 Good afternoon, thanks for coming on behalf of the McLean Center for Clinical Medical Ethics and the Institute for Neuroscience, Quantitative Biology and Human Behavior. I'd like to welcome you to the fifth of our 2015 to 2016 lecture series on ethical issues in the neurosciences. This lecture series was organized by John Moncell, Director of the Grossman Institute, Peggy Mason, Professor of Neurobiology, Mark Siegler from the McLean Center and myself. It's now my great pleasure to introduce today's speaker, Walter Glannon. Walter is a professor of philosophy at the University of Calgary. He received his PhD in philosophy from Yale and has a PhD in Spanish literature from the Johns Hopkins University. He was a former fellow here at the McLean Center back in 98 to 99 and was also a fellow at the Institute for Ethics of the American Medical Association and at the Brochure Foundation. Professor Glannon's main areas of research are in our topic of neuroethics but also in transplantation ethics, free will and moral responsibility. He's published over 130 journal articles and book chapters and is the author or editor of eight books including, in 2007, Bioethics in the Brain and Brain, Body and Mind, Neuroethics with a Human Face in 2011 and most recently, Free Will and the Brain, Neuroscientific Philosophical and Legal Perspectives. Today, Professor Glannon will speak to us on the topic of ethical issues in neuroenhancement and please join me in giving a very warm University of Chicago welcome to Professor Walter Glannon. Thank you Dan and I'd like to thank the McLean Center and the group that organized this series for inviting me to come here and thank you all for coming. Neuroenhancement is, it's one of the hottest topics in the field of neuroethics but it's not new. Students have been taking amphetamines for years. When I was an undergraduate years ago, there are always a few students in my dormitory who had procrastinated and their exams or their final term papers were coming up so they would take speed so that they could stay awake for the evening and write their paper study for their exam. Fundamentally, well some of the issues have not really changed although in other respects there have been some significant changes. Today I'm going to talk about primarily cognitive enhancement which is the, when people talk about enhancement, this is the area they're primarily concerned with. Using normal, what are considered normal levels of concentration focus, the ability to execute certain cognitive tasks, using information, using working memory to concentrate better, study, do better on exams, write better, more effective, more successful grant applications. There are probably more controversially drugs that enable people to stay awake longer and whether that generates expectations for people to do things that they otherwise wouldn't be expected to do. So these generate a lot of ethical issues. What's probably the hottest topic in enhancement today which I won't address or discuss is moral enhancement. When I first heard the idea I thought it was kind of crazy, I mean, how do you enhance people's morality, but there is something very compelling and a lot of work has been written about this, about the idea of using either pharmacologically or otherwise intervening in the brain to increase our moral sensibility, that is our ability to respond to reasons that recognize, that take into account the rights, interests and needs of other people which we all too often fail to do which partly explains the magnitude of harm that exists in the world today. But I'm not going to be dealing with that today. So the objectives, which looks like an enhanced list of objectives, especially as a philosopher, I like to give about two or three and that's it. Anyway, so I'll be talking about different senses of enhancement, understanding neurobiological, mechanisms of cognition enhancing drugs. This is where the, I mean, I think the real issue is not so much efficacy. Studies have shown that they are effective, maybe not to the extent that a lot of people would have thought or would like to think. The issue really is risk and that is long-term risk of chronic use. That's not known and studies are necessary to determine that. So there is considerable uncertainty with the neurobiological mechanisms of chronic use of these drugs and that's where the risk, this is where I think the real ethical issues arise. So assessing the potential benefits of neuroenhancement against the risk. To examine whether improving mental capacities would undermine our understanding of and our attributions of authenticity and excellence. This is one of the objections that has come up, that's been around actually for a while, even before there was much research done on the neurobiological mechanisms. It was the very idea of enhancement that bothered people like Leon Cass and Michael Sandel. I'll be talking about that. I'm also going to be discussing how neuroenhancement might affect expectations in the medical profession in particular since this is a medical audience. And social justice issues, would enhancement exacerbate existing social inequalities? Would it make those who are cognitively better off, even better off and those who are cognitively worse off, worse off? And would that somehow exacerbate inequalities which are partly explained, not entirely, by people's cognitive capacities? So neuroenhancement is, as I said, it has been a social phenomenon for some time, increasingly so. Some studies estimate that approximately 25% of US secondary school students use psychostimulatory ambulance, such as Adderall, Ritalin, and ProVigil, for non-therapeutic uses. So that there's no neurological or psychiatric disorder. Now one thing, I'm going to come to this later. One question is whether there is, or whether one can draw a clear-cut distinction between therapy on the one hand and enhancement on the other. So the traditional distinction was something, any intervention is therapeutic if it treats some illness or disease. An intervention is enhancement if you've got normal levels or normal functioning and you're trying to make them even better. A lot of people, John Harris, for one, have questioned this distinction, arguing that our physical and mental capacities really fall along a spectrum and you can't really draw a line and say that well on this side it's therapy, on the other side it's enhancement. But I think there's a lot to be said for maintaining that distinction and implicitly at least I'm going to be operating on that. One study by Heinz and colleagues, this is in the Journal of Medical Ethics a few years ago established that roughly five percent of the working population in Germany take psychotropic drugs to enhance cognitive functions. So that's just Germany and the U.S. In 2008, one-third of 1,400 readers of the journal Nature admitted that they