Okay, so I have nothing to disclose, but I do have a disclaimer. My disclaimer is that I'm a medical doctor, I'm a neurologist, I'm a neurointensivist, and while I'm going to be discussing medical issues for the next few minutes, I'm also going to be discussing some legal and ethical issues, and I'm neither a legal scholar nor an ethicist, so I'm going to do my best to convey to you the thoughts and ideas of thought leaders in these areas, and what I did is at the end of the slide deck put a detailed reference list that includes not just medical literature, but also articles from the ethical literature, the legal literature, and some links to lectures by very prominent ethicists in case you want to find out more about this. So these are the learning objectives. We're going to go through the evolution of brain death in its historical context, and then appreciate the way brain death is viewed across different disciplines, and some of the very important differences that exist across disciplines. We'll talk about some of the challenges and controversies, the name of this session that brain death faces within these disciplines, and finally conclude with why this is so important, how vital a concept brain death is to our society. So this is the simple version of history that I learned when I was a fellow or maybe even a resident, and it starts in the 1950s when for the first time we gained technology that allowed us to sustain people with catastrophic brain injuries who before this time would inevitably die. And I think there are three major technologies that all contributed to this, and one was the artificial ventilator, the other was CPR, and the third was the defibrillator. And while it's commonplace for us to take care of patients with catastrophic brain injury, I want you to think back to this time, how novel that must have been that the person appeared to be still alive, yet had no brain function. Before this, uniformly, catastrophic brain injury was fatal. And so immediate concerns were raised, primarily by physicians, about our ability to sustain these people with catastrophic brain injury. The first was that for the first time ever, we were using medical technology for no apparent therapeutic gain. You know, before this, medical tools were employed to help people. Here, it wasn't really clear that we were helping people by sustaining their bodies when they really had no brain function. There were financial considerations that were raised for patients, their families, for hospitals, and the emotional burden it would put on patients and their families, having their loved one sort of exist in a hospital on a ventilator with no signs of brain function. And then finally, although this is an alien concept to us now, doctors were worried about being legally culpable of homicide if they were to take away the ventilator. You have to remember, this was before the Karen Ann Quinlan case, which was in 1976, that established the legal permissibility to withdraw life-sustaining therapy. So doctors were worried that if they took away the ventilator from these people, they might be charged with homicide. And this put them in a very difficult bind. And in the 1960s, organ transplantation became a reality, and it was immediately apparent that transplantation would be a lot more successful if circulation of the donors was intact. And it was really anti-rejection drugs that allowed this leap in transplantation technology. And it was actually azathioprine combined with prednisone in 1967 that allowed the first kidney transplant between two people who are not related to each other. And then in 1967, in South Africa, the first heart transplant was done, and the donor was in a coma. And people started to wonder, was this donor dead when the heart was removed, or was it removing the heart that killed the donor? And so because all of these issues were swirling, Henry Beecher, who was the chair of anesthesia at Mass General Hospital, convened an ad hoc committee at Harvard Medical School to address these issues, and they came up with the Harvard criteria. And these criteria were criteria for determining coma that was irreversible, and they suggested in their publication that irreversible coma might be a new criterion for death. And that was sort of the genesis of the concept of brain death. By the 1970s, individual states had different criteria for death. Many but not all states adopted laws that allowed physicians to declare death in patients who had a beating heart on a ventilator. And this led to the very peculiar situation which still exists today, where you could be dead in one state but alive in another state. And this heterogeneity was very suboptimal, so the U.S. President's Commission for the Study of Ethical Issues in Medicine and Biomedicine convened and endorsed the Harvard criteria as the criteria for determining irreversible coma. And it was this commission that was really instrumental in establishing the Uniform Determination of Death Act, which was passed in Congress in 1981. And what this act said, essentially, is that brain death is legally equivalent to death by circulatory criteria. And I've put up the text of the UDDA there. You've seen it in the last talk. And I want to point out the last sentence, that a determination of death must be made in accordance with accepted medical standards. And we'll come back to that. So the UDDA was adopted in some form by all 50 states. In 1995, the American Academy of Neurology published guidelines for the determination of brain death. But controversy was still swirling. It was there from the beginning. It never went away. So the President's Council on Bioethics convened and published a paper called Controversies in the Determination of Death that really reaffirmed the basis of brain death. And then in 2010, the American Academy of Neurology updated and reaffirmed their guidelines. And so I'll start out by saying that currently the majority of the medical, legal, and ethical communities support the idea that brain death is death. And this was sort of something drummed into me from the get-go throughout all of my training, that brain death equals death. And I think there's still a lot of confusion about that. And so now we'll get to the not-so-simple version and where a lot of the controversy comes from. So brain death equals death was controversial since its inception. And the language we use doesn't help. The very existence of the term brain death implies it's something other than plain death. Otherwise it would just be called death. And some of the language that we use