The trachea-transplant “super- surgeon” Paolo Macchiarini seems to be sitting out the Swedish investigations of his misconduct and patients’ deaths in Russia. He is apparently still employed at the International Research, Clinical and Education Center of Regenerative Medicine in Krasnodar, a city in south-western Russia, just across the recently occupied Ukrainian Crimea peninsula. While Macchiarini’s Krasnodar colleague Elena Gubareva eagerly boasted to a Russian newspaper journalist about their success in creating stem-cell derived artificial diaphragm and plans to grow an artificial heart, the foreign star scientist hid in his office until the journalist left.
In the following article I will give an update on Macchiarini’s colleagues in Russia and primarily focus on two German doctors and close associates of the Italian surgeon (who, having grown up in Switzerland, speaks perfect German). Macchiarini met both these friends of his at the Medical University Hannover (MHH), where he joined in 2004 and had been developing the artificial trachea with the funding from the DFG. His collaborator at MHH was the surgeon Augustinus Bader, now stem cell professor at the University of Leipzig. Philipp Jungebluth was Macchiarini’s award-winning medicine graduate at MHH. The young German doctor followed his idol to Barcelona, Sweden and Russia and directly participated in all Macchiarini’s disastrous trachea transplantations.
The most worrisome case of Macchiarini’s patient deaths had its origin in Krasnodar. Yulia Tuulik received an experimental artificial trachea transplant, despite being anything but dying or a compassionate care case. The obviously clueless patient was talked into agreeing to what she assumed to be a cosmetical operation by Macchiarini, Jungebluth, Russian doctors like Igor Polyakov, as well as David Green, then-CEO of the artificial trachea manufacturer Harvard Apparatus. Quote Green to the patient: “We know this material is very safe” and “Paolo is the best surgeon in the world”. The implanted trachea was not only untested in animal experiments (unlike Green and Jungebluth claimed), it was actually even too short. Yet Macchiarini, Jungebluth and Polyakov chose to proceed with it anyway, simply because the other two available transplants were even less suitable. Yulia Tuulik died two years after the operation, horribly, and without much help or sympathy from the Russian doctors. Her story is available as SVT video in Swedish and as Russian-language summary.
After the Swedish documentaries aired and the scandal broke out, some state-controlled Russian media accused the Italian surgeon of being a “charlatan” and of abusing the Russian “Megagrant” funding. This criticism quickly died down. Instead, his Russian colleagues at the Kuban Medical University and the Clinical Research Hospital Nr1 in Krasnodar issued a public statement, where the Swedish evidence against him was described as “reality-twisting”. The Russian doctors declared that all patients, including Yulia Tuulik, qualified for participation in clinical trials and were properly informed before giving their written consent. The decisions about trachea transplants were made by local doctors and Macchiarini in a video-conference together with “the specialists from the Russian Research Center for Surgery in Moscow, Karolinska Institutet (KI) and Karolinska University Hospital (where Macchiarini is about to be sacked from his professorship, -LS), Careggi Hospital in Florence (where Macchiarini used to lead a regenerative medicine center, -LS) and the University of Texas MD Anderson Cancer Center”. No names of the individual participants were given (Update: see reader comment below for participants’ names), yet the Russian doctors offered to make all the documentation available to interested parties to prove that everything was done correctly on their side. However, the statement disappeared very quickly off the internet (a copy is stored here).
Jungebluth meanwhile is back in Germany and now works as resident/junior doctor (Assistenzarzt) in Heidelberg in the Thoraxklinik at Heidelberg University Hospital. It might be a career setback for a prize-winning thorax specialist, who is still listed as Assistant Professor in Karolinska. I approached the Heidelberg clinic directors with an inquiry if Jungebluth’s participation in lethal trachea transplant surgeries in Sweden, Russia and elsewhere was relevant to the patients in Heidelberg. To this, I received the following official statement:
“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 (transplantation of trachea or parts of trachea) 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”.
From the safety of his new job in academic clinical research, Jungebluth defended in a German newspaper his Krasnodar operations and even accused one of the Swedish whistleblowers and his former colleague, Karl-Henrik Grinnemo, of misconduct. Der Tagesspiegel wrote about Jungebluth:
“Previously, however, he had sent documents from which it appears that the Karolinska Institute was informed in advance of the operations in Krasnodar and also involved in the ethical evaluation and approval. Moreover, Jungebluth pointed out that the allegations were preceded by a dispute between researchers of ACTREM. Jungebluth reported his colleague Karl-Henrik Grinnemo to the Karolinska President for having used their data and concepts for a separate grant application of €650,000, without asking – which was reprimanded by the Institute for plagiarism. Shortly thereafter Grinnemo became spokesman of the group of four KI researchers who accused Macchiarini (and thus also Jungebluth) of scientific misconduct in seven publications. Papers, to which Grinnemo had contributed in part himself”.
