Scientific misconduct at an elite medical institute: The role of competing institutional logics and fragmented control

Research Policy xxx (xxxx) xxx–xxx

Contents lists available at ScienceDirect

Research Policy journal homepage: www.elsevier.com/locate/respol

Scientific misconduct at an elite medical institute: The role of competing institutional logics and fragmented control Christian Berggren, Solmaz Filiz Karabag

⁎

Department of Management and Engineering, Linköping University, 581 83 Linköping, Sweden

A R T I C LE I N FO

A B S T R A C T

JEL classifications: O30 D73 I23 L38

The incidence of revealed fraud and dishonesty in academia is on the rise, and so is the number of studies seeking to explain scientific misconduct. This paper builds on the concepts of competing logics and institutional fields to analyze a serious case of medical and scientific misconduct at a leading research institute, Karolinska in Sweden, home to the Nobel Prize in Medicine. By distinguishing between a market-oriented, a medical and an academic logic, the study analyzes how various actors − executives, research leaders, co-authors, journal editors, medical doctors, science bloggers, investigative journalists and documentary filmmakers − sustained or tried to expose the misconduct. Despite repeated warnings from patient-responsible doctors and external academic reviewers, Karolinska protected the surgeon, Paolo Macchiarini, until a documentary film at the Swedish national public TV exposed the fraud which led to public inquiries and proposals for a new national ethics legislation. The analysis illustrates the power of a market-oriented logic focused on brand and image at the research institute and at a leading journal, but also the perseverance of the logics of scientific scrutiny and medical care among practicing doctors and independent academics although the carriers of these logics were less well organized than the carriers of the market-oriented logic. Furthermore, the analysis shows the problem of fragmented control in the academic institutional field. The discussion of remedies compares the Karolinska case, where media actors were instrumental in sanctioning the perpetrators, with a similar instance of medical misconduct at Duke in the US where the government agency (ORI) intervened and shows the limitations of both types of actors. The conclusion highlights the importance of studying misconduct management and institutionbuilding in different fields to develop effective remedies.

Keywords: Institutional logics Institutional actors Scientific misconduct Retraction Academic dishonesty Fragmented control

1. Introduction The incidence of revealed fraud and dishonesty in academia is on the rise, according to several studies of retraction trends in publishing (Grieneisen and Zhang, 2012; Karabag and Berggren, 2016). Studies also indicate a widespread prevalence of other dubious academic practices (Necker, 2014). According to an investigation of image duplications in 20,000 papers, “the prevalence of papers with problematic images has risen markedly during the past decade” (Bik et al., 2016, p.1). Notorious incidents of fraud include fabrication of experiments by the physicist Jan Hendrik Schön at Bell Labs (Muijres, 2013); fake patients and data presented in papers on the treatment of oral cancer by John Sudbo (Ferrie, 2006); invention and manipulation of data by the social psychologist Diederik Stapel (Levelt et al., 2012); and fabrication of data regarding cloning of stem cells by the biotechnology researcher Hwang Woo-suk (Kim and Park, 2013). Scholars have used two principal approaches, individual- and ⁎

organization-oriented, to explain the incidence of fraudulent behavior in science. Individual-oriented studies focus on the role of personality traits such as narcissism and cynicism (Antes et al., 2007) or on microeconomic analysis of individual calculations of risk and reward (Adams and Pimple, 2005; Bouter, 2015). Scholars who focus on organizational dynamics have studied the behavioral impact of factors such as leadership, culture and norms. These studies emphasize that individuals make their decisions in a specific organizational and normative context, influenced by the organizations’ socialization and reward systems, practices and role models (Henrich et al., 2001). Such processes and models then guide the conduct of individual members (Anderson et al., 2007). Both types of studies have expanded our understanding of the reasons behind academic misconduct. However, extant research tends to focus on individuals or organizations without sufficiently exploring the complexity of the institutional field in which these individuals, organizations, and other stakeholders interact, collaborate, or challenge

Corresponding author. E-mail addresses: [email protected] (C. Berggren), solmaz.fi[email protected] (S.F. Karabag).

https://doi.org/10.1016/j.respol.2018.03.020 Received 21 December 2016; Received in revised form 29 March 2018; Accepted 31 March 2018 0048-7333/ © 2018 Elsevier B.V. All rights reserved.

Please cite this article as: Berggren, C., Research Policy (2018), https://doi.org/10.1016/j.respol.2018.03.020

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

2012) and are broadly related to the concept of ethos as articulated by Merton (1973). Researchers have studied institutional fields where an existing logic was replaced by a new dominant logic (Reahy and Hinings, 2009; Kodeih and Greenwood, 2014), but as suggested by Dunn and Jones (2010), institutional fields can become permanently fragmented with multiple logics that compete or reinforce each other. Studies of healthcare organizations, for example, contrast the logic of science and the logic of care (Lander, 2016), including efforts to “hybridize” the logics of care and market orientation (Miller and French, 2016). In an institutional field, outcomes result from the interplay between actors who maintain existing institutional logics and those who alter them (Thornton and Occasio, 2008; Leblebici et al., 1991). Institutional fields are conceived as dynamic and open, i.e. new actors may enter and vie for control of crucial processes (Green et al., 2008), and new practices and rules may evolve from proto-institutions to full-fledged institutions diffused throughout the institutional field (Lawrence et al., 2002). The primary case analyzed in this article involved intra-organizational actors: executives, doctors, and researchers at a research institute and an academic hospital, as well as actors in the extended institutional field: editors at a leading academic journal, contributors to science blogs, documentary filmmakers, and investigative reporters focusing on medicine and health. To interpret their behavior and different roles, it is useful to distinguish between three logics which may compete within the same organizational and institutional field (Goodrick and Reay, 2011). These three, the medical, the academic, and the market-oriented logics, are presented below:

each other. As a result, the suggested remedies mainly address individual ethics training and intra-organizational arrangements, such as support for internal whistleblowers and increased faculty awareness (Honig et al., 2014, Levelt et al., 2012). In a study of corruption and anti-corruption activities, Misangyi et al. (2008) emphasize how both individuals and organizations are embedded in a wider institutional environment and highlight the need to consider the interplay of individual identity, institutional norms, and the macro-organizational context to understand and mitigate misconduct. Moreover, the study suggests that remedies must be preceded by analyzes of how misconduct defenders “favoring [the] status quo will marshal available resources so as to legitimate and maintain that institutional logic” (Misangyi et al., 2008, p.751). Their emphasis on the role of the extended institutional field informs the analysis of the complex case of medical and scientific misconduct presented in this paper. The studied case involves a leading research institute, Karolinska Institute in Sweden, home to the Nobel Prize in Medicine, where an internationally recognized surgeon (Paolo Macchiarini) was employed to develop innovative methods in regenerative medicine and transplantation surgery. In the following years, his transplantations were presented as successes in several leading journals. However, doctors involved in the post-surgical care of the operated patients discovered serious misconducts and six of eight operated patients, in Sweden and abroad, eventually died. Despite this, Karolinska and its President protected the surgeon until a documentary film in 2016 exposed the operations as fraud, instigated public inquiries, and led to proposals for a new national ethics legislation in Sweden. Inspired by institutional theories, this paper focuses on the constellations of involved internal and external actors to answer three questions: 1) Which logics, actors, and structural characteristics sustained the misconduct for so long? 2) What constellation of actors and actions in the extended institutional field was instrumental in exposing the misconduct? 3) What are the lessons of the case concerning remedies for misconduct, and what could scholars learn from studying misconduct management in other institutional fields? In the next section, we discuss theories addressing academia’s changing institutional environment and introduce the notion of multiple institutional logics. Section 3 describes the data and sources utilized in our study. Section 4 presents the Karolinska case from the start in 2010 to the public exposure in 2016. Section 5 analyzes the dynamics of the case to answer the first two questions posed above. Section 6 focuses on remedies and compares the Karolinska case, where nonacademic and non-governmental actors played a critical role, with a similar misconduct case in the United States, where a national ethics agency (ORI) intervened. To proceed beyond these individual cases, we argue, there is a need for studies of misconduct management in other institutional fields. Thus, the conclusion highlights the importance of analyzing and comparing misconduct management in several different fields and the need for new initiatives to develop effective remedies.

• The classical medical logic focuses on patient care and is embodied in

•

2. Competing logics and the problem of fragmented control There is a long history of fraud in science. Broad and Wade (1982) provided an extensive catalog of known or suspected cases of scientific misconduct from Antiquity to the 1980s. To explain these incidents, they emphasized the contradictory character of science as a social system that promotes the development of new knowledge but also creates intense competition: “Science may in one sense be a community, but in another equally important sense, it is a celebrity system… which give[s] undue prominence and immunity from scrutiny to the work of members of the elite” (Broad and Wade, 1982, p.215-216). The idea of competing interests and ideals is a key element in modern theories of multiple institutional logics. Here “logics” are understood as taken-for-granted rules, belief systems and practices in an institutional field (Thornton and Occasio, 2008; Özen and Akkemik,

•

2

the Hippocratic Oath (“First, do no harm”), which requires physicians to uphold a basic ethical standard and to act accordingly. In the medical literature, the Hippocratic tradition has been considered a “taken-for-granted ethical system” (Jotterand, 2005, p.107). After the abuse of patients by the Nazi regime in the 1930s and 1940s, the ethical principles of medical research in human subjects became an urgent issue. These principles were codified in the Declaration of Helsinki in 1964, with several later amendments, which all respected medical research institutes officially adhere to. Although the interpretation of the Hippocratic tradition has been challenged, Miles (2004) argues that it still holds a central symbolic place in the medical community. The academic logic is focused on the intrinsic value of new knowledge and on the principles used to obtain this knowledge. This logic was articulated in Robert Merton’s famous CUDOS principles (commun[al]ism, universalism, disinterestedness, organized skepticism) against the backdrop of the totalitarian ideologies of the 1930s (Merton, 1973). Merton was not concerned with the ethics of individual scientists but rather focused on the “ethos” of academic research necessary for the autonomy of science as a social endeavor (Richardson, 2004). Merton also noted the existence of counternorms, later formulated by Mitroff (1974) as solitariness, particularism, disinterestedness and organized dogmatism. However, as suggested by Anderson et al. (2010, p.370), “there would be no need for a social system to assert a preference for actions aligned with the original norms” if there were no counter-norms. Merton’s principles have been criticized for a lack of sociological realism, but they remain a key reference point for understanding the particularity of academia in contrast to political or commercial organizations (Anderson et al., 2010). The market-oriented logic has a focus on external performance and indicators, such as publication scores, brand image and fund-raising success, and affects both individuals and universities. Studies of academic identity refer to an increasing diffusion of instrumental attitudes, captured ad extremis in the following quote: “Adding to knowledge is no longer the primary reason for academic publication. … As employees, academics are paid to publish, just as

