An interesting article was published recently in “The American Journal of Bioethics” (read HERE), that gives a brief history of the controversial trachea transplants performed by Paolo Macchiarini and his co-workers (see HERE) our previous news about the case).

Macchiarini’s synthetic trachea transplants risks

In 2008, a team led by Paolo Macchiarini and Martin Birchall performed the first transplant of a tissue-engineered trachea in a human, in Barcelona (Spain). The case was published in The Lancet, and catapulted the two surgeons to medical stardom.

Two years later, Macchiarini was hired by the Karolinska Institute in Stockholm as a visiting professor, and as a consultant and surgeon at the Karolinska University Hospital. In March 2011, he was named director of a new research centre, the “Advanced Center of Translational Regenerative Medicine”. In June that same year, he performed the first transplant of a synthetic trachea repopulated with stem cells from the patient’s own bone marrow.

Between 2011 and 2014 he carried out two similar trachea transplants at the Karolinska, four at the Kuban Medical University in Krasnodar (Russia), and one in a two-year old girl at the Children’s Hospital in Illinois (USA). Of the eight transplanted patients, seven have since died, and the only survivor has had his synthetic trachea removed.

Evidence of possible medical malpractice in Macchiarini’s experiments emerged in 2011, and became more concrete over the following years. In 2012, a paper by Macchiarini was retracted for the first time, and in 2014, an institutional investigation for malpractice was launched. Investigations into Macchiarini’s medical conduct continued, and in 2016 he was dismissed from the Karolinska Institute; the Vice-Chancellor and the colleagues closest to the Italian researcher also resigned, even though Macchiarini’s work at the Karolinska University Hospital had terminated in 2013.

The experiments by Macchiarini and his colleagues undoubtedly raise extensive medical and ethical uncertainties. While it might be thought that the Karolinska Institute had pressured Macchiarini to conduct his research, there is no evidence of this; in fact, it seems that the Italian researcher enjoyed great freedom to act.

Patients who received a trachea transplant

When a potential candidate for transplantation was found, a young Icelandic man with a slow-growing tumor in his trachea, he was transferred to Karolinska and offered an innovative treatment, although his life was not at risk at that time.

The other two patients who received a trachea transplant were also not suffering from life-threatening ailments. Thus, it seems that, in these three cases, the urgency of treatment and the potential benefits were clearly exaggerated, which certainly suggests medical malpractice. Furthermore, the scientific bases and the potential risks of the synthetic trachea transplants were not discussed previously, so the medical responsibility rested solely with the surgical team.

Trachea transplant risks not informed to patients

Major information failures also occurred, especially as regards informed consent, since only five of the operated patients signed a consent form. Equally, in none of the three transplants performed was the surgery subjected to the approval of an Ethics committee, as “compassionate use” was invoked.

Windpipe transplant risks and ethical misconduct of researchers. In relation to all of the above, in 2018 the Karolinska Institute announced that it had found seven researchers related with the case responsible for ethical misconduct in the case of six articles published in scientific journals — with Macchiarini being one of the main authors of these articles — and requested their immediate retraction.

Another negative aspect of the work by Macchiarini and his colleagues was their failure to perform extensive preclinical studies, as they had only conducted some experiments in rodents, but had never evaluated synthetic trachea transplants risks in larger animals.

Medical and bioethica assessement

In our opinion, the experiments by Macchiarini and his colleagues are a clear example of how an innovative technique, which would mean clear prestige for those who implemented it, led Macchiarini and his team to carry out a non-experimentally-proven technique in clinical practice, in which the risks-benefits were not correctly evaluated, the essential informed consent was lacking, and it was applied in patients who, it seems, were not at serious risk of death. That is to say, it is a paradigmatic case of how the desire for research and medical notoriety prevailed over the most elemental ethical norms of good medical work.

Justo Aznar

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia