The newly found innocence of Paolo Macchiarini

The newly found innocence of Paolo Macchiarini

The tide is turning for the fallen star surgeon Paolo Macchiarini, who transplanted numerous patients with lethal tracheas made out of dead donor organs or plastic and sprinkled with cells from the bone marrow. Just when Macchiarini started to became the synonym for everything what is bad and evil in regenerative medicine, after two damning investigations by his former employers Karolinska Institutet (KI) and the Karolinska University Hospital, things began to change for the better.

In a surprising decision, the Italian court in Florence cleared the former head surgeon of Careggi Hospital of all accusations of fraud (Macchiarini was accused of extortion, namely of huge sums from patient families while offering to save the terminally ill). This court decision prompted the Tuscan governor Enrico Rossi to immediately lament the loss of a “great surgeon”, who would have done so much good if he only remained in Florence, under proper control. Back in 2010, this politician’s exalting letter of recommendation helped Macchiarini to get the KI professorship despite the many negative references from his medical colleagues.

It got even better: a suspected medical disaster suddenly became a resounding success, thanks to a secret investigation of the Hospital Clinic of Barcelona. A highly criticized first trachea transplant, done in 2008 in Barcelona, left the patient Claudia Castillo in permanent care (see details here). Two months ago, her left lung was removed, because Macchiarini’s transplant never worked out.  Now, various newspapers in Spain and Sweden reported that this operation, published as Macchiarini et al, The Lancet 2008, was performed correctly and its results were published truthfully. The investigation, commissioned by the current medical director of Hospital Clinic of Barcelona, Antoni Castells, criticised solely Macchiarini’s negligent attitude to patient care. This and Macchiarini’s notoriously recalcitrant behaviour alone are said to have led to his departure from Barcelona to the Florentine Hospital Careggi in 2009, where according to the new court decision, the miracle doctor once again did nothing wrong at all to his patients.

doctor-paolo-macchiarini-junto-claudia-castillo-primera-trasplantada-traquea-hospital-clinic-barcelona-2008-14553640052591
18 11 2008 BARCELONA CLAUDIA CASTILLO PRIMER TRANSPLANTE DE TRAQUEA CON EL DOCTOR PAOLO MACCHIARINI DEL HOSPITAL CLINIC IMAGEN DE VIDEO DEL HOSPITAL

Castells told me that only the 2008 Lancet paper was investigated (and found perfectly fine), but not the 5 year follow-up study which Macchiarini published in 2013. This is a bit strange, because the patient Castillo is still in the Barcelona clinic, where her lung was just recently removed. It should not have been very difficult to compare her medical files with the claims of a “a normal social and working life” in the 2013 Lancet publication. In fact, Castells and his team have submitted their own version of a follow-up paper on their patient Castillo, as he declared to me:

“This letter is currently under review in a medical journal. Accordingly, I can only tell you at this time point that we report patient’s follow-up since transplant to last month”.

I asked Castells to share his investigative report with me and my readers, to which he replied:

“I apologize but it is an internal document addressed by the commission to the Medical Direction”.

I also asked to see evidence of the animal experiments which were allegedly performed prior to this human transplant, to which Castells explained:

“Dr. Macchiarini’s proposal to perform the first airway transplantation was reviewed by the IRB [institutional review board, -LS]and the Clinical Ethical Committee of our Hospital, as well as the Catalan Transplant Organization [OCATT,-LS], and approved based on the experimental data provided”.

Castells then confirmed that this summary I made for his explanations was “correct”:

  • no 3rd parties will be given insight into his investigative report made for the Medical Direction.
  • Macchiarini’s ethical approvals for human and animal experiments will not be shared with 3rd parties as well

I also asked Castells about the media reports on Macchiarini’s possibly second trachea transplant recipient, a Spanish woman from the German city of Dortmund, as reported by BBC.  To this, Castells replied:

“the second airway transplantation was not performed since our IRB denied it”.

So what we now have, is a secret investigation which outcome we are supposed to accept on trust alone, without ever seeing the report. Same applies for the ethics permits or their denials, as well as the proof for the existence of animal experiments. They are secret. Of course this makes no sense at all, investigations and documents which no one is allowed to see can only be dismissed as non-existent.  The whole charade puts Spanish authorities in a company they probably would like to avoid: that of the paranoid, human-rights abusing dictatorship of Russia and its own corrupt and secretive investigation of the Macchiarini scandal.

In 2011, Macchiarini was awarded a funding Megagrant by the Russian government, which allowed him to build his organ-growing base at the Kuban State University in Krasnodar and to operate there several patients with his lethal plastic trachea. Most or all of them died, including the most well-known victim Yulia Tuulik. When the scandal broke, the Russian health authority Roszdravnadzor investigated the Krasnodar hospital in the spring 2016 and declared to the media that nothing at all went wrong there. Naturally, the hospital itself saw that Macchiarini was unjustly accused as well and published an indignant letter in his defence. The Roszdravnadzor report is secret, in fact there is even no mention of that investigation of the health authority’s website, as a Russian newspaper article noted. The official Megagrant website is staunchly pro-Macchiarini and pretends nothing at all has happened since December 2015. In fact, according to various media reports, Macchiarini seems to be hiding out in Russia, he is even said to be operating patients there. Mikhail Batin, head of a bizarre foundation “Science for Life Extension”, declared in an even more bizarre August 2016 interview that his partner Macchiarini is preparing the next plastic trachea transplant in Russia right now.

The paper which mustn’t fall

The 2008 Lancet paper concerns not only Macchiarini. Right now, €13 Million hang on it, in 3 clinical trials run by that paper’s crucial last author, the UCL surgeon Martin Birchall. Right now, he and Macchiarini are everything but friends, but back then the situation was different. Macchiarini helped Birchall to a professorship at UCL (the Italian thorax surgeon was one of the reviewers) and the British laryngologist in return assisted Macchiarini with the KI professorship (his and Rossi’s references saved the day). Together the two surgeons operated several patients with stem-cell regenerated tracheas, both cadaveric and plastic ones. All of these interventions were passed off as resounding successes, even if the patients died or were left in permanent emergency care like Castillo. These “successes” helped Birchall to procure immense funding from the British funders MRC and Innovate UK as well as from the European Union for further experiments with trachea and larynx transplants (see my detailed report here). The clinical trials are ongoing now, patients are either already being recruited (for larynx transplant) or about to be (trachea). Should their common Lancet 2008 paper be declared fraudulent, everything might come to a halt, and all the multi-million funding terminated, just as it happened before with the EU-funded multimillion Euro heavy  Biotrachea project, headed by Macchiarini (see my earlier report here). Bottom line: The Macchiarini-Birchall Lancet paper from 2008 must not fall.

There is quite a lot of confusion about that operation on the patient Castillo. Where exactly was the trachea made? The donor organ was harvested from a dead donor seven months before the transplantation in June 2008 took place. This by itself makes the supposition of an emergency life-saving operation, exempt from the required regulatory and ethics approval, simply untenable. In fact, Castillo was in a stable condition, though she had difficulties breathing and because of this unable to care for her children. Macchiarini promised his patient her normal life and her children back, and she agreed. What happened next?

bioreactor
From Macchiarini et al 2008. Copyright: The Lancet/Elsevier

The media reports from 2008 agree only that the decellurisation process (where the donor cells were stripped from the dead trachea carcass) was done in Italy, afterwards it becomes confusing. It is clear as mud where the trachea was regenerated, both geographically as well as from the view point of patient safety and good manufacturing practice (GMP). An excerpt from a 2013 Macchiarini eulogy, a Russian book by Elena Kokurina, states clearly that the decellurised trachea was flown to Bristol, where it was regenerated inside a bioreactor. Afterwards, there was an incident with Easyjet at Bristol airport who refused to transport it, and Birchall paying a pilot friend of Macchiarini’s German student Philipp Jungebluth to fly the trachea to Barcelona (see 2008 news reports here and here). Birchall was reimbursed by his then-employer University of Bristol, and Castillo’s life was saved. Or so the Lancet 2008 paper says.

Where exactly in Bristol was the trachea regenerated? It is rather a simple question, which those involved prefer not to answer. Birchall and another co-author, Anthony Hollander were residing as professors at the medical faculty of the University of Bristol at that time. Hollander was the one who developed a method to turn bone marrow cells into cartilage, key tissue of a trachea. Setting the debate aside whether bone marrow cells can ever differentiate into cartilage, there is no reliable evidence at all that Hollander’s method achieved anything of the kind inside Castillo’s transplant, or in any of the following human experiments Macchiarini and Birchall performed.

Update 24.9.16: in a BMJ interview from February 2010, Hollander insisted that the trachea regeneration procedure was performed in Barcelona and only his bone-marrow-made cartilage cells were involved into the Easyjet incident.