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

persistent corporate fraud (Gabbioneta et al., 2013). Competition and market-oriented logics are diffusing not only among universities but also among journals. This is reflected in the “paramount importance” of impact factors (Macdonald and Kam, 2011) and the trend among leading journals to offer fast-track reviews. The Lancet gives authors the option to publish “a peer-reviewed manuscript within 4 weeks of receipt,” and offers the even faster “Swift + ”, where the editors will provide a decision within 10 working days (The Lancet, 2016). These offers are not combined with any public efforts to scrutinize the papers in other ways. A growing number of journals are committing themselves to the guidelines articulated by the Committee on Publication Ethics (COPE). Similar to the systems for accrediting universities, COPE does not include any independent ethics oversight board, and has never revoked the membership of any journal (Retraction Watch, 2017a). If its updated sanctions policy will have any significant impact remains to be seen (COPE 2017).

salesmen are paid to sell, and with very similar performance targets. And much like salesmen, they now look to their employers to reward their performance” (Macdonald and Kam, 2011, p.184). Some researchers argue that universities are increasingly run like businesses, operated by non-academic managers with a focus on efficiency and easily measurable outcomes (Nagy and Robb, 2008), including maximization of publication scores and image-building (Duarte et al., 2010). Different logics may compete and coexist for extended periods of time. Thus, the medical logic may coexist with the academic logic when doctors search for novel approaches supported by verifiable evidence. However, these logics may be at odds in the context of so-called “compassionate care,” where doctors try unproven methods as a last resort for fatally ill patients. Such experimental and non-tested approaches may, on the other hand, work well with the market-oriented logic that emphasizes the brand value of an organization which aspires to be perceived as an innovator. Merton “identified structural incompatibilities between the ethos of the market and that of science …./the need/to develop a viable balance between markets and sciences” (Kalleberg, 2007, p.132-133). Such a balance between different logics might be in danger if competitive pressure increases within an institutional field. Murray and Dollery (2006), for example, analyze failures in financial accountability and educational quality at Australian universities as an effect of commercialization and fragmented control. They do not include issues of research integrity, but their emphasis on the combined effect of competition and slack control is relevant for understanding academic misconduct, both the reasons for its occurrence and the difficulties in exposing it. A central aspect of the modern academic field is the massive growth of higher education and the ensuing increase in competition (Honig et al., 2014). Worldwide, there are approximately 40,000 higher education institutions (Webometrics, 2012). Their efforts to develop their brands and compete for resources are encouraged by ranking systems, such as the medical school rankings published by QS World University Rankings (topuniversities.com, 2017). At the same time, universities increasingly outsource the key function of scientific quality control to outsiders (i.e., to journals and their reviewers). Scientific journals may be “keystones in the edifice of any serious discipline” (Bedeian, 2003, p.337), crucial to “certify contributions, convene scholarly communities, and curate works that are worth reading” (Davis, 2014, p.200). However, the reliance of research institutions on journals to evaluate scientific merit results in a system of fragmented control with a lack of transparency and potential problems of institutional ascription. If a paper is accepted by a journal, there tends to be little control by other academic bodies (e.g. grading or recruitment committees), as noted by the Dutch committee investigating the Stapel fraud case (Levelt et al., 2012). Similar problems of fragmented control and institutional ascription, where one group of specialists assumes that other specialists have done the necessary checks, have been observed in studies of

3. Methods and data To investigate the activities of various actors in perpetrating, concealing, or exposing fraudulent activities in a complex case of academic and medical misconduct requires access to rich data. Our approach can be described as a meta-case study (cf. Hoyles, 1992), where we combine reports from public inquiries and external reviews with new primary as well as archival data. Inspired by studies of institutional logics, we collected data from medical journals, public inquiries, scientific reviews, video talks, documentary films, email communications and investigator blogs, conducted interviews with key actors and administered two surveys: the first survey was sent to the co-authors of Macchiarini’s “proof-of-concept”-paper in The Lancet 2011 (Jungebluth et al., 2011), the second survey was sent to authors of other papers published in The Lancet in the same year. We were also able to retrieve primary documentary data from Karolinska due to the Swedish Public Access to Information and Secrecy Act. The registrar’s office at Karolinska provided more than 50 documents from the internal process at Karolinska in 2015 regarding the external reviewer's critique, as well as a series of documents regarding the retraction of a Macchiarini paper proposed by the Central Ethics Board (CEPN) in 2016. In addition, the remedy discussion in Section 6 is informed by the report from the Swedish Commission on Academic Misconduct which was published after the exposure of the Karolinska scandal, by an analysis of a similar scientific and medical misconduct case in the United States, and by experiences gleaned from the struggle against doping in the institutional field of international sports. Table 1 presents a list of the publicly available reports and documents used in the study. Table 2 provides a list of interviews. Two key actors, the previous President (Anders Hamsten) at Karolinska and the chief editor (Richard Horton) at The Lancet, rejected or failed to respond to our request for interviews. Table 3 contains a list of other sources such e-mail correspondence, science blogs and documentary films. Table A1 in the Appendix A presents a detailed timeline of the

Table 1 Publicly available reports, inquiries & achieve. Author

Year

Content

Corbascio et al. Gerdin Ekblada Heckscher et al. Asplund KI archive SOU Wallberg Björck and Gantena

2014a 2014b 2014c 2015a 2016 2016 2016 2012–2016 2016 2017 2017

The whistleblowers’ appeals for an investigation, plus analysis of six papers. The review report by the first external reviewer. The review report by the second external reviewer. The public investigation of Karolinska Institute. The public investigation of Karolinska University Hospital. A collection of documents at KI Registration Office. New order for promoting good practices and dealing with misconduct in research. Objections to the public investigation of Karolinska Institute by Heckscher et al., 2016. The review report by the third external reviewer.

a

Commissioned by CEPN (Sweden’s Central Ethics Review Board). 3

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

Table 2 Overview of interviews.a Name

Position and Role

Org.

Date

Location

Length of Interview, min.

Mattias Corbascio

Senior surgeon, MD associate professor (Whistleblower)

11/22/2016

Stockholm

60

Oskar Simonsson

Surgeon, MD Ph.D. candidate (Whistleblower)

11/23/2016

Stockholm

65

Bosse Lindquist Johan Brånstad Prof. Dr. Arne Ljungqvist

Producer of the documentary film “The experiments” Project manager for the documentary “The experiments” Vice President of WADA 2007–2014 Chairman of IOC Medical Commission 2003 − 2014 Executive Committee and Foundation Board Member (WADA), IOC Vice President President of KI (2004–2012) Anonymous

KS KI KS Kl SVT SVT WADA IOC IOC WADA

11/14/2016 11/14/2016 01/18/2017

Stockholm Stockholm Stockholm

50 70 90

01/19/2017

Skype

45

09/20/2017 09/20/2017

Stockholm Stockholm

60 30

Prof. Dr. Ugur Erdener Prof. Dr. Harriet Wallberg KI Manager

KI KI

a Abbreviations: IOC = International Olympic Committee; KI = Karolinska Institute, KS = Karolinska Hospital, SVT = Swedish Public TV; WADA = World AntiDoping Agency.

area of research, create a hub for the virtual European Airway Institute, and accelerate medical innovation at Karolinska (Gerdin, 2015a; Asplund, 2016). In June 2011, an Eritrean studying in Iceland, who had previously suffered from trachea cancer, became the first patient to receive an artificial (plastic) trachea, manufactured at University College London (UCL).1 A few weeks after this surgery, Karolinska distributed a press release which said: “For the first time in history a patient has received a new synthetic trachea pre-treated with the patient's own stem cells” (Karolinska, 2011). Somewhat later, the patient was transferred to Iceland, but had to return several times to Karolinska to treat postsurgery complications. Nevertheless, on the one-year anniversary of the operation, the University of Iceland organized a special seminar to celebrate the “groundbreaking operation” with Macchiarini as an invited speaker. Later, the patient had to return to Karolinska University Hospital again, and in January 2014, he died. An autopsy, performed at the insistence of a patient-responsible doctor who later became one of four whistleblowers (Simonsson, interview Nov. 2016), revealed profound pathologies, as further discussed below. At that time, however, Macchiarini had conducted several more trachea transplantations, each time testing a new plastic implant. Patient 2 was an American diagnosed with tracheal cancer which was not possible to operate in the US due to FDA restrictions. He was operated on at Karolinska in November 2011, then transferred back to the United States, where he died less than four months after the surgery. Patient 3 was a young Turkish woman who suffered from a trachea injury caused by an ill-performed surgery in Turkey that was not cancer-related. The trachea transplantation at Karolinska in August 2012 was followed by a series of life-threatening complications, and she remained at KS for three years of intensive care, until she was transferred to Temple University Hospital in the United States. Here she underwent a new transplantation to replace the plastic windpipe with a trachea from a cadaver, but this could not save her life, and she died in March 20172 (Åstrand, 2017a). The surgery for patient 1 was marketed as a success in a “proof-ofconcept”-paper in The Lancet written by Macchiarini and a large group of authors (see Jungebluth et al., 2011). This paper was submitted four months after the first transplantation and accepted by The Lancet within 4 weeks: “Taken together, these results provide evidence that a

case history. Table A2 in the Appendix A provides an overview of the seven Macchiarini papers which were scrutinized in the external reviews. Table S1 in Supplementary material provides more detailed information regarding the seven papers, the criticism as well as the authors’ responses. Table S2 and S3 in the Supplementary material present the questions and answers in our online survey to 18 co-authors of Macchiarini’s “proof-of-concept”-paper in The Lancet 2011. Table S4 and S5 in the Supplementary material presents the mini-survey regarding publication time to all authors who published in The Lancet 2011. As institutional logics and their interactions cannot be directly measured, and the content and type of data did not permit formal approaches, we used interpretive methods to analyze and understand the role of the various actors, from executives to doctors, researchers, editors, journalists, and filmmakers (Haveman and Rao, 1997; Thornton and Ocasio, 1999). This is in line with a strong tradition in qualitative research which advocates close reading and interpretation, suggesting efforts that combine transparency with “the necessary degree of intuition… that make the analysis creative and fruitful” (Flick, 2014, p.12). 3.1. A note on nomenclature Karolinska, the organization at the center of this study, consists of two entities with blurred boundaries, Karolinska Institute and Karolinska University Hospital. Macchiarini was both a guest professor at Karolinska Institute (KI) and lead surgeon at the Hospital (KS). Macchiarini’s activities were terminated at KS as of 2013, but he continued at KI as before. If important for the analysis, we distinguish between KI and KS, otherwise we use Karolinska for brevity. 4. The dynamics of the Karolinska case 4.1. Groundbreaking surgeries, 2011–2012 In December 2010, Karolinska hired Paolo Macchiarini as a guest professor at the research institute (KI) and as a lead surgeon at the hospital (KS). Two years prior, Macchiarini and several colleagues had transplanted a trachea from a deceased donor to a woman with breathing problems in Barcelona. This pioneering surgery was reported as a success in The Lancet (Macchiarini et al., 2008), which was critical for building Macchiarini’s reputation as a leader in innovative transplantations (Wallberg, interview Sept 2017). A letter to the recruitment committee at Karolinska in support of the surgeon was signed by 14 professors at KI. Macchiarini, whose CV included 130 publications, was believed to be on the verge of a paradigm shift in regenerative medicine. By employing him, the recruitment committee argued, Karolinska would obtain an internationally acclaimed scientist in this promising

1 Prof. Seifalian who led the effort at UCL later revealed in a TEDMED talk that he had minimal knowledge of tracheas and that he developed the artificial windpipe in 10 days (Seifalian, 2013). 2 According to Åstrand (2017b), the operations and care of patient 3 cost approximately USD 11 million, which was paid by the Turkish Health Minister. In an interview in August 2015, Hayrullah Cetir (the patient’s father) said he wanted KS to stop the operations but was threatened that if he insisted all care would be discontinued and the patient returned to Turkey (Åstrand, 2017b).

4

Research Policy xxx (xxxx) xxx–xxx

Abbreviations: KI = Karolinska Institute; KS = Karolinska Uni. Hospital; SVT = Swedish Public TV; Zdf-Arte = French-German Television, PM = Paolo Macchiarini.

successful organ regeneration strategy has been accomplished …. The successful overall clinical outcome of this first-in-man bioengineered artificial tracheobronchial transplantation provides ongoing proof of the viability of this approach, in which a cell-seeded synthetic graft is fabricated to patient-specific anatomical requirements….” (Jungebluth et al., 2011, p. 2003). The apparent success of the operation was supported by an article by one of the Lancet editors on the “surgeon crossing frontiers” (Holmes, 2012), a new paper by Macchiarini and colleagues in the same journal on the engineering of whole organs (Badylak et al., 2012), and another Lancet paper presented as a follow-up of the Barcelona transplantation (Gonfiotti et al., 2014). A paper in Biomaterials that discussed the biocompatibility of artificial windpipes (Ajalloueian et al., 2014) admitted complications in patient 1, but mentioned neither that the patient died seven weeks before manuscript acceptance, nor that the autopsy had reported very serious conditions, such as “that the tracheal prosthesis had achieved insignificant integration and was lying loose in an area of pussy liquid and dead tissue with only about 10% of the proximal anastomosis healed in place” (Gerdin, 2015a). For an overview of the relevant Macchiarini papers, see Table A2 in the Appendix A.

4.2. International expansion The academic publications which presented the surgeries as major advances were accompanied by supportive attention in mainstream media, such as the inclusion of the trachea transplantation in Time Magazine's list of top medical breakthroughs in 2011 (Asplund, 2016; Park, 2012). This further consolidated the reputation of Macchiarini as a leading surgeon in regenerative medicine and was exploited when KI started negotiations with Chinese politicians and businessmen to raise funds for a center in regenerative medicine in Hong Kong. These discussions directly involved the President (Anders Hamsten) at KI and two Macchiarini collaborators who used his reputation as a marketing asset. In January 2015, a contract was signed according to which the businessman Ming Wai Lau donated the equivalent of $US 50 million to a KI research center in Hong Kong, the largest donation in the history of KI (Samuelsson, 2017; KI manager, interview Sept. 2017). Several years earlier Macchiarini had started to perform synthetic trachea transplantations both in the United States and Russia. The American patient, a two-year-old girl in Peoria, was operated on at Children’s Hospital in Illinois in April 2013 in what was initially hailed as a “groundbreaking surgery” (Fountain, 2013). Because of post-surgical complications, the girl died less than three months after the intervention (Moisse, 2013). Four Russian patients were operated on at a hospital in Krasnodar. One of them was used in the documentary film Supercells by the French-German ARTE channel, which presented Macchiarini as a true medical innovator: “Doctors extract stem cells from a patient’s hip bone, manufacture an artificial organ and save her life. In a hospital in Krasnodar, an artificially engineered windpipe is to be implanted into a patient’s chest. Professor Paolo Macchiarini will perform this miracle—and a ballet dancer from St. Petersburg is putting her last hopes in his hands” (Giese, 2012). The patient later wrote a letter to a producer at ARTE: “Everything is very, very bad with me. I have spent over six months in the hospital in Krasnodar. I have undergone over 30 surgeries under general anesthesia. Three weeks after the first operation a purulent fistula opened, and my neck has since rotted. I weigh 47 kg. I can barely walk. I have trouble breathing, and now I have no voice. And it smells so strongly of me that people back away” (cited in Wahlström, 2016). The patient later died, as did a second Russian patient (allegedly in a bike accident). The third Russian was reportedly alive in mid-2016, but the plastic windpipe had been removed. The condition of the fourth operated Russian remains unknown (Asplund, 2016).

a

13, 20 & 27 Jan. 2016 3 episodes (175 min.) Displays suffering patients and misconduct Documentary film 2 (in Swedish)

SVT Displays suffering patients and misconduct

Macchiarini, Star Surgeon: At Any Cost The Experiments

Documentary film 1 (in Swedish)

SVT

58 min + StemCell pitch document 55 min. 2013 Supercells

May 2015

17 min. 05/18/2013

TEDMED talk (video) by Alexander Alexander Seifalian explained how he produced the plastic Alexander Seifalian, professor at University Seifalian trachea for the first patient, and here describes the procedure College London Documentary film and pitch document Displayed trachea transplantations in Russia as a success Zdf-Arte Films Future of Organ Development

24 comments tagged with PM Sep. 2017 Comments on papers that Macchiarini co-authored and The Lancet editorials that praised or defended Macchiarini

Blog entries

Post-publication forum discussions

The nonprofit PubPeer Foundation

26 posts tagged with PM Mar. −Dec. 2016

Nov. 2012 - Dec. 2016 45 posts tagged with PM

The Center for Scientific Integrity, by Adam Marcus and Ivan Oransky Crowdfunded blog, by Leonid Schneider Disseminated information about the process and suspected misconduct Disseminated information about suspected misconduct Blog entries

Forbetterscience.wordpress. com Pubpeer.com

Bengt Gerdin

Science blogs and forums Retractionwatch.com

–

–

Professor, medical doctor, and transplantation 11/20/2016 practitioner at KU Leuven University Professor emeritus, Uppsala University 10/06/2016 Contacted KI & The Lancet, suggested that Macchiarini’s publication contained fraud The first external reviewer Email communication with Karolinska and The Lancet Email communication with KI President 2 (Anders Hamsten) Correspondence Pierre Delaere

Data Sources/Actor

Table 3 Online media, e-mail correspondence, science blogs and films.a

Role

Position and Organization

Access/ Pub. Date

Other Information

C. Berggren, S.F. Karabag

5

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

trachea transplantation) entailed disastrous complications for the patients (Corbascio et al., 2015, p.5).

4.3. External warnings and internal whistleblowers (2011–2015) In September 2011, less than a year after the employment decision, the President (Harriet Wallberg, hereinafter President 1) at KI received a letter from Pierre Delaere (hereinafter Delaere), a Belgian professor at the Laboratory of Experimental Transplantation, KU Leuven University, who raised concerns regarding Macchiarini’s transplantation in Barcelona as reported in a Lancet-paper (Macchiarini et al., 2008). Delaere also objected to the press release from KI after the first synthetic trachea transplantation: “press releases on major ‘breakthroughs’ that are not supported by peer-reviewed publications may bring confusion among the medical practitioners and may mislead patients” (Wallberg, 2017, p.21). When President 1 confronted Macchiarini, he dismissed the criticism by referring to a personal conflict. In the following year, Karolinska was informed that the chief editor of The Society for Thoracic Surgeons had retracted a Macchiarini paper not related to his KI activities (Gonfiotti et al., 2012). President 1 asked the Ethics Council at KI for their recommendations, but the Council disdained the journal’s verdict (scientific misconduct), suggesting that the authors only had made a mistake “which could have been prevented using a more careful search for literature” (Lynöe, 2013, p.1). However, this first retraction of a Macchiarini paper triggered the attention of the investigative blog Retraction Watch, which began to follow his activities. In 2013, professor Delaere contacted Anders Hamsten, the new President at KI (below referred to as President 2), with a letter containing serious allegations of scientific and ethical misconduct, such as the use of artificial prostheses in patients without any previous animal research (Delaere, 2013 in Wallberg, 2017). At this time Macchiarini had published several papers based on the transplantations at KS, and according to President 1 this warranted a thorough investigation (Wallberg, 2017). Because of the post-surgery complications after the first three transplantations, however, KS had decided in October 2013 to cancel any further trachea transplantations (Asplund, 2016, p. 62). This was used by President 2 at KI to refrain from any misconduct investigation. Macchiarini could continue as before at KI and President 2 planned for a permanent professor position. In June 2014, Delaere submitted a new critical letter to KI (and The Lancet). This finally instigated an investigation by the institute’s Ethics Council (Asplund, 2016). In early 2015, the council released a report that disputed Delaere’s critique. The council did not examine the medical records but argued that the patients had been “transplanted on a compassionate basis” (i.e., as the last resort to avoid imminent death). At the time of this statement, two of three patients operated on at KS had died, and the third was in very serious condition. Of the eight patients who underwent transplantation, only two were documented as still alive, and both had their artificial trachea removed. Despite these facts, the Ethics Council argued that the “survival rate can be perceived as not bad” (Lynöe, 2015, p.3). At this time, four doctors involved in the post-surgery care of the transplanted patients had conducted their own examinations of the medical records. As later explained, the starting point for these whistleblowers was the interaction with the suffering patients:

