professional who has been found responsible for wrongdoing.  At that point, the public is alerted.  But because a professional’s reputation is so important to his or her career, the specter of an accusation can permanently stain that reputation and frequently the accusation is not well founded.  So the confidentiality of the process allows a full examination before the public is made aware.  We certainly do want to know about those scientists who have actually done something wrong that impacts science, but we do not, and should not, be concerned with those who are good scientists but caught up in a sometimes very political, internal dispute.

The bolded section is particularly enlightening because it implies that Expressions of Concern, very much en vogue with journals these days, are in all likelihood illegal, and so is the dissemination of such expressions by blogs such as Retraction Watch or other media. Of course the public does not have the right to now about mere accusations of wrongdoing or suspicions of invalid data, which often prove to be wrong. For example, pseudonymous Clare Francis, the venal whistle-blower of Retraction Watch, has scored plenty of false positives but we are not aware that Retraction Watch has been sued in Court yet. By contrast, the public is very much entitled to know about cases of proven invalid data resulting from wrongdoing. This is the spirit of the law and Paul S. Thaler has sensibly conveyed it.

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AAAS, Blog, Corruption, Data Falsification, Due process, Internet crank, Marcia McNutt, Mass hysteria, Open research, Post publication peer review, Research Integrity, Retraction Watch, Science, Science blogs, Science Magazine, Science Transparency, Scientific Crisis, Scientific Reproducibility, Scientific Research, Transparency and Openness

TOP: How Science magazine plans to deal with the intrusion of social media

Not long ago Science Editor Marcia McNutt published an appalling editorial entitled “Due process in the twitter age“, where she claimed that social media created an anxiety and added a sense of urgency to the post-publication peer review (PPPR) of reported scientific research. In a post at Science Transparency, we swiftly retorted that if the scientific establishment kept paying attention to blogs like Retraction Watch to conduct their business, they will only have themselves to blame for the current crisis. In our post we felt compelled to quote a Londoner from the Daily Mail (UK) who described the intrusion of social media in the most eloquent terms:

Social Media has turned us all into the baying masses of the medieval witch hunts, with no mediators of our hysterical views, and with the loudest, most ignorant and angry up at the front with their burning tweeting torches.

It would seem that Science magazine has decided to review their own position regarding how they intend to deal with the piracy of PPPR by social media. Marcia McNutt now claims that Science magazine will spearhead the implementation of TOP (Transparency and Openness Promotion), a set of new standards of transparency and reproducibility for the publication of scientific research. This initiative is inspired by the policy forum piece “Promoting an Open Research Culture” published in Science nearly an year ago. In fact, at Science Transparency we argued in support of this policy.

A Friday Evening Discourse at the Royal Institution; Sir James Dewar on Liquid Hydrogen, 1904 (oil on canvas) by Brooks, Henry Jamyn (1865-1925); The Royal Institution, London, UK.

A Friday Evening Discourse at the Royal Institution; Sir James Dewar on Liquid Hydrogen, 1904 (oil on canvas) by Brooks, Henry Jamyn (1865-1925); The Royal Institution, London, UK.

Transparency, availability of raw data, and full disclosure of all tools required by a person skilled in the art to reproduce the work is surely all that is needed to ensure the validity of reported research. This is true today as it was three centuries ago, when scientists were asked to perform their experiments in front of an audience at the Royal Institution. At Science Transparency we welcome the implementation of these TOP protocols as the best route to do away with corruption in science and to end the current hysteria promoted by social media in regards to the reproducibility crisis, real or perceived.

 

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Ariel Fernandez, Ariel Fernandez book, Ariel Fernandez books, Ariel Fernandez Research, Ariel Fernandez Stigliano, Biochemistry, Biotechnology, Book review, 阿列尔·费尔南德斯, Hasselmann Professor at Rice University, Michael Lynch, Physics at the Biomolecular Interface, Rice University, Rice University News, Springer Soft and Biological Matter

Book Review: “Physics at the Biomolecular Interface” by Ariel Fernandez

Physics at the Biomolecular Interface” is the latest book by Ariel Fernandez (阿列尔·费尔南德斯), the physical chemist and mathematician who developed the center manifold thermodynamics, unraveling the physical basis for the onset of life, and discovered the dehydron (脱水元), an idea that laid the foundation for the new field of epistructural biology. The hardcover is expected by June 8, 2016. The bibliographic information is as follows:

Title: Physics at the Biomolecular Interface

Subtitle: Fundamentals for Molecular Targeted Therapy

Series: Soft and Biological Matter

Author: Ariel Fernández

Publisher: Springer International Publishing, Switzerland

Hardcover ISBN: 978-3-319-30851-7

eBook ISBN: 978-3-319-30852-4

Number of pages: 483

Ariel Fernandez Book Cover

Ariel Fernandez Book Cover

Physics at the Biomolecular Interface, the third book by Ariel Fernandez, is no bedtime reading. Conceptually intricate and highly interdisciplinary but cast in Fernandez’s beautiful supple prose, this monumental work is, without a doubt Fernandez’s opus magnum. It  provides the fundamental scientific framework and discourse to handle biological matter physics, exploring the evolutionary axis of biology from the physicist perspective. In the author’s own words:

…the biological functionality of a soluble protein can only be fully grasped when its aqueous interface becomes an integral part of the structural analysis. Furthermore, the acknowledgment of how exquisitely the structure and dynamics of proteins and their
aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be grasped without dealing with interfacial behavior at multiple scales. This is essentially the dictum that guided the writing of this book.

Ariel Fernandez deals with biological interfacial phenomena in his own unique and transformative way. He introduces what he calls “epistructural tension“, a concept that relates to the reversible work needed to span the aqueous interface that envelops the structure of a soluble protein.  Epistructural tension is, he argues, key to biology when examined at the molecular scale since it steers molecular associations, drives protein folding and functionalizes water at the interface, prompting a substantial revision of biochemical mechanism. The impact of this concept reaches distant fields like enzymology, structural biology and pharmacological design, and the book exploits it within an incredibly broad spectrum of possibilities, spanning vast conceptual territory, from statistical physics to molecular-targeted therapy. For example, Chap. 1 introduces a statistical thermodynamics framework to handle the aqueous interface of a protein, while Chap. 17 describes the epistructure-based design of kinase inhibitors with controlled multi-target activity to treat cancer metastasis and overcome drug resistance. In spite of this astonishing latitude of interdisciplinary research, the conceptual progression remains smooth throughout the presentation, as the reader is guided by Fernandez’s characteristically supple prose.

Dr. Ariel Fernandez, 2016

Dr. Ariel Fernandez, 2016

Some highlights of the book certainly worth mentioning are:

The book can serve as a textbook, as originally intended, and also as an advanced monograph for practitioners in drug design or molecular-targeted therapy interested in the translational aspects of their art.

The book builds on original and highly meritorious research previously reported in professional journals by the author. Here are some quotes on different aspects covered in the new book:

On the discovery of the dehydron: “This is a very radical way of thinking. This is an experiment that actually backs up that radical way of thinking and that’s what’s striking about it.” Peter Rossky, interviewed by the University of Chicago News Office

On the pharmacological designs guided by epistructural patterns: “With tools such as those of Ariel Fernandez, the future certainly looks bright for constructing ever-better agents that can be combined safely and effectively to manage and eventually cure many forms of human cancer.” George Demetri, Review on the work of Ariel Fernandez commissioned by the Journal of Clinical Investigation

On the medical implications of the work of Ariel Fernandez: “The biggest message from this paper by Ariel Fernandez et al. is that a cardiotoxic cause can be identified and steered away from. There are hundreds of agents in development that could benefit from this research.” Thomas Force, interviewed by the Royal Society of Chemistry

On the Ariel Fernandez’s dehydrons as structural markers for molecular evolution: “One aspect of Fernandez’s research that is potentially groundbreaking is the observed tendency of proteins to evolve a more open structure in complex organisms. …This observation fits with the general theory that large organisms with relatively small population sizes — compared to microbes — are subject to the vagaries of random genetic drift and hence the accumulation of very mildly deleterious mutations… In principle the accumulation of such mutations may encourage a slight breakdown in protein stability. This, in turn, opens the door to interactions with other proteins that can return a measure of that lost stability. These are the potential roots for the emergence of novel protein-protein interactions, which are the hallmark of evolution in complex, multicellular species… In other words, the origins of some key aspects of the evolution of complexity may have their origins in completely nonadaptive processes.Michael Lynch interviewed by Rice University News Office on the work of Ariel Fernandez.