had used psychostimulants for non-therapeutic purposes. Over the reasons, well, sustained concentration for longer periods formed better on exams, more successful grant applications, work more effectively and efficiently with less sleep. So these are the main reasons. There's a neurology resident at the University of Calgary who has just done a study, hasn't published the results yet, of neurology residents and whether they use neuro enhancement drugs and the reasons for taking them. So it'll be interesting to see what his results show. They should be coming out soon. One of the first discussions of the idea of enhancement was, well, the chapters in this book edited by Eric Perens in 1998, it said that any intervention designed to improve human form or function beyond what is necessary to restore or sustain good human health. So it's basically, it's an augmentation of mental function, normal mental function. Normal, I'm just going to use that the way most people intuitively, commonsensically use it. That is, there's no impairment, it's a species normal, species typical normal functioning. It suggests increasing the cognitive capacity to focus or concentrate on specific tests. So for example, methylphenidate without ADHD, modafinil taken by people who don't have epilepsy or dysfunctional sleep wake cycles, pilots to stay awake on trans-consonental long flights or surgeons to stay awake longer when they're performing surgeries. I should stop here and say something I should have said a little earlier. The neuro enhancement debate really started in 2003. Now I distributed a paper by Martha Farrah and a group of ethicists and neuroscientists from Nature Reviews Neuroscience, which was published in 2004. Some of you, the fellows I think have that, it's called, I think it's just neurocognitive enhancement, what can we do and what should we do? And that was 2004, but the paper that triggered all of this debate was by a neurologist at Penn, Anjan Chatterjee, and he published a paper in neurology called Cosmetic Psychopharmacology. And he said that there were patients coming to him who did not have a neurological disorder and yet they wanted to improve what they acknowledged, recognized to be normal functions. So he said a number of patients were coming to him to prescribe certain medications to help them improve their neurological and psychiatric mental function. So he wrote this paper, it's really triggered a lot of debate. So that was really the beginning of this debate on neuro enhancement going back to 2003. So there's the augmenting conception of neuro enhancement, which is the conception I think intuitively most people have. So you're trying to increase, you're trying to add to something. And yet in a paper, interesting paper published a couple of years last year, Brian, or actually Julian Savalesca was one of the co-authors on this paper. And they said that, well enhancement can also be a type of diminishment or there's a diminishing type conception of enhancement. That is sometimes the diminishment of a capacity or function under the right set of circumstances could plausibly contribute to an individual's overall well-being. More is not always better and sometimes less is more. And one of the examples they gave was Ritalin, methylphenidate, if it enables, insofar as it enables the individual to reduce the content of their thought in concentrating better. So you have actually in a sense a reduction of the content or the extent of your mental content when you're doing something that enhances your function, but it does so in a way that in a sense diminishes your mental states or the content of those states. So it actually blocks out what would otherwise be distracting stimuli. And then there's what we could call an optimizing conception. This I think is the most plausible. When you think about the risks and the potential benefits when you're weighing all of these things, because there are trade-offs and I'm going to give a couple of examples. This was a very good chapter co-authored by Thomas Metzinger, who was a philosopher from Germany, and Elizabeth Hilt, who I believe now is in Chicago, not at this university. And their idea was that enhancement, it's any intervention in the brain that aims at optimizing a specific class of information processing functions, cognitive functions, physically realized by the human brain. So the goal is not just to improve performance on a specific cognitive task, but to do this as part of promoting flexible behavior and adaptability to the environment. Optimal suggests that there are limits to the extent to which cognitive functions can be improved. This gets the idea of trade-offs. Optimizing. This is an actual case. This is not science fiction that I'm mentioning here. I don't know how many of you are familiar with deep brain stimulation. Most of you probably, okay. So if you're not, so this is for, it's FDA approved, well, it's approved in most countries for motor disorders, Parkinson's, dystonia, essential tremor. It's got a humanitarian device exemption for OCD back in 2008 or 2009. It's still experimental investigative for depression, major depression, and so on Anyway, for some psychiatric disorders. So there was a case, so electrodes are implanted in the brain in a targeted region associated with the dysfunction. Electrical stimulation, the intention is to modulate the circuits that are dysfunctional and to restore normal brain function and the motor function or the mental functions associated, that they mediate. And so their electrodes implanted in the brain, they are connected by leads to a pacemaker, which is usually implanted under the collar bone and they are, they can be controlled by a handheld device or computer. But usually the parameters, the device is controlled by the medical practitioner. There are cases, however, where the patient has to have control. For example, going through airport security could trigger an alarm. I mean, there are other reasons for it. In this case, this was a psychiatric patient. Matthew Sinovic is a neurologist from Germany. Schlafer is a psychiatrist. He's done a lot of deep brain stimulation on psychiatric patients. And Joe Finns, many of you probably know, he's a medical ethicist from New York. This was Schlafer's patient and he had generalized anxiety disorder and OCD. Don't worry, the talk is not going to become one on deep brain stimulation. I just want to make a point here. So the deep brain stimulation improved his symptoms of anxiety and the obsessions and compulsions. And he told the psychiatrist that he was feeling better, but that he wanted to feel even better than that. So the neurosurgeon, the psychiatrist, he asked them to increase the frequency of the stimulator and they did it. And he said that he felt unrealistically good. He was overwhelmed by a feeling of happiness and ease. The significant thing here is that