The Macchiarini case: Timeline

Denna sida på svenska

The events in relation to Paolo Macchiarini, formerly a visiting professor and paid researcher at Karolinska Institutet (KI), that have attracted so much attention have resulted in several investigations and far-reaching measures. Below is a summary of the events in this case.

Numerous measures have been implemented and are planned as a result of the deficiencies identified in connection with the Macchiarini case. The measures are based on the recommendations of the independent investigation led by Sten Heckscher and the internal audit by CLINTEC, the Department of Clinical Science, Intervention and Technology, where Paolo Macchiarini was formerly employed. The following is a brief description of these measures.

2010: Background

Autumn 2010. Paolo Macchiarini is recruited by Karolinska Institutet and Karolinska University Hospital

Paolo Macchiarini is recruited by Karolinska Institutet (KI) as a visiting professor conducting basic research in the field of regenerative medicine/stem cell biology. At the same time, he is employed on a part-time contract as a consultant and surgeon at Karolinska University Hospital.

2011–2012. Artificial tracheas surgically implanted in three patients

Paolo Macchiarini performs three transplantations of synthetic tracheas coated with stem cells at Karolinska University Hospital. According to the hospital the operations are care interventions on the basis of a so-called vital indication (i.e. as an attempt to save the patients’ lives). In November, Macchiarini publishes an article in The Lancet describing the operation on the first patient.

2012. Patient dies

The second of the three patients operated on at Karolinska University Hospital dies a few months after the operation.

2013. The hospital puts a stop to further operations

Karolinska University Hospital decides to stop all future operations with synthetic trachea and not to extend Paolo Macchiarini’s contract as surgeon.

December 2013. Continues to perform surgery in Russia

Paolo Macchiarini commences clinical studies in Krasnodar, Russia, where patients are to be operated on for research purposes. This is an extra-mural activity that has been approved by his department at KI.

2014: Research called into question

January 2014. Another patient dies

The first patient operated on at Karolinska University Hospital in June 2011 dies.

June 2014. The first report of suspected misconduct in research

A first report, by a Belgian researcher, is received by KI, accusing Paolo Macchiarini of misconduct in research – scientific misconduct. The Vice-Chancellor, who according to the Higher Education Ordinance has responsibility for investigating suspected cases of misconduct in research, requests a statement from KI’s Ethics Committee.

June, August and September 2014. Second and third reports of suspected misconduct in research

Two separate reports of scientific misconduct are filed by four doctors at Karolinska University Hospital, according to whom research results have been described in overly positive terms in seven of Paolo Macchiarini’s scientific papers*, which they argue incorrectly describe the postoperative status of the patients and the functionality of the implants. The four doctors are also researchers at KI and three of them are co-authors on some of the papers. *In Nature Communications on trials involving artificial tracheas in rats, and in The Lancet (articles 1 and 2), Biomaterials (article 3), the Journal of Biomedical Materials Research (article 4), Thoracic Surgery Clinics (article 5), Biomaterials (article 6). Articles 1, 3 and 6 are original articles, and articles 2, 4 and 5 are summary articles on the transplantation of a synthetic prosthesis in human tracheas.

August 2014. Paolo Macchiarini responds to the first report

Paolo Macchiarini submits his response to the first report.

November 2014. KI requests an external opinion

KI assigns Bengt Gerdin, professor emeritus at Uppsala University, as an expert to examine the material in the case relating to the second and third complaints against Macchiarini and to issue a statement.

2015: Statements and decisions differ

March 2015. KI’s Ethics Committee comments on the first report

The Ethics Committee at KI issues a statement on the report from the Belgian researcher, writing that the issues raised by the researcher relate to scientific theory rather than to research ethics, and that the accusations of misconduct in research are unsubstantiated.

April 2015. Paolo Macchiarini responds to the second and third reports

Paolo Macchiarini and his co-authors submit responses to the second and third complaints against him, which relate to seven different articles.

April 2015. KI clears Paolo Macchiarini in the first case

KI clears Paolo Macchiarini of scientific misconduct in the case of the complaint levelled against him by the Belgian researcher in June 2014. KI’s Ethics Committee also pronounces on the matter

13 May 2015. External opinion: misconduct in research

Bengt Gerdin submits his special statement of opinion to Karolinska Institutet. He concludes that Macchiarini has been guilty of misconduct in research in the articles reported by the four physicians.

