• 05 februari 2016
• 23
• AV: Malin Gavelin

Anders Hamsten Vice-Chancellor

Hans-Gustaf Ljunggren Dean of Research

Jan Carlstedt-Duke Senior Adviser, Rectorate

RE: A New Investigation of Misconduct in Research on Artificial Tracheae

To initiate an investigation to find new evidence is a diversion tactic with the ambition to trick the media and the general public that the threshold of scientific misconduct has only now been surpassed by the information revealed in the Swedish Television documentary ‘Experimenten’. The truth is that what was described in our Appeal for an Investigation and in the Amendment to the Appeal filed nearly 1½ year ago (Aug 18, 2014 and Sep 24, 2014, Dnr 2-2184/2014) was more than sufficient to prove misconduct on the part of Prof Macchiarini. The independent external expert Prof Gerdin confirmed this in his initial review of the case eight months ago (May 13, 2015). When Prof Gerdin reviewed the information that was submitted after his report was filed, he found no new evidence that could absolve Prof Macchiarini of the charges made against him (Letter to the Vice-chancellor Prof Hamsten Dec 21, 2015).

The purpose of this diversion tactic is to provide KI, under the leadership of Prof Hamsten, with an air of plausible deniability to the images revealed in the documentary. In official statements made by Prof Hamsten internally at KI (Letter from the Vice-chancellor to all KI professors Jan 27, 2016) and in the media, Prof Hamsten states that the condition of the first patients trachea was unknown until demonstrated in the documentary. This is not true. In our Appeal for an Investigation, which was personally addressed to Prof Hamsten, nine films of bronchoscopic examinations which demonstrate the state of the first patient’s airway at 5½, 6½, 8, 11, and 27 months and the third patient’s at 1½, 2 and 6 months after their transplantations were included on a USB mass storage device, as well as an accompanying guide to the bronchoscopic examinations (”Guide to Bronchoscopic Films attached to Appeal”). Furthermore, a written report from each bronchoscopic examination authored by the examiner is included, as well as a direct reference to each film to facilitate comparison of what is stated in the documents to the severe pathology seen in all of the nine attached bronchoscopic films. The ultimate proof that the bronchoscopic images were included in the Appeal for an Investigation is that Swedish Television could only have attained the bronchoscopic films by acquiring the material submitted in the Appeal for an Investigation registered at KI or with the Central Ethical Review Board. Prof Hamsten neglects to mention all further evidence of the catastrophic pathology seen in all three patients found in the biopsies, radiological findings and bronchoscopic examinations include in our Appeal.

Further disinformation is being purported in the media that we would like to address. The patients are described as being threatened with eminent death or suffocation. This is completely false as has been stated repeatedly. The first patient was suffering only from a cough, flew to Sweden on a standard airline flight and went on weekend leave from the hospital to visit friends in another city several hours north of Stockholm, days before his surgery. His general condition is repeatedly described as good and symptom-free in the medical records.

The second patient had no obstruction of the trachea but was suffering from a slow growing tumor that led to thickening of the tracheal wall. On his insurance admission form he wrote that he had no symptoms from his airways or lungs. He came to Stockholm first for examination and then flew home to return one month later for surgery. The cancer was not radically excised and the patient returned to the US with a plastic trachea, but not free from cancer and died after 3½ months secondary to the implantation. This was not by any definition an emergency case, but rather an elective case planned for months in advance.

The third patient did not have cancer. She was living at home with her parents after suffering an iatrogenic injury to her trachea after previous surgery one year earlier. A multidisciplinary conference to discuss her case never took place. This was not an emergency case and the patient was not dying.

Again, all three patients were in stabile clinical status. To describe them otherwise is an attempt to give the impression that the procedures were performed out of necessity. No formal ethical review was performed. All patients were also administered unapproved experimental dosages of drugs and exposed to TGF-beta3, a substance not approved for use in laboratory animals or humans that carries the risk of viral transfer. All patients developed life-threatening complications where two of the patients have died after excruciating suffering. The third patient, a young woman is still alive after years in the intensive care unit having endured over 190 surgical interventions due to the implantation of a dysfunctional plastic tube. She needs bronchoscopic clearance of her airway every 4th hour around the clock. All these facts have been described in detail in our Appeal for an Investigation.

Prof Hamsten was informed personally in detail on Feb 21, 2014 by Dr Grinnemo of the state of the patients operated on at Karolinska and the gross and serial misrepresentation of their clinical outcome in the articles published by Prof Macchiarini. Prof Hamsten stated that Prof Macchiarini could continue to perform the procedures outside of Sweden, and that only his lab work would continue at Karolinska. At this time it was well known that the surgeries were taking place in Krasnodar, as it was clearly stated in the application for extension of Prof Macchiarini’s guest professorship written by Prof Felländer-Tsai (Head of CLINTEC) in October 2013 and signed by Prof Hamsten in January of 2014. Prof Hamsten was also informed that the rat trachea implantations that were performed by Dr Simonson after the patients had been operated in Stockholm demonstrated catastrophic results. Prof Hamsten then informed Dr Grinnemo that he would discuss these issues with Prof Lendahl (Head of StratRegen and WIRM, Secretary Noble Assembly) and Prof Cardell (Head of ENT), both Prof Macchiarini’s superiors at KI.

