Below I am publishing a recent letter to the Vice-Chancellor of Karolinska Institutet (KI) Karin Dahlman-Wright, authored by the four KI medical researchers, Matthias Corbascio, Oscar Simonson, Karl-Henrik Grinnemo and Thomas Fux. They have been for some time attempting to alert KI to the irregularities in patient records and published data by Paolo Macchiarini, but were instead harassed and persecuted under the former Vice-Chancellor of KI, Anders Hamsten. The four whistle-blowers previously made their evidence public in an open letter to KI directorate. In April 2016 they received a prize from Transparency International for their courage.
The KI had much of its leadership as well as of its Ethics Council removed in the wake of Macchiarini-scandal (see updates to this article). Most likely, there will be more resignations among senior scientists and managers, as the investigations progress and conclude. At the same time, the associated Karolinska University Hospital seems to have sneaked out of responsibility, no investigations are being performed there, as Bosse Lindquist, author of seminal Macchiarini documentary, has criticised. The hospital was Macchiarini’s employer and approved all his controversial trachea transplant operations on patients, some performed inside the hospital. Correction: according to Swedish media, the hospital director, Melvin Samsom, initiated an investigation which results are to be expected in August 2016. The external examiner is Kjell Asplund, professor emeritus of medicine and chairman of Smer, the Swedish council on medical ethics.
The evidence presented by the four KI whistle-blowers deals with data irregularities in Macchiarini’s paper in The Lancet (Jungebluth et al, 2011). This first recipient of a plastic “regenerated” trachea transplant was Andemariam Beyene, who died two years later (details see here). The scaffold was produced by the nanotechnology lab of the UCL professor Alexander Seifalian (details in my report here). Unfortunately, The Lancet has ceased replying and even acknowledging receiving my emails (in particular in regard to another misconduct case in regenerative medicine in Sweden, that of Sumitran-Holgersson). The Lancet previously declared to me not to be addressing themselves any available evidence of ethics breach and data manipulation, but instead wait for the results of institutional investigations.
The entire document is available here, below is the abbreviated version.
Stockholm May 9, 2016
Vice-Chancellor Karin Dahlman-Wright
Notification of Suspected Research Misconduct
RE: Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Jungebluth P, Macchiarini P. Lancet. 2011 Dec 10;378(9808):1997-2004. Epub 2011 Nov 24. PMID: 22119609
Since our filing in August 2014 (1) new data has emerged providing evidence of suspected scientific misconduct and data manipulation on the part of Drs. Jungebluth and Macchiarini. This evidence is sufficient in and of itself to warrant investigation and in our opinion retraction of this dubious article. On page 1999 in the last paragraph under the section “Results” the Drs. Jungebluth and Macchiarini claim: “5 months after transplantation, the patient is asymptomatic, breathes normally, is tumour free, and has an almost normal airway (figure 2C)…” To support the statement of ”an almost normal airway” at the time point of 5 months after implantation of the synthetic trachea the authors refer to figure 2A-C on the following page 2000 with the title: ”Postoperative follow-up”. The figure legend of figure 2C states: “Postoperative volume rendered (VR) image. Air in airways is shown in bright blue. Note that the VR technique displays only the factual air and not the scaffold material. Yellow arrows show borders for scaffold insertion.”
The image in figure 2C is a product of a computed tomography (CT) technique called 3D volume rendering (VR) which incorporates the entire CT data set yielding a 3D display that depicts all tissue types from any orientation […] the only possible source of the VR image in figure 2C is the 2nd radiological examination, which was performed on 2011-07-06, an examination performed not 5 months but only 4 weeks (27 days) after the synthetic trachea implantation on 2011-06-09. Review of the VR series from the 2nd radiological examination demonstrates that these images are very similar (figure 1a, b) to the images that Drs Jungebluth and Macchiarini have chosen to use as their 5-month follow up image.
