Negligence, recklessness, unnecessary suffering and death. The career of Paolo Macchiarini has it all in equal measure. Macchiarini was a doctor responsible for the first artificial trachea transplant in the world using stem cell therapy. However his reported success hid a much darker truth that led to the early death of ten of his patients. The survivors have been hospitalised since the surgery and faced serious complications. Expectations and hype surrounding stem cell therapy no doubt contributed to the tragic case but who is responsible and what lessons can we learn to prevent history from repeating itself?
Paolo Macchiarini, a thoracic surgeon, shot to fame in 2008 after completing his first artificial trachea transplant. The patient, Claudia Castillo, had parts of her tuberculosis damaged trachea replaced with tissue taken from a cadaver. Stem cells taken from the patient’s bone marrow were used to coat the donated trachea tissue after its own cells were stripped away in what was described as a medical breakthrough. In a report published by Macchiarini the patient was described as being in in good health. The truth is far less fortunate as following the experimental surgery Claudia has since lost her left lung and has had to receive stents. Stents are scaffolds inserted to support structures and in this case were inserted as the transplant was not successfully mimicking a healthy trachea.
From 2008 to 2015 Macchiarini has performed surgery on 17 patients. There is reason to believe he underwent surgery on several other patients who have been unaccounted for. Out of those recorded nine patients underwent a transplantation using parts of deceased donors trachea and eight using a synthetic trachea. Ten of these patients have been reported dead with all but one suffering from serious complications including brain damage from lack of oxygenation.
In a statement to Nature magazine by Macchiarini he attributed these deaths to anything but the implants. Some of the explanations given included excess alcohol consumption, injuries following an accident, pneumonia and respiratory failure. Is it possible that Macchiarini’s patients were merely extremely unlucky people or was the esteemed doctor hiding the truth? Evidence points to the latter.
In 2015 a complaint filed by doctors working at the Karolinska University Hospital (KUH) accused Macchiarini of fabricating evidence in published papers and downplaying side effects. KUH is the home of the Karolinska Institute (KI), a highly regarded research institution with a reputation for honesty and high quality work. Three of Macchiarini’s transplants were performed here and the doctors that filed the complaint had been responsible for the treatment of these patients. From their report it seems clear that Macchiarini was recklessly putting his patients at great risk by falsifying results that would ensure his continued funding and thus experimentation. Biopsies revealed that the implanted trachea had not sealed itself into the passageway properly and yet Macchiarini claimed in his paper that it acted like “an almost normal airway”.
Macchiarini abused his role responsibilities as a scientist which include not fabricating or falsifying data and following ethical guidelines. He failed to do both of these thus neglecting his moral responsibilities which no respectable scientist should do. In the complaint filed by his fellow doctors they exposed a gross breach of trust. Two of the three patients had no informed consent forms present in their medical records. This suggests they did not understand and hence did not agree to the potential risks of the study.
Informed consent entails that where potential harmful side effects exist they should be clearly communicated to the patient. If the patient understands and consents to the procedure it is ethical to then proceed. Macchiarini insisted that it was common knowledge his procedures were highly experimental and carried high risk and as such that patients were “abundantly aware of that going in”. What we have seen from this man so far however does not indicate we should be willing to trust his word in this matter.
A Swedish documentary on the issue aired in January of 2016 revealed that Macchiarini had misleadingly branded his transplant as medical care to the KUH. Patients going into the surgery would have much greater trust in the operation than they would if it had been correctly labelled as an experimental procedure. Along the same vein this allowed ethical considerations and risk assessments to be sidestepped due to false impressions of safety. Personally I would be much more likely to undertake a surgery I assumed had been tried and tested even if I wasn’t at immediate risk. And this is exactly what happened. Despite Macchiarini’s claims most patients would have survived without the surgery.
This is not the first time studies have been carried out unethically where participants have not understood or been informed of the risks they will be exposed to. An example of this occurring elsewhere is the Tuskegee study in which the African American men enrolled were not informed that they had syphilis. These men did not receive treatment and were instead used to document the progression of the disease. The Macchiarini case is similar in the way that ethics and human rights were violated. However in this case individuals were aware of the desired outcome but were misled as a result of hype and expectations.
The Karolinska Institute where three of Macchiarini’s transplants took place should also take some of the responsibility for what happened. The KUH is not the only hospital where such transplants took place however due to the KI’s prestigious reputation is under the most scrutiny. A cesspit of negligence has been uncovered by investigations fuelled by hospital whistle-blowers. The KI appointed Macchiarini despite negative references due to the expectations created around his promised miracle treatment. Even after human fatalities and suffering the KI renewed his contract in both 2013 and 2015 remaining wilfully ignorant to the clear risks associated with his work.
Despite numerous allegations of misconduct Macchiarini’s work was not just allowed to occur but was also pushed forward by the vice president of the institute. Indeed, risk assessments were avoided and the ethics board omitted in order to achieve progress at all costs. Anyone who spoke against Macchiarini had their career put in jeopardy. The reason for all of this is that Macchiarini promised innovation and breakthroughs in a field surrounded by hype. Similar expectations in the field of medical research has more often than not led to disappointment and damage to patients and reputations.
Stem cell research is no different. We hear much about what stem cell therapy has the potential to do, that it will one day be able to treat diseases such as diabetes for which there is no current cure. Unfortunately such expectations can lead to inappropriate investments and the misuse of resources. Hype produces excitement that can lead to corners being cut with potentially devastating effects as seen in the Macchiarini case. A celebrity will not be prosecuted for serious crimes in the same way as the average citizen due to their perceived importance. In much the same way failures in fields such as stem cell therapy will be ignored or covered up due to expectations surrounding their potential. How can we separate hype from realistic expectations?
It is vital that research institutes set in place strict guidelines that do not allow for the recruitment of individuals with dubious backgrounds. It is also important that those who stand in the way of progress by rightfully raising concerns are not treated like criminals and are allowed to voice their opinions. Fortunately the KI and its associated hospital have put new measures in place that address these issues. However, the KI is not the only facility that was involved. It is my belief that these places should also be held accountable for their role in the debacle and similarly reflect upon their mistakes and make serious changes. The world of research is a cut throat one but it doesn’t have to be. If we start making scientists more accountable for their actions and value human lives over innovation we could see a positive change in the research community. One that has the possibility to save lives.