Neuroéthique : Une éthique de la technologie, avec le Dr. Joseph Fins

JOSEPH FINS: Sure, Wendell. First of all, thank you so much for having me. It is a delight to be here with Carnegie Council and to participate in this wonderful series of podcasts.

I love science fiction, but we don't need to invoke science fiction to make neuroethics interesting. We just had our meeting of the International Neuroethics Society in Montreal, and our theme was, "Bringing Neuroethics to Life through the Life Cycle." It was a response to the often hyperbolic and fanciful science fiction-y kind of predicates that often generate discussions in neuroethics circles, that start like this: "A three-headed cyborg goes into a bar, has liminal capacity, and wants a deep brain stimulator."

They are hypotheticals and do not adhere to reality, so what we tried to do at this meeting was have a counter-meeting and look at the concrete challenges through the life cycle in clinical neuroethics and in research neuroethics. The problem with these hypotheticals about devices that can read your mind is that it delegitimizes important applications of neurotechnologies that are important to understanding how the brain works and actually caring for real people with neuropsychiatric problems.

I would say that neuroethics is not just the ethics of neurology, but it is also the ethics of all the things that happen in the brain, including psychiatric illness, so the divide between neurology and psychiatry is collapsing as we think about the brain. These two specialties, which began in the early part of the century as more closely linked, are coming back and converging upon each other, in part because of the evolution of the neurotechnologies that show that who we are as people and our biologies are inextricably linked.

There are two schools, the fearing doom, Chicken Little-kind of perspective in neuroethics, and then there are people like me, who are doctors, who see the suffering, want to respond to it, and see the tools that are being developed as incredibly instrumental and helpful in unwinding what Wilder Penfield, the great neurosurgeon and founder of the Montreal Neurological Institute-Hospital and the mapper of the homunculus in the brain, called the "mystery of the mind." We are getting closer to understanding it, but it is like an onion, the more you peel back the more there is to peel, then you start crying and have to start all over again.

I am in this latter school, grounded-in-reality neuroethics, and I am concerned to be quite honest about some of my neuroethics colleagues, who sometimes speculate about things we should be fearful about because they can have a chilling effect on research and practice.

WENDELL WALLACH: Let me ask you about one particular area that a lot of people bring up, which is this notion of mindreading, that we are getting toward technologies that are actually going to be able to read your mind and therefore invade your privacy. Give me a sense of where we are and where we are not as far as the development of such technologies.

JOSEPH FINS: I think we are not there yet. It is like modern phrenology at this point. We can say words to you and show that certain areas of the brain activate, areas that pertain to the speech act, but we can't decipher necessarily what you are thinking or what you are saying and what your thoughts are. There is however a whole cottage industry of the importance of protecting cognitive liberty. We can't do that. Does that mean it won't happen? Not necessarily, but it's not imminent.

Having said that, it is very important to have what's called "anticipatory governance." We need to think about future developments so that we are prepared to respond to them, but this is not an immediate threat.

WENDELL WALLACH: There has been this concept about positive and negative rights which gets applied to this question of what kind of neurorights. I don't think we want to go into this in great detail now because this will be a core subject with Nita later in the winter, but can you clarify for us this concept of positive and negative rights?

JOSEPH FINS: I introduced this recently in an article. I think I was the first to do this in the context of the Chilean constitutional reform. They had a constitutional plebiscite in Chile in September, which did not pass, but one of the over 400 elements was about neurorights, and my critique of that was that it was centered on all the things you can't do, the negative rights—you can't intrude on people's privacy. The greater threat to your neuroprivacy is somebody looking at your phone, your emails, your texts, and all that, because that is a repository of your thoughts. It is actually the phenotype or genotype of what you are thinking.

My concern was that in articulating all the negative things you could not do that could violate things like cognitive liberty—you can't intrude upon the brain—would preclude things like deep brain stimulation (DBS) and even neuroimaging because it does reveal information about what areas of the brain are being activated, and my concern was that in focusing on negative rights they were not thinking at all about positive rights, that is, the right to be able to communicate if you are locked in—and we will talk more about these various brain states—the ability to get out of your head and integrate yourself into society in a way that is consistent with other international law, like disability law.

The Americans With Disabilities Act and the UN Convention on the Rights of People With Disabilities talk about the "right to community." In a sense if you can't do certain negative things—like I can't fix your gallbladder if I don't operate on you, so I need to violate your bodily space to take out your inflamed gallbladder. That doesn't mean that I'm committing a tort or injuring you; I'm doing something in the interests of healing and helping.

I think the same dichotomy needs to exist when we talk about neurorights. To sum up, negative and positive rights need to be in a kind of homeostasis with each other. They need to be balanced.

WENDELL WALLACH: Before we get into various mental states that need therapeutic attention, let's stay back with this mindreading question for one more moment. We are seeing sensational articles about let's say a particular neuron responding or areas of synapses firing when there is neuroimaging taking place. For all practical purposes, these are one-off examples, and we have nothing short of neuroimaging devices that can help us even see that far into the brain.

That is at least my understanding, but are you aware of any technologies that might be utilizable to see the neuroresponses of people short of neuroimaging technologies that could be used without people being aware of it? I imagine tactile stimulation if you had that built into your mouse, and that could be perceived, but we don't have anything that gets into detail in understanding what's going on in your mind beyond what can be deduced by your social media record, for example.