This raises the suspicion that Drs. Jungebluth and Macchiarini have chosen to use an image taken only 4 weeks after implantation and claimed that it demonstrates ”an almost normal airway” at 5 months after implantation of the synthetic trachea.
If this is confirmed then this can only be interpreted as scientific misconduct and falsification of data. To suggest that the time of examination has been accidentally misrepresented is not plausible since this was the only examination using the VR technique that was performed after the implantation surgery and before final submission of the article to The Lancet.
Furthermore, inspection of the radiological examination performed on 2011-07-06 that Drs. Jungebluth and Macchiarini seem to have used as a 5-month follow up image does not show findings that by any definition can be considered as “an almost normal airway”. All images from that examination demonstrate severe airway pathology consisting of constriction, fistulation, and air surrounding the synthetic implant already 27 days after implantation.
Furthermore, in the figure legend to figure 2C in the article, the authors states that the blue colored image shows ”Air in airways is shown in bright blue”. In the radiological examination from the very same date, 2011-07-06, from which the figure 2C in the article seems to be taken, the blue colored volume rendered image can be individually analyzed as it is independently saved in the archive. Even if all the tissues and implant are removed, the image cannot be depicted as showing evidence of “an almost normal airway” as it verifies a pathologically constricted right main bronchus 27 days after implantation.
Radiological examination performed on 2011-11-22 (Figures 6a-c, 7), 5½ months after implantation 2011-06-09, verifies bronchoscopic findings of severe airway pathology consisting of bilateral fistulations, obstruction of airway and air surrounding the implant. Stents have been placed in an attempt to obliterate fistulation. The presence of fistulation is indicative of chronic infection and inability of the synthetic implant to heal into the surrounding native tissue, as is the continuous ingrowth of obstructive granulomatous tissue (threatening ventilation) is indicative of chronic inflammation.
Three imaging examinations have been presented above; 2011-07-06 (CT-VR), 2011-08-16 (filmed bronchoscopy) and 2011-11-22 (CT-VR), which clearly and in detail demonstrates the patient’s airway at 4 weeks, at 10 weeks and at 5½ months after implantation. All three examinations demonstrate serious airway pathology and can be regarded as three individual time checkpoints.
Drs. Jungebluth and Macchiarini may postulate that the airway was ”almost normal” at 5 months, which would imply that severe pathology which evidently was present at 4 and 10 weeks would have developed into “almost normal” at 5 months (when the final proofs where admitted to the Lancet) despite any imaging evidence for such a statement and then, after another 2 weeks (at 5½ months) the airway apparently degenerated into its severely pathological state as demonstrated above. This is not just plain absurd, it is of course impossible and an obvious example of gross misrepresentation. Unless proven otherwise, this is in itself sufficient to warrant retraction of the article, independent of the exhausting evidence we have already provided.
In conclusion, we appeal to Karolinska Institutet to investigate this new evidence of scientific misconduct. Drs. Jungebluth and Macchiarini have in all likelihood changed the dates of the radiological exam and neglected to divulge the evidence of pathology seen in the original radiological and bronchoscopic examinations.
More than two years have now transpired since we first reported evidence of serial scientific misconduct on the part of Dr. Macchiarini. This publication, along with a number of previously reported papers are allowed to persist in the medical literature despite that an insurmountable body of evidence demonstrating falsification, omission or beautification of data has been provided by us and the external investigation (1, 7). The continued inability of Karolinska Institutet to act accordingly and retract this article is a testimony to the moral paralysis afflicting this institution and is an insult to the patients and their relatives who have been victimized by its ineptitude.
Matthias Corbascio, MD, PhD, Assoc Prof
Thomas Fux, MD
Department of Cardiothoracic Surgery and Anesthesiology
Karolinska University Hospital,
Solna SE-171 76 Stockholm
Karl-Henrik Grinnemo, MD, PhD, Assoc Prof
Oscar Simonson MD, PhD
Department of Cardiothoracic Surgery
Uppsala University Hospital
SE-751 85 Uppsala