The whistleblowing doctors had accumulated a first-hand knowledge of these complications. “As patient-responsible for the care of patient 3, Thomas (one of the four) had been living at the hospital for two years since this patient required bronchoscopies, i.e. cleaning of the throat, every fourth hour. Otherwise, she would have suffocated” (Simonsson, interview Nov. 2016). In June 2014, the four doctors took the unusual step of officially appealing to President 2 to investigate Macchiarini on suspicion of scientific misconduct in a paper on rat experiments (Sjöqvist et al., 2014). During the summer of 2014, the four doctors received permission to scrutinize the full medical records for the three patients operated on at KS. In an interview, one of the whistleblowers further explained: Just by chance, we also checked with the Regional Ethical Review Board and found out that the ethical approval of the surgery, which we had taken for granted, did not exist. We continued with the Swedish Medical Products Agency and learned that neither was there any approval of the synthetic trachea for clinical implantation, nor for the heavy use of the drugs in high doses which were administered to the patients after the surgery. (Corbascio, interview Nov. 2016). The doctors’ comparison of these discoveries with the statements in Macchiarini’s published work resulted in a comprehensive request to the KI President 2 to investigate dishonesty in six other papers with Macchiarini as the lead author (Corbascio et al., 2014a, 2014b, 2014c). The doctors’ appeals became known externally. In November, The New York Times published an article on a leading surgeon accused of misconduct at Karolinska (Fountain, 2014) and President 2 at KI appointed a professor emeritus of medicine at Uppsala University, Bengt Gerdin, to review the allegations of misconduct. At the same time, managers at KS tried to silence the complainants. “Our key objective was to protect the patient security, but our managers accused us of leaking patient information and threatened us by dismissals. If we had not been so actively supported by our union, we would have been fired, all of us.” (Corbascio, interview Nov. 2016). The external reviewer started a thorough analysis of all the seven publications with Macchiarini as the lead author that were based on his activities at Karolinska (see Table A2 in the Appendix A). In May 2015, he submitted a report that identified serious misconduct in six of them (Gerdin, 2015a). The seventh paper received a milder verdict, but later, a second external reviewer scrutinized all the available data for this paper, including the lab journals that she found lacking basic information regarding statistical procedures and data on specific animals, as well as gross breaches in protocol regarding experiments on animals. The reviewer concluded with a list of serious transgressions in research ethics (Ekblad, 2016). Shortly after the release of the first external review, the Swedish Research Council discontinued research funding for Macchiarini claiming the operations had not received any ethical permission. This could have been the end of the affair, but Karolinska continued to work to absolve Macchiarini, and invited Macchiarini and his coauthors to respond to the external review without allowing the reviewer to answer. More than 30 different responses were submitted to President 2, almost all defending the criticized papers (KI STÖD, 2016). The reviewer later characterized the responses as a mix of false or irrelevant statements and, in Macchiarini’s case, blaming of his co-authors (Gerdin, 2015b). Based on this internal process, President 2 announced his decision to acquit Macchiarini of all fraud allegations at a press conference in August 2015. The Lancet followed up with an

As physicians practicing at the Department of Cardiothoracic Surgery and Anesthesiology…we first became aware of the terrible state of the first patient when we were contacted in order to discuss the possibility of performing a right-sided pneumonectomy (lung removal) to alleviate chronic dysfunction and infection of the entire right lung…. At this time, the third patient had been in our department for over a year and was suffering from multiple debilitating complications…. it became clear that this procedure (the

6

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

editorial that included a stinging attack on the external reviewer: “Although Karolinska has exonerated Macchiarini, the means by which it did so—a flawed initial inquiry completed by a single individual with widely disseminated, damaging, and mistaken findings—suggests that the university needs to review its procedures for investigating allegations of misconduct. Dragging the professional reputation of a scientist through the gutter of bad publicity before a final outcome of any investigation had been reached was indefensible” (Editorial, 2015, p.932).

5. Analysis The introduction to this paper posed three questions concerning: (1) The logics, actors, and systems in the established institutional field that made it possible to sustain Macchiarini’s misconduct for so long; (2) The constellation of actors and actions in the extended and evolving field that finally exposed the misconduct; (3) The lessons and limitations regarding remedies which can be distilled from the Karolinska scandal and similar cases. The analysis below concentrates on the first two questions; the discussion section focuses on the third.

4.4. Non-academic media intervention

5.1. A weak academic logic with a lack of critical examination

The letters from Delaere, the retraction by the editor of The Society of Thoracic Surgeons, the decision by the Swedish Science Council, and the investigation by the external reviewer were interventions from respected academics, but each of them failed to end the support for Macchiarini at KI. However, Macchiarini’s activities had also caught the negative interest of mainstream media. In 2012, the surgeon was accused of fraud in Italy, which was reported in the Swedish popular press (Peruzzi, 2012), and in 2015, Sweden’s public broadcasting services (SVT), started to develop programs about the case. The first program was screened as a part of an investigative series in May 2015. At the same time, a second filmmaker at SVT began to produce an extensive documentary about Macchiarini. The decision at Karolinska to acquit the surgeon raised the stakes (Brånstad, interview Nov. 2016) and the film team expanded to a dozen investigative journalists, archive researchers, and editors. In January 2016, the documentary The Experiments was screened as a series of three episodes, all of them with the suffering patients in focus. The public impact was immense. The admission by Macchiarini in episode three that no animal testing had been conducted or requested by Karolinska before the start of the human experiments contributed to this impact. Briefly before the Swedish television series, the U.S. Magazine Vanity Fair published a lengthy article on the love story between Macchiarini and an NBC reporter (Ciralsky, 2016), depicting the surgeon as an almost surreal conman, and this contributed to the downfall. In a Swedish medical magazine, a professor emeritus who had done decades of research on artificial blood vessels and tested them in extensive animal experiments but ultimately failed, criticized the research approach as unrealistic and denounced Karolinska as “the Chernobyl of ethics” (Risberg, 2016). After the release of the documentary film (later also televised in other countries, such as the UK) and the ensuing media debate, the efforts at Karolinska to preserve Macchiarini’s position could not be sustained. His second term at as guest professor was not extended, President 2 at Karolinska Institute was forced to step down (Vogel, 2016), followed by the chairman of the board. Inquiries were launched to investigate both KS (Asplund, 2016) and KI (Heckscher et al., 2016). The publication of the Heckscher report (2016), with its critique of the institute’s management and recruitment system, forced the resignation of the Director General of the Swedish Higher Education Authority. She was president at KI when Macchiarini was employed and was accused of having actively promoted him, an accusation she has strongly disputed (Wallberg, 2017). Moreover, a public commission was initiated to review the current system of academic misconduct management in Sweden and suggest reforms (SOU, 2017). The whistleblowing doctors received a lot of media attention, but two of them left KS. Almost all of the managers directly responsible for the support and defense of Macchiarini remained in place or were later promoted to new positions (Bäsen and Carlsson, 2016).

To answer the question “Why so long?” it is necessary to analyze the asymmetries between actors and their different logics, both within the principal organization and in the wider institutional field. At Karolinska, the arrival of Macchiarini initially sparked a widespread excitement regarding the prospect of breakthrough clinical innovations, based on a merger of transplantation technology, stem cell research and bio-engineering (Asplund, 2016). The excitement was aligned to an interest within the organization of doing state-of-the-art research, but it also fueled a market-oriented logic at its top with a focus on enhancing Karolinska’s ranking, brand value and fund-raising potential (Heckscher et al., 2016). This market-oriented logic was bolstered when the image of a ground-breaking medical method was diffused in international media. The Guardian, for example, concluded its report on the first trachea transplantation on a high note: “Hopefully this ground-breaking surgery will speed the way for such procedures to become more common in the near future” (Vezina, 2011). The suite of publications in The Lancet from 2011 to 2014 by or in support of Macchiarini further strengthened his organizational position and the support from top management. This increased the disadvantages of dissenting voices such as the four whistleblowers who neither enjoyed any management position nor could report highly cited academic papers or support in mainstream media. Their arguments based on a medical logic and intimate knowledge of actual patient conditions were overwhelmed by the powerful market-oriented logic that boosted the support for Macchiarini. The large group of co-authors involved in Macchiarini’s publishing activities increased the asymmetry between supporting and dissenting voices. The “proof-of-concept”-paper (Jungebluth et al., 2011), for example, engaged 15 co-authors at Karolinska, several of whom were in management positions. This wide authorship could have indicated a commitment to state-of-the-art research at the institute. However, a sustainable academic logic needs to be based on an internal culture of critical scrutiny and examination. There is no indication that Macchiarini was subject to such a culture, e.g. there were no seminars within the network of researchers in regenerative medicine, which would scrutinize the scientific basis of the proposed techniques. Several reports (e.g., Asplund, 2016) emphasize the highly competitive culture at KI, which employs many researchers on fixed-term contracts, a type of culture often associated with ethical misconduct (Anderman and Murdock, 2011; Rick et al., 2008). A critical examination of the new surgical approaches would be even more important from the perspective of the medical logic (“care for the patient”). At KS, such examinations are expected to take place at multidisciplinary conferences (MDCs) that precede surgeries and are intended to bring together different specialist competences when difficult interventions are considered. In the trachea transplantation case, however, the MDC participants failed to ask any critical questions regarding alternative treatment strategies, experimental support for the proposed procedure, or evidence for the positive effects of stem cell

7

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

refute the published results we can proceed no further” (cited in Delaere, 2013). Unfortunately, as Delaere responded, the journal did not ask for “hard evidence” when they accepted the paper. When the external review of Macchiarini’s publications was released in 2015, The Lancet did not inform its readers of the criticism, and as soon as Karolinska cleared the surgeon of any wrongdoing, an editorial in The Lancet supported this decision without qualifications (as noted above). Shortly afterward, The Royal Swedish Academy of Sciences informed The Lancet readers of their concerns, emphasizing that Macchiarini’s “proof-of-concept”-paper (Jungebluth et al., 2011) “does not present the condition of the patient in a correct way and that.… The Academy finds it deeply unfortunate that the well-publicized report about the first operation with an artificial trachea…remains unchanged on the journal’s website” (Claesson-Welsh and Hansson, 2016). Moreover, the legal officer at The Swedish Research Council informed The Lancet’s readers of the lack of ethical permission for the transplantations (Hörnlund, 2016). The only reaction at the journal was an Expression of concern notifying readers that “several new investigations into various aspects of the research are [being] carried out at Karolinska” (The Lancet Editors, 2016, p.1359). This was criticized by commentators at PubPeer, who argued that the journal could be putting patients at risk and asked why The Lancet did not alert readers to the possibility that there could be a problem with the operation (PubPeer, 2017). Macchiarini’s “proof-of-concept”-paper (Jungebluth et al., 2011) was accepted within less than a month (submitted on Oct. 11, accepted on Nov. 7), a short time for reviewing and revising a manuscript also by The Lancet’s own standards. Our survey to all authors who published in The Lancet in 2011 indicates an average of 2–3 months from submission to acceptance (See Table S4 in the Supplementary material). The key issue, however, is not the rapid acceptance of a complex paper on a new method, but the resistance to retract the paper in spite of its serious flaws. Six years after publishing the “proof-of-concept”-paper, The Lancet was still waiting for an official request from KI before contemplating a retraction. In a similar way, Biomaterials accepted a paper by Macchiarini and co-authors after only 15 days (Jungebluth et al., 2013), but despite criticism for misconduct in the external review report (Gerdin, 2015a), the paper remains in the journal without any editorial comment. In July 2016, Karolinska asked this journal to publish an ‘Expressions of Concern’ related to two papers with Macchiarini as the lead author. Similar requests were sent to Journal of Biomedical Materials Research Part A, Thoracic Surgery Clinics and Nature Communications. Apart from the last journal none of them have published any concern.3 The only active editorial intervention is represented by the chief editor of The Society of Thoracic Surgeons, who retracted a paper which was not based on any activity at Karolinska. COPE guidelines state: “Journals are responsible for the conduct of their editors, for safeguarding the research record, and for ensuring the reliability of everything they publish” (COPE, 2016). Despite this responsibility, retraction rates tend to be very low. As indicated by The Lancet webpage, since 1989 this journal has only retracted 9 research papers (re-published papers excluded), 4 short papers and 1 case report. Other highly ranked journals such as Nature and Science exhibit somewhat higher retraction numbers (Fang and Casadevall, 2011), but the general rate of retraction remains low. Thus, the Macchiarini case illustrates not only a resource asymmetry between the market-oriented logic and the medical and scientific logics