Grinnemo did not reply to my emails. Meanwhile, he asked for his name to be removed from his and Macchiarini/Jungebluth common publication in The Lancet. The journal issued a correction, but the media relations manager Seil Collins stated to me that The Lancet will not act on Macchiarini’s papers otherwise:
“there are a number of enquiries related to the Macchiarini case, including the investigation into scientific misconduct which was re-opened and an external investigation into KI’s handling of the case. We will respond to the findings of the current investigations once they have reached a verdict”.
Meanwhile, in Stockholm and elsewhere, Macchiarini’s collaborators were trying to save their funding money. They were granted in 2012 for their project BIOTRACHEA under the FP7-NMP programme of the EU nearly 5.5 million Euros, the funding was supposed to run until March 2017. The main recipients next to Macchiarini himself were Alexander Seifalian from University College London (UCL), Harvard Apparatus and, with a smaller share of €180,000 Augustinus Bader at the University of Leipzig.
As an EU spokesperson stated to me, the grant funding was “suspended in 2014 due to difficulties related to important deliverables” and terminated on “4 May 2015, after the consortium had exercised its right of appeal”. Also, the EU demanded its money back: “the Commission is proceeding with this procedure of requiring reimbursement of all or part of the financial contribution made by its services”.
Yet the bold promise of the EU to return the taxpayers’ money is not entirely credible. In fact, some will even get additional cash from the cancelled funding programme. The trick is: all parties involved have invested what they already received in a way which precludes repayment. As Ylva Hultman, EU Financial Manager at the KI Researcher Support Office excitedly wrote to the members of the failed BIOTRACHEA consortium:
“I am happy to tell you that the Commission has sent the final decision regarding the reporting of costs in BIOTRACHEA. All costs reported are accepted! I will contact everyone separately with your individual calculation, some will receive money and some will need to reimburse. The reason for the reimbursement is that some partners have received more pre-financing than they have spent. I hope that we can solve the payments as fast and smooth as possible”.
At least Macchiarini’s collaborator Bader does not have to pay back to EU anything at all. The two former Hannover colleagues authored several papers together, also on the subject of tracheal transplants. Now, Bader distances himself from the man whom he used to admire. When asked by the University of Leipzig to explain the nature of his trachea-transplant collaboration with the disgraced super-surgeon, Bader had his secretary issue this declaration:
“Mr. Macchiarini used on his patients synthetic matrices, which led to severe complications. For these matrices there were two sources:
Manufacturer 1: Prof. Seifalian, UCL: https://iris.ucl.ac.uk/iris/browse/profile?upi=AMSEI62
Manufacturer 2: Harvard Apparatus, USA: http://www.harvardapparatusregen.com
Prof. Bader transparently published his know-how from animal experiments in 2009. The cooperation ended after the conclusion of animal experiments in 2009. Afterwards, Mr. Macchiarini modified and changed Prof. Bader’s method without his permission and outside of any cooperation. Prof. Bader has nothing to do with these “advanced developments”. He was also never asked on this matter.
Prof. Bader complained already in 2009 with Mr. Macchiarini as well as with Harvard Apparatus in USA to correct this procedure, yet without any success. For the EU project „Biotrachea“ the lab of Prof. Bader only performed in vitro experiments with fibroblasts using the UCL polymer, correctly and on time. The collaboration of Prof. Bader with Mr. Macchiarini ended in 2009 after conclusion of animal experiments on pigs using biological matrices. The paper was written in 2010 and published in February 2012 in Biomaterials [Jungebluth et al, 33(17):4319-26, -LS].
Mr. Macchiarini was hoping for clinical breakthrough through his new position at Karolinska, while using the new synthetic polymers from the US company, initially also those from UCL (POSS). He wanted to do everthing else with his team there, using own technology and cell methods. Therein he substantially supported Harvard Apparatus in public, which allowed the US company to move into the stock market. Mr. Macchiarini registered his own patent on his technology and cell biological concepts and entered cooperation with Harvard Apparatus [evidence on patents here, -LS].