he didn't become completely hypomanic, he retained insight into his condition of what was going on. And he said it was really too much for him and please lower the frequency back down to a level. Who knows at what point he would have become hypomanic and just would have lost insight and the capacity to make decisions in consent, which raises other issues I won't go into. But anyway, so he requested lowering the voltage back to an optimal level and everything was fine. So this is a good case I think that illustrates the optimizing conception of enhancement. That there are, that beyond a certain point enhancing strengthening cognitive capacities can actually lead to pathologies, maladaptive or pathological behavior. So even if one adopts an augmenting conception it has to be qualified. Okay, so some of the neurobiology, this has been, what's known so far from the studies. I mentioned Martha Farrah's paper which was multi-authored, there were about seven or eight authors. Very, very good paper and the studies are very solid on which they base their results. So basically what the drugs do is they increase circulating levels of dopamine in the brain. The aim is to improve attention, concentration, processing and retrieval of information and working memory. Interesting, studies indicate, most studies, okay, that those with a lower, that is an absolute, on an absolute scale, lower baseline of working memory tend to benefit more while those with a higher baseline tend to benefit less. So those with a higher cognitive baseline in most studies do benefit but it's not that significant. Those with a lower baseline, again on an absolute scale, tend to benefit more. So this is one component I think for this, for deflating some of the concern about enhancement exacerbating social inequality. Insofar as intelligence, however you want to define that, or cognitive capacities are part of one component of an explanation for social inequality. The study by De Jong at all, this was in 2008 also, very good study. Actually the paper by De Jong or De Jong is a meta-analysis of a number of studies. Also, and most of the findings in these studies have been replicated in additional studies. Methylphenidate produces inverted dose response curve in experiments with healthy subjects. Moderate doses improve performance on cognitive tasks while higher doses do not affect. In some cases they even impair performance. The drug enhances executive functions on novel tasks but impairs functions on tasks that have been learned. So medaffinal axon dopamine, actually what I just said I'm going to, there's a slide coming up where involving transcanial magnetic stimulation, the same sort of findings. So medaffinal axon dopamine, norepinephrine, and histamine blocking the effects of hypothalamus on sleep, it enables enhanced focus and alertness even when sleep deprived. The outcomes are similar to methylphenidate. So medaffinal enhances alertness, attention, spatial working memory, visual pattern, recognition. These improve moderately and those are the higher working memory baseline and more and those are the lower baseline but not significantly more. So the benefit is not significant. The differences between the cognitively better off and the cognitively worse off is not that significant either. Okay, this, sorry. This is a study by Yukolano and Kaddash using transcranial magnetic stimulation. This is not as invasive, still invasive because it does alter brain, it can alter brain circuitry. These are coils that are on the head so I mean there's no intracranial surgery involved. What these two investigators did was they used transcranial magnetic stimulation to stimulated regions of the cortex when individuals were engaged in certain mathematical tasks and to see whether there were differences depending on which areas of the brain were stimulated. And so what they found was that stimulating an area of the prefrontal cortex improved learning new information but impaired the application of the inflammation. And then conversely stimulating a different area of the prefrontal cortex improved the application of existing information or information that already learned but impaired the learning of new information. So this is a good example of, now it's just one case, but it does, it is consistent with other studies indicating that there are, there can be and indeed often are cognitive tradeoffs. So certain psychostimulants or more invasive forms of electrical stimulation of the brain can enhance or improve certain functions but they often come at the cost of others. So the upshot is, this is not the conclusion, enhancing some cognitive functions with psychostimulant drugs or electrical brain stimulation may come at the cost of other cognitive functions. There do seem to be cognitive tradeoffs. The study results raised questions about the augmenting conception of enhancement and they seem to support the optimizing conception. Okay, so let's now talk about modafinol and sleep deprivation. So prolonged sleep deprivation from chronic use of modafinol could result in adverse metabolic and endocrine changes. Now this is just one of the risks. Again, as I said at the outset, more longitudinal studies are necessary to actually show that this is the case. But it is at least one of the risks. Alteration between sleep and attention or adaptations to the environment. The brain senses that constant attention is a sign of constant demand and this could overload. This is one of the concerns, I didn't mention it was Robert Stickle, the memory researcher at Harvard. He and others have this concern. So I'm not just, this isn't just me. Unnecessary weightfulness can be more problematic than unnecessary sleep. Nora Volkov in JAMA back in 2009 and I think since then she's published some articles on this. It has the same concern of people like Stickle and others about using modafinol. Chronically, chronic use of modafinol. But again, these are risks, they haven't actually been quantified to the point where there could be some sort of precautionary principle or some reasons for limiting or even prohibiting these. The research, the data just aren't there. So the risk of addictive behavior from increasing circulating levels of dopamine with cognition enhancing drugs. Think of the case of the guy with GAD and OCD who wanted to feel even better and he felt too good or too well. Same sort of thing could happen with psychostimulants. So studies indicate that dopamine and norepinephrine don't display linear effects but instead an inverted view curve in their effects on neural and mental function. Healthy individuals run the risk of pushing themselves beyond optimal levels into hypodopaminergic states. Hyper, sorry. Resulting in adverse changes of behavior that enhancement is intended to improve. Similar effects happen, have occurred. The frequency of it has decreased because of