Tissue-engineered tracheas: an assessment of the scientific, clinical and ethical implications

Tissue-engineered tracheas: an assessment of the scientific, clinical and ethical implications

Here I republish the written evidence submitted to by two UK scientists to the Science and Technology Committee of the British House of Commons and its inquiry into Research Integrity, as originally published on November 21st 2017. It deals with the trachea transplants performed by the surgeons Paolo Macchiarini and his former parter at UCL, Martin Birchall. The report’s lead author is Patricia Murray, professor in stem cell biology and regenerative medicine, previously a nurse on a Head and Neck unit. She generously invited me in May 2017 to give a seminar at her department at the University of Liverpool on this topic. Her coauthor is Raphael Lévy, senior lecturer in nanotechnology and imaging at the same university. I wrote about his reproducibility studies on the topic of nanoparticles in this article.

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Prof. Patricia Murray

UCL recently investigated Birchall’s past trachea transplants, and recommended to continue with his two current clinical trials to transplant cadaveric decellurised trachea and larynx, regenerated with bone marrow cells, as I reported here. For some reason, UCL Registrar Wendy Appleby, when speaking as witness on November 21st in front of the Parliament Inqury, found herself unable to answer the rather straightforward question whether the UCL investigative commission advised to continue transplanting trachea or not (watch here, from 11:50 on). Appleby and her UCL were instructed by the Inquiry to address the concerns by Murray and Levy in writing.

Both clinical trials  Inspire and RegenVox were already placed by the supervising authorities on hold, Murray and Levy now call to stop the dangerous and science-unsupported experimenting on misinformed human patients and to return back to the lab.

Following is a copy of the (originally published on the UK Parliament website), Continue reading “Tissue-engineered tracheas: an assessment of the scientific, clinical and ethical implications”

Martin Birchall’s shaky road to mass trachea transplanting

Martin Birchall’s shaky road to mass trachea transplanting

The British laryngologist and UCL professor Martin Birchall is one of the two founding fathers of “bioengineered” trachea, the other one being his former partner, the scandal surgeon Paolo Macchiarini. Birchall presently runs three trachea transplant trials clinical trials, two in the UK and one EU-wide. His patients must however wait to be cured, because the two UK trials, Inspire and RegenVox (with the latter primarily about larynx and upper trachea transplant) were both placed on hold, and the EU funded phase 2 trial TETRA is still far from getting an ethics approval and just now lost one potential trial site after the Medical University Vienna jumped ship. The EU Commission refuses to tell me anything about TETRA, except that it has not applied for ethics approval yet. EU’s Transparence department still evade commenting on how to put this scheduled 48 patient clinical trial in context of the 11 cadaveric trachea transplants by Macchiarini and Birchall, most or maybe even all of which left the patients either dead or mutilated.

In this article, I publish the most recent patient information sheets for the two suspended Inspire and RegenVox trachea transplant clinical trials, which I obtained under Freedom of Information request from the UK Health Research Authority (HRA).  Continue reading “Martin Birchall’s shaky road to mass trachea transplanting”

Oncogene EiC Justin Stebbing, a hypocrite of research integrity?

Oncogene EiC Justin Stebbing, a hypocrite of research integrity?

The cancer research journal Oncogene issued on October 16th 2017 an Editorial on the topic of research integrity:

“The importance of being earnest in post-publication review: scientific fraud and the scourges of anonymity and excuses”.

The editorial contains a list of 8 common excuses dishonest authors used to escape responsibility for manipulated data. It was authored by David Sanders, virologist and professor at the Department of Biological Sciences at the Purdue University in West Lafayette, Indiana, US, as well as Justin Stebbing, professor of cancer medicine and oncology at the Imperial College London, UK, who is also one of the two Editors-in-Chief (EiC) of the journal Oncogene. Sander is one of these rare brave academics who is unafraid to call out scientific misconduct while his peers hide in the bushes and instead even point fingers at whistleblowers like him. As the newspaper USA Today wrote earlier this year, Sanders made himself a very powerful enemy, the star US cancer researcher with Italian origins, Carlo Croce:

“But that didn’t stop Sanders from alleging that Dr. Carlo Croce, a prominent cancer researcher at Ohio State University, falsified data or plagiarized text in more than two dozen articles Croce has authored. For the past two-plus years, Sanders has contacted scientific journals in which the articles appeared to alert them of his concerns. Earlier this month, he went more public with his claims in an investigative piece by the New York Times that delved into years of ethics charges against Croce.

“There are, and I anticipate there will be additional, consequences for my career,” Sanders said Tuesday afternoon while sitting in his office inside the Hockmeyer Hall of Structural Biology at Purdue.

This isn’t the first time Sanders has publicly accused a scientist of bad behavior. In 2012, Sanders had an article by a former colleague retracted on the basis that the colleague used their former deceased research partner’s data in the paper without permission”.