JOSEPH FINS: Let me describe how functional neuroimaging works. It is not even a contemporaneous activity. It is a function of glucose extraction from the blood, which is necessary for the neurons to power themselves up. The motor cortex is doing some work, thinking about moving my arm here. Milliseconds after the electrons fire and the area gets activated there is going to be an extraction of glucose from the blood, and if you have tagged glucose, you see that activation in that area. It doesn't mean that I'm thinking of playing tennis or swimming. It is just that that area has been activated. An electroencephalogram (EEG) is more contemporaneous, but it is a bunch of squiggly lines, and that can be localized, but it doesn't have semantic content per se.

The one area that is interesting is the use of brain-computer interfaces, where people who are locked in, for example, can have a thought about moving a cursor in their head and direct a mouse that is on a screen to spell out words, but it is volitional. It is with the cooperation of the individual. It is not like somebody is reading their thoughts. Somebody has to actively engage, and there has to be an algorithm that is set up to translate these activities with the brain-computer interface. It is not a crypto thing. It requires the cooperation of the individual.

WENDELL WALLACH: Hopefully that's what our listeners are understanding here. These questions about you being mentally violated are not viable in any way, shape, or form with present-day technologies, but as we move toward interfaces either internal or even on the surface, such as virtual reality devices and so forth, where there is a brain-computer interface, then those neuroethical issues that you hear about in science fiction will start to become real, and we need to get into those in greater depth, but we aren't quite there yet.

JOSEPH FINS: Or they may not become real. It may not evolve, or there may be ways of regulating it so it is obviated as a concern. I just think that talking about hypotheticals may attract interest, but it may not be the best way to think through a problem because it may have consequences in real time for real people.

WENDELL WALLACH: Again, for those of you who find this part fascinating, tune in because we will be coming back to it in February or March.

Let's move more toward the area where you have done seminal research, which is to work with people—well, we have a lot of different phrases, don't we?—who are "locked in," "brain dead," or "minimally conscious." I think we all hear these phrases quite often, and they are a little mysterious because there is real concern whether, when we are dealing with people who seem to be not conscious at all or minimally conscious, what becomes appropriate to do with them, what is inappropriate to do, what kind of care they should get, and whether even turning off their life support is valid or not. It seems to be an area where you are doing some of the seminal research, but we probably don't know as much as we would like to.

Let's start with you defining what these terms mean.

JOSEPH FINS: That's a good idea. Let me just take you through the life cycle of a brain injury, as it were, a biography of a brain injury. How about that?

We are not taking about concussions and things like that. We are talking about you having a brain injury where you actually lose consciousness, and that can go in several different ways. You could have a syncopal event, where you lose consciousness briefly, you pass out, and you wake up. We are not talking about that. We are talking about somebody who enters into what is called a "coma."

A coma is an eyes-closed state of unconsciousness that is self-limited in time. It lasts up to a couple of weeks—unless it is medically induced, in which case it can be prolonged, but generally you either recover from a coma and wake up. Anesthesia would be an example of that, or if I spoke too long I presumably could put you into a coma and hopefully you would wake up—that's a joke for our listeners. Wendell is laughing.

A coma is self-limited, and it resolves in three ways: you wake up; you progress to brain death, which is whole brain death, the death of the entire brain including the brainstem; or you move into what is called the "vegetative state." The vegetative state is the isolated recovery of the brainstem, which is that part of the brain that is just above the spinal cord. That part of the brain is responsible for sleep/wake cycles, propelling your heart along, your breathing, and all that.

Notably what makes the vegetative state so confounding and challenging unlike coma is that it is an eyes-open state of unresponsiveness. So the eyes are open but no one is theoretically "home." That becomes very difficult for families because usually the eyes are "the windows on the soul"—I think Shakespeare said that—and if you open up your eyes and you are not aware, it is devastating.

Probably the most famous vegetative person ever was Karen Ann Quinlan, about whom the right-to-die case was established in 1976, but if you read Mrs. Quinlan's memoir of the circumstance of what happened, when Karen opened her eyes there was great excitement. They called the nurses over, and then devastation sunk in when they realized that they were not seeing eyes, that it was just the recovery of her brainstem and not her higher cortical function. Of course the vegetative state is important sociologically because it was linked to the right to die, and the New Jersey Supreme Court, Chief Justice Hughes said that it was a "lack of her cognitive sapient state" that became the moral warrant to allow her to die and have her ventilator removed.

This is important. When they removed her ventilator she didn't die. Why didn't she die? Because she wasn't brain dead, and the distinction between the vegetative state and brain death is that vegetative folks have an intact brainstem, and so long as the airway is protected the brainstem will propel the ventilatory response.

In fact, when we do brain death testing, when people are off the ventilator, their carbon dioxide levels go up, and usually that hypercapnia or high carbon dioxide levels would prompt a breath, and if they don't breathe, they are brain dead, and if they breathe, they are in the vegetative state because they have an intact brainstem.

That is the vegetative state. Initially it was called the "persistent" vegetative state, but now we have different modifiers for it. If the vegetative state—current nomenclature—lasts for three months after anoxic brain injury or a year after a car accident—traumatic brain injury—it used to be called "permanent." Now it is called "chronic" vegetative state. We will get back to that in a second.

