Thursday, July 24, 2014

The New Normal: How the definition of disease impacts enhancement

We’ve all been there. It’s exam week of your junior year of college with two papers due the day after a final. You’re a new faculty member with a semester of lectures to prepare and a lab to get started. You’re a tax accountant and it’s early April. There is simply too much to do and not enough hours in the day to get it all done while sleeping enough to keep your brain working like you need it to. In that situation, where do you stand on cognitive enhancement drugs? Most of us wouldn’t hesitate to grab a cup of coffee but what about a caffeine pill, or a friend’s Adderall? Many discussions about cognitive enhancement eventually come down to this question: where do we draw the line? Currently most of the cognitive enhancers that create unease for ethicists and the general public alike are prescription drugs that were originally meant to treat conditions recognized as out of the realm of “normal” such as diseases or deficits. Therefore, a key step in deciding where we should stand on the acceptability of cognitive enhancement is to determine what is normal and what needs to be medically treated. I’ll argue that one reason there is so much gray area in the enhancement debate is that delineating normal from diseased – particularly in the brain – is hardly a black-and-white matter.

Why does the definition of disease matter? Enhancement is typically defined relative to normal abilities. Anjan Chatterjee of the University of Pennsylvania suggested that “Therapy is treating disease, whereas enhancement is improving “normal” abilities. Most people would probably agree that therapy is desirable. By contrast, enhancing normal abilities gives pause to many.”1 However, many neuroethicists have wrestled with clearly defining enhancement2,3. The director of Emory’s Center for Ethics, Paul Root Wolpe argued (2002) that the enhancement debate centers on the ability of substances or therapeutics to directly affect the brain in ways that are not necessary to restore health and, certainly, to date the cognitive enhancement debate has focused primarily on pharmaceuticals, many of which are approved to treat disorders but can have effects on healthy individuals as well. Perhaps the best examples of this are methylphenidate (Ritalin) and modafinil (Provigil) which are prescribed for attention deficit hyperactivity disorder (ADHD) and narcolepsy respectively, but are increasingly being used by students and professionals to boost cognitive performance at school and in the workplace3-5.


Although drugs such as methylphenidate and modafinil do not directly increase IQ, this measure of “intelligence”, albeit somewhat controversial6, provides another useful example of the distinction between treatment and enhancement. IQ is scored relative to the median performance on a given test, set at 100. This means that because IQ is normally distributed throughout the population, every 15 points above or below that mark represents one standard deviation. Therefore 95% of the population should fall within two standard deviations of the mean and score between 70 and 130. Intellectual disability is defined by a score that is far to the left on the bell-shaped distribution and, by these standards, it would be impossible for a large fraction of the population to fall into this category because the median would then shift[a]. Enhancement, in terms of IQ, would be a potential improvement within the typical IQ range or above it. As ethicist and philosopher Julian Savulescu points out, increasing an individual’s IQ from 60-70 would be considered treatment for a disease but making the same jump from 70-80 is enhancement since the initial score is already within the normal range2. This is not simply a matter of semantics because, while no currently available drugs can boost IQ like this, they are frequently being used for other, perhaps more tangible, cognitive effects. A poll in Nature found that more than 1 in 5 respondents under the age of 35 have used drugs explicitly for cognitive enhancement7 and experts expect these numbers to continue to climb4,8.

In a competitive setting such as a large undergraduate class that is graded on a “curve”, a student’s grade is dependent not just on her performance but on how it ranks among her classmates. Therefore using a so-called study drug without a medical need could be considered cheating and, if it is a prescription drug it would be illegal. In fact, Duke University’s student ethics guide explicitly labels “the unauthorized use of prescription medication to enhance academic performance” as cheating. Therefore, in some cases patients have an incentive to define themselves as diseased and a natural way to circumvent issues of legality and social acceptability is to obtain a prescription. While it is not known exactly how common this approach is, diagnosis for ADHD has increased dramatically in recent years. One study found that outpatient treatment for ADHD increased roughly four-fold in a large cohort from 1987-1997 9 and another, more recent study from the CDC, found a nationwide 42% increase in ADHD diagnosis from 2003 to 201110. There are many reasons for this increase, which likely include a better understanding of the disorder but, as some have point out, this increase coincides with policy changes that allow individuals with intellectual disabilities to be tutored and granted extra time on exams. These benefits, in addition to the increasingly common knowledge that ADHD medications can improve concentration even in healthy users, may make it seem like there is no downside to a diagnosis and might in turn incentivize parents and students to seek out physicians willing to write prescriptions without rigorous examinations. In addition, physicians have the ability to prescribe drugs off-label (in ways not explicitly approved by regulatory agencies) and do so commonly. A prime example of this practice is modafinil, a drug that is approved in the US for sleep disorders such as narcolepsy but was found to be prescribed for off-label indications nearly 90% of the time from 2002-20095.

