Ariel Fernandez, Ariel Fernandez Publications, Ariel Fernandez Stigliano, Bert Vogelstein, Cancer Cure, Cancer Research, Immunotherapy, Keytruda (pembrolizumab), Lynch syndrome, Mismatch Repair Deficiency

Cancer Cure Within Reach: Our Gratitude to Ariel Fernandez and Especially to Bert Vogelstein



Bert Vogelstein and Ariel Fernandez (aged 69 and 60, respectively).

The immune checkpoint blocker pembrolizumab (Keytruda, Merck) has proven most successful to treat solid tumors harboring a DNA mismatch repair (MMR) deficiency.  This striking result recently reported by Luis Diaz Jr., Bert Vogelstein and their collaborators was anticipated a couple of years before by Dr. Vogelstein, a towering figure in oncological research. Ariel Fernandez has now shown that it is possible to generate a drug-promoted phenotype mimicking the MMR deficiency in solid tumors and thereby engineer a generic hypersusceptibility to Keytruda. This sensitivity is achieved through drug-induced metabolic stress on DNA synthesis.

The striking results by Diaz, Vogelstein and coworkers prompted Ariel Fernandez to address the following question: Is it possible to induce the MMR deficiency in any solid tumor, for example through targeted drug-based therapy, and thereby enhance the cancer antigenic activity and diversity to turn the Keytruda-drug combination into a universal cure for cancer?


Ariel Fernandez, Trends in Cancer, 2017

As work at Ariel Fernandez Consultancy reveals, the answer to this question is a resounding yes. The key to the problem resides in identifying a signaling pathway that gets recruited to promote MMR and then identifying a kinase inhibitor that would block that pathway.  The MMR deficiency-inducing kinase inhibitor has been found at Ariel Fernandez Consultancy. The potential of such drug-Keytruda combinations as universal treatments for solid tumors deserves clinical evaluation. Collaborative work is underway at Ariel Fernandez Consultancy to validate this paradigm. This may well be a decisive step in cancer cure.

Related Reading

Ariel Fernandez: “Engineering Tumor Hypersusceptibility to Checkpoint Immunotherapy”, Trends in Cancer (2017) Published online September 4.


Applied Mathematics, Ariel Fernandez, Ariel Fernandez book, Ariel Fernandez Stigliano, Book review, 阿列尔·费尔南德斯, Protein Biophysics, Ridgway Scott

Book Review on “A Mathematical Approach to Protein Biophysics” by Ridgway Scott and Ariel Fernandez: An Introduction to AF’s Solution to the Protein Folding Problem

A new book by Ridgway Scott and Ariel Fernandez is coming out. Its title “A Mathematical Approach to Protein Biophysics” (Springer, 2017) feels unusual at first. Why do we need a mathematical approach to understand proteins? Perhaps we need to be reminded that the major problems in molecular biophysics, such as the protein folding problem, have remained open because they demand a level of intellectual maturity that is not yet commonly found in the biological sciences and can be provided by applied math. And yet, few applied mathematicians have managed to say some relevant to biology partly because, rather than trying to find out how nature did it, they try to tell nature how to do it. Here I am referring specifically to the protein folding problem, whose first-principle solution was finally published by Ariel Fernandez in 2016 (Physics at the Biomolecular Interface, Chapter 3). When we think carefully about these monumental challenges, the need to engage mathematicians in the development of molecular biophysics hardly needs justification. The new book by Ridgway Scott and Ariel Fernandez fulfills the need admirably, serving as a mathematician’s introduction to protein biophysics.