On Biomolecular Interfaces, the previous title by Ariel Fernandez introducing epistructural tension for the first time: “In this book author Ariel Fernandez introduces conceptual advances in molecular biophysics and translates them into novel pharmacological technologies. In so doing, he creates a new discipline named “epistructural biology”, focusing on the reciprocal interactions between interfacial water and protein structure. The epistructural biology approach enables researchers to address core problems in molecular biophysics such as the protein folding problem. The book surveys powerful theoretical /computational resources in epistructural biology to tackle fundamental problems, such as the physico-chemical basis of enzyme catalysis and the therapeutic disruption of protein-protein associations. The latter is recognized by many as the biggest challenge in structure-based drug discovery. A multi-disciplinary approach is exploited to engineer drugs, enabling decisive advances in molecular medicine with a tight control of drug selectivity. This book may well be Ariel Fernandez’s greatest contribution and its conceptual insights will enlighten and inspire readers. The author is also a masterful expositor which makes the book a pleasure to read.” Valentin Andreev.

Another comment on the previous title by Ariel Fernandez: “First and foremost, this book addresses an issue that is very important in protein research, namely, the interactions between a protein molecule and its surrounding water environment. This very complicated relationship is often simplified or ignored in molecular modeling. Such an ill-considered strategy simplifies the model but leads to unrealistic predictions of molecular behaviour. By contrast, this book introduces the reader to Epistructural Biology, a model that covers various important aspects of the protein-water interaction. The model is explained with an articulate clear writing style and backed up with enough mathematics to put the ideas on a firm theoretical foundation. The book is suitable for advanced undergraduate and graduate students. To help the student assimilate the ideas, the chapters include several problems with solutions. This is an excellent introduction for students wanting to get a start in Epistructural Biology.” Forbes Burkowski.

Biomolecular Interfaces may well be Ariel Fernandez’ most authoritative work. In Chapter 3 we find a semiempirical solution to the protein folding problem, in chapter 5 we find a way to disrupt protein-protein interactions for therapeutic purposes (a major challenge in the pharmaceutical industry), in chapter 7 we find Ariel Fernandez’ striking new finding: the catalytic role of packing defects in proteins, ushering a new biotechnology. The applications to drug design in the remaining chapters bring us many surprises, including a quantum mechanics development of the wrapping drug-target interactions pioneered by the author. Ariel Fernandez’ Biomolecular Interfaces is enjoyable and rewarding. Its conceptual richness, style, and breadth of interwoven disciplines, from Statistical Thermodynamics to Molecular Medicine, make it a valuable asset.” Xi Zhang.

To conclude, here is a biosketch of the author as provided by Springer:

Ariel Fernandez (born Ariel Fernandez Stigliano) is an Argentine-American physical chemist and mathematician. He obtained his Ph.D. degree in chemical physics from Yale University in record time. He held the Karl F. Hasselmann endowed chair professorship in engineering at Rice University and was a professor of bioengineering until his retirement in 2012. To date, he has published over 350 scientific papers in professional journals including Physical Review Letters, PNAS, Nature, Genome Research, and Genome Biology. Ariel Fernandez has also published two books Transformative Concepts for Drug Design (2010) and Biomolecular Interfaces (2015), both with Springer, and holds two patents (US 8,466,154 and 9,051,387) on biotechnological innovations. He is currently involved in research and entrepreneurial activities at various consultancy firms.

RELATED READING

ORCID Record for Ariel Fernandez

Selected publications of Ariel Fernandez

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Marcia McNutt, Post publication peer review, PubPeer, Retraction Watch, Science Magazine, Social Media

RE: “Due Process in the Twitter Age” by Science Editor Marcia McNutt

Marcia McNutt is the Editor-in-Chief of Science magazine, a well-known venue to communicate research results, and of other Science journals. She has recently contributed an editorial entitled “Due Process in the Twitter Age” where she tells us readers that the process of post publication revision has now changed because of the prominent role played by social media. Apparently, the anxiety created by social media, where anyone can hide and fire misconduct allegations or spill their anger at the world, fuels quick post-publication revision, putting pressure on journal editors. In other words, according to McNutt, social media influence the post publication fate of research articles because of the anxiety they generate in the scientific audience. Can you imagine a working scientist whose time is so precious reading blogs to judge or evaluate published research? It is hard to imagine that someone in McNutt’s position would say something so egregiously stupid but that’s pretty much what she wrote, I’m afraid.

The absurdity reached a climax when she identified social media outlets that in her opinion cause anxiety in the scientific establishment. She mentioned Retraction Watch, a blog created by two journalists, Ivan Oransky and Adam Marcus, where literally anyone comments anything, and its sister blog PubPeer, a sort of reading club contributed anonymously, where there is no way to tell whether the contributors are anybody’s peers or simply coopt the site to attack people. This leaves us wondering why Retraction Watch founder Ivan Oransky has been named Science’s Garbage Man (Muellsammler der Wissenschaft).