Special statement concerning the seven different papers with principal or co-authors from Karolinska Institutet (in Swedish)

June 2015. Macchiarini’s repudiation

Paolo Macchiarini and his co-authors submit their statements on the content of Bengt Gerdin’s special statement and refute the charge of misconduct in research.

22 June 2015. The Swedish Research Council stops research funding

The Swedish Research Council decides to suspend payment of funding to Paolo Macchiarini. The council says in its decision that the researcher, by his actions, has proved to be a clearly unsuitable recipient of funding from the Swedish Research Council.

28 August 2015. KI clears Paolo Macchiarini in the second and third cases

In an overall assessment, KI confirms that Paolo Macchiarini has not been guilty of scientific misconduct, but states at the same time that his research failed to meet the standards of quality set by KI and the scientific community. KI’s judgement on the matter is made with reference to the new information that has emerged from the comments submitted by Paolo Macchiarini and his co-authors in response to Bengt Gerdin’s special statement. A summary of the differences between Bengt Gerdin’s conclusion and KI’s decision can be found in KI’s decision no. 2 under “Considerations and assessment”.

Decision 1 in the case of suspected misconduct in research in relation to Paolo Macchiarini (in Swedish)

Decision 2 in the case of suspected misconduct in research in relation to Paolo Macchiarini (in Swedish)

November 2015. Paolo Macchiarini is appointed as a researcher for another year

Paolo Macchiarini’s position as a visiting professor is terminated and he is given a temporary position as a researcher at KI up until 30 November.

December 2015. External reviewer stands firm

Bengt Gerdin stands by his conclusion having, on his own initiative, reviewed KI’s decision to clear Paolo Macchiarini and the investigation material received following his own review. Gerdin emails his conclusions to Vice-Chancellor Anders Hamsten.

January 2016: New serious criticism is made

January 2016. Vanity Fair publishes new accusations

Vanity Fair publishes an article in which Paolo Macchiarini is accused of having lied on his CV and elsewhere. KI opens an inquiry into the veracity of the CV which Paolo Macchiarini provided to KI in connection with his employment.

13, 20 and 27 January 2016. The SVT documentary “The Experiment”

The 3-part documentary series “The Experiment” is broadcasted on SVT. The documentary, which closely follows Paolo Macchiarini, shows how patients have suffered and died in connection with failed transplant surgery involving artificial tracheas, and raises numerous issues concerning care and research ethics. The fierce public response to the series causes a crisis of confidence in KI.

28 January 2016. Falsehoods in Macchiarini’s CV

KI’s first investigation into Paolo Macchiarini’s CV concludes that it contains several falsehoods, although none so serious as to justify his dismissal or resignation. The definitive examination is yet to be concluded.

February 2016: Investigations and resignations from management

4 February 2016. New decision concerning Macchiarini’s position as a researcher

Vice-Chancellor Anders Hamsten decides that Paolo Macchiarini’s contract with Karolinska Institutet will not be extended after 30 November 2016.

4 February 2016. The University Board requests an external inquiry into KI’s handling of the case

An external inquiry is launched by the Karolinska Institutet University Board into Karolinska Institutet’s handling of the entire case, from Paolo Macchiarini’s recruitment in 2010 to the present. It is to be led by the lawyer Sten Heckscher. The University Board also decides to give Vice-Chancellor Anders Hamsten their continuing confidence for the duration of the inquiry.

13 February 2016. KI’s Vice-Chancellor, Anders Hamsten, resigns

Vice-Chancellor Anders Hamsten announces his resignation on DN Debatt. At the same time he announces that KI will launch a new inquiry into scientific misconduct against Paolo Macchiarini after having received information that raises questions concerning the data forming the basis of some of Macchiarini’s articles. KI has also received a further report of suspected misconduct in research directed at Macchiarini.

13 February 2016. Nobel Committee members decline to participate

Four professors from the Nobel Assembly at Karolinska Institutet decline to participate in the work of the assembly while the Macchiarini case is being investigated. The four are former vice-chancellor Anders Hamsten, dean of research Hans-Gustaf Ljunggren, and professors Katarina Le Blanc and Urban Lendahl. All of them will be under investigation as part of Sten Heckscher’s inquiry.

15 February 2016. Karin Dahlman-Wright takes up a post as acting vice-chancellor

Pro-vice-chancellor Karin Dahlman-Wright is to step in as acting vice-chancellor to carry out the vice-chancellor’s duties.