The publication particulars are:

Title: A Mathematical Approach to Protein Biophysics

Authors: L. Ridgway Scott, Ariel Fernández

Publisher: Springer International Publishing AG, CH

Pages: 284

Year: 2017

Price: 69.99 US dollars

Hardcover ISBN: 978-3-319-66031-8

Series Title: Biological and Medical Physics, Biomedical Engineering

Topics: Mathematical and Computational Biology



Corruption, Data Fabrication, Data Falsification, Joshua L. Cherry, Joshua L. Cherry NIH, Meta-Research, Misconduct, Post publication peer review, Post Publication Peer Review Scam, Research Integrity, Research misconduct, Science reproducibility, Science Transparency, Scientific corruption

Reproducibility crisis, sure, but the real crisis is who handles the crisis

The New York Times wants to make us aware there is a reproducibility crisis in science. This is hardly news at all. There surely is a problem and has been there ever since science began to be run like a business, with its system of gratification and punishment, with the explosion in the number of practitioners and the number and size of professional journals, the pressure to excel, the emphasis on quantifying the impact, the system of extramural funding, etc. Take any under-regulated activity, create a system of gratification and you have a problem. It is called human nature.

The real challenge for science today is who is handling the perceived crisis. The science establishment got caught off guard on this one. As it turns out, the ones now handling the crisis are precisely those who installed the perception that there is a crisis in the first place. These are, perhaps with a few exceptions, angry people, science drop-outs and losers who found that science is just too difficult for them. The real problem is that the perception of the crisis has created a void in science governance, i. e. who is going to deal with the problem. Nowadays we have journals of scientific integrity (incredibly boring), world meetings on scientific integrity, not to mention blogs, etc. These are fora designed to channel the voice of those engaged in this second-rate activity.

Cancer Research, Carlo Croce, Character Assassination, Civil Death, Clare Francis, Data Fabrication, Data Falsification, Defamation, Defamation lawsuit, First Amendment to US Constitution, Fraud, Ivan Oransky, National Institutes of Health, New York Times, NIH, NIH funding, Office of Research Integrity, Ohio State University, Paul S. Thaler, protected free speech, Research misconduct, Retraction Watch, Scientific corruption, Scientific publication

Stellar cancer researcher Carlo Croce falls from grace: hypocrisy in science

Last week The New York Times published a front-page story entitled “Years of Ethics Charges but Star Cancer Researcher Gets a Pass“.  The article grossly disparages Prof. Carlo Croce, a towering figure in cancer biology and genetics, and his home institution, The Ohio State University. It describes in some detail multiple accusations of misconduct and malfeasance that have been targeting Croce for years.


Dr. Carlo M. Croce, Ohio State University

We are told that Croce has been dodging grave allegations that he falsified data in research supported by more than $86 million in federal grants that have been awarded to him. The investigative task of the Times reporters was greatly facilitated by the fact that the records at Ohio’s courthouses and its university system are completely open to the public. And Ohio State University, which claims it had spent more money supporting Dr. Croce’s research than it had received in grants, was apparently totally responsive to requests for records.

The big problem with all this is that to this day there is no hard evidence of misconduct implicating Croce. Ohio State had repeatedly investigated Croce and cleared him of wrongdoing every single time. How disinterested these investigations were is of course a matter of debate.

Since Dr. Carlo Croce has not been proven guilty of misconduct by the preponderance of evidence, the public does not have the right to know about these investigations and he must be presumed innocent. The integrity of Croce’s career should have been protected. The New York Times article is actionable in Court.

The most astonishing aspect of the story is that neither government agencies nor Ohio State believed Croce would be seriously investigated for misconduct, since he is one of Ohio State biggest rainmakers. This bespeaks of a system corrupt to the marrow and draws a lesson that epitomizes the level of hypocrisy that plagues the science establishment.

Of course we wonder who sent James Glanz, the Times reporter, the documents that appeared in Mr. Glanz’s email inbox, in what his collaborator Agustin Armendariz calls three big dumps. This is anyone’s guess. The Times story mentions Clare Francis, the pseudonym for an agent for the blog Retraction Watch, whose brash nauseating style is reminiscent of Ivan Oransky’s writing…

In any case, that would be discovered in Court if and when Dr. Carlo M. Croce decides to take legal action.