Disease may not just be defined by physicians, or demand from patients, but also on the supply side by drug makers themselves who readily take advantage of the opportunity for direct to consumer marketing in the US (New Zealand is the only other developed country that allows this practice). Indeed, a drug has little value to any company unless there is a market for it and one approach is to convince the public that a common nuisance or frustration (think shyness) is actually a disease (e.g. social phobia). Wolpe (2002) noted that, “what medicine chooses to treat is defined as disease, while altering what it does not treat is enhancement” however I think the inverse is also true, that whatever positive effects medicines have in the absence of a known deficit could also be considered enhancement. Pharmaceutical companies have been branding diseases (or some say disease mongering) for decades with the hope that changing the definition of normal and diseased can broaden the market for their stable of drugs under patent. A recent overt example of this practice is the ubiquitous marketing of testosterone supplements to remedy “low T”  (hypogonadism), a disorder that was once thought be a rare condition but is now suggested to afflict most middle-aged men (if the ads are to be believed). Unfortunately, unnecessarily manipulating this hormone can have serious life-long health consequences, some of which the FDA is now investigating

Wolinsky, 2005

By contrast, an area where the definition of disease may be less important is in age-related cognitive decline. How much mental ability needs to be lost in elderly individuals before the line is crossed into cognitive impairment and who gets to make that decision? If drug safety could reasonably be established then perhaps adults at that stage in life should be able to choose to use cognitive enhancers whether or not their deficits reach clinical thresholds. One could make the case that drugs could actually help to preserve authenticity, another controversial area and a major concern with their use in children and young adults. To reiterate the difficulty in diagnosing disorders of the brain, it is debatable whether even a profoundly debilitating disease such as Alzheimer’s can be definitively diagnosed without post-mortem tissue examination.

Diagnostic practices are sure to change, though, and it is likely that in the near future researchers will discover new biomarkers for neuropsychiatric disorders. However, this will not necessarily make it any easier. It is doubtful that any biomarker will give a clear yes-or-no, black and white indication. As to whether a biomarker indicates something is “out of the range of normal” is also subject to the moving target of what humans consider “normal”. Instead, a normal range will need to be determined, but by whom? Given what is at stake it is hardly cynical to suggest that drug makers will have a significant role and, in the end, physicians will continue to be able to prescribe approved drugs for off-label use5. In the meantime, instead of immediately accepting that drugs with cognitive enhancement potential are always permissible with a doctor’s diagnosis, there should be further discussion between physicians, regulators, ethicists and disability advocates about how that diagnosis is made. This determination will have widespread implications for healthcare providers, insurance companies, drug companies, and the general public and society who are struggling to determine what constitutes “the good life” and ultimate human flourishing.

1) Chatterjee, A. Cosmetic neurology: the controversy over enhancing movement, mentation, and mood. Neurology 63, 968-974 (2004).

2) Savulescu, J. Justice, fairness, and enhancement. Ann Ny Acad Sci 1093, 321-338, doi:DOI 10.1196/annals.1382.021 (2006).

2) Wolpe, P. R. Treatment, enhancement, and the ethics of neurotherapeutics. Brain Cogn 50, 387-395 (2002).

3) Cakic, V. Smart drugs for cognitive enhancement: ethical and pragmatic considerations in the era of cosmetic neurology. Journal of medical ethics 35, 611-615, doi:10.1136/jme.2009.030882 (2009).

4) Greely, H. et al. Towards responsible use of cognitive-enhancing drugs by the healthy. Nature 456, 702-705, doi:10.1038/456702a (2008).

5) Penaloza, R. A., Sarkar, U., Claman, D. M. & Omachi, T. A. Trends in on-label and off-label modafinil use in a nationally representative sample. JAMA internal medicine 173, 704-706, doi:10.1001/jamainternmed.2013.2807 (2013).

6) Weinberg, R. A. Intelligence and Iq - Landmark Issues and Great Debates. Am Psychol 44, 98-104 (1989).

7) Farah, M. J. et al. Neurocognitive enhancement: what can we do and what should we do? Nature reviews. Neuroscience 5, 421-425, doi:10.1038/nrn1390 (2004).

8) Maher, B. Poll results: look who's doping. Nature 452, 674-675, doi:10.1038/452674a (2008).

9) Olfson, M., Gameroff, M. J., Marcus, S. C. & Jensen, P. S. National trends in the treatment of attention deficit hyperactivity disorder. The American journal of psychiatry 160, 1071-1077 (2003).

10) Visser, S. N. et al. Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003-2011. Journal of the American Academy of Child and Adolescent Psychiatry 53, 34-46 e32, doi:10.1016/j.jaac.2013.09.001 (2014).

[a] Not to mention the “Flynn effect", which describes the phenomenon of increasing IQ worldwide over time.

Want to cite this post?

Purcell, R. (2014). The New Normal: how the definition of disease impacts enhancement.  The Neuroethics Blog. Retrieved on , from

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