Macchiarini victim’s family sues trachea makers for wrongful death

Yesim Cetir was a young woman from Turkey, whose vulnerability the scandal surgeon used to test his plastic trachea (twice), a third such operation he performed at the hospital of the Karolinska Institutet in Sweden, and his fifth plastic trachea recipient. Like almost all the at least 17 patients whom Paolo Macchiarini experimented upon with either cadaveric or plastic trachea, Yesim died. Her suffering was long and horrible, her father Hayrullah Cetir dedicated all his waking hours to caring for his daughter. He died himself soon after her, from a neglected cancer.

Since April 2017, Yesim’s family (or in US legalese, the Estate of Yasim Cetir) is suing the company Harvard Bioscience, which spin-off Biostage (in turn formerly known as Harvard Apparatus) produced the bioreactors and the second plastic trachea graft used by Macchiarini on Yesim. Also the manufacturer of her first plastic trachea, Nanofiber Solutions, is being sued at the Suffolk County Superior Court in Massachusetts, USA, case number 1784CV01174. An article in Boston Business Journal indicated that even Macchiarini himself might be subject to the wrongful death lawsuit:

“Now, the estate of one of the deceased patients is pursuing wrongful death claims against both Biostage and Macchiarini”

The publicly available court information is here as pdf backup. On 31 January 2018, the Massachusetts court dismissed the motion by Harvard Bioscience of being absolved of responsibility on their claim they had simply supplied parts of equipment. Harvard Bioscience’s former CEO David Green featured in the Swedish documentary Experimenten while lying to Yulia Tuulik, another victim of plastic trachea, so that she accepts the graft which then killed her. Now company is frantically trying to blame Macchiarini for everything, despite theirs and Macchiarini’s common patent on plastic trachea. According to Boston Business Journal:

“Macchiarini’s research led to the creation of Biostage in 2013. But the company, whose stock is traded over the counter under the ticker “BSTG,” has said that it did not employ Macchiarini or provide him with any compensation, and ended its relationship with him in 2014. In federal filings, the company has also said that it discontinued development of the technology that is cited in the lawsuit in 2014. The company is now developing a different type of replacement organ, but has been burning through cash and laid off most of its workforce last fall”.

Yesim’s story

Yesim Cetir was a victim of a botched operation in Turkey, to fix her hand sweating. It left her with a damage to her trachea, a lung drainage and a chronic cough, which was not life threatening (read Karolinska whistleblowers’ report here, page 24), but her quality of life was restricted. Macchiarini was in 2012 an absolute star of regenerative medicine, a miracle doctor who saved lives as evidenced by his publications in The Lancet, his professorship at Karolinska and the Nobel Prize whispers around it. Of course Yesim and her family were excited that the demigod Macchiarini visited Istanbul and agreed to help her on 25 March 2012. The Turkish ministry of health agreed to pay for the operation, and sent over a half a million of Euro to Karolinska.

The first operation took place at Karolinska University Hospital on 24 June 2012, Yesim’s right lung was removed, so a plastic trachea could be inserted on 7 August 2012. The plastic graft was manufactured by Nanofiber Solutions, the bioreactor for the “regeneration” came as usual from Harvard Bioscience. That graft failed. Macchiarini returned to KI from Russia (where he was preparing a terminally ill baby patient for plastic trachea transplant), to replace Yesim’s graft with a second plastic trachea on 9 July 2013. Somewhere in between, Macchiarini’s student and right-hand man Philipp Jungebluth (the one entrusted with trachea “regeneration” and preparation of the operations) travelled to the University of Gothenburg to borrow a cadaveric trachea from the local regenerative medicine enthusiasts Michael Olausson and Hasse Ejnell (read here). That graft was then returned unused. Yesim’s second plastic trachea was also removed as she was eventually brought to the Temple University hospital in Philadelphia, US, where a lung-trachea transplant failed to save her. She died on 19 March 2017.

