The scandal surgeon Paolo Macchiarini, now professor at Federal University of Kazan in Russia, is preparing to experiment on monkeys using plastic oesophagus. He proclaims previous success in rats, yet today’s decision of his former employer, the Karolinska Institutet (KI) in Stockholm declared that very paper as fraudulent and found Macchiarini and his acolyte Philipp Jungebluth guilty of research misconduct. An earlier decision of the Swedish Central Ethical Review Board (CEPN, read decision here) came on September 6th 2016 to a similar conclusion, with one minor difference. Back then, all senior authors were found “guilty of scientific misconduct”, thus also including Macchiarini’s American collaborator Doris Taylor (who in 2014 almost made him a professor at her University of Texas). Now, all authors except of Macchiarini and Jungebluth have been virtually absolved, while the junior co-authors, the graduate student Sebastian Sjöqvist and the assistant professor Mei Ling Lim received an admonition.
KI now demands the retraction of this 2014 Nature Communications paper:
Sebastian Sjöqvist, Philipp Jungebluth, Mei Ling Lim, Johannes C. Haag, Ylva Gustafsson, Greg Lemon, Silvia Baiguera, Miguel Angel Burguillos, Costantino Del Gaudio, Antonio Beltrán Rodríguez, Alexander Sotnichenko, Karolina Kublickiene, Henrik Ullman, Heike Kielstein, Peter Damberg, Alessandra Bianco, Rainer Heuchel, Ying Zhao, Domenico Ribatti, Cristián Ibarra, Bertrand Joseph, Doris A. Taylor & Paolo Macchiarini
Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
After the CEPN decision, the publisher Springer Nature stopped short of retracting this paper and issued in October 2016 solely an expression of concern. Now, the retraction is unlikely to be avoided.
Suspicion of research misconduct
In a change to Karolinska Institutet’s decision of 28 August 2015 in the matter with reference number 2-218412014, Karolinska Institutet finds that the research presented in the article ‘Experimental orthotopic transplantation of tissue-engineered oesophagus in rats” published in the scientific journal Nature Communications (2014;5:3562) is research misconduct.
Paolo Macchiarini, Philipp Jungebluth, Sebastian Sjöqvist and Mei Ling Lim are responsible for research misconduct in this article.
Paolo Macchiarini and Philipp Jungebluth are today not employed by KI. Actions on labour law grounds are therefore not applicable.
Sebastian Sjöqvist and Mei Ling Lim are both employed by Karolinska Institutet. They are junior researchers who were in a position of dependence in relation to Paolo Macchiarini and other more senior researchers in the research team. In addition the process has been very prolonged in time. These are seen as mitigating circumstances, why they are only issued an admonition (erinrarn). The responsible department head at Karolinska Institutet shall in the next two years or, if their employment is shorter, during their time of employment actively follow up and support the research they conduct at Karolinska Institutet to ensure that the research is conducted in accordance with good research practice.
The journal Nature Communications shall be notified with a request that the article “Experimental orthotopic transplantation of tissue-engineered oesophagus in rats” (2014;5 :3 562) be immediately withdrawn.
Investigation in the now current matter ref. no. 2-72312016
Expert Group for research misconduct at the Central Ethical Review Board
On 26 February 2016, Vice-Chancellor Karin Dahlman-Wright requested that the Expert Group for research misconduct at the Central Ethical Review Board (the Expert Group) make a statement on whether what comes forth from the documents in the matter constitutes research misconduct. The Expert Group should also particularly shed light on whether the description of the results in the article appears to be embellishment, and the participating authors’ responsibilities for the content of the article both before and after publication.
On 18 March 2016, the Expert Group commissioned Eva Ekblad at the Department of Experimental Medical Science at Lund University to review as an expert if research misconduct occurred with regard to the scientific article now in question.
Eva Ekblad worked based on the reported article in its entirety. In her report on 9 July 2016, she considers that the article’s main author committed research misconduct in several respects. These are the refusal or inability to provide all raw data for the results presented in the article, the refusal or inability to provide animal experiment journals for the animals used in the article, a misleading presentation, interpretation and description of results, a gross deviation from the animal ethics permit and misleading the regional animal experiment ethics review board.
Like Eva Ekblad, the Expert Group had the whole article’s contents as the starting point for its assessment. It also confirms that the deficient and incomplete documentation are such a serious deviation from good research practice that it constitutes research misconduct. What is claimed in the article to be successful was not successful. An example of this is that the rats that underwent surgery with the artificial oesophagus and survived for 14 days during which they were examined, in contrast to that stated in the article, had significant weight loss which would not have been the case if the experiment had succeeded. This should have led to the discontinuation of the experiment. Images and figures that should support the claimed research are in many cases inaccurate and misleading. The raw data that the Expert Group studied does not always agree with that in the article, which leads to incorrect conclusions. The methodology is summarily described, original data cannot be extracted from the material in the matter, there is a lack of systematic records and summaries of analyses and how data has been statistically processed and then analysed. The conclusion is that the results in the article do not agree with the outcome of the research conducted, which is research misconduct. In contrast to Eva Ekblad, the Expert Group considers that the shifting information on significant weight losses among the rats involved in the research varies in such away that the deviation from animal ethics permits in this case was not such that it in itself constitutes research misconduct.
With regard to the authors’ responsibility, the Expert Group believes that a scientific article is a shared product with a collective responsibility and if the article is associated with such serious shortcomings that research misconduct can be established, the responsibility falls on all authors. It is established that the majority of the co-authors’ specific contributions to the article are not presented, and that it is word against word on crucial points. The main author Paolo Macchiarini bears the utmost responsibility and Sebastian Sjöqvist and Philipp Jungebluth had central roles in the research process. The Expert Group has some understanding for the more junior co-authors’ position of dependence on Paolo Macchiarini and the other leaders in the research group, but believes that it cannot exempt them from responsibility even if it can be considered as a mitigating circumstance.
The authors’ opinions of the Expert Group’s statement
The authors have been given an opportunity to express opinions on the Expert Group’s statement. What the authors who responded, i.e. 17 of them, primarily stated is presented below.
Paolo Macchiarini, Philipp Jungebluth, Johannes Haag, Silvia Baiguera, Constantino Del Gaudio and Doris A. Taylor have submitted a joint statement. The circumstance that some documentation from the animal experiments has not been able to be relocated cannot be blamed on the researchers, they write. Nobody from the research team was there when the unit was closed and moved. Nor can they be held responsible for the material that was there. It was KI’s responsibility that the documents were taken care of and archived in connection with the move. In addition, they point out that it is not a matter of an artificial, but rather a biological oesophagus and that nowhere in the article is it asserted that this oesophagus could be used as a model for a well-functioning transplant for an oesophagus in a human. They also believe that it is difficult to respond to the opinions expressed as they are vague and lack details, which means that the authors question if the Expert Group understood the article. That it was unintentionally rendered incorrectly in respect of the rats’ weight is admitted as it concerns weight loss and not weight gain, but otherwise, the weigh losses are very well described in the article. All weights were otherwise documented on paper, in electronic documents and in the analyses made. The fact that the joumal published the article contradicts the claim that the study’s results do not have support in what is presented in the article. It is not stated in the article that the oesophagus was well-functioning and that the transplants were successful. Instead, they were very careful to be cautious in their description of the results through word choices such as suggest, indicate and epithelium-like.
Bertrand Joseph [investigated by KI for irregularities in his own papers, -LS] describes his and Miguel Angel Burgillos’ contribution to the research and the article such that Miguel Angel Burgillos analysed the tissue samples that Sebastian Sjöqvist provided him with and that they both contributed to the data analysis of the macrophages presented by Figures 5 d-g.
Doris A. Taylor has, in addition to that stated above, stated that she contributed suggestions on the experiments upon visiting Paolo Macchiarini’s laboratory. Her involvement otherwise consists of her receiving a draft of the text in July 2013 and expressing quite a few editorial and critical opinion and proposing more analyses.
Royal Swedish Academy of Sciences’ statement regarding co-author responsibility
On 3 October 2016, a work group within the Royal Swedish Academy of Sciences’ research policy committee submitted its opinion in principle regarding co-author responsibility for misconduct upon KI’s request.