When people emerge out of the vegetative state they move to a state called the "minimally conscious" state (MCS), which to me is the most interesting state of all. Maybe there are other states of being that are more interesting, but academically it has captured my attention. These are people who appear vegetative, but they have episodic awareness of self, others, or the environment. They might reach for a cup, they might say their names, they might look up when you walk into the room. They do this episodically and intermittently, but they are conscious.

Oftentimes they are not recognized as such. In fact there have been studies that up to 40 percent of people with traumatic brain injury in nursing homes who are thought to be vegetative when carefully examined are actually minimally conscious. So we are missing consciousness. Big deal, right, because consciousness is who we are. We miss it four out of ten times.

These are minimally conscious people, and their brains are completely different than vegetative patients. If you look at the circuitry, those minimally conscious brains are integrated. The vegetative brain is disintegrated, not that it is disintegrated, but it is not working as an integral entity. It is not communicating with itself. We now know that the brain communicates in a thalamo-cortical track. They are circuits that are intact, and that's how it works.

The minimally conscious brain has these intact widely distributed networks that can be the template for consciousness, but what happens here is interesting: Without adequate arousal from the brainstem and without adequate stimulation those pathways which are there are under-activated. There was a great Spanish neurophysiologist named José Manuel Rodríguez Delgado—who I just wrote a paper about in The Neuroscientist.

Long story short, he wrote this book, Physical Control of the Mind: Toward a Psychocivilized Society, in 1969. He had this great metaphor about the brain. He said it is like an interstate highway, but without the cars, trucks, and businesspeople it is just a useless stretch of pavement. The minimally conscious brain is like that interstate highway. It is there—unlike the vegetative brain, in which the highway has been destroyed—but it is not activated, and a lot of the therapeutic initiatives have been to put commerce, trucks, and people on the highway so that it can activate itself. That is the difference between the minimally conscious state and the vegetative state.

The reason people in the minimally conscious state episodically appear aware or not is that they get different amounts of arousal or activation from the brainstem up into the cortex, and this means that you have to do a bedside exam five times to get an adequate sample because they wax and wane over time, and if you get them in their dips they are going to look vegetative. You want to get them as they crest into higher levels of function, and we give them credit for their highest level. Their best grade counts, not their lowest grade.

After the minimally conscious state we call them "emerged." These are people who are reliably communicating to responses. If I say, "Wendell," you will look up consistently or say your name consistently, whereas if you are minimally conscious you will do it every once in a while.

It is a problem because families will have these people in nursing homes, and the families are spending a lot of time with their loved ones, and they bring the doctor in, who is usually not a neurologist or trained in these things—often a geriatrician, internist, or family practitioner who may not know a whole lot about brain injury, but they are providing medical care to these folks—and they will say, "I saw Johnny look up when I came into the room," and the doctor will be skeptical because he doesn't know a lot about this nosology, these diagnostic categories, and then Johnny doesn't do it, just confirming the bias. So it is not believed. There have been tragic cases where families have seen behaviors that were consistent with awareness and consciousness that were dismissed for decades.

WENDELL WALLACH: When we have somebody in a vegetative state is there a high probability or a low probability that they will move to this minimally conscious state? Does this happen often?

JOSEPH FINS: It depends on what kind of vegetative state you are in. If you had traumatic brain injury, you can recover from it probably around 70 percent of the time, if you have had anoxic brain injury maybe 50 percent of the time, but there are time courses that pertain to it. I was talking about permanent and chronic, so three months after anoxia and a year after traumatic it used to be you never got better, but now increased data and surveillance suggests that 20 percent of the time people will emerge out of those brain states, mostly the traumatic brain injuries. If you think about it, if 40 percent of the people are misdiagnosed with traumatic brain injury, that accounts for a large bit of the variance, but it is also inadequate evaluation.

In my book Rights Come to Mind I profile—I have permission to use her name from her mother—Maggie Worthen, who was a subject of a study that was published in Science Translational Medicine by Dan Thengone and Nico Schiff, my close colleague, where over I think a 54-month period we tracked her brain evolving over time, and she had new white matter tracks across the hemispheres and in Broca's area, which is responsible for language, so there were structural changes in her brain over that time.

The problem is, as a public health and a disability rights issue, we send people to nursing homes. They may yet still be in the vegetative state, they morph into the minimally conscious state, nobody notices it, their brains are changing, and there is no surveillance mechanism to go back and check to see if there have been any changes in their responsiveness. So you have a situation where again four out of ten people—remember the musical Hamilton, "The Room Where It Happens"—they are there, people are talking about them, they may be potentially understanding, and no one knows that they are listening. There is evidence of people who appear behaviorally unresponsive processing language based on activations using functional neuroimaging. We don't know what they are understanding, but they are processing, responding to language versus to gibberish.

WENDELL WALLACH: Before we come back to this responding to language I want to get back to the vegetative state and the brain dead basically. Do we clearly understand the demarcation between those two?

JOSEPH FINS: Yes. I think so.

WENDELL WALLACH: This is a central neuroethical issue that I think everybody grasps. We don't want to give inappropriate care or no care at all to people who are in these various states or misdiagnose what state they are in. Have we reached a point where it is relatively clear who may still show a response pattern that can return to at least a viable form of minimal consciousness, or are we still in a realm of mystery?