In between Yesim’s second transplant and her death, Macchiarini scandal exploded, despite Karolinska’s best attempts to cover up his fraud and lethal patient abuse. Swedish journalists uncovered the horrendous deaths and suffering of patients in the 3-part documentary Experimenten, while the glam magazine Vanity Fair exposed Macchiarini for what he basically is: a pathological liar. Macchiarini’s plastic tracheas were finally recognised for what the Belgian thoracic surgeon Pierre Delaere described them before: a tool of execution.

Plastic, because biological failed

Less known is that Macchiarini spoke of using plastic trachea already in 2009, already after he performed two (known) cadaveric trachea transplants. With mixed results, to put it mildly. The first patient, Claudia Castillo operated in June 2008, became only a success story in the sense that through continuous lying Macchiarini succeeded to press her failed decellurised cadaveric bronchus graft into two Lancet papers, with all the ensuing rewards for himself and his British partner Martin Birchall. After that, Hospital Clinic Barcelona forbade Macchiarini further trachea transplants, despite a waiting list of at least 3 foreign patients and a ready stock of decellurised tracheas he prepared . He was also shown the door and had to reluctantly return to Italy by the end of 2009. This is why his second patient, known only as DD, was operated with an off-the-shelf cadaveric trachea in secret, illegally and without any ethics or other oversight, at Institut Dexeus in Barcelona in October 2009. She died after many serious complications, including a detached graft (read here).

Annoyed by the paperwork and driven by the desire to skip regulations around donor approval and safety requirement for decellurisation reagents, Macchiarini had the idea to use plastic as scaffold material (the lecture videos here and here are quite revealing). In a book Megagrant written by his personal biographer and project manager Elena Kokurina, Macchiarini is quoted discussing with her in 2009 his upcoming Master-Class lecture in Moscow:

“Round 5. Synthetic scaffolds. Tracheo-brochial transplantation using artificial polymer scaffold, seeded with stem cells”

Disastrous experience with plastic trachea replacement from the medical past did not deter Macchiarini, because this regenerative medicine enthusiast decided that nanotechnology and stem cells (or what he thought were stem cells, namely bone marrow cells) will turn nanofiber-spun plastic scaffold into a living trachea. Instead of laughing, Urban Lendahl and Ernest Arenas, both world renowned Swedish stem cell biologists, invited Macchiarini in 2011 as guest professor to Karolinska to perform the stem cell miracle. Yesim was one of those victims.

Decellurising tracheas is a complicated business, and Macchiarini tells some rather revealing things on the issue in this 2010 conference lecture. If one doesn’t strip the donor tissue efficiently, it will cause immuno-rejection and kill the patient. If one keeps doing decellurisation cycles, the trachea starts to get soft, and will collapse and kill the patient when implanted. Not that it discouraged Macchiarini and Jungebluth in Barcelona from using many more decellurisation cycles that they themselves had determined as maximum (read here). Claudia Castillo survived because she received a bronchus transplants, others were less lucky, and died.

This problem with cadaveric tracheas is even more exacerbated by storage: in fridge, decellurised tracheas rot, defrosted from the freezer they become even floppier. This was something Macchiarini and Birchall eventually figured out, both from lab tests and watching their patients die. Both soon decided to use plastic tracheas: those are custom-made on demand, can be stored forever and bring little ethical or approval requirements with them. They also kill patients much faster, as both Macchiarini and Birchall soon noticed. Their lessons were different though. Birchall decided to go back to defrosted cadaveric grafts, hoping that his new, vacuum-assisted decellurisation method will stabilise them, but the 15 year old child patient Birchall tested it on in 2012 died also. EU Commission was quite positive and supported Birchall’s efforts in 2015 with €7 Mn for a phase 2 clinical trial, while phase 1 never happened.

Nanotechnology and stem cells!

Macchiarini however simply continued with plastic trachea, while experimenting with different materials: POSS-PCU or PET/Dacron. Up to 11 patients were operated between 2011 and 2014, only one survived because the graft could be removed. This prompted Macchiarini to turn to plastic oesophagus, results of his monkey-torture in Russia (before he became unwelcome there) were recently published.