A source indicated to me that the trachea regeneration was performed under Birchall’s and Hollander’s supervision, but not in any of the clinical laboratories of the University of Bristol. Instead, the university’s School of Veterinary Sciences in Langford was fingered as the place where the bioreactored bone marrow stem cell regeneration magic happened. Indeed, three authors on the Lancet 2008 are affiliated with the School of Veterinary Sciences, but were assigned on the publication instead to Birchall’s Faculty of Clinical Medicine and Dentistry or Hollander’s Department of Cellular and Molecular Medicine. These veterinary scientists, who worked in animal medicine labs and were officially declared in the Lancet publication to have done “all cell-culture work”, suddenly received human medicine affiliations.  When I contacted one of them, Tristan Cogan, with my source information about human transplant being handled in unlikely GMP-certified veterinary labs, Cogan simply directed me to this university’s press office (another former Birchall collaborator from the Bristol veterinary School did the same, Hollander never replied).  About his misrepresented affiliations in the Lancet 2008 paper Cogan declared:

“If you check the online article there is a correction that I pressed for adding my correct affiliation and that for members of my group. I believe this is a link to ‘department of error’s or some similar name on the right of the page [indeed, see here, -LS]. The original article did indeed end up with the wrong address, but I asked that this was corrected”.

I am now waiting for the University of Bristol to process my inquiry in order to find out in which lab the trachea regeneration was performed in 2008. It seems as a rather simple question, but I had to submit a Freedom of Information Act (FOIA) Inquiry to at least break the silence. The inquiry will take its time. Until then, we should certainly be skeptical before trusting a secret decree from the Barcelona Hospital that there was nothing at all wrong with Macchiarini’s experiment on Claudia Castillo.


Update 25.9.16. Upon my FOIA inquiry, University of Bristol started to delete evidence from the internet. A Google cache version of their April 2009 press release , dated 13.9.2016, speaks of cartilage regeneration performed “in Birchall’s lab in the Department of Clinical Veterinary Science” in Bristol. Also this press release article from November 2008 was suddenly removed after my FOIA inquiry.

Professors: innocent victims of snakes at their bosoms? A guest post from Sweden

Professors: innocent victims of snakes at their bosoms? A guest post from Sweden

The following guest post by a Swedish professor under the assumed name of ”Frank Nilsson” (his real identity is known  to me) is an open letter response to a recent article in Svenska Dagbladet by  Sven Stafström, Director General of the Swedish Research Council (Vetenskapsrådet, VR). There Straftröm wrote, in the wake of the Paolo Macchiarini scandal:

“Research misconduct is rare, but when it occurs it is usually individuals or small research teams working under the strong influence of a dishonest research leader. Such a closed environment makes it more difficult to quickly detect cheating. […]

The main responsibility for combating scientific fraud through preventive measures and for investigating suspected fraud and taking action is the responsibility of the country’s universities and colleges – the research organizations. […]

Of course it is also crucial to handle the matter properly, when suspicions of scientific misconduct occur. The Swedish Research Council has repeatedly argued that this should be done in a manner that guarantees independence from the influence of personal connections and other conflicts of interest, research misconduct should be investigated by an independent body”.

Certain previous cases do not make Swedish investigative authorities look good in regard to research ethics.  Maybe this is why VR recently delegated (or surrendered) their investigative responsibilities to the Central Ethics Review Board (Centrala etikprövningsnämnden, CEPN). VR’s own handling of the 2009-2010 investigation of the misconduct by the regenerative medicine researcher Suchitra Sumitran-Holgersson was nothing else but a travesty. The entire report was trashed, and the two external investigators were first baselessly accused by VR of misbehaviour themselves, then delivered to the legal threats of a biotech company owned by Sumitran-Holgersson’s husband (see my detailed report here).  The dishonest, yet acquitted professor kept her position with the University of Gothenburg and even her generous funding continued to flow.  Meanwhile, a new investigation into her human experiments is about to conclude at the Gothenburg university clinic. But: Sumitran-Holgersson’s alleged data manipulations are still not being looked into by her University of Gothenburg. According to my source, no external investigator has been appointed yet, and all complaints by the Dean of medical faculty about image duplications in Sumitran-Holgersson’s papers are being ignored.  Despite everything, VR continues to pay her funding, even though other agencies stopped doing so when the new allegations broke and the hospital investigation began (see my other report here).

Two years before, in 2007, a star plant researcher from Sweden, Ove Nilsson, had to retract a two year-old paper in Science. Until then, Nilsson claimed all the merits for this “Breakthrough of the Year” for himself, but when data proved irreproducible and manipulations became evident, the sole responsible for his Science paper suddenly became the first author and former postdoc in Nilsson lab, Tao Huang. The retraction note and the official investigation by the Swedish University of Agricultural Sciences (SLU) in Umeå placed the blame firmly on Huang, while the principal investigator Nilsson was applauded from all sides for reporting the incident. Shortly after, Nilsson was awarded the prestigious Marcus Wallenberg Prize by the King of Sweden, for his scientific achievements which included this very Huang et al Science paper.  Meanwhile, the accused Huang maintained that his ex-boss was well aware of the data manipulations and even incited those, to speed up publication when competing with two other labs. Obviously, hardly anyone believed Huang, in fact the external investigators appointed by SLU never even attempted to contact him. Against all administrative rules, Huang was never given a chance to present his version before the decision was made.  VR as central authority in Stockholm was not involved at all, since only the Rector of the SLU in Umeå had was entitled to forward the case there (see comments at the end of this The Scientist article). Apparently, this didn’t happen because the issue was already solved by SLU to (almost) everyone’s satisfaction. In 2016, Nilsson, officially a hapless victim of Huang’s secretive cheating, became EMBO member. The details of the Nilsson/Huang case are described in a rejected letter to Science from 2007 by Shi Liu (recovered by a reader of my site). Also the Swedish research misconduct historian Johan Thyberg refers to this case in his book “Scientific Fraud or Legal Scandal?

 

The lesson we are repeatedly told by retraction notices: it is always the malicious scheming junior scientists who abuse the generous trust and bumbling genius naiveté of their professors and group leaders. In fact, the reality is less black and white: it ranges from senior scientists who in their excitement unquestioningly publish too-perfect research data, to those who demand their lab members to deliver certain results and who ostracise or even punish employees who produce contradictory experimental outcomes. And finally, up to those group leaders who actually encourage and even instruct those they are supposed to educate to fake data, as a personal account of a former PhD student on my site narrates. And then of course, there are cases where it was the boss personally who manipulated the data, like Olivier Voinnet.

If a professor does get caught red-handed on faking data, like Sumitran Holgersson: the authorities often prefer not to believe their own eyes. It goes so far that they sometimes discard the evidence and close the case. Just as it happened with Sumitran-Holgersson in 2010 and again with Paolo Macchiarini in 2015, when the then-Rector of Karolinska Anders Hamsten trashed the entire misconduct investigation and extended his professor’s contract, tempted by Macchiarini’s promise of generous funding.

wrong-lab

In the following guest post, the pseudonymous “Frank Nilsson” now accuses the Swedish academic authorities like the Research Council of hypocrisy. This Swedish professor refers to a 2015 case of data manipulation at the University of Uppsala, which involved a professorial couple at the Department of Organismal Biology, Irene and Kenneth Söderhäll, who work on invertebrate immunology and circadian rhythms. The investigation by the Central Ethics Review Board (CEPN) ended up with four retractions and the blame was almost exclusively placed with the former PhD student of Söderhälls, Apiruck Watthanasurorot from Thailand. The committee also recommended for his dishonestly acquired PhD to be revoked by the University of Uppsala. Before the investigation began, Watthanasurorot moved to work as postdoc to the lab of the Nobel Prize winner Bruce Beutler at University of Texas Southwestern in USA (confirmed here). It is not clear where Watthanasurorot is now. What is clear, that both Söderhälls were only found guilty of unintentional misconduct by “negligence”, without any administrative consequences for them. The original Swedish CEPN report is here, the translated English version is available from RetractionWatch. Interestingly, the investigators were not able to reach Watthanasurorot for his version of events, but they somehow found him having admitted his responsibilities for the manipulated figures in his papers.

 


By “Frank Nilsson”, a Swedish professor

  The Director General of the Swedish Research Council (VR), the country’s main agency for the support and development of basic scientific research in Natural Sciences, has published a debate article in one of the largest and most respected Swedish newspapers in which he mentions the Macchiarini scandal and suggests a number of ideas that could reduce scientific fraud in Sweden and protect the public confidence on scientific research. Among other things he proposes to follow strictly the Law and academic procedures, that the concerned institutions take responsibility responding quickly to any claim of scientific misconduct, that an external investigation should be appointed and that if the following investigation confirms the claim they should take strict measures with those who were found guilty.

This sounds as common sense but none of these criteria were followed when a couple of high-ranked researchers at Uppsala University with close ties to the Research Council were accused of scientific fraud a couple of years ago.

One of the two scientists Irene Söderhäll, -LS) was –and still is- the Administrative Head of the Department where scientific fraud was suspected to happen. The other [Kenneth Söderhäll, -LS], a prestigious Professor in the same Department, also worked in one of the Research Council’s important committees that evaluate grant applications. Both were operating with grants from the VR and both were accused of publishing about ten scientific papers with images manipulated in a way that is not acceptable for a scientific publication. The clearest examples of misconduct were available to the public before the investigation started because they were scrutinized and exposed to the public on PubPeer. According to detailed comments posted on PubPeer, some images were more or less duplicated and used to illustrate completely different samples or experiments.