JOSEPH FINS: I think it's more mysterious to some rather than others.

WENDELL WALLACH: I think we are asking you as an expert. We are not talking about those who have relative degrees of ignorance but those who have looked at this in depth.

JOSEPH FINS: I think the clinical criteria for brain dead are adequate and serviceable in most cases. The problem is that they are not always deployed in practice the way they have been articulated.

Basically a person who is brain dead is what is called "whole brain dead," which includes the brain stem. That is the distinction between the clinical exam between a brain dead person and a vegetative person, but it can be quite disturbing.

Let me tell you about the Lazarus reflex. Have you heard of the Lazarus reflex?

WENDELL WALLACH: No.

JOSEPH FINS: This happens occasionally, very rarely. I have seen it once in my career. A patient is lying there, is brain dead, you remove the ventilator, and they are not able to breathe, but sometimes they bring their hands up as if in prayer, and that is a cervical reflex. That appears to be a lot, but it is a spinal reflex, their heartbeat has stopped, they are no longer alive, and they are brain dead because they did not breathe after being deprived of oxygen and the carbon dioxide goes up 20 mmHg, and they don't breathe.

When you are drowning, it is not the lack of oxygen that causes you to take that deep breath that makes you drown with the water, it is the elevation of your carbon dioxide, at which point you can no longer resist the reflex and you have to take a deep breath, and in that process people drown because they inhale water. It is not hypoxia, it is hypercapnia, or elevated carbon dioxide. That reflex is gone in brain death because that comes out of the brainstem.

There have been some interesting developments in the context of brain death, most notably the Jahi McMath case in California. She was a teenage woman who had a devastating complication from a tonsillectomy, was declared to be brain dead, but it was contested.

One of the great challenges is that there are going to be liminal cases where patients—brain death criteria were established by an ad hoc committee chaired by Henry K. Beecher at Harvard in 1968, and if you read it, they invoke Pope Pius but they do not invoke a whole lot of neuroscience. There are very few things in medicine today that depend on 1968 technology, so there might be liminal cases where patients may still have functional activity below the level of our clinical exam.

I think we need to begin to think about incorporating some functional imaging sometimes in questionable cases, and there are some efforts underway right now to rethink brain death criteria across the globe, which I think is a good thing, but you can also overdo it and get false positives or false negatives, depending on which side of the equation you are on.

Here is work that is happening up at Yale, which is fascinating and which I would love to share. It is this thing called BrainEx—like the FedEx brand, but it's called BrainEx. These investigators, whose lab I had a chance to visit right before the pandemic, have this dialysate fluid, as it were, that can revivify brains and brain cells. What they have done is taken brains of decapitated pigs from a slaughterhouse, hooked these pig brains up into this fluid, and they regenerated electrical activity in those cells.

The question is: Are those brains still dead? My answer is yes because brain death is the death of the entity working as a unit. It may not be individual cell death, which is where you get the confounding with some of the EEGs and other things, but it is really whole brain death.

I do think you can distinguish brain death from the vegetative state with skilled clinical examination and the like, but it is obviously a question of great interest. I think this BrainEx fluid is not to revitalize brain dead pigs, as it were, but rather to infuse areas in the brain after somebody has had a stroke, tissue that is dying, and try to reanimate selected areas and bring those cells back within the context of an otherwise alive brain.

WENDELL WALLACH: Let us transition to your research itself because I think this will be fascinating for our listeners. You have been working with covertly conscious patients and others, and you have been working with deep brain stimulation and functional imaging. Can you tell us a little bit about what drove your research, what you were trying to discover, and what you did discover?

JOSEPH FINS: My research is the product of a rare thing in science, a wonderful collaboration and friendship with a neurologist called Nico Schiff, who is a brilliant neurologist here at Cornell. About 25 years ago we bumped into each other in the coffee shop. We had both been students of Fred Plum, who was his mentor and was the neurologist in the Quinlan case, and in fact was the person with Bryan Jennett who discovered the persistent vegetative state. I was editing an ethics column for the Journal of Pain and Symptom Management, where the plan was that somebody would submit a case and I would line up commentators who would argue pro and con, pro and pro, or whatever.

There was this case that was submitted about a patient who had advanced cancer, who had been depressed, and the question was: Should she get a lot of morphine, which could suppress her breathing—which was a real issue in the late 1990s about the right to die— but the more interesting question was: What about the role of antidepressants in somebody who had been depressed who seems to be in a coma? That is still an unsettled question. I asked Nico to write a commentary about this. It is like, "The patient appears to be unawake, but what's really going on inside their head?"

Fast-forward 20 to 25 years later, and now we are realizing that people can have covert consciousness in the intensive care unit (ICU). Brian Edlow at Massachusetts General Hospital has used functional MRI to show that people who appear to be in a coma may actually be aware.

Jan Claassen up at Columbia did a study using EEG showing that people who appear to be in coma may actually be aware. That is, when they are given a volitional prompt and asked to do something they do it in their head.

This goes back to work that was first done by Adrian Owen in 2006—we did some follow-up studies here at Cornell—where a patient who is in a chronic state, in the minimally conscious state, or somebody you don't really know their brain state, you say, "Imagine doing something." The classic paper was in Science in 2006: "Imagine playing tennis. Imagine walking around your house. Imagine disaggregating linguistically similar words, like 'the riverbed creek' and 'a creak in your neck.'" When you ask them to volitionally play tennis they light up their motor strip, when you ask them to walk around their house they light up their parieto-occipital region, which is for spatial navigation, and when you ask them to disaggregate linguistically similar words they activate the language area.