A long article appeared in The New York Times prior to that, “Years of Ethics Charges, but Star Cancer Researcher Gets a Pass“, detailing the case of Carlo Croce and the role of Sanders the whistleblower, and the Ohio State University, who were mostly covering up the affair. Croce hit back: he is now suing the newspaper, and in separate lawsuit, also Sanders at a New York court, as reported by Retraction Watch.

Hence, Sanders knows first-hand what research misconduct is and how to act upon it. Indeed, the editorial was his idea, and his co-author Stebbing joined afterwards. As Sanders wrote to me:

“The impulse for the editorial and the list was from me.  We discussed the inclusion of particular items and how they were described together”.

Stebbing indeed is not much of a whistleblower, quite the opposite, he can be in fact seen as victim of such. His own publication was heavily criticised on PubPeer, for suspected western blot band duplications. And the piquant bit is: Stebbings, together with his first author  Georgios Giamas (now Reader in Biochemistry at the University of Sussex, UK) offered on PubPeer explanations which sound very much as what he himself has been ridiculing in the Sanders & Stebbing editorial in his journal Oncogene. Continue reading “Oncogene EiC Justin Stebbing, a hypocrite of research integrity?”

DFG Senator Roland Lill explains how to do science properly

DFG Senator Roland Lill explains how to do science properly

My earlier article about strange image irregularities in the publications of the German mitochondria researcher Roland Lill seem to have motivated this pre-emeritus biochemistry professor of the University of Marburg to come to PubPeer and address the issues. While in his earlier statements he simply waved off all concerns of western blot band duplications, this time and with other papers he admitted those, while presenting the original Western Blot scans. Together with the first author on two such papers, Janneke Balk, Lill explained why copy-pasting western blot bands, sometimes on top of other gel images, had nothing at all sinister in it, but used to be somewhat of a normal research practice 10-15 years ago. And in some cases, gel bands can naturally duplicate themselves.

Any advice on research integrity from the side of a Senator of the German Research Foundation (DFG) and of the German Academy of Sciences Leopoldina is certainly most valuable, this is why I will present here his explanations, so the younger generation of scientists can learn about correct figure preparation, including the proper use of gel band copy-paste function. The past evidence was forwarded to me by a reader of my site.  I will also offer Professor Lill and you for debate another example from his past publication, where a western blot was duplicated in different context. This was forwarded me from yet another reader of my site.  Continue reading “DFG Senator Roland Lill explains how to do science properly”

After misconduct investigation, Irina Stancheva left Edinburgh, in secret

After misconduct investigation, Irina Stancheva left Edinburgh, in secret

A scientist was “dismissed” by the Department of Biological Sciences at the University of Edinburgh, UK. All evidence points towards that it was the cell biologist Irina Stancheva who specialises on the epigenetics and regulatory methylation of DNA, and who departed from the university recently, after a forced leave. She also has an impressive record on PubPeer, where her publications were flagged for suspected data manipulations around 2 years ago. The suspicions were mostly of western blot band re-use and duplication. Around same time, an investigation started about these PubPeer issues, and by now Stancheva’s name does not feature of the Department’s list of academic staff. A archived version from December 2016 does feature Stancheva, but not that of August 2017. Her institutional website was deleted just hours after I sent my email inquiries to her former faculty colleagues. Continue reading “After misconduct investigation, Irina Stancheva left Edinburgh, in secret”

Alexander Seifalian, UCL’s Persian Scapegoat

Alexander Seifalian, UCL’s Persian Scapegoat

The London university UCL has now completed the investigation into the affair around their past honorary professor and now disgraced thoracic surgeon Paolo Macchiarini and the trachea transplants. Subject of the investigation were: the two plastic tracheas UCL produced (one sent to Karolinska Institutet and implanted in patient Andemariam Beyene in Stockholm, another used by UCL laryngologist Martin Birchall to treat Keziah Shorten, who previously received a cadaveric trachea from Macchiarini as requested by UCL) as well as four more cadaveric trachea transplants, namely the very first such intervention organised by Macchiarini and Birchall in Barcelona in 2008, on patient Claudia Castillo, as well as the three trachea transplants which took place under UCL oversight in London, on paediatric patients Ciaran Lynch, Shauna Davison and a 3-year old child who was transplanted just in May 2017 at the same Great Ormond Street Hospital (GOSH). The offhand revelations about the last transplant in this UCL report came as surprise, since it was otherwise kept secret.

