Neurology portfolio project on cognitive enhancement

Part I

Jim and Steve are good friends and love to play tennis against one another, probably because they are quite evenly matched. The games are very exciting for them and it helps balance their lives. They are both very competitive and are always trying one-up each other. To this end Jim’s wife purchases a lighter racket for his birthday, and with this new and improved racket Jim can now add a few extra mph on his serve, this edge has noticeable effects on his game and he begins to win more than the average number of matches with Steve. As they are walking back to the locker room one afternoon, Steve remarks about how Jim’s new racket has really helped his game and inquires about it.

At this point, please stop and consider whether you think is it fair for Jim and Steve to continue to play tennis even though Jim has a technical advantage by virtue of his lighter racket. Is it ethical for them to play if the object of the game is to win? Is it ethical for them to play if the object of the game is maximal competition?

Over dinner with his wife, Steve remarks that if he only had a lighter racket he might again be winning his share of matches against Jim. Soon they are on their way to the sporting goods store to buy a lighter racket and Steve’s wife asks why if the point of playing tennis with Jim is to have a fair competition should we have to buy a new racket, why can’t Jim just use the old racket and save us the money? Steve says that Jim will not stop using the new racket because Jim likes the elevated playing the racket provides and will not go back to a heavier racket, so the only answer is for Steve to get the new lighter racket too and level the playing field again. And this is exactly what happens. Now, Jim and Steve are having even closer matches with faster serves, and the competition and excitement has increased to the point where a few people come regularly to watch their games. In fact their most recent match on Friday went for 3 hours and as they were walking back to locker room Steve reflects on how tired the match made him and how they were both missing a lot of points because of their fatigue. The idea dawns on Steve that if he could become more accustomed to playing while being this tired it might give him an advantage against Jim. So for the next month Steve wakes up every morning and runs until he becomes as tired as he did that day on the court and over time he finds that it takes more and more running to make him that tired. The next time Jim and Steve play the match goes for 2.5 hours and it is very exciting, but it is clear to Jim, Steve and the ever growing number of spectators that Steve was not as tired during that match and even more, Steve appeared faster on his feet and these abilities allowed him to very clearly appear as the dominant tennis player. As they are walking back to the locker room Jim remarks about Steve’s superior speed and stamina.

Do you think Steve’s early morning running is fair? Does Steve have an ethical duty to disclose to Jim about how his early morning running is helping his tennis game? Is it just for Steve to maintain this advantage if Jim is unaware about the physiological benefits of running?

Because they are such good friends, Steve tells Jim his about how his early morning running is enhancing his speed and stamina. At home, Jim realizes that if he is ever going to be competitive with Steve again he too will have to make early morning running a regular habit. Well, Jim is very competitive so he decides to run, and he runs until he is extremely tired. In fact Jim’s runs starts earlier and finish later than Steve’s. While having dinner with his son, the medical student, Jim complains about how his muscles are very sore from all this running. His son remarks that if he eats more protein his muscles will recuperate faster and he may be able to increase the benefit he receives from all this running. Jim follows the advice of his son and increases the caloric content of his diet, his increased fat and protein intake has a very noticeable effect on both his early morning running and his grocery bill. When Jim and Steve play their match it goes on for 3.5 hours and is very exciting, the level of their play has elevated greatly and many spectators at the tennis club now watch their match. In set 15 of the last game of the match in front of a not insignificant crowd, Jim hits a drop shot and as Steve advances for the return he pulls his calf muscle and fails the return, losing the match to Jim.

Later in the doctor’s office Steve asks his physician why his muscle gave out on him, and after his physician explains this he recommends ibuprofen to help ease his pain with his joints so that he can get back to his early morning running sooner. The physician also makes the recommendation that Steve should be consuming more calories given the extent of his physical activity. Later, when Steve goes to buy some choice beef cuts from Nikolas his favorite butcher in Greek town, Nikolas pulls him aside and says that his ancestors from the home country ate the testicles of the bull to derive its strength and that Steve should too. And so with the reader’s suspension of disbelief, Steve’s oral ingestion of bovine sex steroids undeniably augments his strength and stamina. Later on the tennis court in an unequivocal demonstration of physical superiority Steve enjoys a resounding defeat of Jim, this time in front of local news media coverage.

