A Bioethicist’s Response to “When is a Brain Really Dead?”

Today’s post is a response by Dr. Bryan Pilkington to Dr. Stan Terlecky’s July 15, 2019 Terlecky’s Corner post entitled, “When is a Brain Really Dead?” Dr. Pilkington is an Associate Professor at Seton Hall University.

Last month’s Terlecky’s Corner post raises the question, “When is a brain really dead?” The reanimation – to borrow Terlecky’s phrase and his caution about its use – of porcine brains is both exciting and concerning. The excitement is due, as Terlecky notes well, to the possible benefits of such work: “potentially impacting several health scourges of our time including Alzheimer’s disease, Parkinson’s disease, and other age-related neurodegenerative disorders.”[1] He also notices that ethicists will be busy sorting through these and future studies, especially if the human brain gets involved.

Brain

This is how the usual dialectic goes when addressing ethical questions about emerging medical technologies. Undoubtedly, there will be lectures and papers from ethicists raising the usual kinds of questions, many titled with some version of, “We can, but should we?” These are not endeavors without merit; ethical analysis often lags behind research; in many cases, something has to be created in order to have something about which to raise questions. In fact, one of the important tasks of ethicists in this realm is to serve as watchdogs: to give caution, to aid researchers in thinking through possible concerns, and in some instances – at least with respect to IRB oversight – to say “no.”[2] However, though this is a useful and important role, it comes at a cost. Many times, those raising these kinds of concerns are termed “the ethics police”[3] and this image has hurt collaboration on research and made more challenging the necessary interprofessional tasks that medical research and healthcare practices are.

So what should be said in response to this kind of research? What are the answers to Terlecky’s list of ethical questions? The questions require longer answers than the space of a blog post admits, but I’ll take a shot at two sets of questions, suggesting a model for answering them and those remaining.

The first set comprises a list of real and immediate questions about one of the practical consequences of this research: organ donation. Will donation rates plummet? Will the organ shortage increase because there will be hold outs who think reanimation is possible? Will public trust diminish as this research moves forward?[4] Will families request that additional healthcare resources be spent on loved ones who meet the legal definition of brain death? An answer which avoids the problematic policing approach but takes seriously the importance of these questions is to engage in an extended conversation with researchers, ethicists, healthcare practitioners and administrators, and members of their communities about new technology, how it might be used, and its far-reaching implications. We must not shy away from these hard questions nor from recognizing the potential value of certain kinds of research, but we must also keep in mind the possible negative externalities that could result. This approach raises more questions. Should this research be halted if it damages public trust? Should it be stopped if fewer organs are donated? These questions lead to further questions. If the organ shortage is a primary concern, is it appropriate to connect it to this research? The conversation I am suggesting must consider that, as well. Some have argued that the sale of organs should be allowed and that this would alleviate the shortage[5], others have raised concerns about the commodification of human beings if such sale is legalized[6] – the breadth of the needed conversation is wide, as answers to questions about organ sale are connected to ethical concerns raised about porcine brain experimentation.

A second set of questions hover around the definition of death and the sources upon which we rely to answer those questions. Terlecky helpfully asks about the legal, ethical, and spiritual determinations of death. From where or in what do we root our conceptions of life, of human flourishing, and of death? Are they religious? Are they legalistic? Are they rooted in metaphysical conceptions of the person that we learned in our undergraduate philosophy courses? The kind of conversation I am suggesting is most effectively held when we bring the deep and rich traditions that inform our thought to bear on the subject matter under discussion. It is not a simple task to work through various traditions and try to understand how others think about reanimated porcine brains, human brains, and death, but that is what is needed. As physician and ethicist Lauris Kaldjian recently asked of his colleagues,[7] did you take a course about the existential questions in medical school? Though rhetorical, the suggestion is powerful. How should we respond to this research? In the same way we should respond to all research that raises significant ethical questions, by practically reasoning together.

 

References:

[1] Terlecky, S. 2019, July 15. “When is a Brain Really Dead?

[2] ​Evans, J. 2012. The History and Future of Bioethics: A Sociological Account. Oxford, United​ ​Kingdom: Oxford University Press.