Blog, Character Assassination, Clare Francis, Defamation, Defamation lawsuit, Expression of concern, Hilda Bastian, lawsuit, Mass hysteria, McCarthyism, National Institutes of Health, NCBI, NIH, NLM, Office of Research Integrity, Paul S. Thaler, Post publication peer review, Post Publication Peer Review Scam, Reporting Retractions, Research Integrity, Research misconduct, Retraction, Retraction Watch, Scientific corruption, Scientific Misconduct, Scientific publication, Scientific Reproducibility

Handling scientific post-publication events: Legal action required

Hilda Bastian is an NIH contractor for PubMed Health and PubMed Commons at the National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine (NLM). She also seems to be a prolific science writer. Bastian recently informed the blog Retraction Watch that the NLM is planning a prominent display of Expressions of Concern (EoC) published by scientific journals. By her own admission, Hilda Bastian is not versed in scientific matters. Given what she intends to do, let us hope she is versed in legal matters, or at least willing to seek legal advice.

In the US, as in most societies under the rule of law, a person is deemed innocent unless proven guilty, and any suggestion that may affect someone’s reputation without hard proof constitutes defamation. By Bastian’s own admission, only about 25% of EoCs typically result in retraction. This begs the question: What do the authors whose papers received the remaining 75% of EoCs plan to do?

Lawyer Paul S. Thaler, a towering figure in scientific integrity may be the ideal person to assist such people determine their legal options. 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 bold section is crucial because it implies that EoCs are in all likelihood illegal, and so is the dissemination of such statements. The public does not have the right to know about mere accusations of wrongdoing, or suspicions of invalid data resulting in EoCs. According to Hilda Bastian such EoCs are likely to be wrong in 75% of the cases. For example, pseudonymous Clare Francis, the venal whistle-blower of Retraction Watch, has scored plenty of false positives eliciting EoCs mostly in the 75% of valid papers. Yet we are not aware that Retraction Watch or other related venues have been sued yet. Hopefully, Hilda Bastian will reflect about her plans and seek legal advice before charging ahead.




Adam Marcus, Anonymous Peer Review, Blog, Character Assassination, Civil Death, Clare Francis, Defamation, Defamation lawsuit, Donald Trump, Expression of concern, Ivan Oransky, John Ioannidis, Joshua Cherry, Joshua L. Cherry, Joshua L. Cherry NIH, Post publication peer review, Post Publication Peer Review Scam, Reporting Retractions, Research Integrity, Retraction Watch, Science, Science blogs, Science Journalism, Science Transparency, Scientific corruption, US President

Anonymous peer review is fine, while anonymous post-publication review is not

When a scientist submits a paper for publication to a journal, he entrusts the journal editor with the task of finding peers would be able to review the paper and are knowledgeable enough to assess its scientific merit. The names of the reviewers are typically concealed to the author. The intent is to grant the reviewer complete freedom in his candid assessment without fear of retaliation. The system is imperfect, very much so, but during the last three centuries scientists have not managed to come up with anything better.

Post-publication peer review (PPPR), on the other hand, cannot be said to be imperfect. It is not even wrong. It is a grotesque aberration. PPPR is usually anonymous but in this case we have absolutely no assurance that the reviewer of the paper is a peer of the author, that is, someone capable of passing serious judgment, or rather someone with an ax to grind launching his or her personal attack. There is simply no editor that arbitrates PPPR, just reporters or science outsiders, like Ivan Oransky, who typically know nothing of the scientific subject of the paper and who merely reproduce a note in a journal or a piece of gossip or an opinion without adding any value. The consequences of this lack of leadership are dire for science: about 90% of the attacks launched by Oransky’s blog Retraction Watch under the pseudonym Clare Francis are either false or lacking merit, even if they manage to elicit an “expression of concern” (an illegality stigmatizing a person presumed innocent unless proven guilty). If US president Donald Trump branded reporters as a pathetic dishonest bunch, just imagine what he would have to say about blogs like Retraction Watch, where the founding reporters usually know nothing about the science related to their mini-scandals.