Uppsala University was reluctant to start an investigation and was apparently satisfied with the claims from its two scientists, who denied any wrongdoing and accused instead one of their former students [Apiruck Watthanasurorot , -LS] as the only one responsible of the manipulated images. However, this student was not a co-author of some of the papers in question [Jearaphunt et al 2014 and Lin et al 2008, officially proven to contain “image manipulations”, -LS]. An external investigation was delayed until a letter from a professor from another University was addressed to the Central Ethical Review Board (CEPN).

Once an expert group has investigated the case, obtained access to most of the original files (some of them were never found) CEPN concluded that the two accused scientists had been ”negligent” and ”dishonest” but not really responsible of fraud or misconduct themselves, which was thought to be the sole responsibility of the young student. This conclusion was apparently not consistent with the interpretation of the very same body when it released, later on, the conclusions of its investigation of fraud in the Maccharini’s Nature Communications paper. In this later case, CEPN concluded instead that all co-authors were responsible of misconduct, even if some junior authors should be judged more benignly than more senior authors, especially Macchiarini, who was the main author. In their investigation of the faked Uppsala papers (four of which have been recently retracted), CEPN concluded that it was a foreign, junior author who must take the major responsibility and not the Swedish, senior professors.

Even if CEPN had appointed different scientists for each of these two investigations, such an extraordinary divergence in the criteria used for the judgement of whether a scientist is responsible of scientific fraud does not appear as a sound basis for the work of the Board and its reputation.


 

Beall-listed Frontiers empire strikes back

Beall-listed Frontiers empire strikes back

The Swiss publishing business Frontiers was placed by the US librarian Jeffrey Beall on his well-known and hotly disputed list as “potential, possible or probable predatory publisher”. Frontiers however was not prepared to take this lying down. The publisher’s Executive Editor Frederick Fenter first tried it nicely. Shortly before Christmas 2015, he flew to visit Beall at his University of Colorado in Denver, with the senior manager Mirjam Curno in tow. Curno is incidentally also board member and trustee of the Committee on Publication Ethics (COPE). Afterwards, Fenter stopped being nice. In August 2016, he bombarded around ten senior officials at the University Colorado in Denver with letters and a dossier (see below) demanding that they make sure Frontiers is removed from their employee’s private list.

Thing is: University of Colorado has nothing to do with the so-called Beall’s List. The list is part of the librarians private blog on WordPress (same platform I use). In fact, this is the disclaimer which Beall placed on his site clear for all to see:

“These views represent the personal opinions of the author (Jeffrey Beall)  and may not reflect the position of the University of Colorado Denver or the University of Colorado System”.

Beall’s listings of certain open access publishers and journals are his private opinions, and are to be respected as such under the freedom of speech. He didn’t impose his black list of open access publishers as a reference for all those other libraries and funding institutions which chose to orient their decisions on the Beall’s List. In fact, the reason why they do so is the conspicuous absence of any “certified” or “official” black lists elsewhere. Instead, we have white lists, such as DOAJ, OASPA and COPE, and Frontiers is on all of them: as a paying COPE and OASPA member and as a sponsor of DOAJ. One could interpret this whitelisting connected to exchange of money as a kind of conflict of interest, which makes white lists less reliable indicators than black ones. Also, some small or non-profit open access publishers simply can’t afford these costs of whitelisting. Does it make them evil predators? Not necessarily. Others, like the medical journal white list of ICMJE, are joined by self-enlisting, there is no oversight (see my report here). All Fenter had to do to get his Frontiers medical division certified as “following ICMJE guidelines”, was to type in the journal names correctly. Finally, the “executive editor” Fenter also announced in 2015 that Frontiers will be joining WAME, though this “world association of medical editors” does not accept publishers as members, for the simple reason of editorial independence.

On the other hand, there are really no personal incentives to run a black list. It is rather nerve-wrecking, one makes hardly any friends, but plenty of enemies, in fact Beall-bashing is a rather popular sports among academics on social media.  Next, how to finance the blacklist? Certainly not by charging the blacklisted journals or those who don’t want to be listed. Even if any independent funding subsidies should came along, such official blacklisting body would spend all this money on legal costs after the first unhappy publisher decides to deploy the lawyers. In short, blacklisting journals “officially” is likely to be simply not doable in practice. Which leaves us for the foreseeable future with the lone blogger Jeffrey Beall and his private hobby of evaluating open access publishers.

Another interesting point is: Beall is accused of unjustly naming Frontiers as predatory publisher. Yet the whole category of “predatory” publishers was invented by Beall himself, it is not an official term and is in fact much disputed. There are enough academics who claim there is no such thing as predatory publishing. Thus, Beall is being criticised for unjustly placing a publisher into a category which he invented himself.

Neither are Beall’s professional duties at his university library affected by his views on these open access publishers. Beall is in no way involved into University of Colorado decisions to subsidise article processing charges (APC) of their authors. If any Denver-based researcher should claim APC support for his or her publication in Frontiers, it is completely outside Beall’s influence.

Now, that Frontiers disagrees with this librarian’s privately held views, the publisher demands of his academic employer to impose disciplinary measures or coercion against Beall. Extending Fenter’s logic, every single academic employee who publicly criticises Frontiers is to be made to retract such criticisms under threat of sacking. Will Fenter next write a letter to Giulia Liberati’s employer, University of Louvain, regarding her revealing report  on reviewer experience at Frontiers? Or to University of Glasgow, the employer of Guillaume Rousselet, for venting his frustrations about his editor experience? A bizarre supposition indeed, but: this is in fact exactly what Fenter already did previously.

In early 2015, a conflict between Frontiers medical chief editors and the Swiss publisher escalated. Back then, Frontiers had just been expelled from the Nature Publishing Group (NPG) family. While NPG merged with the German publisher Springer to SpringerNature, Markram-run outlet was left behind with the mother company Holtzbrinck, also based in Germany. In these turbulent times, the Frontiers medical editors demanded in a Manifesto the enforcement of medical publishing standards and editorial independence in line with the ICMJE guidelines, which the publisher in turn rejected as going against their own rules and principles. As the result, Fenter dismissed all of the 31 critical editors in a single executive decision (see my report here). But he didn’t stop there, the Executive Editor wrote a complaint letter to the academic employer of one of these editors, as reported by ScienceInsider. Fenter claimed that one former Frontiers chief editor “coerced others to give up their voice and band behind him, and made false and unfounded allegations“. In fact, the emails made available to me suggest quite the opposite of coercion: all editors joined the protest enthusiastically and out of their own accord. Just as in the letter to Beall’s university below, Fenter offered the university officials his help steering their decision process with this letter from May 11th 2015:

“In my capacity as Executive Editor of Frontiers, a Swiss-based open-access scholarly publisher, I would like to bring to your attention our recent interaction with a member of your institution, ____ in cc to this email. In his position as Chief Editor of Frontiers in ____, we have disagreed with ____ on the definition of editorial independence and authority over medical publications, which has unfortunately led to the dismissal of a number of Chief Editors in several Frontiers medical journals.

In the spirit of full transparency, Frontiers has reported this incident to the boards of the three organs that publish ethical guidelines for medical publishing: ICMJE (which lists Frontiers in ____ as a complying title), WAME and COPE (to which Frontiers will join as a member in 2015).

You can find the full details of this disagreement in this blog post: http://blog.frontiersin.org/2015/05/07/frontiers-acts-to-defend-distributed-editorial-independence/

Should this be of interest to your institution’s ethics committee, I am at your disposal to address your questions or concerns”.

Now, Fenter used his established strategy again. This time, he was even assisted by at least 3 Frontiers Editors-in-Chief (EiCs; it is not clear if or how coordinated these efforts were).  Below I quote and offer links to full versions to letters by Idan Segev, (Frontiers in  Neuroscience), Axel Cleeremans (Frontiers in Psychology) and Martin Klotz (Frontiers in Microbiology). As EiCs, these editors are entitled to a Frontiers honorarium of €15,000 per year which depends on their publishing a certain number of papers per year (not just receiving as submissions, see my earlier report and editorial contracts).

ransom-note-colour

The following is Fenter’s letter to University of Colorado officials, with a link to a large dossier he assembled to prove his point about greatness of Frontiers and wrongness of Beall.


“Dear XXXX

Please allow me to present myself as the Executive Editor of Frontiers, the open-access publisher based at the Swiss Federal Institute of Technology in Lausanne,  Switzerland. I would like to bring to your attention the irresponsible and unprofessional actions of one of your colleagues, Mr. Jeffrey Beall – actions that have no place in a university community that values intellectual reputation and that claims to defend the highest standards of intellectual honesty.

As you know, Mr. Beall maintains a blacklist of “predatory publishers.” In October 2015, he added Frontiers to this list, an action that is both unjust and unfounded. Recently, it has come             to our attention that he is circulating a document (included in        the report sent with this letter) in which he “justifies” his blacklisting, which is based on the comments of a very few angry or even discredited bloggers. In the attached letter, Mr. Beall himself states this: “The evidence has accumulated. I think the scientific community has made this decision for me.” His slanderous position is entirely based on hearsay and weak proxy arguments, on which he refuses to take a stance dignified of a research librarian. His presumptive use of the word “community” is particularly baffling—Frontiers is a community-driven publisher, with an international editorial board of 60’000 researchers and over 140’000 distinct authors. Just in the University of Colorado system we have 137 editors and 257 authors.  I provide some additional information      on this in the attached report.

