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 on 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 gathered by blogger Alla Astakhova, 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.

Update 10.10.2016. I had to submit another FOIA inquiry to University of Bristol just to find out why they removed the two press releases. They replied: “The press releases referenced were removed whilst the University reviewed its procedures in relation to this request. They will now be reinstated“.

14 thoughts on “The newly found innocence of Paolo Macchiarini

  1. Lest we forget, of course, the hundreds who died in the early trials of heart transplants. So many dying, that the trials were radically reduced until further knowledge was gained.
    And liver transplants. In 1970, only a 15% survival rate at first year follow up…….with kidney transplants much the same.

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    1. Hi Trace,
      It’s good to see you online & engaged in discussion. I’m sorry for your loss; it’s unimaginable that a terrible cancer could strike a young, vibrant, healthy girl.

      Your point makes sense but history tells a different story. Bioethicist George Annas has a good straightforward discussion of the issues in early heart transplantation; see p. 91 and following: http://digitalcommons.law.wne.edu/cgi/viewcontent.cgi?article=1287&context=lawreview

      Kidney transplants followed a slightly different trajectory, perhaps because they were not as sexy as heart transplants or whatever. The 1954 transplant between identical twins was successful: https://en.wikipedia.org/wiki/Kidney_transplantation

      Short version: without effective immunosuppression, organ transplantation is a failure, if not fatal.

      Ethical principles have evolved since those days and it’s not so such what’s acceptable risk but rather what information must be provided to patients and the acceptable balance of risk vs. potential benefit. Greater risk for greater potential reward, certainly but the potential reward needs plausible data to support it.

      Many people who are upset about Macchiarini are troubled that inadequate and false information was provided to several patients who got synthetic tracheas. In his own words Macchiarini realized almost immediately that the POSS/PCU trachea used in patient 1 at Karolinska was not going to work. By not accurately publishing his results physicians and patients were denied crucial information. It’s difficult to know why Birchall decided to try the POSS/PCU trachea because the transplant was done before publication of patient 1 in Lancet 2011. It appears Birchall and colleagues came to the same conclusion about this material, as suggested by the husband of a woman who was scheduled to be transplanted by Macchiarini in 2011/12 – they warned him off: https://www.facebook.com/groups/198660840207194/permalink/1028665673873369

      In an interview in the Swedish documentary Experimenten, Birchall’s colleague Dr Sahdu said he couldn’t see that the plastic trachea would work at operation. BBC4 Storyville will broadcast the documentary in English in October. It’s well worth watching.

      Video and print interviews with patient 1 (Mr Andemarian Beyene) are extremely troubling. All the interviews pre-date public revelations about Macchiarini’s work so it’s not the case that they’re effected by hindsight. When he learned his cancer had returned, Mr Beyene said his first response, after Macchiarini proposed the synthetic trachea transplant, was to say no, he preferred to live 2 or 3 years and die rather than be the first to test a synthetic trachea. Macchiarini told him he tried it pigs successfully, which was false. Macchiarini also put pressure on Mr Beyene, telling him the proposed transplant was the only way he would see his children grow up. Mrs Beyene went further, saying that Macchiarini explicitly guaranteed them that Mr Beyene would live 7 to 10 years if he agreed to the operation. Widely accepted principles of respect for persons and autonomy prohibit physicians from attempting to convince patients to undergo experimental intervention.

      We don’t know what happened with patients who got cadaveric trachea transplants at Careggi because Macchiarini hasn’t published detailed information. News reports claim his optimistic assessment differed from that of another expert: (Google into English) http://tinyurl.com/hj92t9o

      There’s a passing reference to an SAE (serious adverse event) involving use of IORT during trachea transplant, logically involving a patient with cancer of the trachea. European Commission Community Research and Development Information Service (CORDIS) Biotrachea Project reference: 280584 Periodic Report Summary 1 http://cordis.europa.eu/result/rcn/141304_en.html
      “Due to an adverse effect of Intra-operative Radiotherapy (IORT) in a single patient this will not be continued clinically until it has been fully evaluated in pre-clinical models. A murine model has been established for this purpose.”

      Surgery date in this press release (Google into English) http://tinyurl.com/jrjfcls

      Details on patient, age and nationality, and use of IORT outside recommended calculated treatment area p. 8: http://doc.mediaplanet.com/all_projects/6030.pdf

      Same patient? Dunno but worrying nonetheless.

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  2. I am watching the BBC programme about Paolo Macchiarini – how anyone could think a plastic trachea could meld with live tissue is beyond belief – anyone involved in this quack medical procedure should be disbarred from practising any form of medicine.

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  3. The fact that he was allowed to operate on these patients without clear evidence that they had a chance to lead to a successful outcome is outrageous. There were no animal trials and tests to support the validity of this type of operation. From the evidence shown in the BBC ‘3 part series’ some patients and families were told there had been successful outcomes with pigs and the Russian lady was not clearly told of the potential risks. In fact Paulo was seen on film agreeing that the plastic trachea was in fact the wrong dimension to be successful yet they STILL went ahead with the operation. She had a tracheotomy and although uncomfortable for her it didn’t seem to be life threatening. She was desperate to cover up the ‘hole’ in her throat and you could tell cosmetically it really upset her. In my opinion Paulo and his team took advantage of this. A Russian doctor told her to ‘stop crying and be positive’ after the operation and in fact she couldn’t breathe and was suffocating from the plastic trachea. If she had been my wife I would been asking all the questions that weren’t being asked potentially because of the size of the “ego’s” and personalities in the room with her. In the interview after the operation paulo claimed she could now ‘breathe and play with her son’ which she COULD do before anyway, as was seen on film before the operation. The Karolinka Institute senior team are just as liable as paulo. They supported his procedures without all of the facts and evidence. How do I know? Because in the interviews in part 3 they did not have the specific details to answer the interviewer and yet they had publicly defended his actions which were entirely based on the specific steps he had taken which WAS the detail. At the end of the day it’s a simple position, no operations should have taken place before animal trials and proof that a plastic windpipe could successful be accepted by a human body to work safely and correctly. From all the evidence in the 3 part series this was never the case. He should be prosecuted, the Karolinka institute should be prosecuted and they should be made to stand up and accept they made incomprehensible errors and mistakes that led to the death of almost all of the transplant patients. Why are all the patients not dead? For me it seems to be because other medical professionals are helping keep them alive. Paulo and the KI should be ashamed of themselves, God bless the families and loved ones of those who have passed away!

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  4. So little said about the actual Harvard company that developed the plastic trachea and – watching the TV programs made unbelievable claims about them. Why are they getting off scott free, surely he was just the plumber and basically he had an equipment failure?

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    1. Well, Harvard Apparatus is now Biostage, David Green was removed as CEO, and they have found another stem-cell-keen surgeon, now from Mayo Clinic. Instead of trachea they now focus on plastic oesophagi, and instead of bone marrow cells on adipose tissue, which they insisted to me was pluripotent. What can go wrong?

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