seeding of the plastic windpipe (Asplund, 2016). The scant interest in critical examination and reflection is indicated by the reactions of Macchiarini’s co-authors to the review comments from New England Journal of Medicine (see below) as well as their reactions to Gerdin’s comprehensive review. Of the more than 30 responses submitted to President 2 during KI’s internal processing of this review, only one supported the whistleblowers’ critique—and she was later accused of misconduct herself. Almost all of the respondents defended the criticized papers or sought to absolve themselves of any guilt (KI STÖD, 2016). Despite scathing criticism of the “proof-of-concept”paper (Jungebluth et al., 2011), its evidence and its ethics, only 4 of the 27 co-authors inside and outside Karolinska requested to be withdrawn from the author list. In November 2016, we sent a survey to the 18 remaining authors with viable addresses, asking if they had checked the revised paper before its submission, had considered contacting The Lancet regarding remedies, and whether they would consent to a retraction. After two reminders, the survey garnered only four responses (see Table S2 and S3 in the Supplementary material). One respondent, not from Karolinska, answered all the questions with: “Judging from later reports the main conclusion of the paper is not correct. The paper does not describe a functioning technique in regenerative medicine.” 5.2. Fragmented control and resistance to retract The reluctance of Macchiarini’s co-authors to admit impropriety illustrates the problem of fragmented quality control in the academic institutional field (cf. Karabag and Berggren, 2013). As noted above, research institutions increasingly delegate the responsibility of ensuring scientific rigor and integrity to the academic journals: “Journal editors have a central position in communicating research, they also have the most important role in ensuring the integrity of its published record” (Marusic et al., 2007, p.347). This outsourcing is congenial with a general diffusion within academia of a market-oriented logic, where the investment of resources in the careful internal scrutiny of papers before external submission is no priority. However, such an outsourcing is critically dependent on the assumption that leading journals adhere to a logic of scrutiny and skepticism. The Karolinska case illustrates the difficulties when the journals too are influenced by a market-oriented logic, celebrating and supporting selected contributors and delegating critical investigations to the authors’ home organization, which normally has more limited access to qualified international reviewers. As observed by researchers analyzing corporate fraud, assumptions regarding external control are sensitive to institutional ascription: “professionals ascribe professional diligence to other professionals. Professional networks are thus clearly vulnerable if an integral link in the network − in our case, the audit firms − fails to meet those expectations” (Gabbioneta et al., 2013, p.499). After the first synthetic trachea transplantation, Macchiarini approached The New England Journal of Medicine (NEJM), but this journal did adhere to a logic of rigorous scrutiny. Its critical reviewers highlighted the absence of data from animal studies, the lack of the ethics permission, and weak evidence for crucial statements, and so NEJM rejected the paper (Björck and Ganten, 2017). Instead of carefully analyzing this report within the author group, Macchiarini resubmitted the manuscript to The Lancet, and after a rapid review process, the paper was accepted. The critical comments from NEJM were never made public, which may be a generally accepted behavior. However, this practice underlines the lack of transparency in the academic institutional field and its system of control, and has recently been challenged by senior editors, who argue that reviewers’ reports should be routinely published alongside articles (Retraction Watch, 2017b). As noted above, The Lancet contributed to Macchiarini’s international reputation by several more publications. By contrast, Delaere’s efforts to persuade the editors to consider his dissenting views were turned down: “For The Lancet to publish an alternative view it would need to be backed by hard evidence. Without compelling hard facts to

3 In addition to journal website searches, we asked the editors if they had published any concern. The Editor of Journal of Biomedical Materials Research-Part A informed us that they did not publish any expression of concern regarding Del Gaudio et al., (2014) since the paper was not an original research article or a case report, but a review article dealing with tissue-engineered synthetic substitutes for tubular organs including trachea, oesophagus, bile ducts and the bowel, with 113 references of which Paolo Macchiarini was a co-author on only five of the references. He also stated that Karolinska should oversee its routines.

8

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

to use the method clinically, cancer researchers at the University of Texas and Rice University engaged two statisticians to evaluate the findings. The statisticians spotted serious errors (Baggerly et al., 2008), but Duke did not react (Kolata, 2011). In 2008, a third-year medical student at Duke warned university officials of suspected misconduct, but to no avail (Mulcahy, 2015). Two years later, a trade publication, The Cancer Letter, reported that Potti had falsified his curriculum vitae, which forced him to resign (Oransky and Marcus, 2016). After this revelation, Duke started an investigation, as did The U.S. Office of Research Integrity (ORI). Five years later, ORI announced that Potti had engaged in research misconduct by using falsified data in several publications (ORI, 2015). However, no significant sanctions followed. External commentators noted that “despite the grand scope of the faked research, no one else at Duke was reviewed or cited by federal investigators” (Mulcahy, 2015). Both the Duke and Karolinska cases are concerned with scientific and medical misconduct. Both involved perpetrators with large groups of collaborators who received enthusiastic support in the media, at their research institutes, and from high-impact academic journals. In both cases, whistleblowers as well as researchers at other universities sounded the alarm, but were turned down. The consequences, however, were different. In Sweden, the public impact of the SVT documentary forced the resignation not only of Macchiarini, but also of top executives at Karolinska without a formal review by any ethics board. The Duke case was exposed in a professional journal with limited circulation, and then slowly processed by a national integrity agency, which cleared all but a single perpetrator. These cases illustrate two different ways to expose and sanction academic misconduct. In the Karolinska case non-academic media interventions were crucial both for the exposure and the public sanctioning of the misconduct. This poses questions about the sustainability and engagement of these types of external actors. In the Duke case, external media intervention was crucial for revealing the misconduct, but a government agency assumed responsibility for further investigations and for sanctioning the offenders. The outcome poses questions about the effectiveness of such control. An optimistic reading of the Karolinska case might focus on the role of academic websites and documentary filmmakers in the extended and evolving institutional field and argue that the media acts as a watchdog to combat misconduct (Becker et al., 2013). A pessimistic reading might point out the varying reliability of online communities and the unpredictable impact of external media interventions, noting that the first attempt of SVT to expose the Macchiarini misconduct had minimal impact. Moreover, although social media and public opinion may be more powerful than legal processes, they tend to be transient, and are no substitute for institutional reforms (cf. DiMaggio, 1988; Misangyi et al., 2008). Policymakers are normally inclined to the Duke approach (i.e., the involvement of government agencies). Thus, the Swedish Commission on Academic Misconduct in 2017 proposed common standards and a nationally unified way of handling suspected misconduct. However, the substantive impact of this proposal on ethics and integrity is uncertain. One problem is that a national board needs to adopt a legalistic approach (i.e., evaluate if the suspected perpetrators have intentionally broken the rules). Such an approach would probably have led to the acquittal of the entire KI leadership, its President as well as its chairman. Moreover, the proposed change in misconduct management will have no impact on the institutional logic and the wider institutional field, including the academic journals. The report proposes that if the national board establishes that research misconduct has occurred, the involved institution should inform all relevant stakeholders, from employers to editors, of the decision (SOU, 2017), but the journals do not need to react. The problems of fragmented control and asymmetric entry versus exit will probably continue. The Karolinska case, the comparison with Duke, and the proposed Swedish legislation demonstrate significant limitations in current forms

at Karolinska. The case also exemplifies the problems of fragmented control and asymmetry between rapid entry and slow exit at leading journals. This increases the difficulties to expose misconduct in the established academic fora. 5.3. Exposure − the key role of external actors in the extended institutional field To understand why it was possible to expose the misconduct at Karolinska in spite of these asymmetries, it is important to note the strength of the medical logic among care-responsible doctors and other external actors, including investigative journalists in the extended institutional field. The concerns of the whistleblowing doctors who witnessed the post-surgery suffering of several patients first hand seemed to be futile at first but turned out to provide science bloggers and independent journalists with crucial information. This sparked the interest of mainstream media actors, from The New York Times to Sweden’s public television provider, SVT. The involvement of this media was crucial to the outcome at Karolinska and to the wider discussion of scientific and medical ethics in Sweden. However, when a team of SVT’s investigative journalists first produced a highly critical program in May 2015 (Åstrand and Frisk, 2015), there was no substantial public debate, and a few months later Karolinska exonerated Macchiarini. As described in the account above, this exoneration reinforced the efforts of another team at SVT. The release of the second documentary in January 2016 exposed the misconduct to an audience of 600,000 people (Lindquist, interview Now. 2016). The filmmaker and his team had no academic or medical credentials, but consistently appealed to the medical logic − the fate of the patients, in Sweden and in Russia. By asking basic questions, such as “Did you do any rat experiments before the human surgeries, and if so, can I have a look at the records?”, the image of a miraculous new transplantation surgery was deconstructed and Macchiarini and several of his supporters were forced to resign. The outcome demonstrates the power of the medical logic if professionally personalized by mainstream media actors, although the deeper organizational impact was limited. The role of such non-academic actors as ethics watchdogs remains to be acknowledged. When, for example, the Swedish commission on academic misconduct management released its report in 2017, the role of unofficial or non-academic actors in the extended institutional field was not mentioned at any of its 297 pages (SOU, 2017). 6. Discussion: beyond Karolinska and academia The Karolinska case exemplifies the power of institutional actors to support dubious operators with a gift for international marketing and rapid publishing and to protect them in contexts of mounting external criticism. The analysis also illustrates how a coalition of whistleblowers inspired by a medical logic, and supported by a scientist at another university, science blogs and established media actors may undo such protections, if the misconduct can be captured as an emotive drama with human suffering. Is the case of Macchiarini and KI unique? It is illustrative to compare Karolinska with a case at Duke University (hereinafter Duke)4 in the United States, where another “star researcher” announced a breakthrough method (Oransky and Marcus, 2016): the use of genomic signatures to select cancer patients who would benefit from chemotherapy. The new method was hailed as “a very, very exciting tool” (Barbash, 2015) in the fight against cancer when it was presented in 2006. The findings were published by the lead researcher, Anil Potti and his co-authors in Nature Medicine and other leading journals. Eager 4 We thank an engaged reviewer for highlighting the similarities with the case of Anil Potti and Duke University.