This atmosphere of dishonesty provides a fertile soil for PPPR, where a few snipers like Joshua L. Cherry (NIH/NCBI?) strive. As readers may recall, Joshua L. Cherry has been identified by Science Transparency. Cherry is truly obsessed (read Cherry’s exchange with Prof. John Ioannidis), but unfortunately not with producing good science. When he launches personal attacks, Cherry disguises under multiple pseudonyms and e-mails, he cowardly shoots from the shadows, yet his style remains unmistakable: He obsessively insists in performing statistical analysis of large datasets with no scientific understanding of the data, or obsessively tries to reproduce data in a field he knows nothing about, failing miserably. Unfortunately, Joshua L. Cherry is the kind of byproduct that Retraction Watch and other such blogs generate. Were it not for the lack of leadership in PPPR, Cherry would have probably remained a scientist perhaps not incapable of generating interesting ideas. Yet, like many at Retraction Watch, he got trapped in futile battles against windmills.

As the Romans used to say: video meliora proboque, deteriora sequor ( I see the best and verify it, but I follow the worst). Tragic, tragic…

Anonymous Commenter, Clare Francis, Defamation lawsuit, First Amendment, Joshua Cherry, Joshua L. Cherry, Joshua L. Cherry NIH, Nature, NCBI, NIH, Post publication peer review, Post Publication Peer Review Scam, PubPeer, Reputation Damage, Research Integrity, Scientific corruption

The Travesty of Post Publication Peer Review

 It is well known that Chinese people have a practical and pragmatic bent. I recall having asked a successful professor what it would take to publish in Nature. He replied:

“You need to do very good work, make a lot of friends in your field and, above all, make sure to befriend the editors. To secure publications in good journals it is always best to start a courtship with the editors, find out what gets them excited. This approach often bears fruit.”

The whole publishing game seemed quite cynical to me at the time. Eventually, that conversation lead me to quit science altogether.

An untold truth in science is that success rests primarily on who you know, rather than on the merits of your work. Not surprisingly, the mechanism to protect the integrity of research reporting, the peer review (PR) system, has turned into a true scam, corrupt to the marrow. The anonymity of the PR process, implemented originally to guarantee freedom of opinion, in practice has become a vehicle for reviewers to promote their self-serving agenda, encouraging ax-grinding by the author’s competitors and complacency by the author’s friends. Editors contribute substantively to the scam by cherry-picking reviewers for the authors they like and rejecting papers without even sending them out for review (often to reduce their workload) whenever the author is not perceived as influential enough to bring them some benefit by treating him well.

If PR is a scam, post-publication peer review (PPPR) is a travesty to a grotesque degree. Here we don’t even know if the reviewers are the actual peers of scientists or simply angry frustrated people trying to bring down the authors. Our own polls conducted on 11 scientific publishers reveal that over 90% of anonymous PPPR is not pursued by the journals after it is found to be frivolous.  At least in PR, the journal editors are entrusted by the scientific establishment with picking reviewers who are supposed to be the author’s peers. But with PPPR, anything goes, as people with no verifiable credentials are allowed to hide in their anonymity to take comfortable shots at whoever they pick as their target.  At Science Transparency we have identified one such sniper: Joshua L. Cherry, the NIH/NCBI contractor still on the loose.

PPPR has thus turned into a farce where anyone gets to say anything, no matter how crass his views are. The channel for these people is the internet, the vast repository where angry people get to pour their vitriol and get the feeling that they are being heard. This matter is admirably described in an article entitled “Why Is Everyone on the Internet So Angry?” that seeks to identify the psychological root of the problem.

Of course, the root of the PPPR phenomenon and the anger it promotes can be found in the internet. “These days, online comments have become extraordinarily aggressive without resolving anything,” said Art Markman, a professor of psychology at the University of Texas at Austin.  Yet, the possibility of an anonymous attack offers a vehicle of self-realization for the frustrated scientist, and the internet enables this possibility and enables the person to be heard, finally! This emboldens him and fuels his anger.