If most would agree that the increased ingestion of dietary protein by both Jim and Steve to create a competitive advantage is ethical, wouldn’t it also be ethical to consume the bull’s testosterone? If not, what is the difference? If so, then can one argue it is unethical to consume purified or synthetic testosterone for the same reasons? Finally if it is wrong for Steve to eat the bull’s testosterone for a competitive advantage, is it also wrong for him to be taking ibuprofen a synthetic compound designed for the same purpose with a different albeit less potent effect? Why?

Part II

Steve and Jim’s friendly tennis game functions as an instructive metaphor for the relentless competition faced by those alive in the world. At each step in the escalation of their game, one is confronted with ethical considerations concerning the disparity in the relative playing field, whether technological, physiological, or otherwise. For most of us the stakes of competition are much greater than those of friendly tennis matches and so these ethical considerations of competition take on greater significance. Survival is not easy and methods that can confer a competitive advantage inevitably become widespread phenomena. This reality has important ethical implications for the direction of medicine because as medicine slowly unveils the natural world, the field will be faced with continued pressure to do more and more with that understanding. Currently when we use the word “medicine”, we typically mean the capability to reverse, slow, or eliminate disease and restore ourselves to a previous level of health. Health, the goal of “medicine”, derives from the verb, heal, derived from Anglo-German heilen, or to make whole, an interesting insight into the ancestry of this discipline. In the context of medicine the concept of health or whole is informative when we are less than whole, but it does not inform us as to the absolute value of a “whole”. Should medicine only be concerned with making “wholes”, but not defining them? I contend that we in medicine do not have the luxury of that ignorance.

Our understanding of this natural world has progressed such that in our current time medicine has achieved a limited but effective ability to reliably predict and modify certain biological outcomes through applying our collective model of human physiology. In neurology, an increased understanding of nervous function has powerful implications not only for restoring health, but public policy, ethics, and ultimately our progression as a species. In light of the fact that all of modernity has derived from the increased neurocognitive capabilities of Homo sapiens we must turn our attention to advances currently being made in this field and ask ourselves one simple and real question. Is it ethical to take a pill that makes you smarter? It’s a complicated question and the subject of great debate. The issue cannot be ignored in light of data suggesting the pervasive use of psychostimulants. Maher reports that 1/5 of the readership of Nature had used a cognitive enhancing drug at one time. Consider that 350,000 individual prescriptions for modafinil were written in 2003 in the US, a time when the incidence of narcolepsy, its indicated use, was 135,000. Outram’s review indicates that on college campuses stimulant use has consistently hovered around 3-4%.

In expanding on the ethics of using medicine to enhance human cognitive performance I would like to address three issues. First, I would like to define what we mean when we say “smarter” by reviewing the current understanding of neuro-cognitive function. Next I will outline the current and well-established battle lines that frame the debate from an ethical standpoint. Finally I will register my opinion on the ethics of cognitive enhancement in well persons.

Lanni et al divide neurocognitive performance into three primary dimensions: memory, attention, and creativity. They indicate in their review¹ that a multitude of distinct molecular pathways govern the magnitude of these functions. Memory is categorized as either implicit or explicit; the former (also called procedural, or non-declarative memory) consists of learned habits, motor functions, and feelings whereas the latter (also called declarative memory) relates to the verbal reconstitution of facts or ideas that can be called into consciousness. Currently, the mechanism by which an explicit memory is encoded into long term memory (a phenomenon called long-term potentiation) involves increased synaptic connectivity and neurotransmission within the neural pathway governing the subjective experience of that memory through plastic changes secondary to gene transcription via NMDA signaling and ultimately CREB modulation. It is thought that these gene products are proteins that help stabilize the synaptic connectivity responsible for a memory and that repetition enhances this effect. Certain compounds that have shown efficacy in enhancing memory formation and recall include acetylcholinesterase inhibitors, AMPAkines, NMDA modulators, adenosine blockade (caffeine), signal transduction enhancers (phosphdiesterase inhibitors), and CREB modulators (still preclinical).