 

After a fight with UCL over the plastic trachea patent in 2013, which finished off Macchiarini’s already strained friendship with their newly appointed professor Birchall, the Italian surgeon sought new partners. Nanofiber Solutions provided a solution, and instead of POSS-PCU trachea Macchiarini switched to one made of PET, commercially known as Dacron. Later on, Harvard Apparatus started to supply the plastic trachea. The advantage: there, he held a patent. The disadvantage: EU Commission, which gave Macchiarini and his partners €5 million for a clinical trial with POSS-PCU tracheas, was not amused an stopped the impending carnage. No, not because patients were dying. Because PET/Dacron material lacked novelty, so the project BIOtrachea was terminated in 2014 (read here).

Yesim and 3 other Macchiarini patients received a plastic trachea made by Nanofiber Solutions (here is the relevant statement from the company to Karolinska). The bioreactors to “regenerate” the grafts with bone marrow cells were supplied by Harvard Bioscience and (according to the book Megagrant) by their German subsidiary Hugo Sachs Electronics. Yesim second graft was made by Harvard Bioscience also, just like the one for the little girl Hanna Warren in April 2013, who according to that book Megagrant was supposed to be the very first recipient of the plastic trachea. The US authority FDA namely kept refusing approval for 2 years. This is why other trachea transplant patients from 2011-2012, Chris Lyles, Yulia Tuulik, and probably even Yesim, were what Macchiarini said about the very first plastic trachea victim, Andemariam Beyene:

“An extra chance: if everything works out with him, all will be well with Hannah”.

Yesim’s case was a horrible disaster from the very beginning. This is probably why the book Megagrant never mentions her story or her name (unlike 7 other plastic trachea recipients). All that can be found as reference to Yesim in that 240 page Macchiarini eulogy from 2015 is a reproduced defensive letter he sent to Nature in late 2014, apparently when this Nature News article was prepared (again, follows a translation from Russian, hence probably differing from unavailable English original):

“Finally, third patient, was probably the most difficult. It was a young woman from Turkey, whose condition was most difficult from the very beginning. When she arrived from Istanbul to Stockholm, the first bronchoscopy determined a wide fistula between middle bronchus and right lung artery. Because already in Turkey she experienced multiple and increasing haemorrhages from that site, the multidisciplinary team decided to first try to stabilise her. Her life expectancy at that time point was between three and six months. Trachea transplantation could only be scheduled if the first “stabilising” operation was successful. I performed that operation, and in the process we unfortunately determined total absence of the trachea, something we didn’t know before, and which we couldn’t see during previous examinations. She has multiple problems, which remained also after  the transplantation in 2012 and because of which she had to remain in the hospital all that time. It is a miracle she is still alive”.

Of course Macchiarini lied there, as he did in regard to all other of his victims.

Meanwhile:

• Swedish authorities dropped charges of manslaughter against Macchiarini on the advice of experts the state poresutor invited: the Gotheburg trachea transplanters Olausson and Ejnell, both qualified to pass such advice as they also were found guilty of research misconduct and medical ethics breach (read here).
• General Attorney Office in Gothenburg will now decide if to re-open the Macchiarini investigation on manslaughter charges. In this regard, only the victims’ families can pledge a review, who in this case likely to be the bereaved of Yesim and Andemariam Beyene
• Biostage (former Harvard Apparatus) switched from plastic trachea to plastic oesophagus, and established a collaboration with their new thoracic surgeon partner Dennis Wigle at Mayo Clinic, in Minnesota, US. Preclinical results were published in the journal Scientific Reports, with Biostage CEO as first author: La Francesca et al 2018 .
• One year ago, first human patient was treated with a Biostage oesophagus implant at the University of Texas Health Science Center in Houston, a 75 year old man suffering from cancer. Compassionate use is the easy way to experiment on humans, as Macchiarini’s example has taught.
• Biostage stock floundered, but they still are able to raise money. In December 2017, they won Connecticut Children’s Medical Center as investor.
• Macchiarini now helps his right-hand man Jungebluth to sue me in Berlin court. He submitted his expert witness opinion as sworn affidavit, being perfectly safe from legal consequences of lying under oath in a German court, since it is not clear where Macchiarini actually is to be found now. For sure he does not actually live at his official home address in Spain, but pursues surgery gigs all over the world. The court hearing is on 24 May 2018. Please donate!

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