[3] Klitzman, R. 2015. The Ethics Police? The Struggle to Make Human Research Safe. Oxford: Oxford University Press

[4] ​Moschella, M. 2018. Brain death and organ donation: A crisis of public trust. Christian Bioethics 24(2):133–50.

[5] ​Cherry, M. ​2005​. ​K​​idney for Sale by Owner: Human Organs, Transplantation, and the Market. Georgetown University Press.

[6] Pilkington, B. 2018. A Market in Human Flesh: Ramsey’s Argument on Organ Sale, 50 years later. Christian Bioethics 24(2):133–50.

[7] Kaldjian, L. (Personal communication during lecture in Grand Rapids, Michigan, March 25, 2019).

When is a Brain Really Dead?

When is a brain really dead? The answer to this question was made far more complicated by the recent work of Dr. Nenad Sestan and colleagues at Yale University. Their astonishing paper entitled “Restoration of brain circulation and cellular functions post-mortem,” appeared in the journal Nature[1] this April. In it, the authors were able to demonstrate that brains taken from slaughtered animals (pigs in this case), could be “reanimated” 4 hours later in the laboratory – and made at least partially functional for some 6 hours thereafter. I use the word reanimated with some trepidation – it implies the brains were dead and somehow brought back to life. That is not quite the story – rather, the organ turns out to be far more resilient than we previously realized and the research team simply identified a way to tap into that inherent resiliency.

A brief description of the research study: 32 brains from slaughtered pigs were delivered to the research team on ice. Within 4 hours, the scientists carefully perfused the brains using a proprietary surgical procedure, pumping apparatus, and oxygen and nutrient-rich solution collectively termed BrainEx. The team then analyzed the brains for specific cellular, metabolic, and electrical activities. What they found was incredible. The BrainEx perfusion system restored a number of brain functions, including glucose and O2 utilization and concomitant CO2 production (indicative of metabolic function), induced inflammatory responses (suggesting an active immune system), active microcirculation (evidence of structural integrity), and electrical activity (with neuronal firing).

Figure of porcine brain connected to perfusion system
Connection of the porcine brain to the perfusion system via arterial lines. The pulse generator (PG) transforms continuous flow to pulsatile perfusion. Source: Figure 1B, Nature 568, 336–343 (2019).

With respect to the last point, it should be noted the investigators were well aware of the ethical concern that full restoration of brain function could potentially lead to a state of “consciousness.” What it would mean for a disembodied brain to attempt to operate without peripheral sensory input, and what the organ might remember, was simply too much to consider; the brains were treated pharmacologically to assure no coordinated higher level cognitive activity was possible. Said another way, the renewed brains could not begin to think.

Overall, the results suggested to a first approximation, functional activity of the otherwise dead brain had been restored. Importantly from an experimental standpoint, control perfusates were without effect – the brains degenerated much like untreated specimens.

Against the backdrop of these remarkable results are the inevitable ethical questions that follow. Returning to the one posed above – when is a brain really dead? If our understanding of brain death requires a deeper examination, how then do we determine legally, ethically, and/or spiritually, when a person truly dies? What are the implications of this work on the issue of organ donations? Is a brain death as currently defined sufficient to permit the harvesting of a person’s organs? Will (and should) donations ebb as people begin to question the legitimacy of declarations of death. Also, could future brain reanimation experiments include restoration of conscious thought? Certainly the ability to control the brain in this manner permits the testing of drugs in new ways – potentially impacting several health scourges of our time including Alzheimer’s disease, Parkinson’s disease, and other age-related neurodegenerative disorders.

Naturally, science requires replication, expansion, and more careful delineation of what is, and is not possible with the technology described. But what enormous doors have been opened for neuroscientists, neurologists, neuropharmacologists, cognitive scientists, and the many others interested in the structure and function of the brain. I suspect ethicists will also be very busy sorting through these and the inevitable follow-up studies – especially as applications involving the human brain are contemplated.

SRT – July 2019

[1] Vrselja Z, et al., Nature 568, 336-343 (2019). PMID: 30996318