Clearly journals have only themselves to blame for the sorry state of post publication revision. As McNutt’s editorial piece makes it abundantly clear, ineptitude is the sole culprit of the current crisis. When a player in science policy says what McNutt has said, it leaves us wondering about the fate of research. Hopefully such nonsense will not prevail, otherwise research is doomed as we know it.

Perhaps the following quote by a lucid Londoner commenting in the Daily Mail (UK) may help Marcia McNutt put in perspective the scientific impact of social media:

Social Media has turned us all into the baying masses of the medieval witch hunts, with no mediators of our hysterical views, and with the loudest, most ignorant and angry up at the front with their burning tweeting torches.

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美国国立卫生研究院, Howard Hughes Medical Institute, John Ioannidis, National Institutes of Health, NIH, NIH funding, Peer Review, Principal Investigator, Research grant, Study Section

Peer Review: Is NIH Rewarding Talent?

In a striking analysis published in Nature, Stanford University researcher John Ioannidis, the expert on metadata investigation at the Stanford Prevention Research Center, has seriously questioned the way the National Institutes of Health fund research proposals. He and his colleague Joshua Nicholson have argued in what seems like a rousing condemnation of the status quo that peer-review, the process by which study sections review and rank research applications, is totally broken.  The researchers argued that peer review at NIH (简称) encourages “conformity, if not mediocrity”, favoring proposals submitted by people who know how to network and play the petty games of academic sociology, rather than those by people who have original and potentially influential ideas.

These conclusions rest heavily on the observation that only 40 percent of scientists with highly cited papers (say, those with more than 1000 citations) are principal investigators on NIH grants. That is, those scientists whose peers value their work most highly are often not receiving NIH support for that work.

Of course, the analysis may be imperfect. Here is my critique for one: Using high citation level as a proxy for originality is probably not entirely correct (but then what is a good proxy for originality?). It is also possible that a good percentage of these investigators have not even applied for NIH funding in the first place. And, finally, they may have other sources of support for their research, most likely, the Howard Hughes Medical Institute (should we then conclude that HHMI funds more original research than NIH?).

It is perhaps true that the peer review system is broken. The majority of the authors of the most influential papers in medicine and the life sciences seem not to have NIH funding according to Ioannidis and Nicholson, and their funding rate is possibly less than average. Perhaps the most disturbing observation, the one that truly needs the closest scrutiny, is that study section members are almost always funded while their citation impact is typically low or average: they are not the high-impact innovators.

This leaves us with a sad reflection. Probably a truly innovative idea cannot be appreciated by the peers, while if peers can readily grasp it (to the level they are willing to fund it), it is probably not innovative.

NIH is seemingly aware of this problem and has earnestly tried to address these concerns introducing specific award categories such as the Pioneer and New Innovator Awards. Perhaps Ioannidis and Nicholson may be willing to evaluate the efficacy of these categories in capturing true talent.

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Argentina, Ariel Fernandez, Ariel Fernandez Patent, Ariel Fernandez Stigliano, Biotechnology, Converging Technologies, Dehydron, 阿列尔·费尔南德斯, National Science Foundation, NSF, ProWDSciences, Sangtae Kim, Weishi Meng on Ariel Fernandez

Converging Technologies at ProWDSciences: Protein-Water-Dehydron-Bingo!

Translational research involving converging technologies is clearly the way of the future for drug discovery and the pharmaceutical industry. At least, this is what we are being told by leading scientist Sangtae Kim in a recent NSF lecture on Converging Technologies. The great Sangtae Kim himself appears to have followed this mantra when he founded the biotech company ProWDSciences, where “ProWD” stands for Protein-Water-Dehydron. As the name informs us, ProWD Sciences is all about converging technologies. The idea is enshrined in the unfamiliar word dehydron (脱水元). Dehydron is the central concept of epistructural biology, a new scientific field developed by Ariel Fernandez to deal with the complex physics of the protein-water interface. To properly define dehydrons, a multiscale theory of biological water may be required, as Kim would say. Yet, as described in the book Biomolecular Interfaces, we may say that dehydrons refer to structural deficiencies in proteins that promote interfacial tension, are endowed with catalytic properties and serve as selectivity filters for drug design.  As the research of Ariel Fernandez suggests, the dehydron may well be the point of convergence of nanotechnology, biotechnology, molecular engineering and learning technologies, the sort of convergence that Kim described in his NSF lecture. Time will tell us how this technological convergence will enable the rational design of safer anticancer drugs with optimal selectivity control.