Despite our attempts to talk to Mr. Beall—whom I met with personally on 14 December 2015 for a two-hour presentation of our program—he refuses to articulate any justification for his action, preferring rather to hide behind the biased and subjective comments of others.

Frontiers’ Open Access publishing model is founded on rigorous, collaborative and transparent peer review, driven by the broad research community and enabled by innovative, cutting-edge digital technology. Our goal is to deliver a trusted, scalable scientific publishing service to the whole research community, through respected journals whose quality is reflected in outstanding impact metrics. In the attached report you will seethat:

  • Frontiers publishes several of the most-cited journals in the world;
  • Frontiers is internationally recognized and has a strong track record of bringing innovative IT solutions to scientific communication and is winner of the 2014 ALPSP Gold Award for innovation in publishing;
  • Frontiers returns millions to the scientific communities each year (for example in 2015, the total for waivers, honoraria and awards exceeded 3 million dollars);
  • Frontiers articles are picked up by the press thousands of times each month.
  • Mr. Beall himself is not considered an objective voice in the debate and has expressed strong bias against open-access publishing. This is of course his right, but there is ample evidence that his use of the blacklist is not characterized by sufficient intellectual integrity.

Mr. Beall has published a set of established criteria by which he claims to make his assessment (many of which themselves display his inherent bias). We provide a point-by-point analysis of our operations according these very same criteria—it is ludicrous that we have to undertake this exercise, but since he refuses to deliver         an explanation, we took the time and effort to demonstrate that Frontiers operates professionally and ethically according to the criteria he invokes. The statement on his blog that he has carefully analyses each program (where there is no evidence of such) is a sign of malicious intent to damage our reputation.

I am sure you understand the seriousness of the situation. A member of your academic community is making unsubstantiated public accusations of unethical              practice against Frontiers. He will not engage with us to explain or justify himself. This attack against the integrity of our international editorial boards and against the 240 employees of Frontiers will not be allowed to stand.

Please let me finish with an anecdote that illustrates the confusion and loss of credibility that Mr. Beall’s actions bring upon your institution, as well as on ours. We were contacted by the CLOCKSS archive about our participation; this organization has the mission to guarantee the permanent archiving of scientific literature.  Shortly after starting the process, we were informed by their publisher relations manager that they “do not work with Publishers on Beall’s list.” I called the director and requested they make an informed decision based on facts (which you now also have at your disposition). We were subsequently welcomed into the program, and CLOCKSS promptly announced the partnership on their website (https://clockss.org/clockss/News#CA8). The fact we are mentioned on “Beall’s list” is time consuming and damaging to our reputation, but I hope you see that it also tarnishes your institution by association.

Specifically, the document that Mr. Beall has circulated reveals the scandalously sloppy nature of his work (especially for a research librarian), and we will be filing an ethics complaint with your University on this point.

I am writing to you personally because your university is directly implicated in this absurd and slanderous action, and I believe you have the authority to correct the situation rapidly and effectively. I have put Professor XXXXX, in copy.

Please let me know if you would like to discuss the matter further. I would be pleased to take the requisite time to provide you with any additional information you need to make an informed decision concerning the actions of your colleague, Mr. Beall. In fact, I would be pleased to fly back to Colorado to discuss this in person with you, if you so desire.

Frontiers is working to improve the way research is validated and disseminated             through the development of open-science tools; this is a bold experiment that frightens some traditional-minded thinkers. In fact, I would much rather be spending my time exploring how Frontiers might expand its collaboration with the University of Colorado, which, as a large and prestigious institution, is particularly well positioned to become a leading voice as these developments unfold – as it has been with your institution’s involvement with MOOCs, for example. Mr. Beall’s biased and ill-informed blacklisting of Frontiers and its innovative approach is certainly not the most effective way for the University of Colorado to participate in the open-science revolution.

Very much hoping to have the opportunity to discuss these matters with you,

Very best regards,

Frederick Fenter, Ph.D.

Executive Editor,Frontiers

ENCL:          Report  “Jeffrey               Beall’s   Blog: Frontiers’ Position

CC:   XXXXX;  Kamila Markram, CEO of Frontiers”


Idan Segev, from Hebrew University, Israel,  EiC of Frontiers  in  Neuroscience and closest collaborator of Frontier’s founder and supreme Editor-in-Chief Henry Markram, spoke in his letter to University of Colorado officials about “Frontiers beauty”. This beauty seems to be even measurable, by the lovely impact factors of Frontiers journals:

“Note  that Frontiers is very heavily indexed by Thomson Reuters, who have awarded impact factors for 19 of our journals so far – several of the Frontiers journals with impact factors over 5. Such IFs cannot be  obtained  if  our  processes  are  as  sloppy  as  Mr  Beall  alleges”.

Segev also insists Frontiers rejection rate is around 30% (and not 20% as they used to write to potential authors or 10% as they admitted internally). He also explains how ethical publishing is maintained at Frontiers: by placing their own senior manager as COPE trustee:

“Frontiers is very aware of ethical issues concerning scientific publications; so much so that our Editorial Director, Dr Curno, is a council member of the Committee on Publication Ethics: COPE”.

Segev then comes to talking hard business and accuses Beall of slander, while making the University of Colorado responsible:

“I view the attack of your employee – Mr. Jeffrey Beall – as an attack on my credentials as a scientist as well as on my own University (and the Hebrew University is one of the leading universities in the world). […] As he works in your University, I expect you to take action and make sure that Frontiers is taken out now from his “black list”.”

Axel Cleeremans, from Université Libre de Bruxelles, Belgium, is Editor-in-Chief of Frontiers in Psychology. To make clear who the University of Colorado is dealing with, he also signed his letter at the bottom as “Member of the Royal Academy of Belgium”. Cleeremans made clear that Beall is not qualified to interpret the predatory publisher concept which the offending librarian himself invented:

“There simply are no grounds in fact to include Frontiers on this list, as it is not even a “potential” predatory publisher. None of the criteria developed by M. Beall apply, and one is thus left wondering about the extent to which this is some sort of personal vendetta that M. Beall is now engaged in. This, needless to say, impinges on the reputation of the University of Colorado”.

Cleeremans then demands that the Denver University forces Beall to amend his private blog, so the Belgian professor’s own Frontiers journal doesn’t suffer:

“I am therefore asking you to take action in this respect. While Frontiers in Psychology has now grown to the point that M. Beall’s antics can do little to damage its reputation, it is simply unprofessional and detrimental to library science for the University of Colorado to let this continue”.

Martin Klotz, from City University of New York and EiC of Frontiers in Microbiology, addressed his letter directly to Beall. He first of all corrected his interlocutor that Frontiers is not at all owned by the Nature Publishing Group. However, Klotz previosuly insisted on something else in his own CV, when proudly proclaiming himself as “Editor-in-Chief: Frontiers in Microbiology (Nature Publishing Group, IF 3.941)”.  In his letter to Beall, Klotz now makes clear what he thinks of his blog activities regarding Frontiers:

“I am losing context between your status and role as an academic librarian with tenure at a premier academic institution (https://scholarlyoa.com/about/) and your black-listing of Frontiers as a “predatory publisher” in the public domain (your site), which is based on blogger comments and hearsay instead of accessible results of academic research”.

Just like Cleeremans, Klotz keeps defending his own Frontiers journal as impeccable. Based on this argument, they demand the whitelisting of an entire large publishing family. Regardless of what other Frontiers journals are up to: Frontiers in Human Neuroscience happily keeps on publishing papers about afterlife and clairvoyance and autism-causing bread, Frontiers in Public Health waved through a paper promoting chemtrail conspiracies. Even Segev’s own beautiful Frontiers in Neuroscience showed worrisome peer review deficiencies by publishing an utter nonsense paper or silencing critical reviewers in order to accept a bad study. Frontiers in Pharmacology fell for a most blatantly manipulated paper from Malaysian cheaters (the peer review took less than a month), and retracted a peer reviewed plant pharmacology paper for “insufficient scientific quality”. These and other cases of questionable scholarly publishing went unmentioned, as if they don’t exist. Or maybe these impactful Frontiers publications are simply “hearsay” and deluded ravings of “discredited bloggers”.

Macchiarini acolyte Philipp Jungebluth lost surgeon job in Heidelberg

Macchiarini acolyte Philipp Jungebluth lost surgeon job in Heidelberg

In the wake of the scandal around the fallen star surgeon Paolo Macchiarini, his German acolyte Philipp Jungebluth now lost his job as resident/junior doctor (Assistenzarzt) in Heidelberg in the Thoraxklinik at Heidelberg University Hospital.

This is what Kirsten Gerlach, assistant to the clinic director, told me today:

“Dr. Jungebluth is no longer employed at the Thoraxklinik, Universitätsklinikum Heidelberg. He left the Klinikum at his own request“.