No information is provided by the investigative report on how that child is doing now, in fact it seems no evidence like laboratory books, research data or patients’ medical files was ever requested and the committee relied solely on the opinions provided by the very people they were supposed to investigate: Paolo Macchiarini, Martin Birchall and GOSH paediatric surgeon and past director Martin Elliott. In fact, the report seems to become very nebulous or even creative with its use of alternative facts to avoid implicating Birchall in anything unethical at all. The only guilty party in this medical scandal is incidentally also the only non-clinician and the only non-white character in the entire Macchiarini affair: the nuclear physicist Alexander Seifalian, a Persian-Armenian and dual citizen of Iran and UK, whose lab manufactured two plastic tracheas. He was already sacked by UCL in July 2016, accused of bribery. Seifalian is also bowel cancer survivor, which did not prevent UCL of accusing him of failing to oversee the abroad clinical application of his produce just when he was receiving chemotherapy.

These are the results of UCL investigation in the nutshell:

  • All UCL-employed clinicians involved in trachea transplants, in particular UCL’s chief trachea transplanter Martin Birchall, are fully acquitted from any suspicion of misconduct or clinical wrongdoing. Even Macchiarini seems partially exonerated from the gist of the UCL report, because:
  • The maker of the two plastic tracheas, Alexander Seifalian, is to take all the UCL-related blame for the failed  transplants (as well as other plastics implants in India, Iran and Switzerland). His fault is to have manufactured these products though his UCL lab lacked GMP (Good Manufacturing Practice) certificate. Only this lack of GMP-quality seal was what apparently made plastic tracheas too dangerous to implant in humans.
  • All five cadaveric trachea transplants under the scope of investigation were considered ethically, medically and scientifically justified. Deaths of the patients were explained with new discoveries of recurrent cancer, or demands of other patients for the same hospital bed.
  • Birchall’s clinical trials with cadaveric tracheas (phase 1/2a INSPIRE, and by extension, also EU-wide phase 2 TETRA) are to go ahead as planned and to recruit patients. Same positive recommendation for Birchall’s related trial RegenVox on cadaveric larynx, decellurised and “regenerated” with same technology as tracheas.

Continue reading “Alexander Seifalian, UCL’s Persian Scapegoat”

EU commemorates dead patients of Macchiarini & Birchall with a phase 2 trachea transplant trial TETRA

EU commemorates dead patients of Macchiarini & Birchall with a phase 2 trachea transplant trial TETRA

The European Commission now took 40 days to deny my second Freedom of Information (FOI) Inquiry about the TETRA phase 2 clinical trial with cadaveric trachea transplant they are currently financing with €7 Million. This is EU’s second attempt to become world-leading manufacturer of industrial trachea transplants, after the €5mn Biotrachea led by the scandal surgeon Paolo Macchiarini was terminated mid-term. No, not because EU had any concerns for the patients, quite the opposite: he was given a clean ethics vote to go ahead. Biotrachea was terminated by the EU because the plastic tracheas Macchiarini wanted to use lacked novelty, as the documents I obtained revealed.

The TETRA trial, led by Macchiarini’s past collaborator, the UCL laryngologist Martin Birchall, was already on the brink of being terminated in the wake of the Macchiarini scandal, as EU previously indicated to me. Now, exactly the opposite happens. The trial is being prepared at full speed despite the fact that its predecessor phase 1 trial INSPIRE was suspended (because of my reporting), never recruited any of its four patients and it most likely never will. That trial is also led by Birchall (details here), it is likely that its Innovate UK funding has ran out meanwhile. EU however seems to signal that they will go ahead with phase 2 trial even if phase 1 never happens. After all, there are those 10 patients who received a cadaveric trachea transplant  (here and below) and were operated under hospital exemptions between 2008 and 2012 by Macchiarini and Birchall. At least half of these 10 are dead, the lucky survivors either had their graft removed or live with permanently installed stents to prevent their rotting airways from collapsing (INSPIRE’s and TETRA’s clinical promise is actually that the patients will never need a stent). But this disaster seems exactly the reason for EU to try it again, and on a much, much bigger scale: 48 patients are scheduled to receive cadaveric tracheas. Probably because it will create employment.

The EU spokesperson ceased long ago answering my emails, after I declined to be instructed over the phone (strictly off-the-record) why EU’s approach to trachea transplanting is right; this is why I had to resort to FOI. The official time limit to answer my FOI inquiry from July 1st 2017 was 15 days, but the EU first pretended not to have received my postal address, then said they need more time, then said they need extra time to assemble the documents for me, and finally, the Director-General of the European Commission, Robert-Jan Smits, wrote to me on September 11th. He basically told me again to get lost and that he will never release any information (read here his past rejection of my FOI inquiry). His reasons, as before: the trachea transplant trial is a business enterprise and revealing any of its progress might endanger the financial interests of its stakeholders, and then there are privacy concerns. Exactly, Smits decided that the public must under no circumstances find out whom exactly the EU is giving this public’s money for research on humans. I am not making it up, read Smits’ letter yourself hereContinue reading “EU commemorates dead patients of Macchiarini & Birchall with a phase 2 trachea transplant trial TETRA”