Interestingly that first paper was called, "Detecting Awareness in the Vegetative State." The title almost gave me a stroke—no pun intended—because it was so disingenuous. The vegetative state was first described by Jennett, who is a neurosurgeon in Scotland who came up with the Glasgow Coma Scale and Glasgow Outcome Scale, and Fred Plum, as "a state of wakeful unresponsiveness."

If somebody is asked to do something and on their scan they do something, they light up their motor strip, they are not unresponsive. They are not wakeful and unresponsive. They are responsive. So it seemed like a misattribution to the vegetative state, and I called this in a paper that I wrote in The Hastings Center report right after that "non-behavioral MCS," that these people were liminally conscious, but they were not demonstrating the behavior.

This is an important distinction about covert consciousness, the difference between what you see and what is actually happening, as it were, "under the hood." It is like in genetics, where you have genotype and phenotype. All those flowers in Mendel's garden that appeared to be the same under the genetic hood were different. Some were heterozygote, some were homozygote-positive, but they were different and in the next generation their progeny would look different.

So we have this discordance between what you see at the bedside and what is happening in the brain, and that is materially important because prognostically it makes a huge difference. It says, "Not everybody who appears vegetative is in fact vegetative," because they may have covert consciousness or what has been described as cognitive-motor dissociation.

WENDELL WALLACH: Do we need brain-imaging systems to recognize this?

JOSEPH FINS: Yes, you do. If any science geeks out there want to read a great paper just for its brilliance, it is the Jennett and Plum paper about the persistent vegetative state, and they describe it as "a syndrome without a name." I did a deep dive in reading it as literature. That is drawing upon my Wesleyan roots that you and I both share, reading the text. If you read the text Jennett and Plum say about the vegetative state that it "seems wakeful without responsiveness."

Fred Plum was a great writer and a great editor, an excellent wordsmith, so that word "seems" gets underlined. Why did he say that? He said that because in 1972—to answer your question—they had no way of knowing that somebody who appeared vegetative truly was vegetative because they only seemed so, and they were intuiting without saying the possibility of covert consciousness, which I think is brilliant because they knew the limits of what they know and did not know. Oliver Wendell Holmes, the anatomist, the father of the jurist, and was a pragmatist—

WENDELL WALLACH: Who I was named after.

JOSEPH FINS: Right. He was Holmes Sr. He said—to paraphrase—"The difference between a superior mind and a vulgar mind is precisely that the former knows what it doesn't know." So when Jennett and Plum write, "It seems wakeful without responsiveness," they knew they couldn't say it is wakeful without responsiveness. It just seems so, and that is why we need that neurotechnology.

I want to digress a little bit to tell you where this insight came from for me. I did not realize this even when I wrote my book Rights Come to Mind. It was kind of an unacknowledged debt to Saul Bellow, the Nobel Laureate. Do you know this story about him? He was in a coma.

In the mid-1990s I was very young and I was at this conference where I went on right after Saul Bellow and Edmund Pellegrino, who is one of the founders of bioethics, and then a 30-something-year-old me goes on. It is like going on The Ed Sullivan Show after The Beatles or something. How do you follow that?

Saul Bellow talked about his experience having had scombroid poisoning, which is like histamine poisoning, from bad fish in the Caribbean. He was medivac-ed up to I think Boston University and was in an ICU, and everybody thought he was in a coma, but he is having these daydreamy kind of hallucinations, and he is aware. He was nearly 80 when this happened. It is rare for an 80-year-old to survive this. It is even rarer that they have a Nobel Prize in Literature to tell the tale.

He is telling this story. He is in the ICU, he thinks he wants to die, and then he has a flashback to his childhood, movie theaters, and his beloved Chicago. All kinds of memories flood in, and then he thinks he wants to die. Then this attractive woman comes to visit him at the bedside. He later in this reverie realizes: Well, she seems very nice. Wow. She's my wife—Janis was her name—I don't think I want to die. He tells this story.

Meanwhile Janis is at the bedside being very dutiful and playing Handel's Water Music because he liked that. Hearing his talk immediately preceded by a year or so that case that I described where I ran into Nico Schiff, and we were thinking about the inner life of this person with a coma.

After hearing Saul Bellow I never, ever, ever—when I was making rounds at the bedside and we were talking about prognosis or whatever, I would say, "Okay, guys"—men and women, guys generic—"let's take it out of the room and talk about the prognosis in the hallway so the patient can't hear because we don't know what they are hearing." Covert consciousness.

Let me make one last quick point. This is an example where the art was ahead of the science. Saul Bellow described what we would come to understand scientifically 25 years later.

WENDELL WALLACH: Let me bring a digression in here because you referred to Wendell Holmes Sr. For those who don't know Wendell Holmes Sr., you might know him because he wrote the poem "Old Ironsides" about the old battleship, which still today can be seen in [Boston Navy Yard].

In any case he for all practical purposes was the man who started the germ theory of medicine. He deduced that childbed fever, which was killing off many women, was being carried by probably doctors from one woman to another, and yet we had absolutely no idea what germs were at that point. This was even a few years before Semmelweis demands that there is this sterilization process that physicians should engage in.