Update 13.09.2016: Gerlach now specified to me in another email:

“Dr. Jungebluth left the Thoraxklinik on 31. August 2016 at his own request”.

Jungebluth was Macchiarini’s award-winning medicine graduate at the Hannover Medical University (MHH), which had huge plans on regenerative medicine back then, with living tracheas, lungs and hearts growing inside plastic boxes. The loyal young graduate then followed his idol Macchiarini to Spain, Russia and Sweden, where he hands-on participated in all their disastrous trachea transplantations. He also said untruth about plastic trachea having been first tested on animal models, before human subjects were tricked into sacrificing their lives. There was no animal testing, even Macchiarini eventually admitted it.

His loyal student was also involved into the first ever trachea transplant in human in Barcelona, published as Macchiarini et al, 2008. It is still being hailed a success, despite the overwhelming evidence to the contrary which is being ignored by the journal The Lancet (see my report here). According to Jungebluth’s own medical doctorate thesis (made at MHH under Macchiarini’s supervision), the laboratory preparation of donor trachea began in November 2007, the transplantation of a “regenerated” cadaver trachea into the patient Claudia Castillo took place in June 2008. In fact, it was not an entire trachea, but just one bronchus, which might have save this patient’s life thanks to a stent (she lost a lung though, see details here). According to today’s report by the Spanish newspaper El Periodico, the hospital ethics committee in Barcelona found that Macchiarini committed “fraud” and hid subsequent complications.

There is no evidence that also this trachea “regeneration” and transplant method was initially tested in animal models. The proof-of-principle study on pigs (Go et al 2009), which Jungebluth co-authored and attached to his dissertation, was submitted for publication only in May 2009. Apparently, noone at Jungebluth’s dissertation commission at MHH noticed this irregularity, or bothered to check if they did.

From my earlier communications with one of Jungebluth’s medical examiners at the MHH in Hannover, I learned that it was simply assumed, apparently evidence-free, that the animal experiments were already performed, while the intervention on the patient Castillo were deemed as an “individual cure attempt”, which needed no ethics permit. Peculiarly, the Hannover doctorate commission never asked Jungebluth to provide any documentation that he really performed any animal testing in Barcelona. When I repeatedly attempted to contact the Office of Research Management of University of Barcelona or the University’s animal research ethics committee about the animal experiment ethics permits, I received dead silence back. It is safe to assume Jungebluth et al tested their trachea transplants on humans first, before moving on to animals. That is, if these later publications reflect any reality, which can be doubted under the circumstances. A notorious paper on oesophagus regeneration in rats which Jungebluth co-authored with Macchiarini (Sjöqvist et al 2014), was determined as fraudulent on September 9th 2016 by the Swedish Ethics Board, all authored were found guilty.

Another Macchiarini “experiment” which Jungebluth happily participated in, was the bizarre science-free stuffing of blood cells and erythropoietin down their patient’s windpipe. This happened at the Karolinska Insitutet (KI) in Stockholm, the plan was to somehow achieve tissue regeneration.  It was this intervention which most likely killed the patient, yet the disaster did not prevent the authors to turn it into a success, in the journal Respiration (Jungebluth et al 2015), long after the patient’s death.

Jungebluth and Macchiarini were repeatedly accused of research misconduct by the KI medical researchers Matthias CorbascioOscar SimonsonKarl-Henrik Grinnemo and Thomas Fux. In a dossier from May 2016 (published on my site), the KI whistle-blowers listed evidence for data manipulation and misrepresentation of patient’s conditions regarding Jungebluth’s and Macchiarini’s first plastic trachea transplant into the patient Andemariam Beyene, who died two years after receiving the transplant (details see here). The paper in question was The Lancet (Jungebluth et al, 2011).

Peculiarly, the German doctor Jungebluth treated Macchiarini’s trachea transplant patients like Beyene at Karolinska, despite that he had no permit to work as a doctor in Sweden, as noted in the investigative report by the Karolinska University Hospital:

“He [Jungebluth, -LS], was directly involved in the care of the patient, he was contacted to advise on drug treatment, and he stood as an 2nd operator at two bronchoscopies. The German thoracic surgeon seems at times to have acted as a link between Macchiarini and patient. Reportedly from the Board, he is a licensed as physician since 2016-03-18 and has no special appointment working clinically in Sweden”.

The most recent accusation by the KI whistleblowers related to the Jungebluth-Macchiarini poster from August 2012, “ First in Man Synthetic Nanofiber Trachea”, co-authored by Jed Johnson (described as “Chief Technology Officer (CTO) at the company Nanofiber Solutions that synthesized the tracheal scaffold described in the poster”). The entire dossier is available here. According to the newspaper Dagens Medicin, the patient whose state is deceptively presented on the poster is Chris Lyles, the second person to receive a plastic trachea. Lyles died shortly after.

jungebluth-poster
Jungebluth poster, see dossier here

 

Previously, the Heidelberg clinic directorship seemed to have little issues with what Jungebluth did before, in Sweden or in Russia. This is what I was told by Gerlach on March 8th 2016:

“Dr. Philipp Jungebluth is employed as Assistenzarzt in the Thoraxklinik since 2014. He is currently in the process of specialist training as thorax surgeon. He works scientifically in the area of regenerative medicine in the laboratory, on cells.  The criticized therapy methods (trachea transplantation or tracheal division) are not being performed or offered in the Thoraxklinik-Heidelberg. We can offer no comment on the reported events at Karolinska-Institute (KI) in Stockholm, since these are not connected to the Thoraxklinik”.

Seems the German university clinic has changed their supportive stance in the meanwhile.

Macchiarini and the bonfire of greed

Macchiarini and the bonfire of greed

The aftermath of the Paolo Macchiarini scandal: many dead or mutilated trachea transplant patients, many stellar academic careers destroyed or damaged beyond repair, the reputation of the once world leading Karolinska Institutet (KI) in shatters and even the Nobel Prize itself is dented. The latter is because several members of the 50-head strong committee of the Nobel Prize in Physiology or Medicine were forced to resign:

  • Urban Lendahl, KI professor of genetics, quit his postas Nobel Committee Secretary General already in February, due to his involvement into Macchiarini recruitment. Lendahl also used to be Macchiarini’s superior, as director of three research centres in stem cell research and regenerative medicine: DBRMStratRegen and WIRM(the Wallenberg Institute for Regenerative Medicine).
  • Hans-Gustaf Ljunggren, former KI Dean of Research resigned from this post and Nobel Committee in February 2016. Ljunggren decreedin August 2015 together with the then-Rector Anders Hamsten that Macchiarini did not commit any misconduct, and trashed the results of the Bengt Gerdin investigation.
  • Katarina Le Blanc, immunology professor and Macchiarini co-author, who is apparently herself under investigation on suspicion of misconduct and data manipulation.
  • Anders Hamsten and Harriet Wallberg-Henriksson were asked to resign by the new Secretary of the Nobel Assembly, Thomas Perlmann, after the KI report was published. Both ex-Rectors played a crucial role in the Macchiarini recruitment and the cover-up of his patient abuse and misconduct.

Two more members of the Committee were possibly asked to step down, but this information is not confirmed. Bo Risberg, emeritus professor of surgery at the University of Gothenburg and longstanding Macchiarini critic (see his earlier guest post for my website), proposed “a moratorium for two years to the Nobel prize” and for the award money to be donated to Macchiarini’s victims and their families.

The corrupt Ethics Council of KI was dissolved by the new Rector Karin Dahlman-Wright, other heads rolled as well. Two investigations, one by KI and one by Karolinska University Hospital revealed a culture of cover-up and disregard for basic research integrity and medical ethics. Meanwhile, the entire KI University Board was dismissed by a governmental decision.

What drove so many scientists and doctors to support Macchiarini and his outrageous visions? It seems, the driving force was, just as elsewhere in science, greed. Greed for research funding and the fame and power it brings. And Macchiarini attracted many millions of Kronen, Euros, Dollars and even Roubels, and he kept promising even more. It seems the lust for money and fame made everyone at Karolinska switch off their brains. As the result, innocent people have died.

Money for magic

“Stem-cells” is a magic word which opens many funding coffers, especially if combined with “regenerative medicine” and clinical applications directly on patients, to cure incurable diseases. Macchiarini offered all of this. Trachea is a very complicated organ, very difficult to transplant (mostly due to its blood vessel structure), and Macchiarini offered a simple solution.  He based his claims on long-discredited research about alleged pluripotency of bone marrow cells (see my analysis here) and a magic box called bioreactor. When a dead piece of trachea cartilage or even a plastic pipe is stuck in there and seeded with bone marrow cells, it will grow a living organ. There is no scientific evidence for that, but nevertheless Macchiarini and his colleagues were showered in funding money, including millions of euros from the European Union for his project Biotrachea (see my coverage here) and AmbuLung (there, Macchiarini was accused by the project coordinator Nova Lung GmbH of confidentiality breach and intellectual property theft) . In fact, the EU happily continues to fund a clinical trial on cadaver trachea transplants, regardless of the death and suffering its coordinator Martin Birchall brought together with Macchiarini upon their earlier research subjects (see my detailed report here). The bioreactor fairy tale sounds just too great.