more careful implantation and adjustment of stimulation parameters. But in deep brain stimulation, this was one of the sequelae of deep brain stimulation for Parkinsonism early on. The motor symptoms were controlled but at some of the patients it resulted in compulsive behavior, hypersexuality, gambling. And it was because of the limbic region of the basal ganglia that was being affected by the stimulation. So the mechanism here could be, well in some respects it could be similar. So this is one of the concerns about the risk. Prohibition, I mean does it mean that just because there are risks that they should be prohibited? No, I mean the data just don't support it. The data are incomplete and inconclusive, need for more clinical trials, testing the safety and efficacy. I'll underline safety there, not so much efficacy. And without that there's no justification for a precautionary principle that would limit or prohibit its use. It really should be a matter of autonomy, individual choice. But autonomy entails responsibility. So if an individual is going to engage in or take a neuro-enhancing substance, then he or she should also take responsibility for any of the consequences of that. Medical costs, someone once suggested to me that maybe enhancers should pay higher insurance premiums. A lot of this will depend also on the country in which the individual, the healthcare system. But anyway. So I think for now without better data it really is an issue of autonomy. There is a problem about individuals going to their healthcare providers and asking for prescriptions for these things. And I'm going to mention that. So at the outset I was talking about whether the therapy enhancement distinction is a helpful one that a lot of, that our functions, our physical and mental functions, fall along a spectrum and it can be oversimplified and misleading to say that, well, at this point in the spectrum we should be talking about therapy and at this point we should be talking about enhancement. But if you're talking about normal function versus illness or disease, I think there are reasons for keeping the distinction, at least practical, pragmatic reasons. I mean here's, I mentioned this case of, sorry, I keep coming back to deep brain stimulation. There was a study published in 2010. This is a Canadian group led by Losano really in Toronto for patients with early stage Alzheimer's. And they stimulated the brain and wouldn't you know it but the cell phone went off. No, the iPhone went off, no. So the, sorry I do this to my students all the time. Memory, the working, spatial working memory did improve in some of the patients. And you know the question was some of the descriptions of this case after it came out was that, well this is enhancement. Well they have a pathology and the intervention improves their condition. So I mean I thought of this as more of a form of therapy. I suppose whether it's therapy or enhancement is going to be, depend on how one describes these interventions or what the outcome, the goals of it are. So there are reasons for describing interventions for pathologies as therapy and interventions for improving functions within a normal range as enhancement. And in fact if you read the FARA article right at the beginning in the introduction, they talk about mental function enhancement for mental function and healthy people versus treatment for mental dysfunction and people who are ill. So they do draw the distinction. Even they're talking about neurocognitive enhancement, what can we do, what should we do. But they do draw the distinction right from the outset between normal functioning and healthy people and pathologies, illness, disease. And that is not for them enhancement. So deep range simulation is one way that we could do, we could enhance people, but in light of what's involved I don't think many people would opt for that, unless they have to. Okay so I've talked about addictive behavior. Okay propranolol, this beta blocker which, this is an indirect enhancer, I can't think of a better way to describe it. This is disturbing to me because a lot of my students take this. And why do they take it? They don't take it because they have arrhythmia or they are hypertensive. They're nervous when they give a presentation at a conference or in class. And several of them have told me that it calms them down and they think it improves their performance. So it doesn't directly enhance their cognitive capacity to, you know, using working memory or doing a presentation or responding to questions. But it dampens the biological response to anxiety or stress. But and I say it's disturbing not so much because I'm concerned about excellence or authenticity. It's because one of them told me that he, when he crosses the street, he was using it pretty much on a chronic basis. He wasn't so much concerned about traffic or anything. He didn't seem to have the same fear response. Now this is subjective but I mean there is some concern about whether natural fear or, yeah, fear responses to certain stimuli would be effective. I mean there is an authenticity excellence objection to this and I'll get to it in a few minutes. So, you know, are the risks worth the benefits? Again, it's really a question of individual autonomy unless and until we've got better data about the risks. Now there are, you know, these have to be, you know, the research is necessary to test these things. This is a more problematic in moral enhancement which I don't have time to get into but research into the addictive potential for example of a neuroenhancing drug, it raises ethical questions. So the participants would be healthy subjects with no history of addiction. The goal wouldn't be to understand addiction as such but only whether the drugs designed to enhance cognitive functions would cause addictive behavior. So those in the experimental arm of the trial receiving a psychostimulant with heightened dopaprenergic effects and the reward system would be exposed to a potential addictive substance. This is, this was discussed by Heinz et al. I mentioned them. They noted the 5% of the German population engage in enhancement. But their main concern in this article in the Journal of Medical Ethics was with the risk of research trying to determine the risk of neuroenhancing drugs. What they say is to date no single variable has been identified that reliably predicts addiction to neuroenhancers. To identify such precise factors a substantial number of subjects would have to be exposed to potentially addictive drugs and prospective studies. Since these healthy volunteers do not have a disease, the risk-benefit ratio for such exposures remains rather unfavorable. There's also potential conflict between the researchers' duty of respect for subject autonomy and the duty of non-maleficence, which always comes up in the doctor-patient relationship, but we