The only reason I am bringing that in is that I think there is a parallel here to where we are and what you have been saying about our understanding of brain activity as we can deduce it from these people who are in vegetative or other states. We are still in a very primitive period in neuroscience in terms of what we understand and what we don't understand, comparable to how little we understood that even germs existed at that time. We are building from the available observations of some astute physicians and of course now the availability of some technology that can help us see when a patient is engaged in mental activity around your questions even through there is no behavioral activity going on at all. This is still very much a frontier as I am perceiving it.

JOSEPH FINS: When I am on the road giving talks and going through this whole nosology of the vegetative state, minimally conscious, and all that stuff, I have an image on the side of the slide of a Vesalius print of a skeleton contemplating a skull, which is 16th-century anatomy. I say, "People are going to look at my slide, if it were to survive, with the same notion of how primitive that is." I have used this phrase, that we have to have what's called "nosological humility." I am a pragmatist. My bioethics is Dewey and pragmatism. It is all contingent, and it is all evolutionary. So we have to have humility about what we know, and these categories are getting refined.

What is interesting right now—and it is a little further ahead in psychiatry than it is in disorders of consciousness research—is that we are going through a transition between what we observe and mechanism of injury and illness.

In psychiatry we had the anecdotal psychiatrist who had a gestalt impression of what you had, and then we had the Diagnostic and Statistical Manual (DSM), which was based on public health data and probability, and now we are moving into "Which circuit is deranged?" There are subtypes of depression, each of which responds to different kinds of medication, for example. I think the challenge is making the transition from the DSM to a circuit-based approach or in neuroscience and neurology moving from behavioral criteria to criteria based on neuroimaging.

Here's the paradox: Not everybody who can do things on a clinical exam in a minimally conscious state can do the same task in a scanner, so the sensitivity and specificity is not there. Our metrics are evolving, but the notion of the primitive—we know so much more than when I was a medical student. I think my students are going to have advantages that I will never see.

The key word you used was "technology," and the thing that has revolutionized this whole area is the neurotechnology. I once wrote an epilogue to the Oxford Handbook of Neuroethics. It is an 800-page Oxford handbook edited by Judy Illes and Barbara Sahakian. I said something to the effect that, "If there is such a thing as neuroethics"—because I am not sure it is different than ethics in general, but I am becoming convinced—"it's an ethics of technology." It is an ethics made possible by technology and an ethics whose responses are often technological.

I think this notion of covert consciousness is how technology has brought to us an ethical problem that heretofore we did not know existed, but neurotechnology can be the remedy to that problem because it gives us a way for these people to communicate. I will give you two examples. One is you say to somebody—and again this is still investigational—"Imagine playing tennis." If you want to say yes, imagine playing tennis. If you want to say no, imagine walking through your house. The very technology that reveals the problem now provides a way for the person to get out of their head and communicate.

Deep brain stimulation is another response to people who are in these liminal states of consciousness.

WENDELL WALLACH: Let's go down that a little bit because I think we have focused very much on the brain-imaging side of this, but we have not focused at all on your work in deep brain stimulation. I have a feeling that for many of our listeners it is Greek when we talk about deep brain stimulation, but it has actually been going on for a while, and it is being used as a valid clinical treatment for certain diseases. Perhaps you can talk about that a little bit.

JOSEPH FINS: It is being used as a vetted treatment that is paid for by the Centers for Medicare & Medicaid Services for drug-refractory Parkinson's disease, and it is an investigational intervention for lots of other things from obsessive-compulsive disorder (OCD), which has what is called the "humanitarian device exemption," and the work we are doing using DBS to treat people who are in the minimally conscious state.

WENDELL WALLACH: Before we talk about what you are doing with it, what is it? How is it done?

JOSEPH FINS: It is a pacemaker for the brain, like there is a pacemaker for the heart. In fact companies that make pacemakers for the heart also make deep brain stimulators. It is basically a wire bilaterally implanted into various parts of the brain—depending on what you are trying to stimulate the target would be different—and this wire is hooked up under the skin to a battery pulse generator that exists in your chest, usually one on each side, and each of these electrodes have four contacts, each of which can be turned on or off, the size of the charge, the frequency, and with all those manipulations you can have an effect. One of the challenges is that if your charge is too high or the field is too big you get into an adjoining area, and you could have an adverse effect or a side effect that would be uncomfortable or disquieting to the patient or subject.

WENDELL WALLACH: You mentioned how it is being used for Parkinson's.

JOSEPH FINS: It is a great story. This guy, Alim Benabid—who won the Lasker Award with Mahlon DeLong from Emory for elucidating Parkinson's disease—is a neurosurgeon in France, and he was doing what's called a pallidotomy. The way they used to treat Parkinson's disease—and sometimes still do—is to burn a hole in part of the brain with an electrode to decrease certain symptoms, but before they do that they stimulate the area to be sure they know where they are, the proper area, and they can tell based on the sound of the nerves. Each nerve has a different "song" that it sings. It is beautiful. As you are going in you hear different chirping sounds, and the skilled neuroelectrophysiologist can hear, "Oh, now we know where we are." To me it sounds like birdsong.