17 February 2016. Proposal that Karin Dahlman-Wright should become acting vice‑chancellor

The KI’s executive committee, the University Board, decides to ask the government to appoint Karin Dahlman-Wright as acting vice-chancellor of Karolinska Institutet following Anders Hamsten’s departure. At the same time a decision is made to initiate the process of recruiting a new vice-chancellor

18 February 2016. Acting vice-chancellor appointed by the government

The government decides to appoint Karin Dahlman-Wright as acting vice-chancellor of Karolinska Institutet. Dahlman-Wright was made pro-vice-chancellor on 1 January 2016 and has been a professor of molecular endocrinology since 2009.

February 2016. Misconduct investigation resumed

Acting vice-chancellor Karin Dahlman-Wright decides to reopen the case of scientific misconduct concerning Paolo Macchiarini and to have the seven scientific papers examined by the expert group for misconduct in research at the Central Ethical Review Board (CEPN).

19 February 2016. Appointment procedures tightened

KI’s Recruitment Committee tightens up and clarifies procedures for reviewing job applications.

22 February 2016. Dean of research resigns

Citing the Macchiarini case, the dean of research Hans-Gustaf Ljunggren, asks to be allowed to step down from his position.

22 February 2016. Advisor to the vice-chancellor resigns

Citing the Macchiarini case, professor Jan Carlstedt-Duke asks to be allowed to leave his post as advisor to the vice-chancellor.

22 February 2016. Paolo Macchiarini given notice

Paolo Macchiarini, who has a position as a researcher at Karolinska Institutet up until 30 November 2016, is told that KI is considering dismissing him.

March 2016. Work begins on proposed measures

KI’s acting vice-chancellor asks the acting pro-vice-chancellor to carry out a systematic inventory at KI to identify any faults or failings that require rectification, and to propose measures where necessary.

March 2016. CEPN re-examines Macchiarini’s articles

KI’s acting vice-chancellor decides that Paolo Macchiarini’s scientific articles are to be re-examined, this time by the expert group for misconduct in research at the Central Ethical Review Board (CEPN). The new investigation concerns the seven scientific articles that Professor Bengt Gerdin considered in a statement to be misconduct in research, but which KI’s former vice-chancellor decided was not.

3 March 2016. The government makes a decision concerning the nomination committee

The government decides to task a nomination committee with submitting proposals involving in part new members of the Karolinska Institutet administrative committee, the university board.

5 March 2016. KI decides to overhaul the Ethics Committee

KI decides that it is necessary to clarify the work on research ethics at KI and that the role of the Ethics Committee should be re-considered.

18 March 2016. Expert appointed to review the case of misconduct in research

The expert group on misconduct in research at the CEPN tasks Professor Eva Ekblad, as an expert, to review the case relating to the article Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats, published in Nature Communications on 15 April 2014.

23 March 2016. KI decides to dismiss Macchiarini

The Staff Disciplinary Board decides to dismiss Paolo Macchiarini from his temporary post as a researcher at KI.

1 April 2016. New administrative board members proposed

The government receives proposals for the members of the KI University Board whom it is to appoint.

21 April 2016. New board members appointed

The government decides on new government-appointed members of the University Board based on the proposal submitted by the government’s nomination committee.

22 April 2016. New case investigated by KI

Karolinska Institutet decides to examine a new case of suspected fraudulent activity in research in which Paolo Macchiarini took part as a researcher. The case involves a scientific article that had been published in Respiration in 2015 that was uncovered in an inventory conducted by the university to uncover misconduct in research at KI.

May 2016. Additional report of suspected misconduct in research

The four doctors who reported Paolo Macchiarini in 2014 submit another report of suspected misconduct in research concerning an article that already forms part of the ongoing inquiry.

22 June 2016. Paolo Macchiarini served as a suspect in a criminal investigation

The public prosecutor officially serves a write against Paolo Macchiarini informing him that he is suspected of gross negligence causing manslaughter and bodily injury.

21 June 2016. KI appoints new dean of research

Professor Anders Gustafsson, former dean of researcher training, is appointed the new dean of research at Karolinska Institutet.

9 July 2016. Expert submits report to CEPN

The expert, Eva Ekblad, notes in a statement that there are some uncertainties concerning the animal experiments that formed the basis for the article Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats, published in Nature Communications on 15 April 2014.