Ariel Fernandez and Sangtae Kim

Ariel Fernandez (left) and Sangtae Kim toying with a dehydron-based molecular design at the Morgridge Institute for Research (University of Wisconsin-Madison)

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Defamation, Defamation lawsuit, Karolinska Institute, Laura and John Arnold Foundation, Macchiarini, Meta-Research, Misconduct, Paolo Macchiarini, Retraction Watch, Scientific publication, Transplant surgery

Paolo Macchiarini portrayed by Retraction Watch: defamed, probably, vindicated? Never!

As the peer review system appears to be failing and bogus research keeps surfacing, post publication peer review (PPPR) is becoming a necessity. The problem is who conducts PPPR (*). Certainly an indiscriminate blog run by nonscientists nudging journals into reaction, where anyone can voice their opinion or make misconduct allegations is not the way to go about it. A similar opinion is held by Paolo Macchiarini, the eminent surgeon who saved human lives and was defamed but never vindicated by Retraction Watch. Paolo Macchiarini has chosen to write an open letter in Retraction Watch to voice his opinion on the blog. The fact that he has chosen this course of action after being cleared of misconduct, instead of suing Retraction Watch for defamation (at least for now), attests to his good nature, and may seem perplexing to some.

 

Paolo Macchiarini

Paolo Macchiarini ASSOCIATED PRESS

Surgeon Paolo Macchiarini achieved international fame for inducing the formation of tracheas from implants containing stem cells. His career has seen reversals of fortune, especially when Macchiarini was portrayed as having committed misconduct by Retraction Watch. The blog echoed and disseminated a provisional highly damaging report by a single individual that had only seen a portion of the evidence, thus defaming Macchiarini. With all the available evidence at hand, Macchiarini’s home institution, the Karolisnka Institute, refuted the damaging accusations and issued a very different veredict: Macchiarini acted “without due care,” but did not commit misconduct. Rather than suing Retraction Watch, Macchiarini responded in the blog itself, voicing his critical opinion on the blog and reacting (quite gracefully) to the gross abuses he endured.

In his opening paragraph, Macchiarini agreed (as we do) that the general goals of Retraction Watch may be commendable, notwithstanding the defamation he suffered at the hands of the bloggers. In his open letter, Macchiarini takes issue, and rightly so, with the gross breach of confidentiality by Retraction Watch, as the investigation of his research practices was being officially conducted. Allegedly, Retraction Watch even infringed the confidentiality of patient’s medical records, a major ethical breach possibly actionable in Court.

Retraction Watch has frequently reported false allegations of scientific misconduct against Paolo Macchiarini and other scientists. These nefarious allegations have found their way to the blog, and their dissemination constitutes a gross breach of confidentiality guidelines.  We should emphasize that in the case of Macchiarini, Retraction Watch was NOT reporting on a retraction, or on a case of scientific misconduct. In the words of Macchiarini:

“The alleged misconduct was reported to the editors of the very well-respected journals involved, and to my institution, who at the time of the leak were going through the normal process of official investigation.  This was nothing more than academic ‘gossip’.”

No, Paolo Macchiarini! We disagree with you. This is defamation, pure and unadulterated, and you are possibly entitled to massive reparations for the damage that Retraction Watch has inflicted to your reputation.

Retraction Watch lives dangerously by its unique set of rules, whereby the infringement of confidentiality in investigations of alleged scientific misconduct is entirely permitted. They chose to live dangerously, as they do not conform to the basic tenet of societies that function under the rule of law, whereby a person is innocent unless proven guilty in a court of law. Retraction Watch fails to grasp the essential operating principle that the defendant must be protected by confidentiality because he/she is a-priori presumed innocent.

Retraction Watch lives dangerously indeed.  False accusations of scientific misconduct are common in science and are often motivated by the desire to destroy someone’s career.  A blog that indiscriminately publishes any allegation real or false at any stage of investigation will only enhance the efficacy of false accusations. We concur with Macchiarini in that Retraction Watch has grossly overstepped its mark by providing a platform for nefarious gossip and malfeasance in a way that hurts the academic community.

(*) There are serious efforts to curate the corpus of scientific publication. These efforts are largely sponsored by John and Laura Arnold, a young billionaire couple from Houston, that is currently financing large-scale meta-research projects. One such project is the Meta-Research Innovation Center at Stanford, or METRICS. These projects aim at effectively addressing major issues like reproducibility.

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