He is stimulating this part of the brain to find out where he is going to ablate or destroy the brain, and he notices the tremor stops. He has this epiphany. He says, "Well, maybe I don't have to destroy brain. Maybe I can stimulate brain instead and have the same effect," and that is of course how deep brain stimulation for Parkinson's disease was discovered, and that was around 1986, he wins the Lasker Prize, and could well win the Nobel Prize.

He is a lovely man. He is humble, smart, very gracious, and still doesn't know—as of the last time I spoke with him; maybe he has figured it out by now—if the effect of the stimulation is stimulatory or inhibitory because it is a tangled web. You can inhibit an inhibition or stimulate a negative or a positive, so you do not know what you are actually doing, but he did know that it decreased the tremor and increased the fluidity of movement.

It all was born with Parkinson's disease as it were. There were earlier examples of electrical stimulation of the brain including Delgado and others, but now we have ramifications in other areas for OCD, which is kind of a tremor of the mind, of thought, and that has approval as a humanitarian device exemption, which means it is safe but efficacy has not yet been proven conclusively, and also in depression—Bart Nuttin for OCD, Helen Mayberg for depression.

These are very promising areas of inquiry, and our work has been stimulating the thalamus in the context of traumatic brain injury. We first reported our results in Nature in 2007 in a patient who was in the minimally conscious state who had been brutally assaulted, couldn't eat by mouth, couldn't talk, was bed-bound, and sometimes moved his eyes to communicate. That was it. With deep brain stimulation bilaterally to the intralaminar nuclei of the thalamus he was able to say six- or seven-word sentences, say the first 16 words of the Pledge of Allegiance, tell his mother he loved her, and, as I recount in my book Rights Come to Mind, go to Old Navy and voice a preference for the clothing that he wanted his mother to buy.

This is still investigational, but it was the first use of deep brain stimulation in the minimally conscious state, and to me it was the restoration of agency ex machina. A little bit of electricity brought it home.

I will tell you a story that to me was the high point of this. We were writing the protocol. I spent ten years on the ethics of the protocol because as a medical ethicist you can imagine how difficult this was. We were doing a phase I study, which is proof that it is not toxic, without the hope of benefit in a patient who could not give consent. It is putting electrodes in someone's brain. The challenge was: How do we do that without the possibility of consent?

My argument was that we were confusing the provision of consent with respect for persons. It is one thing to do something to somebody who can consent without their consent or over their objection. It is quite another thing to do something to restore agency so people can participate in decisions. That argument eventually won and we had approval from the Food and Drug Administration and multiple institutional review boards (IRBs) to do this intervention.

WENDELL WALLACH: Has that argument gone much beyond your making the case for this? It is a fascinating argument, that restoring agency is a legitimate justification for doing therapeutic interventions without informed consent.

JOSEPH FINS: It was not without consent; it was without the subject's consent. It was surrogate authorization, surrogate consent.

I think it just shows the confusion about the application of a principle versus the principle itself. Generally informed consent is a good proxy for respect for persons, but it isn't always so, and I had to disaggregate that. Fortunately it worked out well. If there had been a bad outcome, maybe I would not be on this podcast right now.

What was fascinating was that one day we were done with the study and we were doing post-trial stimulation parameters. I told you how each electrode has four contacts. It is very laborious because every time you change something you have to do all this testing, and it takes hours. It was a hot summer day. The subject's name was Greg—I have permission to use his name. He was obviously getting tired and it was the end of the day, and one Ph.D. of physiatry says, "Greg, do you want to stop?"

He says, "Yes."

I looked at my watch and recorded the time. I think it was 2:00 or something. It is written about in the book. I said, "At that moment, we had given him back agency, not at the level of informed consent and refusal but dissent and assent." He was back in the room. He was telling us what he wanted to have done.

It was a vindication of sorts because when we wrote the IRB protocol and we were using surrogate consent, I put in this little codicil, that if a patient ever regained capacity, we have to re-consent them. He did not get to that level of consent, but rather assent and dissent, but it was the restoration of this person through a little bit of electricity.

WENDELL WALLACH: What a wonderful story that is.

Let's transition, though, a little bit. These have all been treating therapeutically conditions of diminishment in one form or another, but you mentioned to me just yesterday actually when we were chatting that it is possible that this technology might be used for enhancement purposes, not just therapeutic purposes. Can you tell us a little bit about that?

JOSEPH FINS: First of all, I think it is important as we had our terminology to start about what are all these different brain states, sometimes people think this is enhancement, and I think we need to distinguish restoration with enhancement, and there is an important distinction. It is conceivable that one could take a person with normal function and make them function better with one of these devices, but then we get to the point of what we call "ethical proportionality" because the burden/benefit is we have to put an electrode in your head, which makes it risky. Is the benefit likely?

In 1977 the National Commission that wrote The Belmont Report: Ethical Principles and Guidelines for the Protections of Human Subjects of Research, the three principles which became four principles, also wrote a report on psychosurgery, and one of the prohibitions was on enhancement. They said it is okay to treat pain, it is okay to treat epilepsy, things like that, but they were against enhancement. I think that is an important bright-line distinction. I think it violates proportionality. Also it creates the potential of a super-digital divide as it were, where those who can be enhanced will be enhanced and those who won't will fall to the wayside.