August-September 2016: External investigation completed

30 August 2016. Further report of suspected misconduct in research

Karolinska Institutet receives another report of suspected scientific misconduct, this time concerning a scientific poster used to present Paolo Macchiarini’s research at a scientific conference in 2012.

31 August 2016. Kjell Asplund’s external investigation presented

Kjell Asplund’s investigation, “The Macchiarini Case”, has examined the circumstances surrounding Paolo Macchiarini’s activities at Karolinska University Hospital. The investigation is fiercely critical of the hospital as well as of Karolinska Institutet and notes, amongst other things, that the operations constituted research and not healthcare, and that KI was proactive in the hiring of Macchiarini, who was initially employed at both institutions.

Press release on Stockholm County Council’s website and the press conference from 31 August 2016 (in Swedish)

Karolinska Institutet comments on Asplund’s investigation

2 September 2016. Lars Leijonborg, chairman of the university board, resigns

Citing the Macchiarini case, Lars Leijonborg informed the minister for higher education and research that he is stepping down as chairman of Karolinska Institutet’s university board.

5 September 2016. Sten Heckscher’s investigation and internal review is presented

Sten Heckscher’s investigation, “Karolinska Institutet and the Macchiarini Case”, criticises KI on several counts: insufficient regard to the rules; the recruitment of Macchiarini in 2010 and the decision to extend his contract in 2013 and 2015, which was taken in breach of proper procedure; partial responsibility for the transplantation procedures carried out at Karolinska University Hospital; shortcomings in following-up on Macchiarini’s research at KI; failure to properly investigate his extra-mural activities and flawed handling of the misconduct case. The same day saw the presentation of KI’s internal review of Clintec, the institution of clinical science, intervention and technology, where Paolo Macchiarini was employed as a researcher.

The external review of Karolinska Institutet’s handling criticises KI on several points. Article and two press conferences from 5 September 2016.

Karolinska Institutet comments on Heckscher’s investigation of the Macchiarini case.

The investigation “The Karolinska Institutet and Macchiarini case” (English Summary)

Heckscher: “A lot of surprises in the course of the investigation”

Institution review of Clintec (in Swedish)

6 September 2016. The university board tasks the vice chancellor with drafting an action plan

The Karolinska Institutet’s university board tasks the vice-chancellor with drafting a plan of action for how the university will remedy the serious failings identified by the Heckscher investigation. The plan is to be presented at a board meeting on 10 October.

9 September 2016. Statements from CEPN

The expert group for misconduct at the Central Ethical Review Board (CEPN) submits its report finding Paolo Macchiarini and his co-authors guilty of scientific misconduct in research in the article Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats, as published in Nature Communications on 15 April 2014.

September 2016. Heart-Lung Foundation calls for return of grants

The Swedish Heart-Lung Foundation asks KI return grants worth a total of SEK 1.1 million which the foundations had granted to Paolo Macchiarini during the period 2012–2014.

19 September 2016. Acting vice-chancellor requests investigation

KI's acting vice-chancellor, Karin Dahlman-Wright, asks Karolinska University Hospital, in view of the CEPN's statement of 9 September, to urgently investigate potential shortcomings in animal-handling at the animal facility where Paolo Macchiarini conducted his research.

10 October 2016. The university board endorses the action plan

The university board decides to endorse the direction as set out in the vice chancellor's action plan, which is a consequence of Heckscher's external investigation of KI's handling of the Macchiarini case and KI's internal review of Clintec, the institution of clinical science, intervention and technology. The investigation and the internal review have highlighted deficiencies and given recommendations that have formed the basis of the action plan. The action plan is based on three main areas: The internal culture and management at KI, quality issues including regulatory compliance, and organisational issues including the interface with Karolinska University Hospital.

After the Heckscher investigation: Action plan ready for KI. The action plan (pdf)

12 October 2016. Investigation into shortcomings in animal-handling

The then director of R&D at Karolinska University Hospital submits a report at the request of KI's vice-chancellor on urgent investigation of potential shortcomings in animal-handling.

24 November 2016. New chairman appointed by the government

The government appoints four new members to the university board. New chairman to be Mikael Odenberg, former cabinet minister and CEO of the Swedish National Grid. Other new government-appointed members are Liselotte Höjgaard, who has been a head of department at Copenhagen's Rigshospitalet since 2000, Björn Stensaker, who is a professor at the Department of Education at the University of Oslo, and Göran Stiernstedt, a consultant and adviser at the state commission on knowledge support.

KI‘s new chairman: “There is reason to go over things again“

20 December 2016. KI comes to new decision in misconduct case

Karolinska Institutet makes a decision in a misconduct case that relates to Paolo Macchiarini and about which the expert group for misconduct in research at the CEPN has issued a statement. KI's decision is that Macchiarini and three co-authors are considered guilty of misconduct in research in regard to the article in Nature Communications from 2014. For two of the more junior authors, there are mitigating circumstances.

20 December 2016. Professor in the Nobel Assembly steps down

Urban Lendahl, professor of genetics at the Department of Cell and Molecular Biology at Karolinska Institutet, chooses to step down as a member of the Nobel Assembly by reason of his behaviour in the Macchiarini case.

December 2016. Decision on external investigation into animal management

Based on the R&D director's report of 12 October 2016, KI's acting vice-chancellor, Karin Dahlman-Wright, and the director of Karolinska University Hospital, Melvin Samsom, decide to appoint an external investigator to investigate whether there have been shortcomings in the review of animal management, and if so, how it can be improved. Patricia Hedenqvist, senior lecturer in Laboratory Animal Medicine at the Swedish University of Agricultural Sciences, is asked to head up the investigation.

19 March 2017. Patient dies

The last of the three patients to have been given an artificial trachea surgically implanted by Paolo Macchiarini at Karolinska University Hospital dies at a hospital in the USA.

Comments on the death of a patient who had previously had an artificial trachea surgically implanted at Karolinska University Hospital

21 March 2017. Research article withdrawn

The article entitled “Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats”, published in Nature Communications in 2014, is withdrawn by the authors, with reference to the technical failings that have emerged from reviews of the article.

April 2017: New vice-chancellor appointed

27 April 2017. Ole Petter Ottersen to be new vice-chancellor

The government decides to appoint Ole Petter Ottersen as the new vice-chancellor at Karolinska Institutet at the suggestion of the university board. The new vice-chancellor will take up his position on 1 August 2017.

Ole Petter Ottersen on becoming the new vice-chancellor of Karolinska Institutet

30 September 2017. Investigation into Paolo Macchiarini's animal experiments

An external investigation into Paolo Macchiarini's animal experiments at the animal departments at Karolinska University Hospital in Huddinge (2011–2016) revealed failings in the supervision of Macchiarini's group, the way in which they conducted animal experiments and compliance with ethical authorisations. The investigation was commissioned in December 2016 by KI's acting vice-chancellor, Karin Dahlman-Wright, and the director of Karolinska University Hospital, Melvin Samsom.

Investigation into Paolo Macchiarini's animal experiments

12 October 2017. Preliminary investigations closed

The Swedish Prosecution Authority decides to close down the preliminary investigations of Paolo Macchiarini relating to tracheal surgery and other operations performed at Karolinska University Hospital where he had previously been employed as a surgeon.

30 October 2017. CEPN issues statement on six articles

The expert group on misconduct in research at the Central Ethical Review Board, CEPN, issues its statement concerning six articles of which Paolo Macchiarini was the principal author. All authors must make statements before the vice-chancellor of Karolinska Institutet makes a decision in the case.

9 November 2017. The Swedish Higher Education Authority (UKÄ) criticises KI

In a supervisory decision, the UKÄ directs sharp criticism at KI with respect to issues relating to Paolo Macchiarini's activities at Karolinska Institutet during the period 2013 to 2016. The UKÄ has reviewed a number of issues that fall under the authority's supervisory responsibility.

30 January 2018. Researchers found guilty of scientific misconduct

Karolinska Institutet’s vice-chancellor Ole Petter Ottersen reaches the decision to find Paolo Macchiarini, Philipp Jungebluth, Bernhard Holzgraefe and Håkan Kalzén guilty of scientific misconduct. The case relates to the article “Autologous peripheral blood mononuclear cells as treatment in refractory acute respiratory distress syndrome”, published in 2015 in Respiration.

25 June 2018. Seven researchers responsible for scientific misconduct

On 25 June, the President of Karolinska Institutet made the decision to find seven researchers responsible for scientific misconduct in research. The case concerns six articles published in the scientific journals The Lancet, Biomaterials, The Journal of Biomedical Materials Research, and Thoracic Surgery Clinics. Paolo Macchiarini is one of the main authors of the articles. Karolinska Institutet is requesting that the six articles be retracted without undue delay.

Links

Organisation