Human attention is normally divided into two functional categories; a tonic overall attention “tone”, and a second “dynamic” attention (selective). There is also an evolving idea of networks of attention, of which three have been named; an alerting network (maintains cognition), an executive network (controls cognitive process and analyses), and an orienting network (directs the executive network/enhances its function). The effort of attention has been described as the interplay of many cortical and subcortical areas, including the lateral prefrontal cortex, anterior cingulate gyrus, and basal forebrain with multiple neurotransmitters, chief among which are cholinergic and catecholaminergic. Since the development of the blockbuster drug methylphenidate in 1944[source], most of the drugs developed have interacted with the catecholaminergic system (norepinephrine and dopamine).

Human creativity remains probably the most elusive cognitive function, but it is no less a capability. Many original theories on creativity relate this function to increased hemispheric asymmetry. Right hemispheric activity has classically been related to increased creativity. It may be that creativity is an epiphenomenon involving the frontal cortical functions of working memory and attention. Some investigations have related increased creativity with increased frontal lobe activity as well decreased left hemisphere inhibition of right hemispheric structures. Aside from hallucinogens, psychotropic drugs, and other dissociative compounds, there has not been much interest in generating compounds that increase creative thinking. In fact Lanni et al comment that many creative thinkers in history have displayed impulsive and disorganized traits, and they hypothesize that modern agents such as methylphenidate and amphetamines may in fact stifle creativity by activating the frontal cortex and reducing the cognitive flexibility associated with creativity.

Part III

Authors such as Schermer, Mehlman, Goodman, and Outram have closely assessed the ethical implications of taking “smart pills”. The subject has also gained attention from the President’s Council on Bioethics, in their 2003 report headed by Leon Kass, Beyond Therapy. In these works, the ethical objections to the use of these drugs are normally divided into the following categories;

1. Issues of risk and safety. Since no drug is without side effects, will adverse effects outweigh benefits?

2. Issues of coercion. If an efficacious agent is identified, will others be forced to follow suit in order to remain competitive? What will become of those who abstain?

3. Issue of distributive justice. Who gets it? What about those without access to “smart pills”, what will become of them?

4. Issues of cheating. If you create a work while cognitively enhanced, does it truly belong to you?

Safety

If there were no side effects from using cognitive enhancing drugs, it would be very difficult to argue against their use. This is obviously not so. For example a stimulant used for the treatment of ADHD, methylphenidate, is also a commonly used study aid among students of all ages. The drug can cause loss of appetite, dry mouth, mood lability and jitteriness. This compound also has high abuse potential. Donepezil, a cholinesterase inhibitor developed to aid the symptoms of Alzheimer’s dementia, has been shown to increase working memory in non-demented controls. Here the trade-off is nausea, vomiting, diarrhea, and insomnia. So in constructing an ethical framework for the judicious use of cognitive enhancing substances what should inform our cost/benefit analysis? Cakic supports the notion that ethical objections to cognitive enhancing substances because they are dangerous hinges completely on the side effect profile. In his review he comments that large proportions of the world’s population safely use caffeine (a widely recognized cognitive enhancer). Yet by virtue of its milder side effect profile there are not the same ethical objections to its use. What about those compounds with side effects? Arguably a well person taking a drug for a non-medical purpose that results in a side effect that makes him unwell cannot be condoned. Really? This notion must be challenged. Why should a regulatory body prohibit an informed citizen form taking risks with his health in pursuit of his own end if that body does not absorb the cost of the associated risk (in the case of an insured patient)? This is exactly what a professional football player does every time he steps on the playing field. Yet when that same player chooses to use anabolic steroids and we question the ethical nature of that decision, we cannot argue against that act from the perspective of safety because the act may be no more or less safe than playing the game in the first place. I believe it is ethical to use compounds with side effect profiles if their use is informed and the cost of the use is not born by the collective.

