The UCL Special Inquiry into Regenerative Medicine Research

University College London (UCL) has published the findings of a Special Inquiry into Regenerative Medicine Research, a lengthy document that seeks to understand the role of one of the UKs foremost research institutions in the rise and subsequent fall of Paolo Macchiarini. By way of brief background, Macchiarini was considered to be a leading researcher and pioneering surgeon in the field of regenerative medicine for tracheal and airway "tissue engineering" until a series of troubling revelations - associated with several tragic deaths - culminated in his public exposure in 2016.  Many aspects of the story, especially the role and personality of Macchiarini himself, have been covered by the media (including social media), and it is clearly a complex scenario. Macchiarini could not though have achieved his notoriety alone, indeed he became an internationally respected figure in the wider tissue engineering community, and the UCL report provides a substantial insight into how senior academics and hospital clinicians became associated with him personally and professionally.  The report is especially compelling as it has been written by some of the UK's leading academics and clinicians with an international reputation for excellence and probity including in the broad field of tissue engineering and regenerative medicine (TERM), and who have had access to at least some key documents and people. This makes it a more reliable document than some previous media reports, as well as essential reading for all researchers in the TERM field (as well as bioethicists, lawyers, and clinicians more generally). Inevitably though while resolving a number of issues, it also raises questions where more information is needed, and perhaps some of these unanswered questions could only be resolved in a legally empowered inquiry. Before considering these though, it is important to bear in mind the following:

• TERM is a broad field that is largely concerned with the development of therapies that promote the successful healing of human tissues in situations where this would not otherwise occur naturally.  While more research is needed, it is a field that offers potential solutions where current clinical interventions are either limited or do not exist.  Many thousands of scientists, engineers and clinicians are engaged in sound and responsible research all over the world (including at UCL), and in parallel other experts including regulators and industries are working equally hard to reduce risks while bringing benefits to patients.  The Macchiarini story is not a reason to curtail this activity, but it is essential that it informs practice, especially proper governance in responsible translation to the clinic.
• The clinical cases covered by this inquiry involved sometimes subtly different interventions, and this diversity is greater when considering all of the surgical procedures where Macchiarini was involved outside of the UK. When patients die, this is always a tragedy for them and the families left behind. Even if interventions were classed as palliative, this does not negate questions related to the governance of an experimental medical procedure and informed consent (questions that lay largely outside of the scope of this inquiry, but questions that should arguably be now addressed using a robust instrument).

While UCL's report on the special inquiry is both detailed and insightful, it also recognises the scale and complexity of investigating experimental clinical interventions involving more than one organisation (and therefore the limits to this type of investigation). The subject of the inquiry was the primarily the role of UCL staff in forming a relationship with Paulo Macchiarini (including the award of an honorary chair), and the role of the institution in a series of operations that sought to apply experimental TERM-like technologies in human tracheal/large airway surgery. In places the inquiry also considered interactions between academic and clinical staff, and aspects of local compliance with legal, regulatory and governance requirements.  In my experience of working in a mixed clinical-basic science environment, senior staff understand very clearly which organisation they work for (it is printed on their payslip), and also to whom they are responsible to when working (which could be an NHS Trust), irrespective of the honorary contracts they hold. In simple terms, if a clinician is treating a patient, they are responsible to the relevant NHS Trust irrespective of which organisation is printed on their personal payslip. Likewise it is the NHS organisation governance that applies when treating patients, irrespective whether the intervention is established or experimental.

Outside of the remit of this report lie a number of as yet unanswered questions. For example is the current legal, regulatory and ethical framework fit for purpose, and if "yes" then were established legal/governance processes and procedures accidentally or deliberately bypassed in some clinical cases covered by this inquiry (and indeed others around the world)? While my experiences suggest that our existing legal and regulatory framework is both robust and fit for purpose, this is a question that can only be addressed fully by a wider pool of experts (including in law, ethics and regulatory affairs). It is also a question that is arguably more pertinent to the hospitals concerned rather than their associated universities, and it seems therefore likely that this UCL report is only a first step towards gaining a better understanding of these events in the UK and beyond.