Notification to the journal
On 18 July 2016, KI notified the editorial staff of the journal Nature Communications of the investigation that is under way and asked them to consider an “Expression of concern”, which the journal did on 14 October 2016.
Main author’s and co-authors’ responsibility
With regard to the authors’ responsibilities, the Expert Group believes that a scientific article is a shared product with a collective responsibility and if the article is associated with such serious shortcomings that research misconduct can be established, the responsibility falls on all authors. It is established that the majority of the co-authors’ specific contributions to the article are not presented, and that it is word against word on crucial points. The main author Paolo Macchiarini bears the utmost responsibility and Sebastian Sjöqvist and Philipp Jungebluth had central roles in the research process. The Expert Group has some understanding for the more junior co-authors’ position of dependence on Paolo Macchiarini and the other leaders in the research group, but believes that it cannot exempt them from responsibility even if it can be considered a mitigating circumstance.
Based on all authors’ accounts of their input, KI divides them into three groups
1 . Senior authors who have a chief responsibility for the research.
Paolo Macchiarini and Philipp Jungebluth have both had a chief responsibility for the design of the experiments, the execution of the animal experiments, the interpretation of the results and the authoring of the article. They therefore have the chief responsibility for the misconduct present in the research and the published article.
Junior authors with a good insight into all or large parts of the research process.
Sebastian Sjoqvist was a doctoral student when the animal experiments were under way. He is the first author and in “author contributions” is stated to be the one who, together with Philipp Jungebluth, operated on the animals and was responsible for data collection. In addition, Sebastian Sjöqvist together with Paolo Macchiarini wrote the text for the article. Mei Ling Lim was a postdoc in the research team and in “author contributions” is said to be the one who carried out cell and molecular biology analyses and contributed, together with Philipp Jungebluth and Paolo Macchiarini, to data analyses and interpretations/explanations of collected data. According to her statement, she was only responsible for statistical analyses of her own analyses. However, “author contributions” and other documentation, including the appended text with traceable changes, provides support for her having a more central role in the work. Sebastian Sjöqvist and Mei Ling Lim are therefore deemed to have had a good insight into all or large parts of the research and therefore have a shared responsibility for the misconduct. They are both junior researchers who were in a position of dependence on Paolo Macchiarini and other more senior researchers in the research team, which may be seen as a mitigating circumstance, and they therefore cannot be considered to have the same responsibility for the misconduct as Paolo Macchiarini and Philipp Jungebluth.
The other authors have carried out and had responsibility only for a limited part of the research. In their replies, they have presented what they did and none of the external reviewers have criticised their contributions. According to the journal’s rules, as co-authors, they have been able to see and review the final version of the text so all authors of course have a certain responsibility for the final text. Many of the co-authors also mention that they do not have the expertise to assess the whole of the text, but rather that they have expertise in their own limited area. In modem medical research, cooperation between many researchers with widely different competencies is very common. In light of this, KI assesses that the other authors cannot be held responsible for the misconduct in the research in question.
Sanctions and other consequences
Paolo Macchiarini has earlier been dismissed by KI’s Personnel Disciplinary Board in March 2016. Philipp Jungebluth is not employed at KI today. Actions against them on law grounds are therefore not applicable.
Sebastian Sjöqvist and Mei Ling Lim are both employed by Karolinska Institutet. They are both junior researchers who were in a position of dependence in relation to Paolo Macchiarini and other more senior researchers in the research team. In addition the process has been very prolonged in time. These are seen as mitigating circumstances; why they only are issued an admonition (erinran) instead of being considered for disciplinary actions by KI’s Personnel Disciplinary Board. The responsible department head at Karolinska Institutet shall in the next two years or, if their employment is shorter, during their time of employment actively follow up and support their research to ensure that the research that they conduct at Karolinska Institutet is done in accordance with good research practice.
KI will immediately contact the joumal Nature Communications and request that the article “Experimental orthotopic transplantation of tissue-engineered oesophagus in rats” Nature Communications (20 I 4;5 :3 5 62) be immediately withdrawn.
Decisions in this matter have been made by acting Vice-Chancellor Karin Dahlman-Wright after presentation by acting Pro-Vice-Chancellor Henrik Grönberg and General Counsel Helén Törnqvist.