Coercion

The objection to cognitive enhancement from the standpoint of coercion essentially states, “If one attains a competitive advantage by taking a drug, the other now must take it in order to remain competitive, and therefore the other has been coerced.” In exploring the issue of coercion, Goodman argues that the use of cognitive enhancing drugs would be ethical by distinguishing their use according to the following dimension: Would using cognitive enhancing substances aid outcomes that are zero sum or non-zero sum? For example it could be argued that professional sports are zero sum outcomes because there is only one victor and thus the use of performance enhancing substances are unfair to the competitor not using them, and hence their use is coercive to others. But, Goodman supports enhancement if the activity involved is non-zero sum. As an example of a non-zero sum outcome he cites is a graduate seminar where everyone can contribute, but no outcomes are affected by the actions of the other, and hence an individual cannot be coerced. I do not believe in Goodman’s dichotomy between zero sum and non-zero sum activity as a method of distinguishing the ethical use of cognitively enhancing substances. All activity is zero sum because each decision carries an opportunity cost. If we choose a non-zero sum activity we forego engaging in competitive behavior and have to some degree become less competitive, a strict application of opportunity cost. Furthermore, if one argues that coercive behavior is unethical for zero sum activity, than all adaptive, disruptive innovative behavior is unethical if it forces others to change, whether I’m a caveman who objects to the use tools or an accountant who refuses to use a keyboard for fear of developing carpal tunnel. Arguing against the use of cognitively enhancing substances from the standpoint that it may coerce others is tenuous in that it potentially implicates all competitive activity as unethical.

Distributive Justice

If efficacious cognitive enhancers continue to be developed, the issue of distributive justice becomes germane if only the rich have access to the benefits of the use of these drugs. I believe from a technical standpoint overcoming this ethical objection will prove far easier than other current issues of distributive justice that plague our world; food, water, medicine, education, and freedom. If cognitive enhancement comes about through neuro-modulation using small molecule mediators, providing these compounds on a grand scale is well within the reach of current manufacturing capabilities, whether or not there will be political will for widespread dissemination becomes the crux of the debate. An ethical framework for cognitive enhancement must be inclusive to all members of society, but if creating them is going to necessitate distribution asymmetry, should these drugs be developed in the first place? It is easy to imagine a scenario in which individuals seek to withhold such compounds and their benefits from others for reasons having to do with policy, defense, and state. This issue is not easily resolved, and there is no ethically defensible position of selective distribution, yet we must ask the central question, would we allow our enemies to have them? Policymakers are faced with the challenge of expanding the myriad complicating factors in search of an answer that balances ethical conduct and practical concern.

Issues of Cheating

Goodman explores two examples of chemically enhanced performances; that of baseball star Raphael Palmeiro’s anabolic steroid use, and the Beatles’ use of psychotropic drugs. Goodman argues that the two activities are sufficiently different to warrant separate ethics, consistent with the observed public outrage of Palmeiro’s steroid use when compared to the tacit approval of the presumed increased musical creativity of the Beatles. What explains this differential treatment? Are the accomplishments of the enhanced truly their own depending on the activity? The President’s Council on Bioethics (PCB) argues that for us to arrive at an ethics of enhancement in sports, we need to define what the ethos of the sport is. Traditionally is has been framed as victory, or a reward, as a matter of dessert based on merit. Schermer picks up this point and asks what is it we want to praise about sports? He suggests in contrast to the PCB that the result (winning or losing) does not matter, but what matters in sports is not simply performance but a display of a type of human excellence not currently subject to enhancement and a much harder term to define. Schermer summarizes the current state of surreptitious steroid use in professional sports by positing that as long as their remains external rewards (money, fame…) from playing sports well, cheating behaviors may or may not be ethical but they are rational. He also argues that in enhancement in professional sports, “…causes spectators to miss out on display of natural efforts that gives sports moral meaning.” I agree with Schermer’s summary and would ask anyone who watches sports why they do, is it for the demonstration of human excellence or for the homeruns and KO’s? If it is the former reason, faster times and bigger hits do not increase or decrease the drama of the trial of the human spirit that defines excellence in sports, and likely competing while enhanced against unenhanced opponents decreases this relative human excellence, I would argue it is unethical to use in this way. However, if one watches sports for the latter reason, then it is ethical for the players to take these substances if it increases the pleasure of those spectators who seek these goods. Whether or not it is ethical to lie about taking them is a separate issue.