could extend it to the researcher-research-subject-participant relationship, especially no actual disease or disorders being investigated. It has to be weighed against the duty to generate scientific knowledge. So how important is the scientific knowledge that needs, that requires research to generate the scientific knowledge? We're talking about enhancers versus some intervention which is traditionally considered to be some form of therapy for a disease or dysfunction or pathology. So again, the question is should there be a prohibition? If there's no disease, if the benefit is modest and the risk is unknown, the ethical calculus for some, Heinz, not others, not everybody, but for some is that it provides reasons against it. And I mean another issue here is prescribing drugs to improve normal cognitive functions might be an inefficient use of limited health resources in a publicly funded health care system. This is one thing I hear in Canada. I don't know what it would be like in the U.S. where they have a different system. Okay, so placebo-controlled clinical trials would be needed to establish the safety and efficacy. Scarcity of health resources and more urgent need for prevention and treatment of neurological and psychiatric diseases intuitively at least should give lower funding priority for enhancement research. There seems to be a stronger justification for funding research aimed at establishing safer and more effective interventions for restoring normal brain function than raising it above a normal level. So what should a just society pay for? I mean these are broader questions. Some people might think that these are beyond the scope of the enhancement debate. I don't. What should a just society pay for in distributing limited health resources to its citizens? Treatment that ensures or restores normal function and cognitive functions is necessary for a decent minimum level of well-being. So let's think of health care, all these interventions, as contributing to the welfare of the population. And so far as neuro enhancement raises cognitive functions above a healthy level, it's questionable whether the state should pay for resources associated with enhancement, even if it could afford to pay for them. Some people say we should leave it up to the individual. Again, a matter of individual autonomy. Okay, let's get back to the trade-offs. I'm raising this because I was at a philosophy conference and there was a philosopher who kept bringing up this issue of the idea that some people only need four hours of sleep. And maybe if maybe they're just wasting those extra three hours. I'm sure a lot of you don't even get that much. So I mean one study here is that some people can function well in four hours of sleep per night. So the proverbial seven hours. So this is not medical, okay. Is it necessary? So for those, this is the comment I heard from the philosopher. Those who only need four hours of medaffin could enable them to avoid wasting the three unnecessary hours and allow more time for meaningful and productive activity. I'm not making this up. Now among other things, it may be too much, assuming too much to claim that chronic use, if it's chronic, would not have any effects on neurophysiology other than sleep wake cycles. Okay, but suppose, okay, so here's the philosopher now. Suppose that medaffin will safely enable the surgeon to perform more surgeries outside the four-hour period. So the surgeon would be, this is all hypothetical, okay, more focused and alert for longer waking periods. Would it be reasonable for him or her to increase the number of surgeries they perform? So this is a question that arises. I've not heard people, medical professionals, raise this. It's usually people, some people in the bioethics community, about these expectations. Would it be reasonable to expect them to increase the number of surgeries they perform? If the answer is a weak or tentative yes, then that raises the question of how you weigh individual professional autonomy versus consequentialist considerations. At some point fatigue would set in, more surgeries would be performed, but some patients operated on near the end of the wake cycle could be at risk. For me, I think it's just extending some of the same issues that have been around for a long time. So they might be responsible for more surgeries, but they wouldn't be more responsible for performing an increase in the content of responsibility, would not entail an increase in the degree of responsibility. So I mean this is just one of the possible ways in which enhancement might affect the way people think. Would we, and it's, I don't even know, I mean it's just something to think about. Would professional expectations increase and would that be reasonable because of the effects of these drugs? So this philosopher said that if he were to undergo a surgery like coronary bypass and he had a choice between a surgeon who was not on midaphanel and one who was, he would say he would take the one with midaphanel. So, but again, the research is needed to determine whether, you know, what sort of effects that would have. Okay, sleep-related cognitive impairment would still be an issue. Maybe the temporal extent of it would change a bit with the drug, but fundamentally I'm not sure the issues would change. Okay, authenticity and excellence now. This, as I said at the outset, this was one of the first ethical objections to the idea of enhancement that the person taking the drug wouldn't be the author of his or her actions. They couldn't take credit for what they did. They couldn't be praised. Usually it's described in positive terms, not negative or blame for it. So something else is doing the work. And I can't take credit because I am not doing it. Some alien thing, something external to me is doing all the work. The positive results would be due to the drug rather than the efforts of the person taking it. They wouldn't be our own. Leon Cass in his book, Beyond Therapy, says the lack of authenticity which would be associated with this idea of neuro-enhancement is part of his critique of enhancement in general. It's a departure from genuine, unmediated and in principle self-transparent human activity. Michael Sandel in the case Against Perfection, also he doesn't focus on neuro-cognitive enhancement as such, but enhancement broadly construed. Basically the idea is excellence in achieving goals as a result of one's own efforts in exercising one's natural capacities. Neuro-enhancement undermines excellence by making outcomes depend on a psychoactive drug rather than one's own sustained physical and mental effort and character traits. Neuro-enhancement is symptomatic as a desire for perfection and absolute control of our lives. So it's hubristic and that's the objection. Oh wait a minute, not to the butt yet. Using propranolol, this is the sort of indirect enhancer, for