9

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

of managing research integrity. Scholars and policymakers searching for remedies to misconduct may need to study different national regulations and their effectiveness in exposing and penalizing unethical behavior. In addition, it could be productive to study misconduct management in other institutional fields, for example, international sports. Sports and academia are both intensely competitive, involve numerous actors and stakeholders, and affect national and organizational branding, pride, and prestige. Both offer large rewards for high performance and depend heavily on international recognition. Both have experienced profound changes in professional norms, from amateur ideals to full-time workers in sports, from scholars to entrepreneurs focused on quantifiable performance in academia (Honig et al., 2014), and both struggle with problems of individual and institutional misconduct (Yesalis and Bahrke, 2002). In contrast to academia, however, sports have built international institutions to detect and penalize also advanced forms of misconduct. This required the efforts of institutional entrepreneurs to change the rules of the game and the logic of the competition (Battilana et al., 2009). Under the leadership of the previous athlete Arne Ljungqvist, later vice president at Karolinska, sports bodies in Sweden started to develop anti-doping policies, but confronted problems when athletes met drug-using competitors in international tournaments (Lager, 2011). After several scandals, including the exposure of a doping system of industrial proportions during the Tour De France in the 1990s (Dimeo, 2014), governments and sporting bodies came together in 1999 to form WADA, the World Anti-Doping Association, an independent body not controlled by any sporting organization or government (Hanstad et al., 2008). WADA, where Ljungqvist was elected vice president, developed an International Anti-Doping Code that was ratified worldwide. WADA has also assumed responsibility for accrediting testing laboratories and to operate an international facility for storing all test samples, which is of indispensable value when previous tests need to be re-analyzed with more advanced methods. Thus, WADA can be viewed as an exemplar of international institution-building in the support of fairness for the common good of the entire field.

external actors, such as journal editors, science bloggers, investigative journalists and documentary filmmakers. It illustrates the power of a market-oriented logic focused on brand and image at a leading research institute and at leading journals, but also emphasizes the perseverance of other logics, the logics of academic scrutiny and medical care, even when the carriers of these logics are weakly organized in relation to the carriers of the market-oriented logic. The game-changing interventions of non-academic actors in the studied case underlines the importance of considering the institutional field of academia as an evolving and open system (cf. Green et al., 2008; Lawrence et al., 2002), where actors invisible in established arenas may be critical to support the subordinate logics. The Karolinska case may be exceptional in some respects, but the diffusion of a market-oriented, competitive logic within academia is not. Within the EU, for example, governments and intergovernmental organizations strongly promote university-industry collaboration and the concept of entrepreneurial university (see European Commission, 2007). This may raise their external output, but the question how these collaborations and concepts affect their medical and academic logics remains unresolved. The analysis in the paper is in line with studies of other forms of misconduct (Misangyi et al., 2008), which show that misconduct is seldom committed only by an individual or a single organization but must be understood in a wider context. This points to the relevance of comparing ethical problems and misconduct management in different institutional fields: science, sports, corporate fraud and corruption. Such comparative studies could inspire ideas and efforts to develop new and innovative approaches, including international capacity building, and through that affect institutional field within academia more effectively than existing remedies.

7. Conclusion and suggestions for future research

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declarations of interest None. Funding

This study contributes to the research on misconduct management in several ways. The literature on institutional logics emphasizes that logics are multiple and points to the interplay between actors at different levels − individuals, organizations and macro-level institutions (Thornton and Ocasio, 2008). Nevertheless, existing studies of scientific misconduct tend to focus either on personal traits (Antes et al., 2007) and individual calculations or on socialization processes and management systems in specific organizations (Henrich et al., 2001). To our knowledge, this paper is one of the first to analyze academic misconduct and interpret actor behavior using the concepts of institutional fields and competing logics. The analysis illustrates the value of studying the variety of actors in the extended institutional field, from intra-organizational actors such as executives, research leaders, co-authors and practitioners (in this case care-responsible doctors) to

Acknowledgements We thank Mattias Corbascio, Oskar Simonsson, Harriet Wallberg at KI, Bosse Lindquist, Johan Brånstad at SVT, Arne Ljungqvist, Ugur Erdener at WADA, Bengt Gerdin at Uppsala University, and Pierre Delaere at KU Leuven University for sharing their knowledge and documents with us. We are grateful for incisive comments from many colleagues, in particular, Fredrik Tell at Uppsala University, Lars Lindkvist, Ksenia Onufrey at Linköping University, Jan Löwstedt at Stockholm University, Ben Martin at University of Sussex, Şükrü Özen at Izmir University of Economics, Lauri Wessel at Freie UniversitätBerlin and four constructive anonymous reviewers, as well as the editors Martin Kenney and Mario Biagioli.

10

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

Appendix A

Table A1 A detailed timeline of the case misconduct history.*

(continued on next page)

11

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

Table A1 (continued)

(continued on next page)

12

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

Table A1 (continued)

* Color code: The green lines are activities that support and sustain PM and his misconduct.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) ** PM did several types of transplantations. This timeline only includes those who received synthetic tracheas. 1 President 1 (Harriet Wallberg, 2004 − 2012). 2 President 2 (Anders Hamsten, 2013 − Feb 13, 2016). 3 Abbreviations: KI = Karolinska Institute, KS = Karolinska Hospital, Kuban Medical University = KMU, PM = Paolo Macchiarini, CEPN = Central Ethical Review Board of Sweden.

Table A2 The seven Macchiarini papers subjected to external reviews after publication. Paper 1. Jungebluth P., Alici E, Baiguera S., Le Blanc K., Blomberg P., Bozóky B, Crowley C., Einarsson O., Grinnemo K., Gudbjartsson T., Le Guyader S., Henriksson G., Hermanson O., Juto J.E., Leidner B., Lilja T., Liska J., Luedde T., Lundin V., Moll G., Nilsson B., Roderburg Christoph, Strömblad S, Sutlu T., Teixeira A. I., Watz E., Seifalian A., and Macchiarini P. 2011. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-ofconcept study. The Lancet, 378(9808), 1997–2004. Paper 2. Badylak, S.F., Weiss, D.J., Caplan, A. and Macchiarini, P., 2012. Engineered whole organs and complex tissues. The Lancet, 379(9819), 943–952. Paper 3. Jungebluth, P., Haag, J.C., Lim, M.L., Lemon, G., Sjöqvist, S., Gustafsson, Y., Ajalloueian, F., Gilevich, I., Simonson, O.E., Grinnemo, K.H. and Corbascio, M., Baiguera S., Del Gaudio c. Strömblad S. and Macchiarini P. 2013. Verification of cell viability in bioengineered tissues and organs before clinical transplantation. Biomaterials, 34(16), pp.4057–4067. Paper 4. Del Gaudio, C., Baiguera, S., Ajalloueian, F., Bianco, A., and Macchiarini, P. (2014). Are synthetic scaffolds suitable for the development of clinical tissueengineered tubular organs?. Journal of Biomedical Materials Research Part A, 102(7), 2427–2447.] Paper 5. Jungebluth, P., and Macchiarini, P. 2014. Airway transplantation. Thoracic Surgery Clinics, 24(1), 97–106. Paper 6. Ajalloueian, F., Lim, M.L., Lemon, G., Haag, J.C., Gustafsson, Y., Sjöqvist, S., Beltrán-Rodríguez, A., Del Gaudio, C., Baiguera, S., Bianco, A. and Jungebluth, P., Macchiarini P. 2014. Biomechanical and biocompatibility characteristics of electrospun polymeric tracheal scaffolds. Biomaterials, 35(20), 5307–5315. Paper 7. Sjöqvist, S., Jungebluth P., Lim M. L., Haag J. C., Gustafsson Y., Lemon G., Baiguera S., Burguillos M. A., Del Gaudio C., Rodríguez A. B., Sotnichenko A., Kublickiene K., Ullman H., Kielstein H., Damberg P., Bianco A., Heuchel R., Zhao Y., Ribatti D., Ibarra C., Joseph, B., Taylor D. and Macchiarini P. 2014. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. Nature communications, 5. Article number: 4562 (RETRACTED in the 14 Oct 2016).

Note: All papers related to Paolo Macchiarini in this study feature him as the lead author [since according to the medical research tradition the last author is the lead author].

13

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

Appendix B. Supplementary data Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.respol.2018.03.020.

Ciralsky, A., 2016. The celebrity surgeon who used love, money, and the pope to scam an NBC news producer. Online news on Vanity Fair (downloaded on 25 September 2016 from https://www. vanityfair.com/news/2016/01/celebrity-surgeon-nbc-newsproducer-scam). Claesson-Welsh, L., Hansson, G., 2016. Correspondence: tracheobronchial transplantation: The Royal Swedish Academy of Sciences’ concerns. Lancet 387 (10022), 942. Corbascio, M., Fux, T., Grinnemo, K-H., Simonson, O., 2014a. Formal Appeal for an Investigation of Scientific Misconduct. Report submitted to KI Registrator (18 August 2014). Stockholm. Corbascio, M., Fux, T., Grinnemo, K-H., Simonson, O., 2014b. Analysis of Clinical Outcome of Synthetic Tracheal Transplantation Compared to Results Published in 6 Articles by Macchiarini, et al. Report submitted to KI Registrator (August 2014). Stockholm. Corbascio, M., Fux, T., Grinnemo, K-H., Simonson, O., 2014c. Amendment to the formal appeal for an investigation. Report Submitted to KI Registrator (24 September 2014). Stockholm. Corbascio, M., Fux, T., Grinnemo, K-H., Simonson, O., 2015. Allegations of Scientific Misconduct against Professor Paolo Macchiarini, Comment to Prof Paolo Macchiarini’s answers. Report submitted to KI Registrator (Re: 2-2184/2014). Stockholm. Davis, G.F., 2014. Why do we still have journals? Adm. Sci. Q. 59, 193–201. Del Gaudio, C., Baiguera, S., Ajalloueian, F., Bianco, A., Macchiarini, P., 2014. Are synthetic scaffolds suitable for the development of clinical tissue-engineered tubular organs? J. Biomed. Mater. Res. A 102 (7), 2427–2447. Delaere, P., 2013. Mails to Richard Horton, The Lancet, regarding the need to debate the problems of trachea transplantation (between 16 July and 6 September 2013). Leuven. DiMaggio, P.J., 1988. Interest and agency in institutional theory. In: Zucker, L.G. (Ed.), Institutional Patterns and Organizations: Culture and Environment. Ballinger, Cambridge, MA, pp. 3–21. Dimeo, P., 2014. Why Lance Armstrong? Historical context and key turning points in the ‘Cleaning up’ of professional cycling. Int. J. Hist. Sport 31 (8), 951–968. Duarte, P.O., Alves, H.B., Raposo, M.B., 2010. Understanding university image: a structural equation model approach. Int. Rev. Public Nonprofit Market. 7 (1), 21–36. Dunn, M.B., Jones, C., 2010. Institutional logics and institutional pluralism: the contestation of care and science logics in medical education, 1967–2005. Adm. Sci. Q. 55 (1), 114–149. Editorial, 2015. Paolo Macchiarini is not guilty of scientific misconduct. Lancet 386 (9997), 932. Ekblad, E., 2016. The Review of alleged misconduct in the paper Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats by Sjöqvist, Macchiarini et al., 2014 The review report by the second external reviewer(granskning i ärendet O1-2016). Lund. European Commission, 2007. Improving Knowledge Transfer Between Research Institutions and Industry Across Europe: Embracing Open Innovation (EUR 22836 EN). European Communities’ Publications, Luxembourg. Fang, F.C., Casadevall, A., 2011. Retracted science and the retraction index. Infect. Immun. 79 (10), 3855–3859. Ferrie, H., 2006. Medical Research Fraud. Online news on Vitality Magazine (downloaded on 27 August 2017 from http://vitalitymagazine.com/print/medical-researchfraud/). Flick, U., 2014. Mapping the field. In: Flick, U. (Ed.), The SAGE Handbook of Qualitative Data Analysis. Sage Publications, London, pp. 3–18. Fountain, H., 2013. Groundbreaking Surgery for girl born without windpipe. Online news on New York Times, downloaded on 15 September 2016 from http://www.nytimes. com/2013/04/30/science/groundbreaking-surgery-for-girl-born-without-windpipe. html). Fountain, H., 2014. Leading Surgeon Is Accused of Misconduct in Experimental Transplant Operations. Online news on New York Times (downloaded on 15 September 2016 from https://www.nytimes.com/2014/11/25/world/leadingsurgeon-is-accused-of-misconduct-in-experimental-transplant-operations.html). Gabbioneta, C., Greenwood, R., Mazzola, P., Minoja, M., 2013. The influence of the institutional context on corporate illegality Accounting. Organizations and Society 38 (6), 484–504. Gerdin, B., 2015a. Statement of opinion on assignment ref. 2–2184/2014 − investigation of scientific misconduct, Report submitted to KI Registrator. Stockholm. Gerdin, B., 2015b. Correspondence with President Anders Hamsten regarding the response of Macchiarini et al. to the allegations of misconduct. Uppsala. Giese, W., 2012. Supercells: The first artificial organ made out of stem cells, k22 Film, Entertainment. Mainz. Gonfiotti, A., Jaus, M.O., Barale, D., Baiguera, S., Polizzi, L., Jungebluth, P., Paoletti, M., Pistolesi, M., Macchiarini, P., 2012. RETRACTED: Development and validation of a new outcome score in subglottic stenosis. Ann. Thoracic Surg. 94 (4), 1065–1072. Gonfiotti, A., Jaus, M.O., Barale, D., Baiguera, S., Comin, C., Lavorini, F., Fontana, G.,