Clinical work with the described synthetic PET (Harvard Apparatus USA) or UCL polymers (POSS) were performed by Macchiarini himself, without consultation [with Bader,- LS] and with support of Dr. Jungebluth in the lab. Prof. Bader was never involved into any of these studies, after the experiments on pigs have concluded, he also never supported those”.
Are we dealing with the lone voice of reason in the whole Macchiarini scandal? Should the regenerative medicine research community have listened to Bader’s advice instead of Macchiarini’s? Not necessarily. Bader’s own research has been previously questioned as well.
The Bavaria-born doctor used to be briefly a celebrity in Germany because of his alleged discovery of a stem-cell derived miracle wound healing cream. The discoverer Bader was lauded on serious state-owned television, even the highly respectable Süddeutsche Zeitung (SZ) defended him from all accusation of quackery and called his “Momentum Bionics” therapy “a miracle” which rescued not only burn victims, but even patients with multiple sclerosis. Bader’s recipe, according to the admiring medicine editor in SZ:
“Growth factors for the blood and patient-own stem cells from the blood or bone marrow. Other growth factors and signaling molecules for the immune system are included in the therapeutic mixture”.
The article insisted, Bader’s scientific evidence was published in peer-reviewed literature. Yet even his own official university site gives no clues as to what his magic cream is and how or where it was validated. Nevertheless, Bader used to cooperate with ten different clinics, and intended to test his therapy on a thousand of patients. Apparently, not much came out of it.
Since then, Bader started some stem cell businesses to promote his Momentum Bionics cures (websites deleted now, but backups here). He also has been apparently active in Thailand, where his stem cell activation therapy was peddled by a Munich-based gynecologist Michael Klentze (whose other business associate in Thailand was the stem cell miracle doctor from Heidelberg, Christoph Ganss of TICEBA). Bader denies his anti-aging business engagement with Klentze, and claims that his name was used without permission. The respective websites were deleted (though I made backups here and here).
Also, Bader seems to be a regular participator at dubious anti-ageing and regenerative medicine conferences. In October 2015, he was supposed to give a talk at the Mallorca Conference on “So-Called Uncurable Diseases”. A brief look into the program leaves strong doubts if this bizarre conference had any connection to proper medicine: the presentations from German doctors were about dangers of vaccination, “curing Parkinson’s without chemistry” and “cancer prevention with acupuncture”. After I contacted the University of Leipzig prior to this conference, Bader denied his intention to participate.
The main problem of the regenerative medicine research may be the very researchers whom the funding bodies chose to task with it. In this regard, Sweden meanwhile has another scandal, as I recently reported.
Update 7.04.2016. I received information from Lisen Samuelsson from KI Legal Department regarding the accusations Jungebluth raised against Grinnemo:
“A report towards Dr. Karl-Henrik Grinnemo concerning research misconduct was made by Dr. Philip Jungebluth on April 11, 2014. The report pertained whether the use of data was allowed, if false information had been given and if information had been distorted. On April 28, 2015 the Vice-Chancellor [Anders Hamsten, -LS] decided that Dr. Karl-Henrik Grinnemo had been careless on many occasions in his research but he was not found guilty of research misconduct (Case nr 2-1309/2014)”.
“No names of the individual participants were given, yet the Russian doctors offered to make all the documentation ”
Here is link to file wich reports on this videoconference from 2011, avaiable in English from official web page of Macchiarini’s Megagrant. All names are there.
“Karolinska University Hospital, Stockholm, Sweden: Kuylenstierna Richard, Lars Olaf Cardell, Mats Holmström.” Obviously from the file, they received information about medical state of patients planned for operations.
Click to access report_videoconf_eng.pdf
However, different versions were provided by participants about what was actually discussed. Macchiarini insisted in his interview to Russian lenta.ru that the conference “approved” his choice of patients for operations, while Swedish participants insisted there was only general discussion and presentations.
Bosse Lindquist in his interview described the controvercy about this videoconference here:
He also mentioned in the end of interview some official who supported giving Macchiarini Megagrant and later become Minister in Russian government. The name of this Minister is not provided. Bosse also said that he tried to find some records from this videoconference but have not succeded.
Interesting. From the videoconference report:
“Specialists from National Research Centre of Surgery named after B.V. Petrovsky, Russian Academy of Medical Sciences, Moscow, presented case of the patient who had cadaveric tracheal transplant.”