This is an area where I think the technology could lead to challenges. The challenge with deep brain stimulation for enhancement relates to what we call in ethics the proportionality, the relationship of burdens to benefits. It is a hypothetical benefit but a very real burden that we are putting electrodes in someone's brain, and that becomes what we call "ethically disproportionate."

What is going to change and is already beginning to change is noninvasive interventions, where the burdens are less so the proportionality is potentially more favorable, and you might be willing to take a more hypothetical risk. The challenge is that this creates a digital divide, and it also violates the prohibition of the National Commission against enhancement. So I think we should talk mostly about restoration and less about enhancement.

WENDELL WALLACH: It is interesting that many of my pro-enhancement colleagues want to argue that, why, if they are willing to take the risks, recognizing that there may be real dangers for the first people willing to accept invasive enhancement technologies, drugs, or whatever they think might be helpful, that they should have the right to give informed consent to do that and take the risks? I have always argued that that does not really solve the problem because what if something goes wrong, then who is responsible for you if you are reduced in your capacity?

JOSEPH FINS: Right, right.

WENDELL WALLACH: Unless you have an insurance company or policy that is willing to cover that totally then you actually put the society in the position of having to take the proportional risk even if you are willing to take the treatments yourself.

JOSEPH FINS: Right. Informed consent is necessary, but it is not sufficient, for all the reasons that you articulate, but it is a very interesting question about who gets to make the decision for these things.

Currently I have a grant with the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative interviewing patients and their families—I use "patients," but they are subjects—who are participating in a DBS trial for moderate to severe brain injury. These are people who can give their own consent, so they satisfy that criteria.

What is interesting is that these patients had a severe brain injury, their family members for years have been making decisions for them as they nurse them, as it were, back to health, and now they are in this position where they are in this clinical trial and there is kind of a push me/pull me about who gets to make the choice. Legally and ethically it is the patient's choice because it is their brain, their body, and their life. There is this very interesting delegation of allowing people to make risky choices because the consequences of the decision are greatest for them.

In this study, though, we are very careful about independently establishing the decision-making capacity of the subjects to be able to make that choice, and if they don't have decision-making capacity, they cannot participate in this trial. But the relationship between parents and children or spouses—it's interesting. The patients—I'm calling them "patients;" they're subjects, just to disaggregate the confusion—are more willing to assume what has been described as "the dignity of risk" because they understand the burden of their lives. Again, they are invoking a kind of proportionality and making a choice that works for them.

I think proportionality can shift, and I think this is an area that requires additional attention, but again your taking the risk cannot absolve all the others of responsibility. I as a clinician or as an IRB chair or whatever I'm doing am implicated in the choice as well, so it is not a unilateral decision. That is why simply looking at informed consent is too limited.

WENDELL WALLACH: The interesting thing about this is that it comes up in a vast array of technologies that might improve our life situation but might actually create burdens, so even radical life extension has this problem. You may be able to extend the life of the body but not extend the life of the mind, and then who is responsible for you if you live an extra-long life but you have no capabilities or diminished capabilities? It still then becomes the responsibility of the health community, of your family, or of others. There is still this deep problem of when the risk has actually been understood in terms of where it is proportional and who will be held responsible if things go awry.

This is totally in a different realm, but you are writing a biography of Lewis Thomas, who may be known to many of our listeners as a best-selling author whoseLives of a Cell: Notes of a Biology Watcherwon the National Book Award.

JOSEPH FINS: He was somebody who crossed the science and humanities divide. He wrote poetry in medical school to make some extra money, published in The Atlantic even. Later in life, Franz Ingelfinger, who was one of his senior residents when he was training at Boston City Hospital after graduating from Harvard Medical School, heard him give a lecture and said: "Why don't you write this column? You can do whatever you want. We're not going to pay you, but we're not going to edit it." It became "Notes of a Biology Watcher," and they were just elegiac, beautiful essays. He was a great admirer of Montaigne, and he mastered the essay form.

He was also a great observer of nature. One of the things that I think is wonderful about Lewis Thomas is that he was also a great scientist, immunologist, and administrator. Understanding the trajectory of his life in a way is understanding the trajectory of midcentury medicine, where it succeeded and where it failed. I think at the end he had regrets about the divorce between the humanities and the sciences, something I in my career have tried to unify in the work that I do. I think bioethics is that kind of convergence.

I think at a certain point in your life you run out of mentors and you have to look to great historical figures for guidance, so I see this as a form of self-therapy. I love reading his stuff and going through his papers. I am just getting into it. It is early on. Scientists love to be in the lab, historians love to be in an archive, and I think I have a little bit of each, so I hope that I will live long enough and this podcast will survive long enough to come back and celebrate the publication of a book, but it is going to be a long time from now.

WENDELL WALLACH: I could be wrong, but I think that future practitioners as neuroscience develops further are going to look back to you as a mentor and an inspiration.

JOSEPH FINS: Thank you.

WENDELL WALLACH: Thank you ever so much, Joe. This was truly wonderful, and we are always appreciative of you sharing your time, your insights, and your expertise with us.

I hope this has been a rich and thought-provoking discussion for you, our listeners. Thank you for tuning in, and a special thanks to the team at Carnegie Council for hosting and producing this podcast. For the latest content on ethics and international affairs be sure to follow us on social media at @carnegiecouncil. My name is Wendell Wallach, and I truly hope we earned the privilege of your time.