taking some of the edge off anxiety when experiences and musical performance could improve them in some respects, but it could weaken the emotional response associated with audience interaction and detract from the meaning and positive feeling one gets from these. I knew, well I interviewed sort of a violinist from Washington who was taking propranolol on a chronic basis because she was very anxious before performances and recitals and she said that it actually did improve her performance, but there was something missing. She said it's very subjective, it's not the sort of thing, it would be very difficult to quantify in some way, but she said there was something missing from her performances and she also felt guilty because she had this concern about authenticity and excellence, that the drug was doing a little too much and she wasn't doing enough. Not everyone feels this way, but it is one of the responses that people have. And she did basically say that propranolol could threaten authenticity and excellence, that his performance anxiety is a state that one should face and overcome through one's own efforts rather than through psychopharmacology. Now not everyone would agree with this, but this was one concern she had. So that there could be an emotional cost to engaging in this indirect neurocognitive enhancement. Now coming back to Sandell and Cass' objections, Alan Buchanan, a very nice, concise book on enhancement in response to Sandell, some of Sandell's concerns and criticisms, basically says the desire to improve the capacities and dispositions in which we make choices does not imply a desire to master or perfect them. So it doesn't entail a hubristic wish for complete control of our lives. Even in a world of pervasive and powerful biomedical enhancement, we still have plenty of opportunities for appreciating that many of the good things in our lives are not our accomplishments, not subject to our will. So enhancement doesn't entail this sort of desire for complete control over what we do in our lives. So taking one of these drugs doesn't guarantee outcomes either. Just because you have the drug doesn't mean that you're going to get what you want. Outcomes that would have obtained with the drug, it would depend on, I think I should have said without the drug, sorry, it would depend on how one used any cognitive boost it provided. Many achievements result from the combination of personal effort and enhancements. So many people have pointed this out, well, why do we focus on drugs? What about trainers, tutors, all other forms of enhancement that are around us? And many of us, most of us avail ourselves of these things. Why should we focus on drugs? I mean, there is this idea that something special about the brain and the brain-mind relation and that the effects are more immediate, but if we're talking about the ethics or the ethical objections to enhancement, that has to be qualified by all the other types of social, cultural enhancements that we have in our lives. So it has to be contextualized. Great quote from Margaret Talbot in the New Yorker in 2009. It was on enhancement. She said, even with the aid of a neuro-enhancer, you still have to write the essay, conceive the screenplay, or finish the grant proposal. And if you can take credit for what you've done on caffeine or nicotine, then you can take credit for work produced on provigil. So, again, why are we distinguishing, why are we focusing on psychotropic drugs when we have all these other forms of enhancement? And what is it about taking a psychotropic drug that has all these ethical concerns of the other stone? Okay, social justice issues. This is, apart from authenticity and excellence, this idea that I've mentioned this a few times, that enhancement would somehow exacerbate existing social inequality. So there may be coercion from employers or employees to use neuro-enhancing drugs to increase productivity. That would be minimized if the effects of neuro-enhancers on those with a high cognitive baseline are minimal. This is why it's so important to have the data so that people don't have a misrepresentation, a misunderstanding of what these drugs actually do. And Farah and De Jong, in particular, they pointed this out in their papers, that concern about the potential impact of the drugs on productivity may be out of proportion to their actual effects. There are positive effects, but they're modest. If the cognitively worse off experience more positive effects on the drug than the cognitively better off, then the general use of enhancers would not exacerbate social inequality. Not that it would improve it, but it wouldn't make it worse. Okay, this is a very, I mean, basically the idea is the dotted line is that you've got the worse off that is cognitively better off and worse off above a decent minimum of physical and mental capacity. So this is a baseline of normal species typical functioning. And if the worse off that is comparatively are above that decent minimum, then there really isn't or shouldn't be an ethical issue, okay? As long as they're above that decent minimum. This is an idea that in philosophy comes from Harry Frankfurt. It's not so much inequality per se that matters. It's where people fare relative to or in terms of a baseline, a decent minimum of functioning necessary for a decent minimum level of well-being. So in B, if you've got the worse off below that minimum and you could somehow give them the enhancers or the drug, whatever you want to call it, the intervention, whether it's therapeutic or enhancing, to bring them above the baseline, then I think there would be strong more compelling moral reasons to do that. But if they're both above the decent minimum, I don't think it really matters that much. And the, you know, A is really, I mean, this is the model that most of the research involves. That is, the worse off are still in absolute terms pretty well off. We're not badly off. Okay, so some concluding remarks. There have been groups that have given recommendations on the presumption that mentally competent adults should be permitted to engage in cognitive enhancement. This was a group, wow, it's been seven years already, Hank Realy and others, similar to the work that Martha Farrah and her co-authors did. This was a group of ethicists and neuroscientists, legal theorists. So they came up with these recommendations. They were published in Nature. And the four main recommendations were, there's got to be evidence-based approach to the evaluation of long-term risks and benefits. This, I think, is the most important issue. And until we get the data, it's incomplete, inconclusive, and the debates are not going to be as constructive as they otherwise could be. Formulation, implementation, enforcement of policies regarding use of cognition, enhancing drug support, fairness, protect individuals from coercion. I