Transplanted with donor decellularized trachea on Dec 7, 2010: https://mariakonovalenko.wordpress.com/tag/paolo-macchiarini/
Guess that answers the question of how she’s doing if she was being considered for a plastic trachea
Ms. Iglikova https://www.tts.org/component/tts/?view=presentation&id=13624
” 25 y.o. female with subtotal stenosis of trachea, stridor and “Polyflex” stent had undergone transplantation of trachea received by methods of regenerative medicine in 2010. The early postoperative period was accompanied by the moderate respiratory insufficiency, hemoptysis, expressed bronchial secretion. Sinus tachycardia and high levels of red blood and white blood cells, C-reactive protein and procalcitotnin have been connected with introduction of growth factors. By the moment of discharge breath was free, a gleam of trachea on all extent was satisfactory, in transplant wall we revealed squamous cell ephitelium. Patient does not require immunosupression. In 6 m. we observed progressive deterioration of breathing and revealed stenosis of tracheal transplant. We need to perform tracheoplasty with T-tube. Twice we try to detubate patient but in short period restenosis occurred. So patient continue having T-tube in trachea.
Conclusions. In some patients with critical subtotal stenosis resistant to accepted management tracheal transplantation may be curative option with satisfactory short-term results. Long term results occur challenges either to patients or doctors and need a lot of efforts to control specific conditions.”
(sorry if this is a duplicate)
From the videoconference report:
“Specialists from National Research Centre of Surgery named after B.V. Petrovsky, Russian Academy of Medical Sciences, Moscow, presented case of the patient who had cadaveric tracheal transplant.”
See above for report on her outcome.
If their level of medicine is as good as their level of English, then I would be very worried about being a patient in that clinic.
A reader forwarded me this 2014 presentation by Harvard Apparatus.
• Regenerated organs for transplant
• initially for trachea cancer / trauma
• Six successful human transplants using our scaffolds
• $770m per year market in developed world
• Deep pipeline: collaborating with MGH, Mayo, Texas Heart and Karolinska on lung, esophagus, heart valves and heart
• Defensible: patents, orphan exclusivity, first-mover
• Capital efficient: small trials, rapid approvals
• Committed to shareholders and patients – CEO owns 5%
Clinical Success With Regenerated Tracheas:
• Six patients to date, using our scaffolds and bioreactors
• Three previous patients, using our bioreactors
• Four of six alive at August 15
• The two that did not survive died of unrelated causes (car accident, unrelated surgery)
• Three surviving patients recently passed 1 year anniversary post-surgery. The fourth was 2+ months post-surgery at August 15.
• The first US transplant (FDA approved IND)
• Target life-threatening medical conditions
• Trachea cancer, organ transplant; not skin, bone etc.
• FIH under compassionate use reduces late-stage failure risk
• Fast path to market – small trials, rapid follow up
• Favorable reimbursement profile
• Orphan status likely – 7/10 years exclusivity
• Grant funding, e.g., Russia $6.7m, EU $5m
• Use trachea as platform to other organs
• Collaborate with leading surgeons and institutions
• Prof. Macchiarini at The Karolinska Institutet
• Dr. Ott at Massachusetts General Hospital
Clinical Trial Design Proposal:
• 8 sites: US x 4, EU x 4
• Single arm, open label
• Lung function as primary endpoint
• Compare FEV1 before surgery and at 90 days
• Submit FDA IND in 2015
• End trial mid 2017, possibly shorter in EU
• Assumes Fast Track, Accelerated Review, Priority Review and Breakthrough Status
The full presentation is available here.
Another excellent post. Just a tangential issue: Alexander Seifalian is listed as “Chariman of the Board of Trustees” of Open Access Publishing London (OAPL), a Beall’s-listed OA publisher with a messy history that I have blogged about at length.
OAPL “went quiet” over a year ago – the website is still up but they haven’t published anything recently, leaving a number of papers “stuck in limbo”, accepted but not published, which puts the authors in a very tricky situation. I emailed Seifalian alerting him to this on 17th March 2015 but he didn’t reply.
Il était une fois, I was on bit of a kick and began constructing a comprehensive list that contained the info on editors from journals considered “predatory,” just to see if there were any patterns in the group. I was determined to catalogue the totality of each person’s editorial affiliations to see who the highest offenders were. After a while, I started losing track. The sheer number of repeat offenders was overwhelming & one thing became readily apparent- most people aren’t satisfied with being on just one questionable board.
So, I’ll see your OAPL and raise you——
A Sci Forchen:
and An Avens:
One should keep away from the Krasnodar and Heidelberg clinic. Amazing that these [people, -LS] still have jobs. Only questionable hospitals employ these kind of people.
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