Schermer also asks a very important question that relates to this notion of human excellence. What is the value of effort? Who is more deserving of credit, a less gifted student who works very hard to earn average marks or a brilliant student who takes a pill and gets the same mark with almost no work? This idea is central to the main critique against cognitive enhancement. If you enhance, you potentially cheat yourself of the value of hard work. What is the value of hard work? Mehlman summarizes this point beautifully by stating that it is not that cognitive enhancing drugs make the activities easier, it is that by virtue of the ease they are less meaningful. Mehlman suggests that if we are threatened by shortcuts, which “smart pills” could easily provide we fail to experience the fulfillment of achievement, an experience critical to ego function and maintenance of willed and intended action. This lack of ego driven function may alter the experience of improvement resulting from goal directed behavior to a phenomenon that happens to us. Mehlman asks if we move to this point, will our achievements be our own? Goodman comments on this notion of “achievements happening to us” and by stating that our current notion of goal directed achievement is a cultural entity and that many artists, innovators, scientists, and leaders in previous cultures attributed their accomplishments to forces not their own. Johann Sebastian Bach commonly signed his finished compositions, SDG, standing for soli Deo gloria, “the glory of God alone” stating his belief that all achievement came from God regardless of whatever pills, balms, foods, spells or muses were used to aid in the creation. If Bach were alive today would he inform us that we are misattributing our accomplishments to ourselves apriori?

Conclusion

Debating the ethics of the use of cognitive enhancing substances has great relevance to the field of neurology because likely any advances will come from the investigators in this specialty. I believe that if we are to create an ethical framework for dealing with these compounds we must more fully explore the aforementioned issues surrounding safety, coercion, and justice. However, I agree with Goodman, that the central issue regarding the ethics of these drugs will rest in defining what is the value of an accomplishment and what is the value in the process of accomplishing. We must seek to understand what is the value of “hard work”. My chemistry professor emphasized on the very first day of lecture, “If you learn only one thing in this class, please let it be that the universe does not permit free lunches.” I believe this statement of cosmic accounting can be applied broadly; these compounds are not inherently good or bad but in their use. There is some inherent meaning to struggle and hard work that the use of “smart pills” threatens to compromise. We must recognize that their use should not allow us an “easier” path. If their use threatens the integrity of the human struggle by creating the illusion of doing more with less, or getting something for nothing, we have foolishly deceived ourselves, and we will bear the cost of that folly. However, if we recognize that while these drugs may alter our neuro-cognitive functioning they necessarily cannot leverage the value of human struggle, then by holding true to this ethic and with proper humility we may yet more ably pioneer uncharted territories.

References

Adan A., Serra-Grabulosa JM. 2010. Effects of caffeine and glucose, alone and combined on cognitive performance. Human Psychopharmacological Clin Exp 25:310-317.

Bogle KE, Smith BH. 2009. Illicit methylphenidate use: A review of prevalence, pharmacology, and consequences. Current drug abuse reviews 2:157-76.

Cakic V. 2009. Smart drugs for cognitive enhancement: ethical and pragmatic considerations in the era of cosmetic neurology. J Med Ethics 35:611-615.

Goodman R. 2010. Cognitive enhancement, cheating, and accomplishment. Kennedy Institute of Ethics Journal Vol. 20:145-160.

Kass L. Beyond Therapy: Biotechnology and the pursuit of happiness. 2003. President’s Council on Bioethics.

Lanni et al. 2008. Cognition enhancers between treating and doping the mind. Pharmacol Res 57(3):196-213

Mehlman M. 2004. Cognition enhancing drugs. Milbank Q 82(3):483-506

Outram S. 2010. The use of methylphenidate among students: the future of enhancement? J Med Ethics 36:198-202

Schermer M. 2008. On the argument that enhancement is “cheating”. J Med Ethics 3485-88