References Åstrand, Y., Frisk J., 2015. Interview materials of Macchiarini: Star surgeon: at any cost. SVT.se’s interview materials (downloaded on 20 September 2016 from https://www. svt.se/nyheter/granskning/ug/referens/ug-referens-stjarnkirurg-till-varje-pris). Åstrand, Y., 2017. Macchiarini’s last patient died (in Swedish: Macchiarinis sista struppatient död). News at SVT.se (downloaded on 20 March 2017 from https://www.svt. se/nyheter/lokalt/stockholm/struppatient-dod). Åstrand, Y., 2017. My daughter was Macchiarini’s guinea pig (in Swedish: Min dotter var Macchiarinis försökskanin). News at SVT.se (downloaded on 2 March 2017 from https://www.svt.se/nyheter/lokalt/stockholm/min-dotter-var-macchiarinisforsokskanin). Özen, Ş., Akkemik, K.A., 2012. Does illegitimate corporate behaviour follow the forms of polity? The Turkish experience. J. Manage. Stud. 49 (3), 515–537. Adams, D., Pimple, K.D., 2005. Research misconduct and crime lessons from criminal science on preventing misconduct and promoting integrity. Account. Res. 12 (3), 225–240. Ajalloueian, F., Lim, M.L., Lemon, G., Haag, J.C., Gustafsson, Y., Sjöqvist, S., BeltránRodríguez, A., Del Gaudio, C., Baiguera, S., Bianco, A., Jungebluth, P., Macchiarini, P., 2014. Biomechanical and biocompatibility characteristics of electrospun polymeric tracheal scaffolds. Biomaterials 35 (20), 5307–5315. Anderman, E.M., Murdock, T.B., 2011. Psychology of Academic Cheating. Academic Press, Burligton, MA. Anderson, M.S., Ronning, E.A., De Vries, R., Martinson, B.C., 2007. The perverse effects of competition on scientists’ work and relationships. Sci. Eng. Ethics 13 (4), 437–461. Anderson, M.S., Ronning, E.A., De Vries, R., Martinson, B.C., 2010. Extending the mertonian norms: scientists' subscription to norms of research. J. Higher Edu. 81 (3), 366–393. Antes, A.L., Brown, R.P., Murphy, S.T., Waples, E.P., Mumford, M.D., Connelly, S., Devenport, L.D., 2007. Personality and ethical decision-making in research: the role of perceptions of self and others. J. Empirical Res. Hum. Res. Ethics 2 (4), 15–34. Asplund, K., 2016. The Case of Macchiarini (in Swedish: Fallet Macchiarini. Utredning av verksamheten med transplantationer av syntetiska luftstrupar vid Karolinska Universitetssjukhuset). The public investigation report (2016-08-31), Stockholm. Bäsen, A., Carlsson, T., 2016. The patients are sacrificed, the leaders are rewarded (in Swedish: Patienterna Offrades, Ledningen Belönades). Online news on Expressen Daily (downloaded on 10 December 2016 from https://www.expressen.se/nyheter/ patienterna-offrades-ledningen-belonades-1/). Badylak, S., Weiss, D., Caplan, A., Macchiarini, P., 2012. Engineered whole organs and complex tissues. Lancet 379 (9819), 943–952. Baggerly, K.A., Coombes, K.R., Neeley, E.S., 2008. Run batch effects potentially compromise the usefulness of genomic signatures for ovarian cancer. J. Clin. Oncol. 26 (7), 1186–1187. Barbash, F., 2015. Scientist falsified data for cancer research once described as ‘holy grail, ’ feds say. Online news on Washington Post Daily (downloaded on 25 July 2017 from https://www.washingtonpost.com/news/morning-mix/wp/2015/11/09/scientistfalsified-data-for-cancer-research-once-described-as-holy-grail-feds-say/?utm_ term=.6e1035a16db0). Battilana, J., Leca, B., Boxenbaum, E., 2009. How actors change institutions: towards a theory of institutional entrepreneurship. Acad. Manage. Ann. 3 (1), 65–107. Becker, L.B., English, C., Vlad, T., Han, J.Y., 2013. What kind of a dog is that? Examining the relationship between public assessments of media and of other institutions. Paper presented to the Midwest Association for Public Opinion Research (downloaded on 25 September 2016 from http://www.grady.uga.edu/coxcenter/Conference_Papers/ Public_TCs/Becker_English_Vlad_Han_MAPOR_11_11_2013.pdf). Bedeian, A.G., 2003. The manuscript review process: the proper roles of authors, referees, and editors. J. Manage. Inquiry 12 (4), 331–338. Bik, E.M., Casadevall, A., Fang, F.C., 2016. The prevalence of inappropriate image duplication in biomedical research publications. MBio 7 (3 p), pe00809–16. Björck, P., Ganten, D., 2017. Report on potential research misconduct regarding six publications with Dr. Paolo Machiarini as the senior or corresponding author. External Review 3 Report submitted to CEPN on June 16, 2017. Bouter, L.M., 2015. Commentary: perverse incentives or rotten apples? Account. Res. 22 (3), 148–161. Broad, W., Wade, N., 1982. Betrayers of the Truth. Fraud and Deceit in the Hall of Science. Simon and Schuster, New York. COPE, 2016. Cooperation between research institutions and journals on research integrity cases. A guidance from the Committee on Publication Ethics (downloaded on 17 November 2016 from http://publicationethics.org/resources/guidelines-new/ cooperation-between-research-institutions-and-journals-research-integrity). COPE, 2017. COPE sanctions policy. The Committee on Publication Ethics’ policy document (downloaded on 13 March 2018 from https://publicationethics.org/files/ COPE_SanctionsPolicy.pdf).