think if the knowledge of the actual effects that they have would minimize that and minimize enhancement-related socio-economic disparities, I think the last two go together. Research priority, I think prevention and treatment of neurological and psychiatric disorders. Again, going back to the first paragraph of the Farrah article, Farrah article. If you're dealing with a disease or illness, research priority should be given to that rather than improving normal neurological and psychiatric functions. There are scientific and ethical problems with trial design and endpoints. I didn't really get into this. This could be a major issue for the research necessary to do these studies, especially with moral enhancement. And the data thus far inconclusive need for more longitudinal studies. There's no justification given the lack of adequate data for a precautionary principle prohibiting or limiting individual right to enhance. And basically, I would say user beware. I mean, so we should give weight to autonomy if individuals want to enhance, they should be able to. I didn't get into the idea of whether physicians would be permitted to prescribe these drugs. But if you want to raise that, that's fine. But if individuals do exercise their autonomy taking neurocognitive, neuroenhancing drugs, they have to take responsibility for the costs of any adverse effects. And let's just use costs very broadly there. So I will emphasize autonomy, but the idea of responsibility as well. Thank you. Thanks, that was very thought provoking. I'm thinking in the social justice realm that there's another concern, which is that you've made a non-level playing field. And while I take the quote that you took from the New Yorker article, there is a huge difference between caffeine and nicotine, which anyone can go out, as long as they're, in the case of nicotine over 18, they can go out and buy versus one of these prescription drugs. And so taking aside whether this is fair or not to the person, it's really changing the rules for everybody else in society. Yeah. I mentioned the Heinz article, one of the things he does is he says there is a significant difference between caffeine and some of the psychostimulants in terms of the effects on the brain, and that significant difference has ethical implications. But could I ask you, you said something about level playing field at the outset, so what could you... Well, if some people have access to X-drug and it works beautifully and enhances their cognitive output by X percent, and therefore they get a bigger chunk of whatever pie they're looking for, the people that don't have access to that enhancer are working at 100 percent, and are losing out on the pie. It would depend on the effect that the enhancer actually has. Studies indicate that the effects are modest. Also, I mean, another question is if you're talking about a level playing field, if the playing field is not level to begin with, what are some of the other factors? And if there are other factors that could explain why the playing field is not level, what those factors interact with these sorts of things that people are doing? Would they augment? Would they increase the effect? Would they cancel it? Would they neutralize it? I mean, that's another issue. So one of the problems, I mean, it's that you're... Sorry, for me getting at it, is trying to isolate the question of taking a particular drug, some sort of a substance, and thinking about the effect it's going to have, taking it out of the context, the social, cultural, the larger context in which all of these things work. If you're talking about a level playing field, what are all the different factors that make people socially, as well as cognitively better off or worse off? Hi. My question was on exactly that point. When I saw your... Thank you very much. I learned a lot from your talk, and I really enjoyed it. But the social justice point, it seemed to me that the picture that you showed removed all those contextual things that you just referred to. And so, and I understand that what you were trying to map out was this question of how much one cognitive situation benefits compared to another. And so if you only think about a community in terms of its cognitive situation before they take the pill, then you could claim that there was not such a big justice issue. But it seemed to me listening to you at that moment that it's almost like you were implicitly saying that this was a cognitive justice issue as opposed to a social justice issue. Because if you factor in... I know you weren't actually saying that, but as I heard it, that's how it struck me, because if you then have to factor in all the contextual stuff, who's going to have access to these drugs? And who could maybe maximize the benefit that they bring because they could or could not hire tutors and all that stuff that was talked about in the New Yorker article, then I think maybe the social justice issue becomes more complex because the contextual factors affect... they might create greater irregularities in terms of how access and also how you can arrange your life to maximize the benefits that could come from using these drugs. Okay, so the cognitive enhancement would be one component of the whole context you're talking about. So if you're talking about social justice, that's just one component. What's not known is how in these studies, they're studying the effects of these substances on the brain and the mind. What's not known, what's not included in the studies is how they interact with these other factors. And until studies do say something about the interaction of all of these different factors, how cognitive enhancement, how taking a drug is going to improve an outcome, a desired outcome, without taking into account all these other factors, non-neurological, non-neuro physiological factors, then the question of whether, to what extent, cognitive enhancement is going to affect social justice, I think there's just no answer to that. Yeah, I have a couple of questions. So to the extent that I think to some extent your distinction between therapy and enhancement is artificial because to a large degree, whether or not diseases are defined in part by our therapies. And when the therapy works, then we call it a disease. So for ADHD, if you have a kid in a classroom with 40 other kids and he's running around and not being quiet and you give him the drug and he sits down and concentrates, is that enhancement or is that treating a disease? So I think it's a very complex issue that is oversimplified by that distinction. The other thing is you call for more evidence. I think it's pretty clear what speed does to people. And the fact that you have to crash, there's a law of the universe. Energy cannot be created or destroyed, right? You have to pay back. When you stay up all night taking speed, the next day you're going to