is vague, like a function of the entire brain. I'm not sure exactly what that means. Does that include hormonal function, like pituitary function? And so those are all issues. But I'm not going to dwell on semantics. I think there are some more important issues. And really the two main points that I want to convey to you in this talk is that whether brain death equals death really depends on the perspective from which you're asking the question. You could ask this from a medical perspective, a legal perspective, a biological perspective, moral, ethical, and philosophical perspectives, sociological, cultural, and religious perspectives. And you might come out with different answers depending on which perspective you're asking from. And I think importantly, conflating these perspectives may be responsible in part for a lot of the controversy and confusion that still persists and probably has grown in recent years. What I'm going to posit to you in this talk, and we can discuss it later, is that whether brain death equals death, I think from a medical perspective, it's pretty clear that it does. However, there are significant challenges, some of which you've heard about. From a legal perspective, I think it's equally clear that brain death equals death. But here too, there are challenges. From a biological perspective, I think it's a lot less clear. And saying that brain death equals death, at least in a traditional sense, encounters a lot of challenges. And from moral, ethical, and philosophical perspectives, the answer is yes, no, and maybe. It's complicated. It really depends on the particular ethical stance that you're approaching this from. And we'll go through a little bit of this. So let's start out with a medical perspective. So brain death is equivalent to death from a medical perspective. In my mind, this is pretty clear. Why? Because standards in medicine are set by authoritative medical bodies. They're often codified in guidelines based on evidence, or when there's no evidence, an expert opinion. There's a medically agreed upon state that constitutes brain death. There's general agreement that it is death. And there are standards for its determination. So therefore, when a patient meets these criteria, from a medical perspective, they are dead. But there are major challenges that threaten the integrity of the medical diagnosis of brain death. The first one is a lack of global agreement and consistency. Not all countries recognize brain death. The vast majority do. Of those that do, there are some foundational differences in the definition. So in India and the UK, brain stem death alone is sufficient, whereas in most of the rest of the countries, it requires demonstration that the entire brain has died. A survey of global practices found major differences in very key components of diagnostic procedures across the world. And perceptions of brain death vary internationally. I put Brazil's study, there was one interesting study from Brazil, where the authors looked at the time it took from declaring brain death to removing the mechanical ventilator. What they found was very interesting. In Brazil, if brain death was being declared to facilitate organ donation, removal of the mechanical ventilator happened very quickly, within a couple of hours. But in patients that were not eligible for organ donation, it often took days. So even in Brazil, I'm not sure that physicians view brain death the same way, depending on whether the patient is a candidate for organ transplantation or not a candidate for organ transplantation. In the US, there's a lack of national consistency and standardization. Each hospital has its own policy. When I arrived at Penn, which is a health system with six or seven hospitals, no two brain death policies were alike, even within our health system. There's considerable variability in practice. This has been demonstrated in the literature repeatedly. There's a lack of adherence to guidelines. You heard about the study from Angela that was done in 2016. This study covered the majority of US hospitals and found very significant differences between brain death policies in the US and guidelines. I put a quote up there from their conclusions, that hospital policies in the United States are still widely variable and not fully congruent with contemporary practice parameters. I think, disturbingly, there's a lack of understanding and competence among physicians. One study surveyed physicians in 2019, and of the physicians that responded, the vast majority said, yes, I am competent to declare brain death, but only 25% of them said they followed AAN guidelines, 10% didn't do any apnea testing. Of those who got an ancillary test, over a quarter of them did that if the patient breathed during the apnea test, which, if you know what you're doing, should automatically exclude you from going any further, that patient is not brain dead. There's really little reason to suspect that this is not more widely generalizable. These together, and especially the last two, to me imply that it's reasonable to hypothesize that misdiagnosis of brain death is not rare. I think that carries fairly grave implications. How about from a legal perspective? I think, similar to a medical perspective, this is fairly straightforward. Laws are created by legislative bodies. The equivalence of brain death and death was established by an act, and is codified in state laws and statutes, and so, therefore, legally, brain death equals death, but laws are not immutable. They're subject to interpretation by courts, and legal problems and challenges have definitely arisen. The first is inconsistency in state laws, and while all states have some version of the UDDA, the statutes vary in their language and requirements. Some specify who can determine brain death, others don't. Religious objections, as you heard in New Jersey, a family can object on the grounds of religion to the declaration of brain death, and I just want to point out, to me, that means that even legally, there's some question in somebody's mind about whether brain death is death. Can you imagine a legal objection to death by circulatory criteria? So having to keep a cold corpse with no heartbeat in an ICU because of a religious objection, my guess is that that's not fathomable to most of you, so why do we have religious objections to brain death? It means, in somebody's mind, they're not quite the same thing, and then informed consent laws vary from state to state. There have been inconsistent legal rulings, and as an example of this, is consent needed to declare