It all started in 2008-2009 with the SEK 30 Million (ca. €3.2 Million) per year given to KI by the Swedish Research Council, specifically earmarked for stem cell research. This 5-year grant was about to become permanent upon subsequent evaluation. KI used this money to lure the Italian star scientist to perform his stem cell miracles in Stockholm. More and come money came from Swedish public funders and charities (see list here).

By 2015 however, Macchiarini was in a tight spot. The deaths of his patients became known, police began investigations for manslaughter and the investigative report by the surgery professor Bengt Gerdin found him guilty of misconduct (see details here). Even worse, the Research Council suspended in June 2015 his grant funding for the “Development of natural and cultivated bioartificial esophagus”, because there was no ethics permit for the transplants. The guest professor Macchiarini became untenable and very close to being sacked. Remarkably, the miracle surgeon managed to extricate himself from this predicament and even to get his professorship contract at KI extended by one year. How did he achieve this, you wonder? He simply bribed them with a promise of 10 Million Dollars in funding.

competition

An offer they can’t refuse

From the KI investigative report by the Heckscher commission (see Google-translated chapter 9, provided by Liz Woeckner) we learn that Macchiarini declared at a September meeting with his KI superiors, Rector Hamsten and head of CLINTEC department, Li Felländer-Tsai:

“that he had been contacted by an American philanthropist who offered him a large research donation. […] The donation manager was informed that it concerned a possible donation of 10 million US dollars (approximately 80 million Swedish kronor). The donor wanted to support a research center in translational and regenerative medicine that was based on a research plan that Macchiarini had developed.
According to the responsible for the donations the US donation would have been at that time the Karolinska Institute’s third largest donation ever”.

On October 5th, some weeks after he saved Macchiarini from the consequences of Gerdin’s investigative report, the greedy rector Hamsten emailed his guest professor:

“Hope life at your end has now returned to a more relaxed and enjoyable state. […] As a matter of priority on my side, I would like to return to the briefing, the initial discussion we had regarding the potential donation from the lady in the US. Also, we need to touch base again regarding the intermittent bridging employment we need to get in place for you, prior to proceeding with the tenure”.

Also the head of the Ear-Nose-Throat clinic Lars Olaf Cardell was greatly interested in this donation. He met in October 2015 with Felländer-Tsai and the Dean of Research Ljunggren, where Cardell

“took up the funding deficiency at Macchiarini’s research group resulting from the Research Council’s funding withdrawal. […] When it came to Macchiarini’s employment contract renewal, the American donation offered a solution”.

The discussions on this potential cash shower continued into January 2016, lawyers as well as university director were involved. A general donation agreement was drafted to be presented by KI to the prospective donor.

A grain of truth

It does sound a bit unrealistic, knowing Macchiarini’s tendency to tell untruth. Did he once again fib everyone? Even Hamsten insisted to the Heckscher investigative committee that “he had never regarded the donation proposal to be realistic”. I actually didn’t believe in it myself, until I learned that… Macchiarini was not entirely lying. The mysterious US benefactor did exist, only the donation was never ever considered to go to KI, but straight into the miracle surgeon’s own pocket.

Macchiarini entered a business relationship with a surgeon colleague with whom he transplanted in April 2013 a plastic trachea into the 2-year old US-American patient, Hanna Warren (she died not even 3 months after). This surgeon was Mark Holterman, a deeply religious yet rather medical ethics-agnostic professor at the University of Illinois, College of Medicine at Peoria. Holterman and Macchiarini both seem to hold the peculiar view that any agreement between doctor and his patient is sacred and no governmental institution should ever interfere with their petty ethics concerns or regulations. Basically, if a doctor and patient should agree that a chronic migraine can be cured by an experimental brain removal procedure, no authority should ever quibble against a signed patient’s consent. In fact, Holterman himself operated another 2-year old child, with a non-life threatening leak in the oesophagus, which left his patient with “irreversible brain injury and cerebral palsy”, as Chicago Tribune reported. The responsible Rush University Medical Center, where Holterman performed this operation, was in February 2016 made to pay $30Mio malpractice settlement to the victim’s family.

In April 2015, Holterman recruited Macchiarini as consultant for his company Alliance for the Advancement of Cellular Therapies (AACT), with the modest salary of $10,000 per month (allegedly Macchiarini was first promised $300,000 per year). This is what AACT was about, as Holterman announced in December 2015 in a round email to a long list of doctors:

“We at AACT feel very strongly that the FDA is overstepping their regulatory mandate and interfering with the “practice of medicine”, by interjecting themselves into the physician-patient covenant, interfering with the patient’s right for treatment, and, in the case of autologous cells, placing restrictions on a person’s own healing capacity”.

On July 27th 2015, Macchiarini and Holterman flew to California from Chicago to meet two female investors, who offered them millions in funding. However, unlike Macchiarini told to his KI superiors, the money was never intended to go to Sweden. It was designated for his and Holterman’s AACT business in the US. It is not clear if the donation ever happened, but the naïve and greedy Karolinska certainly never was part of this.

Go west!

Of course, the greediest character by far in the whole scandal is Macchiarini himself. Already from his work in Italy he was known to police for coercing desperate patients’ families into paying him huge sums for private operations. He never felt he was earning enough though. In fact, the professor of regenerative medicine was unhappy with what KI was paying him. There are rumours that he earned much more in Russia, thanks to the governmental “Megagrant” which brought Macchiarini to Krasnodar. In any case, Macchiarini wanted to go where the really big money is: to America.

In this regard, Macchiarini was negotiating in 2013 with two universities: the University of Illinois Urbana-Champaign and their Carle Illinois College of Medicine on one hand and on the other hand the University of Texas, represented by the MD Anderson Cancer Center and primarily by the Texas Heart Institute, where Macchiarini’s collaborator Doris Taylor was according to my evidence pulling all strings to get him a professorship. Taylor is a cardiologist who is also convinced that any organ can be resurrected by decellurisation and the magic of bone marrow cells. Her speciality is the heart, but she also co-authored the notorious oesophagus regeneration paper with Macchiarini (Sjöqvist et al 2014), which was on September 9th 2016 determined as fraudulent by the Swedish Ethics Board. Since job-wise it looked very promising at both places, Macchiarini’s plan was apparently to grab both offers: a purely academic job in Texas and a clinically oriented one with focus on human experimenting in Illinois.

The miracle surgeon was officially interviewed in February 2014, first by the University of Illinois at Urbana-Champaign, Department of Bioengineering, and then by the Texas Heart Institute and MD Anderson. The University of Illinois  first offered a $650,000 annual salary for a full time faculty position in a Memo of Understanding (exclusively available here), which their Carle Health Care Incorporated and Macchiarini signed on December 23rd 2013. It was a very nice Christmas present for a doctor who has been actually very naughty before, what with Hanna Warren and several others of his plastic trachea transplant recipients already being dead. The offer then fell to some measly $200,000 per year, and by March 2014 the two US-universities somehow changed their minds completely. Both negotiations about professorship recruitments ended abruptly.

In June 2014, Holterman tried to help his business partner with a recommendation letter which he sent to his own College of Medicine at Peoria (exclusively available here), expressing “enthusiastic and unreserved support of Professor Paolo Macchiarini’s consideration for the Breakthrough Grant funding mechanism”. Obviously, it didn’t help. But Karolinska still stood behind their lethal professor, hoping in vain for the 10 Million from his mysterious Californian donors. Until the media attention broke the toxic spell.

Is Guillaume Moissiard that Voinnet co-author now under investigation by CNRS and ETH?

The research misconduct scandal around the former star plant scientist, CNRS research director and currently ETH Zürich professor Oliver Voinnet is not over, and finally also some of his close collaborators and possible “partners in crime” start to feel the heat. One of Voinnet’s former co-authors is now being investigated by the French research society CNRS and the Swiss university ETH Zürich, according to the available information. It is likely to be Guillaume Moissiard.

A reader notified me about this September 8th 2016 news release on the site AlphaGalileo:

“Scientific misconduct: CNRS and ETH Zurich are setting up a commission of inquiry

Over the past few weeks, serious doubt has emerged regarding the figures featuring in several Molecular Biology publications. The CNRS and ETH Zurich have decided to set up a scientific commission of inquiry, with CNRS in the lead and contribution from ETH Zurich, which will be composed of experts. Their role will be to establish the facts.

In this context, institutions have a duty to act in strict compliance with ethical standards, which do not allow any public statement to be issued prior to completion of the process in order to ensure that an in-depth analysis is carried out, in which all parties can freely express their views. In the same logic and to guarantee that the inquiry is conducted serenely, the name of the experts forming part of the commission cannot be disclosed at this stage.

When the process is completed, the two institutions will decide if disciplinary measures have to be taken. The results and the consequences of the inquiry will then be made public”.

With ETH and CNRS involved, one was bound to think about Voinnet. Indeed, the ETH spokesperson explained to the Swiss newspaper Neue Züricher Zeitung, it was not about Voinnet himself, but about his former co-author, who was however not named. This makes perfect sense, because it is highly unlikely Voinnet tricked out all of his lab members by manipulating data in total secret and without their knowledge. Most scientists would notice if their own first-author papers contained different research data as what they originally submitted to their principal investigator (PI). Sadly, too often it is the case that such junior researchers eagerly accept the deal of papers and career in exchange of selling out their basic principles of research integrity. It is therefore to be expected that several of former Voinnet lab members, many of whom are now PIs and professors themselves, knew about and quietly tolerated his manipulations of their data. Or were even actively engaged therein.

Unfortunately, so far ETH chose not to investigate or even interview any of them, not even his ex-team member and presently ETH professor as well, Constance Ciaudo. CNRS exercised only a symbolic punishment over Patrice Dunoyer, who admitted to having personally manipulated data in three now retracted publications (Dunoyer et al., Plant Cell, 2004; Dunoyer et al., EMBO J, 2010 and Sansregret et al., PLoS Pathogens, 2013). This scientist, who was tasked to head Voinnet’s Strassbourg lab when the boss moved to Zürich, was apparently excluded from CNRS employment for a period of 1 year, of which however 11 months were suspended (details here).  Dunoyer has no connection to ETH and still remains in his post as group leader at CNRS in Strasbourg.

Who can it be then? We know the investigation is led by CNRS and supported by ETH. Which means: this scientist used to produce the questionable research in Voinnet’s former lab in Strasbourg and has meanwhile moved to ETH Zürich. Which would make Ciaudo a candidate, but in case of tenured ETH employers it is unlikely the lead of investigation would go to CNRS. Or, the alleged co-conspirator is now working at some CNRS institute in France, after having left Voinnet’s Swiss lab.

Like Guillaume Moissiard. He had to retract a fraudulent paper in PNAS, which he published together with Voinnet while still in France (Moissiard & Voinnet 2006). he is also first author on a Voinnet lab paper (Moissiard et al, 2007) which was proven to contain manipulation in every single figure. Yet the journal RNA chose to only correct it (see my report heremy report here). Another paper with Moissiard’s involvement was corrected by EMBO J for some manipulated data (Haas et al 2008). After such successful research at the CNRS institute in Strasbourg, Moissiard then moved together with his boss to Zürich and recently left. Where to? He apparently got a new research job with CNRS, as a group leader, according to this information.

All available evidence fingers Moissiard. There are actually no other co-authors on manipulated Voinnet papers who fit the above described pattern. Unless of course there are more manipulations, which do not know about yet. In fact, this is not that unlikely. A previously corrected scientifically apparently irreproducible paper in Science (Dunoyer et al 2010) proved to have even more worrisome data irregularities than the journal chose to see (see new PubPeer concerns which came up after the correction). The journal keeps silent about this. Cell meanwhile simply refused to scrutinise suspicious Voinnet papers because his original data was unavailable (see news post here).

For background, see my earlier extensive reports, which also contain further links:

Olivier Voinnet case: correcting the uncorrectable

Voinnet aftermath: ethical bankruptcy of academic elites

Macchiarini investigations outcome: the Karolinska Institutet

Macchiarini investigations outcome: the Karolinska Institutet

The second main investigation into lethal patient abuse by the thorax surgeon and regenerative medicine “pioneer” Paolo Macchiarini is now concluded in Stockholm. After the Karolinska University Hospital (Karolinska Universitetssjukhuset, KS) published their investigative report on August 31st (see my coverage here), the Karolinska Insitutet (KI) now followed suit on September 5th.

This KI investigation was led by the former president of the Supreme Administrative Court of Sweden Sten Heckscher, who was assisted by the journalist Ingrid Carlberg and the Finnish biochemistry professor Carl Gahmberg. Interestingly, the very person who appointed Heckscher in February 2016 as external investigator, the Chairman of the KI University Board (Konsistoriet) Lars Leijonborg, surprisingly resigned just last Friday.

Given the professional specialisation of Heckscher as lawyer and policeman, his investigation focused on the administrative aspects, and not on science or medicine (which possibly was supposed to be covered by the KS investigation).

These are the results, according to the English-language summary and the translated Swedish full report:

Hardly surprising, the decision of the then-Vice-Cancalelor Anders Hamsten from August 2015 to trash the Bengt Gerdin investigation and to declare Macchiarini free of misconduct, was now seen as “poorly justified”. Otherwise: Macchiarini’s recruitment was inappropriate and done against all warnings (as already determined by the KS report), he was neither supervised nor evaluated and his research documentation disappeared after he left. Finally, the report suggests that KI bears no direct responsibility for the plastic trachea transplants which killed or maimed all of the 8 patients of the KI professor Macchiarini.

The others did it

Just as the KS report was pushing the bulk of the responsibility to the KI, now it is vice versa. According to the Heckscher report, which addressed the three plastic trachea transplant operation detailed by the KS counterpart, these were not clinical research, but health care, and thus it was the hospital which was primarily responsible:

“The operations took place at the hospital – where Macchiarini was also employed – and within the framework of health care. The decisions to perform the operations were taken at the hospital by hospital personnel, who also held all the pre-surgery discussions. According to the regulations pertaining to hospitals, responsibility for the decisions to carry out the operations – as well as how the operations were carried out – therefore unequivocally lies with the Karolinska University Hospital.

We believe, however, that KI also has a certain responsibility for the transplantations. There are many instances of KI employees being involved in the discussions preceding and following up surgery. KI has also, in several contexts, cited the transplantations as part of its own activities. For example, they have been quoted as research successes in KI’s evaluations of how research funding has been utilized”.

With that little responsibility for human experimenting just next door, it is rather unsurprising that the Heckscher report absolves KI of all responsibility on what their own professor did in Russia. There, the star surgeon and scientist transplanted several patients with plastic tracheas, all of whom are likely dead now (unless you trust Macchiarini and Russian official sources). The Heckscher team decrees:

“The only significant connection between Macchiarini’s activities at KI and the operations in Russia is Macchiarini himself. Our conclusion is therefore that KI cannot be held responsible for Macchiarini’s work in Krasnodar”.

Thus, KI is found not responsible for the death and suffering of all the eight patients whom their own star scientist transplanted with his “stem-cell regenerated” plastic tracheas, in Sweden and in Russia. KI is however criticised for not having properly scrutinised Macchiarini’s “extra-occupational activities” when they had a chance to do so, in 2012 and 2015.

Bad references

As already determined by the Karolinska Hospital counterpart-report, Macchiarini was recruited to KI despite negative references and warnings. The blame is assigned to the former Vice-Chancellor Hamsten (who resigned already in February 2016), while Macchiarini’s boss at the KI’s Department of Clinical Science, Intervention and Technology (CLINTEC), Li Felländer-Tsai, is absolved from guilt (just as by the KS report):

“Macchiarini was recruited to Karolinska Institutet and the Karolinska University Hospital in 2010 as visiting professor at KI (30 per cent) combined with an employment as consultant at the hospital (30 per cent). At KI, he was posted to the department of CLINTEC. His recruitment was initiated by then vice-chancellor of KI in the autumn of 2009. The vice-chancellor took an active part in and had personal contact with Macchiarini during the recruitment process in a way that constituted a breach of the delegation of authority and that created some confusion about who had responsibility for his recruitment. To the head of CLINTEC, it seemed like the decision was already taken and the recruitment process a mere formality”.

The earlier published report by the Karolinska Hospital mentions several instances of negative references provided by Macchiarini. Now, the Karolinska Institutet file names these sources:

“In August 2010, Professor Sven-Erik Dahlen, Head of Unit Experimental Asthma and Allergy Research at the Institute of Environmental Medicine, Karolinska Institutet, was contacted by an Italian colleague, professor of pulmonary medicine and asthma researcher Leo Fabbri, University of Modena and Reggio Emilia. Fabbri recited according to Dahlen “serious criticism of the PM’s research, clinical review and general character” and thought Dahlen would dissuade their colleagues at KI from recruiting Macchiarini. [..]

The email mentioned to Dahlen two points in Macchiarinis public CV which Fabbri claimed were incorrect. According to Fabbri, Macchiarini was not like he declared a professor of surgery at the University of Barcelona. Nor had he been Professor of Surgery at Hannover Medical School. In Barcelona Macchiarini had according to Fabbri only a temporary appointment at the hospital and had to quit “when he neglected the duties”.

Other sources of references were the larynx surgeon Martin Birchall in London (who now has his own line of regenerated trachea experiments in humans), Alvar Agusti and Manuel Bernal, two professors of medicine at the University of Barcelona, as well as Tobias Welte, professor of pulmonary medicine at the Hannover University School of Medicine (MHH).Welte was also one of the examiners at Philip Jungebluth’s medical doctorate defence (more about Jungebluth and his dissertation here). This was what Dahlen summarised in his email to the director of CLINTEC’s Ear-Nose-Throat division Lars Olaf-Cardell:

“Altogether, we have a positive reference from London (Martin Anthony Birchall), a negative from Florence (Leo Fabbri) and two negative from Barcelona (Alvar Agusti and Manuel Bernal). We will receive a copy of the critical letters which Tobias Welte in Hanover wrote to colleagues in Barcelona before Macchiarini’s employment there (this, however, Barcelona chose to ignore when he was hired). All referees agree that he  is a technically dazzling surgeon. From Florence and Barcelona came forward consistent evidence that he has a distinct personality that makes him difficult to accept both adversity and
opinions regarding the surgery that does not coincide with his own. […] From Southern Europe: sweeping, yet consistent allegations of negligence in terms of dealing with the truth, lack of collegiality, poorly consideration for patients and families as well disrespect for the rules (both actual and moral). The accuracy of his long and impressive resume has been questioned by Florence and we therefore requested Thursday additions in the form of certificates on three key points concerning the hand of service. These have not yet been received”.