At this time KI should have immediately initiated an investigation but instead did nothing. After this first meeting at least 9 attempts on our part were initiated to bring attention to these circumstances and implement a moratorium and an investigation to prevent further patients from being put in what seemed to be life-threatening danger. It should be noted that at this time, that Prof Delaere (ENT, Leuven, Belgium) spanning from 2011 to 2013, had filed several warnings concerning the danger of performing this procedure when no animal data existed. On March 7, 2014, Dr Grinnemo accompanied by his mentor Senior Prof Sylvén, met with Prof Hamsten and with Prof Macchiarini’s superiors Profs Felländer-Tsai, Cardell, and Lendahl. All meeting participants received a copy of our compilation reviewing the discrepancies between the medical records of the three patients in comparison to the published work by Prof Macchiarini.

On April 25, 2014, we contacted Profs Felländer-Tsai, Cardell and Lendahl with an email titled ”Time to act” where it is written ”as I have informed you earlier, it has become obvious that Paolo and Phillip have been conducting false advertising about the results of  the synthetic grafts. What is worse is that Harvard Biomedical and other associated companies are using Paolo’s data as proof that the tracheal grafts work. At the Paris meeting Phillip showed the falsified data and since Karolinska Institutet is not doing anything about this, Paolo and Phillip are not challenged. See the email from Delaere that confirms this fact. He has informed the KI leadership on multiple occasions without receiving any response. Furthermore, at the bottom of the email you can see that Paolo’s five-year follow-up in The Lancet from 2013 is also falsified since that patient now needs a pneumectomy. [The first tissue-engineered airway transplantation: 5- year follow-up results. P, Macchiarini P. Lancet. 2014 Jan 18; 383 (9913): 238- 44.] This was of course known at the time of publishing. As you understand Karolinska Institutet must act now otherwise more patients can be subjected to serious injury and more misleading publications accepted. Considering the fact that you chose not to act on the Nature Communications publication, we will soon see decellularised oesophagus grafts in patients, using this article as support.” Further on it states “an investigation must be initiated NOW!”.

Fearing that Prof Macchiarini would soon start to implant decellularised oesophagus in humans, based on the manipulated results he had published in Nature Communications, we contacted Prof Felländer-Tsai on May 6, 2014.

On May 23, 2014, Prof Felländer-Tsai was again contacted in order to set up a meeting to hand-over our formal appeal for an investigation of Prof Macchiarini and Dr Jungebluth’s research on rat oesophagus.

On May 26, 2014, Prof Felländer-Tsai responds “In order for me to understand everything I need all the papers sent to me.” On the same day all documentation was sent to Prof Felländer-Tsai including figures concerning the falsified oesophagus results as well as the letter we sent to Nature Communications, which details the evidence surrounding the research fraud and misrepresentation as presented by Prof Macchiarini in the rat oesophagus article.

A new meeting was held on June 12, 2014 with Profs Felländer-Tsai, Cardell, Lendahl and Assoc Prof Hermanson to again discuss the findings in the article published in Nature Communications.

On July 29, 2014, Prof Hamsten was again contacted because…”It turns out that there is no ethical approval to perform the trachea transplantations and the biopsy results in the article published in The Lancet in 2011 are fabricated. Furthermore Macchiarini has neglected to disclose complications and patient outcomes. Since this is extremely serious and must be one of the largest scandals in regenerative medicine, we would like to meet with you as soon as possible.” This request for a meeting was repeated on August 5, 8, and 11, 2014.

On Aug 14, 2014, after we had warned and reminded KI both in writing and verbally on multiple occasions during the last six months, we now received the instructions from Prof Hamsten that if we suspect research fraud, the first step would now be to submit a written notification. We therefore filed our Appeal for an Investigation on Aug 18, 2014. Further information mounted and we submitted an Amendment to the Appeal on Sept 24, 2014. On October 13, 2014 we submitted the documents to the Central Ethical Review Board. No official action was taken on the part of KI until an article in the New York Times (Nov 24, 2014 “World leading surgeon is accused of misconduct in experimental transplantoperations”) described the filed reports. The next day Prof Gerdin was designated as an external reviewer.

The handling of the investigation of Prof Macchiarini by KI has been a biased farce where because of moral paralysis yet another young patient with a benign diagnosis was operated in the summer of 2014 in Krasnodar, and subsequently also developed severe complications. This is several months after we had informed KI and years after others had submitted repeated warnings dating back to 2011. Up until our warning in February of 2014, several patients had died after horrific complications and mutilating procedures. The question that needs to be asked is what is more important for the individuals responsible for a renowned research institute than to immediately act when an insurmountable volume of evidence indicates that patients are being subjected to life-threatening research procedures that have no ethical approval or legal legitimacy?

A new internal investigation is an exercise in futility. Instead an independent external review of KI’s handling of the case should be initiated. The fundamentals of the Helsinki Declaration have been consciously transgressed, and consequently responsible parties should be prosecuted. The FDA should be informed so that proceedings can be initiated in an eventual wrongful death case of a two year-old child who underwent surgery in Peoria, Illinois. We also suspect that attempts to defraud the US government have transpired during attainment of Orphan Drug Designation from the FDA for HART-trachea. Furthermore, families and authorities in US, Russia and Turkey should be contacted since at least 6 of their relatives and citizens have been subjected to these experiments.

With Great Concern,

Matthias Corbascio, MD, PhD

Thomas Fux, MD

Karl-Henrik Grinnemo, MD,

PhD Oscar Simonson, MD, PhD