sleep all night. And that's known. And then you see people who are speed freaks, you know that there is something about it that will make people want to take a lot of it. So I don't think we need that much more evidence about the detrimental effects of it. You know, the question is, should people be allowed to expose themselves to that? And should doctors be involved in it? And what kind of profit should doctors make when they're doing that and the incentive is there? It gets extremely complicated. Commender, do you want me to respond? Oh, yeah. Yeah, there have been noted deaths of people taking dextronomphetamine for enhancement. The other drugs, the issues seem to be a little different. I mean, fundamentally you could throw them all under the same, in the same category. But I think there are differences that could be significant between the different types of enhancers and the reasons people use them. But I agree with what you say about speed. So thanks for a very interesting talk. I wanted to ask for you to provide a little bit more detail about what you mean by these drugs being a matter of adult autonomy. So do you think that they should be available on demand without a prescription? Or if a prescription is required, what should the standard be? And I also wanted to ask very quickly, would you say the same thing about physical augmentation? So I suppose somebody wanted to take anabolic steroids or have elective surgery in order to make themselves perform better physically in the near term. Do you think that that should also be sort of available as a matter of adult autonomy? Okay, so intuitively I would agree to the idea that someone should have the autonomy to take them. The problem is when the availability depends on a medical professional prescribing it. Even if you want to say that the individual has a right to it, that would be at most a positive right. It would be a claim on someone else, which doesn't necessarily entail an obligation or responsibility of the other person to do something to meet that claim. So, and I didn't... What? So no, okay, so someone goes to a doctor and they say, I want this prescription. If you're going to talk about autonomy and the idea of a right, it's at most a positive right. It's not like a negative right of refusing treatment that you don't want, okay? If we're talking about a positive right, rights entail obligations or responsibilities on other parties. And the question, it's a very important one, is what obligation or responsibility does a medical professional have with these issues? Should they be prohibited from prescribing a drug which a patient wants to... Well, you know, the example you gave. So that's, you know... So the patient with the individual... Yeah, patient autonomy, how does that relate to professional responsibility? These things have to go together. Good, okay, yeah, sorry. Want to respond back a second? Can I say one more thing to Dan? Okay, sorry. Is it okay? Okay, I'm just trying to think of a case. So testosterone replacement therapy, okay? So I think I did say, and I should emphasize, I mean, you're right about the artificial distinction. A lot of these functions follow along a spectrum. So there are some men who want testosterone replacement to feel better. They're just not feeling that well. There are others for whom it could be the cause of anemia, it could be the cause of osteoporosis, and so that, you know, without getting into the therapy enhancement distinction, I would just say that there are more compelling medical reasons for intervention in a case where the levels are so low that they do seem to involve disease or some sort of pathology. And so we have to be careful in describing the condition along that spectrum. Thanks, Walter. So I have a question. You didn't address any part of this with regards to children, where parents are making the decision on behalf of their kids. And I guess my one question I'd like to pose to you is do you think the enhancement therapy debate is more important or as irrelevant to pediatrics as it might be in adults? No. Okay. More important because, well, among other things, if we're talking about someone who doesn't have decisional capacity, other people are making decisions for them, and that's just one factor. Developing brains, developing bodies, I would say it's even more important the issues. And these have to be, again, contextualized with all the other enhancements that we have. But yeah, I mean, those two issues I mentioned are just two of them. So I would say, yeah, it's more important. Waiting to a 30-year non-fundable study. Thank you. This might be slightly off topic, or maybe it's on topic, but it might not be something you thought about. But I've read that the armed forces have been giving pilots drugs, and I'm not sure which ones exactly to keep them flying longer on longer missions and presumably more deadly missions. And I wondered if you see any substantive difference. I don't know whether what they're doing with that is an experiment or simply a practice that they're not really examining. But if you see any substantive difference between that and, say, the mustard gas experiments that they've also done on the members of the armed forces in both cases without informed consent, obviously. Is there a difference between them? It would depend on the goal, what the intent of the intervention is. I mean, just what is it that those providing the substance intent to bring about? Consent issues, risk issues, all of these are there. I should also point out that a lot of the things that I mentioned and some of the devices that are used, that is electronic devices, have come from research involving DARPA. So a lot of these things actually are coming from the military. So there are concerns. So I mean, the consent and the risk issues are the same. But there are substantive differences based on the different substance. Nice way of putting it. Before we got to thank Professor Glannon and a couple of announcements. First, he mentioned a few times during your lecture about the possibility of moral enhancement. Julian Savalescu will be coming here on February 24th to deal with that issue. So be prepared for that one. Second, to know that there's going to be a little bit of a hiatus for a few weeks. And our next session will be on December 2nd when Jason Carlawish from Penn will be talking about status, capacity and autonomy in enrollment of subjects in research. And then lastly, with Mark in the back of the room, I could not possibly do other than to mention that on November 13th to 14th, the McLean Center's Annual Clinical Medical Ethics Fellow Conference will be taking place over in the law school and you're all invited to come to that. So unless Mark, you have another announcement, I think that takes care of it. Please join me in thanking Professor Klein and for a very similar... Thank you.