Welte then described Macchiarini as “a brilliant surgeon, very innovative”, “a real academic researcher with good and relevant research proposals”. His key concern was that this star clinician was “very difficult to negotiate and cooperate with”. The information about the negative references was however never forwarded to the Recruitment Committee at Karolinska:

“The reason for this, according to the prefect Felländer-Tsai, have been that it was not needed because the Recruitment Committee shall only make a scientific assessment of the applicant”.

Also the certificates of Macchiarini’s professorships which Felländer-Tsai requested on the account of the negative reference outcomes seemed not to have been closely examined. Instead, she and Cardell wrote  to the regional president of Tuscany for a “better” letter of reference. Which they promptly received, the entire communication is available exclusively here.

Nobody checking anything

After the outrageously biased recruitment, Macchiarini’s employment as KI-professor was extended twice in 2013 and 2015, without any evaluation:

“Our inquiry shows that KI initiated no real evaluation and assessment of Macchiarini’s work at KI, neither ahead the contract extension in 2013, nor ahead the contract extension in 2015. For the 2013 extension there were countless circumstances that should have warranted such an evaluation. This includes the uncertainty surrounding the reason for the legal action taken against Macchiarini in Italy in the autumn of 2012, and the objections to Macchiarini’s activities raised by the Karolinska University Hospital in 2013 that made the hospital decide to stop further transplantations and terminate its part of Macchiarini’s contract”.

Back in 2013, Karolinska hospital banned Macchiarini from operating, but made sure his medical licence in Sweden was extended. His professorship and research into regenerative medicine at KI continued, and the experimental bit, involving human research subjects: that was apparently “outsourced” to Russia. An authoritarian state, known for its corrupt medicine, bureaucracy and its even more corrupt, actually farcical, justice system.

The Heckscher report apparently did not address the scientific side of the Macchiarini scandal, (though one of the Committee’s members, Gahmberg, is a biomedical scientist). It would have been very informative nevertheless, given that two KI’s own internationally recognised stem cell researchers ( Urban Lendahl and Ernest Arenas) recommended Macchiarini’s employment in the notorious 2010 letter to the  KI rector Harriet Wallberg-Henriksson (which I publish here). Wallberg then played a key role in Macchiarini’r recruitment and claimed to have been unaware of his dishonest CV or bad references. In 2012, Wallberg-Henriksson wrote to Macchiarini an email, with Lendahl and the Dean of Research in cc:

“Dear Paolo, I am writing to inquire whether you are available for a meeting in August. Based on your extremely successful time at Karolinska Institutet I would like to meet with you and discuss (together with the Dean of Research, professor Martin Ingvar) the possibility of a more permanent position for you”.

The fact that Macchiarini had to retract a paper for plagiarism (Gonfiotti et al 2012) was only seen as problematic because it could affect his big funding and professorship. So a supportive verdict was reached in early 2013 by the corrupt Ethics Council of KI (meanwhile dismissed), under pressure from Wallberg-Henriksson and CLINTEC boss Felländer-Tsai, later on approved by the new rector Hamsten.

In fact, the former university head Wallberg-Henriksson had a unusually close relationship to her guest-professor Macchiarini:

“The guest professor accrued his private relationships with KI’s top management, hospital management, and donors, in a way that does not occur frequently. He and the rector had their own meetings without the knowledge or presence of the people who are in the line between the principal and the guest professor. Guest professor also gives the impression of having worked relatively informally, contracts and written agreements were missing in several cases where the internal audit perceive that such ought to be”.

Now, the KI chancellor Wallberg-Henriksson was sacked from her post by the cabinet minister for research and education, as soon as today’s report was published.

With science left largely aside, Heckscher’s investigation focused on the administrative side of the scandal:

“We criticize KI for its nonchalant attitude towards regulations – sometimes enshrined in the constitution – governing how public authorities are to manage their business. Not only are many public documents, such as external e-mails, not registered”.

This calls to memory another misconduct case at Karolinska Institutet. An investigative dossier about the data manipulations by the former KI scientist Suchitra Sumitran-Holgersson, addressed to the above mentioned Dean of Research Ingvar and submitted by hand to the KI registrar, disappeared into thin air, in fact it was also never registered as well (see my detailed report here).

Macchiarini was previously accused of data manipulation and research misconduct by the four KI whistle-blowers. The Heckscher commission found out that KI was not really eager to investigate those accusations:

“The six cases of alleged scientific misconduct concerning Macchiarini were administrated and examined in different ways. Sometimes no action at all was taken, sometimes the case was referred to KI’s internal Ethics Committee, and sometimes an external investigator was engaged. […] In none of the reported cases did KI turn to the Central Ethical Review Board as directed in the Higher Education Ordinance. […]It also appears as if KI did not ensure that the external investigator [Gerdin, -LS] received all the information he requested”.

Friends at CLINTEC

Proving whether or not and what data exactly Macchiarini has faked at KI will be difficult now, since his research documentation disappeared. He simply either destroyed it or took it with him when he left, while none of his superiors sought it as important to make sure any backup copies stayed at KI. Macchiarini’s ex-boss Felländer-Tsai apparently saw this as perfectly normal procedure, as the Heckscher report suggests:

“CLINTEC, the department where Macchiarini was based, is unable to provide complete information about the documentation of the visiting professor’s research at KI. The reason given is that Macchiarini and the rest of the group has left the department. It is unacceptable that a disbanding of a research group has such far-reaching consequences that documentation concerning completed research at KI can no longer be traced”.

GMO release

In  fact, it it is not just that Macchiarini’s research notes disappeared. It is likely some animal experiments were either done on humans first, or not at all. Once again, humans (patients Beyene and Lyles) went under Macchiarini’s knife first, to test the water for rats:

 “In May 2012, he received permission to conduct animal experiments related to the trachea. Then it was concerned about attempts by both decellularized cadaver body as synthetic – artificial – frame. It may be noted that patients 1 and 2 by that time had already undergone surgery at Karolinska University Hospital. […]

Our investigation shows that the so-called bioreactor is not mentioned in any meeting minutes from Macchiarini and Sylvén [Christer Sylvén, boss of one of Macchiarini-whisteblowers, -LS], research took place only from March 2012 on. However, there is evidence that one of Macchiarinis employees may have worked “with non-sterile plastic tubes and cells with the so-called bioreactor “already. The timing is however uncertain”

The research documentation was gone together with Macchiarini anyway, just as in the next critical case. Macchiarini and his international collaborators published a report in a highly respected journal about successful artificial oesophagus transplantation in rats.  This is what the Heckscher commission found out in this regard:

“no animals have been ordered under the Animal Ethics statutes 6-11, 8-11 and 160-1137 despite at least permit No. 160-11 appears to be the basis of the scientific article Sjöqvist et al, Nature Communications 2014. Inquiry asked in this regard the prefect [Felländer-Tsai, LS] and head of the unit at CLINTEC (either  Cardell or Göran Gynther, head of division, -LS], but got the answer that because the research team leader not longer at KI department, they can not comment further in the matter”.

Why didn’t the CLINTEC head Felländer-Tsai backup Macchiarini’s research data? Well, as I found out, they used to be close friends. Felländer-Tsai was invited to Macchiarini’s fraud-wedding with the duped journalist Benita Alexander (see this Vanity Fair story for details), which was supposed to be ordained by the Pope himself. Unlike Vladimir Putin and Barack Obama, Felländer-Tsai was invited as a real and not as an imaginary guest, and so was her colleague Cardell. The former informed the groom-to-be that she wouldn’t be able to attend due to family engagements, but sent a present. Other real guests scheduled were, aside of Macchiarini’s lab members like Jungebluth, the families of the very patients who died after being transplanted with plastic trachea by the miracle doctor: those of Christopher Lyles (mentioned among other Macchiarini patients in my special report) and Hannah Warren. The sister of this two-year old victim of human experimenting was supposed to be the flower girl at Macchiarini’s lie of a wedding.

These two friendly clinician colleagues, Felländer-Tsai and Cardell, are still in their positions at Karolinska, while everyone around them has been (voluntarily or not) taking their hats for months.


Note: this article has been updated twice since it first appeared, on 5.09, 6.09 and 7.09, to include information from the translated full version. For some reason, KI decided to publish their full Swedish-language report in a format unsuitable for machine translation. Elizabeth Woeckner found a way around it, here are the Google-translated chapters 6,7,8, 1011 and 12, highlight are hers. Macchiarini’s funding and ethics permits available separately  here. Many thanks to Liz.