14

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag Sibila, O., Rombolà, G., Jungebluth, P., Macchiarini, P., 2014. The first tissue-engineered airway transplantation: 5-year follow-up results. Lancet 383 (9913), 238–244. Goodrick, E., Reay, T., 2011. Constellations of institutional logics: changes in the professional work of pharmacists. Work Occup. 38 (3), 372–416. Green Jr., S.E., Babb, M., Alpaslan, C.M., 2008. Institutional field dynamics and the competition between institutional logics: the role of rhetoric in the evolving control of the modern corporation. Manage. Commun. Q. 22 (1), 40–73. Grieneisen, M.L., Zhang, M., 2012. A comprehensive survey of retracted articles from the scholarly literature. PLoS One 7 (10), pe44118. Hörnlund, A., 2016. Clarification regarding ethical review of Paolo Macchiarini's research. Lancet 387 (10030), 1816. Hanstad, D.V., Smith, A., Waddington, I., 2008. The establishment of the World AntiDoping Agency: a study of the management of organizational change and unplanned outcomes. Int. Rev. Sociol. Sport 43 (3), 227–249. Haveman, H.A., Rao, H., 1997. Structuring a theory of moral sentiments: institutional and organizational coevolution in the early thrift industry. Am. J. Sociol. 102 (6), 1606–1651. Heckscher, S., Carlberg, I., Gahmberg, C., 2016. Karolinska Institute & The case of Macchiarini (in Swedish: Karolinska Institutet och Macchiarini-ärendet: En extern granskning). The External Review Report. Stockholm. Henrich, J., Boyd, R., Bowles, S., Camerer, C., Fehr, E., Gintis, H., McElreath, R., 2001. In search of homo economicus: behavioral experiments in 15 small-scale societies. Am. Econ. Rev. 91 (2), 73–78. Holmes, D., 2012. Paolo Macchiarini: crossing frontiers. Lancet 379 (9819), 886. Honig, B., Lampel, J., Siegel, D., Drnevich, P., 2014. Ethics in the production and dissemination of management research: institutional failure or individual fallibility? J. Manage. Stud. 51 (1), 118–142. Hoyles, C., 1992. Mathematics teaching and mathematics teachers: a meta-case study. Learn. Math. 12 (3), 32–44. Jotterand, F., 2005. The Hippocratic Oath and contemporary medicine: dialectic between past ideals and present reality? J. Med. Philos. 30 (1), 107–128. Jungebluth, P., Alici, E., Baiguera, S., Le Blanc, K., Blomberg, P., Bozóky, B., Crowley, C., Einarsson, O., Grinnemo, K., Gudbjartsson, T., Le Guyader, S., Henriksson, G., Hermanson, O., Juto, J.E., Leidner, B., Lilja, T., Liska, J., Luedde, T., Lundin, V., Moll, G., Nilsson, B., Roderburg Christoph Strömblad, S., Sutlu, T., Teixeira, A.I., Watz, E., Seifalian, A., Macchiarin, P., 2011. Tracheobronchial transplantation with a stemcell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 378, 1997–2004. Jungebluth, P., Haag, J.C., Lim, M.L., Lemon, G., Sjöqvist, S., Gustafsson, Y., Ajalloueian, F., Gilevich, I., Simonson, O.E., Grinnemo, K.H., Corbascio, M., Baiguera, S., Del Gaudio, C., Strömblad, S., Macchiarini, P., 2013. Verification of cell viability in bioengineered tissues and organs before clinical transplantation. Biomaterials 34 (16), 4057–4067. KI STÖD, 2016. Collection of Documents (Number: 2–2184/2014.). Karolinska Institute Registration Office, Stockholm. Kalleberg, R., 2007. Robert K. Merton: A modern sociological classic. J. Classical Sociol. 7, 131–136. Karabag, S.F., Berggren, C., 2013. Back to the Merton Ideals? Corporate Fraud, Scientific Dishonesty, and the Need to Reform Academic Institutions and Identity. Paper presented at DRUID. Barcelona, June 17–19. Karabag, S.F., Berggren, C., 2016. Misconduct, marginality and editorial practices in management, business and economics journals. PLoS One 11 (7), e0159492. Karolinska, 2011. First successful transplantation of a synthetic tissue engineered windpipe. KI Press Release (accessed on 15 September 2016 on https://ki.se/en/news/ first-successful-transplantation-of-a-synthetic-tissue-engineered-windpipe). Kim, J., Park, K., 2013. Ethical modernization: research misconduct and research ethics reforms in Korea following the Hwang affair. Sci. Eng. Ethics 19 (2), 355–380. Kodeih, F., Greenwood, R., 2014. Responding to institutional complexity: the role of identity. Organ. Stud. 35 (1), 7–39. Kolata, G., 2011. How Bright Promise in Cancer Testing Fell Apart. The New York Times (July 7). Lager, G., 2011. The Doping Hunter: Arne Ljungqvist (in Swedish: Dopingjagaren: Arne Ljungqvist). Stockholm Ersatz. Lander, B., 2016. Boundary-spanning in academic healthcare organisations. Res. Policy 45, 1524–1533. Lawrence, T.B., Hardy, C., Phillips, N., 2002. Institutional effects of interorganizational collaboration: the emergence of proto-institutions. Acad. Manage. J. 45 (1), 281–290. Leblebici, H., Salancik, G.R., Copay, A., King, T., 1991. Institutional change and the transformation of interorganizational fields: an organizational history of the US radio broadcasting industry. Adm. Sci. Q. 36 (3), 333–363. Levelt, Noort, Drenth Committees 2012. Flawed science. The fraudulent research practices of social psychologist Diedrik Stapel. Netherlands, 28 November 2012. Lynöe, N., 2013. Response to the request recommendation/advice concerning the retraction the PM’s retracted paper by Karolinska Institute President, KI Ethics Council. 13 February 2013 (registration number: KI 8081/12-609). Lynöe, N., 2015. Response to a letter from Pierre Delaere. Karolinska Institute, KI Ethics Council. March 6. Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, M.A., Rees, L.E., Cogan, T.A., Dodson, A., Martorell, J., Bellini, S., Parnigotto, P.P., Dickinson, S.C., 2008. Clinical transplantation of a tissue-engineered airway. Lancet 372 (9655), 2023–2030.

Macdonald, S., Kam, J., 2011. The skewed few: people and papers of quality in management studies. Organization 18, 467–475. Marusic, A., Katavic, V., Marusic, M., 2007. Role of editors and journals in detecting and preventing scientific misconduct: strengths, weaknesses, opportunities, and threats. Med. Law 26 (3), 545–566. Merton, R.K., 1973. The Sociology of Science: Theoretical and Empirical Investigations. Press, Chicago and London: The University of Chicago. Miles, S.H., 2004. The Hippocratic Oath and the Ethics of Medicine. Oxford University Press, Oxford. Miller, F.A., French, M., 2016. Organizing the entrepreneurial hospital: hybridizing the logics of healthcare and innovation. Res. Policy 45 (8), 1534–1544. Misangyi, V., Weaver, G., Elms, H., 2008. Ending Corruption: the interplay among institutional logics, resources and institutional entrepreneurs. Acad. Manage. Rev. 33 (3), 750–770. Mitroff, I.I., 1974. Norms and counter-norms in a select group of Apollo moon scientists: a case study of the ambivalence of scientists. Am. Sociol. Rev. 39 (4), 579–595. Moisse, K., 2013. Girl Dies After Groundbreaking Trachea Transplant. ABCNews (8 July 2013). Muijres, K., 2013. Fraud: comparison among different fraudsters and their techniques. Social Cosmos 4 (1), 64–70. Mulcahy, N., 2015. Huge cancer research fraud, but only one doc blamed. Medscape (November (17)). Murray, D., Dollery, B., 2006. Institutional breakdown? An exploratory taxonomy of Australian university failure. Higher Educ. Policy 19 (4), 479–494. Nagy, J., Robb, A., 2008. Can universities be good corporate citizens? Crit. Perspect. Acc. 19, 1414–1430. Necker, S., 2014. Scientific misbehavior in economics. Res. Policy 43 (10), 1747–1759. ORI, 2015. Case Summary. Potti, Anil. https://ori.hhs.gov/content/case-summary-pottianil. Oransky, I., Marcus, A., 2016. When Universities Stonewall Investigations of Research Misconduct. https://www.statnews.com/2016/04/05/universities-researchmisconduct/. Park, A., 2012. Top 10 Medical breakthroughs. Time.com http://healthland.time.com/ 2012/12/04/top-10-health-lists/slide/lab-grown-body-parts/. Peruzzi, B., 2012. World-leading surgeon from Karolinska arrested for fraud in Italy (in Swedish: Världsledande kirurg från Karolinska gripen för bedrägeri i Italien). News On Aftonbladet Daily (downloaded on 30 November 2016 from http://www. aftonbladet.se/nyheter/article15522294.ab). PubPeer, 2017. Search result of keyword Macchiarini word. (search conducted on 26 September 2017 on https://pubpeer.com/search?q=macchiarini). Reahy, T., Hinings, C.R., 2009. Managing the rivalry of competing institutional logics. Organ. Stud. 30 (6), 629–652. Retraction Watch 2017a. It’s official: When journals behave badly, there could be some punishment. Blogpost by Retraction Watch (downloaded on 6 March 2018 from https://retractionwatch.com/2017/12/19/official-journals-behave-badlypunishment/). Retraction Watch 2017b. Make reviews public, says peer review expert. Blogpost by Retraction Watch (downloaded on 6 March 2016 from http://retractionwatch.com/ 2017/11/27/make-reviews-public-says-peer-review-expert/). Richardson, A., 2004. Robert K. Merton and philosophy of science. Soc. Stud. Sci. 34, 855–858. Rick, S., Loewenstein, G., Monterosso, J.R., Langleben, D.D., Mazar, N., Amir, O., Ariely, D., 2008. Commentaries and rejoinder to the dishonesty of honest people. J. Market. Res. 45 (6), 645–653. Risberg, B., 2016. Karolinska is the Chernobyl of ethics (in Swedish: Karolinska −Etikens Tjernobyl). Läkartidningen 5, Jan. 29. SOU, 2017. New order for promoting good practices and dealing with misconduct in research (in Swedish: Ny ordning för att främja god sed och hantera oredlighet i forskning), SOU 2017:10. Samuelsson, M.L., 2017. Misstänkt korruption bakom KI-etablering i Hongkong. Online article on Universitetsläraren (downloaded on 13 September 2017 from https:// universitetslararen.se/2017/08/31/misstankt-korruption-bakom-ki-etablering-ihongkong/). Seifalian, A., 2013. Future of organ development, TEDMED live talk at Imperial College (downloaded on 18 September 2016 from https://www.youtube.com/watch?v= DR4D24bDPaQ). Sjöqvist, S., Jungebluth, P., Lim, M.L., Haag, J.C., Gustafsson, Y., Lemon, G., Baiguera, S., Burguillos, M.A., Del Gaudio, C., Rodríguez, A.B., Sotnichenko, A., Kublickiene, K., Ullman, H., Kielstein, H., Damberg, P., Bianco, A., Heuchel, R., Zhao, Y., Ribatti, D., Ibarra, C., Joseph, B., Taylor, D., Macchiarini, P., 2014. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. Nat. Commun. 5. The Lancet Editors, 2016. Expression of concern—Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 387 (10026), 1359. The Lancet, 2016. Swift+: We publish randomised controlled trials (RCTs) faster, The Lancet journal information (downloaded on 16 December 2016 from http://www. thelancet.com/lancet/information-for-authors/fast-track). Thornton, P.H., Ocasio, W., 1999. Institutional logics and the historical contingency of power in organizations: executive succession in the higher education publishing industry, 1958–1990. Am. J. Sociol. 105 (3), 801–843. Thornton, P.H., Ocasio, W., 2008. Institutional logics. In: Greenwood, R., Oliver, C.,

15

Research Policy xxx (xxxx) xxx–xxx

C. Berggren, S.F. Karabag

wake-macchiarini-scandal). Wahlström, J., 2016. The forgotten patient (in Swedish: Den bortglömda patienten). Article on Filter (downloaded on 27 August 2016 from https://magasinetfilter.se/ granskning/den-bortglomda-patienten/). Wallberg, H., 2017. Objections to the public investigation of Karolinska Institute by Heckscher et al., 2016 (in Swedish: Invändningar mot Rapporten Karolinska Institute och Macchiarini-ärendet- en extern granskning, September 2014, submitted to Justice Ombudsman (jo.se) on January 16 2017. Webometrics, 2012. Number of universities and HEIs. University ranking list (downloaded on 12 December 2016 from http://www.webometrics.info/en/node/24). Yesalis, C.E., Bahrke, M.S., 2002. History of doping in sport. Int. Sports Stud. 24 (1), 42–76.

Suddaby, R., Sahlin-Andersson, K. (Eds.), The Sage Handbook of Organizational Institutionalism. SAGE, London, pp. 99–129. topuniversities.com, 2017. QS World University Rankings by Subject 2016–Medicine, (downloaded on 15 August 2016 from https://www.topuniversities.com/universityrankings/university-subject-rankings/2016/medicine#sorting=rank+region= +country=+faculty=+stars=false+search). Vezina, K, 2011. First Synthetic Organ Transplant Used to Treat Cancer Patient. MIT Technology Review (downloaded on 6 March 2018 from https://www. technologyreview.com/s/424621/first-fully-synthetic-organ-transplant-saves-cancerpatient/). Vogel, G., 2016. Karolinska Institute vice-chancellor resigns in wake of Macchiarini scandal. Online news on Sciencemag (downloaded on 25 August 2016 from http:// www.sciencemag.org/news/2016/02/karolinska-institute-vice-chancellor-resigns-

16