brain death? The American Academy of Neurology's position is no, but let's contrast two contemporaneous cases, both of which occurred in children where the parents refused brain death testing. The first was the case of Alan Calloway, a six-year-old in Montana who was declared brain dead after drowning, and the court ruled that brain death testing is a medical procedure, and like all medical procedures, requires consent, and since the parents have the sole right to consent, the hospital could not go forward with declaration of brain death. At the same time, there was the case of Miranda Lawson, a two-year-old admitted to Virginia Commonwealth University who was brain dead after choking, and there, the court ruled that there's no consent needed to declare death, and they allowed the hospital to proceed, so two completely conflicting legal rulings. There's even been legal questioning that the American Academy of Neurology criteria are the accepted medical standard, and remember, the UDDA said that brain death has to be determined in accordance with medical standards, and this was the case of Aiden Halew, a 20-year-old in Nevada declared brain dead after she suffered anoxia during surgery. Her father filed suit to prevent discontinuation of mechanical ventilation, and the district court said, no, the doctors follow the AAN criteria, so the patient is dead, and therefore, you can stop mechanical ventilation, but the father appealed, and it went to the Nevada Supreme Court, who reversed the district court's ruling and said that it's not clear that the AAN criteria are accepted medical standards, because look at how variable practice is across the country, and furthermore, they said that, you know, the Nevada brain death statute was based on the UDDA, which was enacted in 1981, and at that time, it was the Harvard criteria that were the standard, and so those should be the criteria in Nevada, not the AAN, and luckily, the Nevada legislature later ruled that AAN criteria should be the standard, but even in court, our standard for determination has been challenged, and there are other legal challenges, too, and take the case of pregnancy and brain death. In 2013, there was a case of Marlies Munoz, who was a 33-year-old woman, 14 weeks pregnant, who was declared brain dead in Texas after having a PE and a cardiac arrest. Her husband said to the hospital, take away the ventilator, but the hospital refused, because they said that would violate the Texas Advanced Directive Act, which prohibits withdrawing life-sustaining treatment in pregnant patients, and the court ruled that since she had died, that really didn't apply, and the ventilator wasn't sustaining her life, but I have a question. How would this case be decided now in the aftermath of Dobbs v. Jackson Women's Health Organization, which overturned Monroe v. Wade? If abortion is illegal in Texas, and there's a fetus, would they have ruled the same way? I don't know, but I have a sinking feeling we're going to find out fairly soon. From a biological perspective, okay, two minutes left, I think that ideally a biological definition of death should be applicable across species, and there is no great biological definition of death, but Walter Cannon, I think, had the best one, and he said that what distinguishes an inanimate from an animate object is the use of energy-consuming processes that oppose entropy, and so death is the permanent cessation of these processes that resist entropy and disintegration of the organism, and brain death really doesn't seem to fulfill this definition, and technology is further blurring the line about what's reversible and irreversible, and I've put a bunch of examples up there, including reanimation, and recently investigators at Yale were able to restore cellular and circulatory function across many organs hours after circulatory death in pigs, and I've put up two very interesting articles here that demonstrate that, and I think the most striking argument is that of the Harvard bioethicist Robert Truog, and he said that in law and medicine, we draw bright lines, but biology doesn't work that way. For example, when you turn 18, legally you're an adult. Suddenly you have all these rights you didn't have the day before. Biologically, you are no different than you were the day before. In medicine, when a patient of mine has a fever of 101.5, my fellows and residents and APPs draw cultures, but if they have a fever of 101.4, they don't, because we've drawn a bright line there, but physiologically there's no difference, and brain function operates along a spectrum too, and drawing a bright line biologically at a certain threshold and calling that brain death is arbitrary biologically, but totally legitimate medically and legally. There are many moral, ethical, and philosophical perspectives. It can be viewed as a philosophical construct, a moral construct, a social construct, and a biological construct, and I think one of the problems we've run into is that the predominant ethical view uses the fact that brain death is biologically death to justify brain death ethically, and I think this has a lot of problems. Since I'm running out of time, I won't go through this in more detail, but I'm happy to discuss it, and I'll just conclude by saying that there's lots of evidence that this is not as simple as it seems. Brain death is complex and widely misunderstood, and a lot of the confusion comes from conflating medical, legal, and ethical perspectives with a biological one, and as a concept, brain death functions adequately, but it's far from perfect, and here are some quotes that have been used by many to describe brain death. So, too flawed to endure, too ingrained to abandon, superficial and fragile consensus, well settled yet still unresolved, but it's undeniable that brain death serves a vital societal role, so I think it's desirable to bolster and augment public trust in brain death and the organ transplantation process. There are many solutions that have been proposed, some more realistic than others. I've put some of them up there, and I think that continued efforts to iteratively improve brain death are probably the most realistic and pragmatic path forward, and Angela talked about some of the ongoing efforts. So, I'll leave you with this quote from Edgar Allan Poe, which I think sums it up and really summarizes a lot of the problems that exist right now. So, thank you very much, and here are my references.

brain death

medical perspective

legal perspective

ethical perspective

philosophical perspective

sociocultural perspective