Would a Therapy for Down Syndrome Change Lives For Better or For Worse?

By Sarika Sachdeva

This post was written as part of a class assignment from students who took a neuroethics course with Dr. Rommelfanger in Paris of Summer 2016.

Sarika Sachdeva is an undergraduate junior at Emory studying Neuroscience and Behavioral Biology and Economics. She is involved with research on stimulant abuse and addiction under Dr. Leonard Howell at Yerkes National Primate Research Center.

Researchers around the world are working to develop treatments and cures for all kinds of genetic disorders and abnormalities, but what happens when the people affected by the condition don’t want it taken away? New breakthroughs in treatment are often controversial for non-fatal conditions such as Down Syndrome, which causes inhibited neural communication and leads to learning delays as a result of an extra copy of chromosome 21 (Rochman, 2015).

Recently, a study from the Boston University Medical Center claimed to have identified differences in gene expression that are found in people with Down Syndrome. Previously it was thought that most of the effects of Down Syndrome occurred prenatally, but comparisons between toddlers and adults with the disorder revealed that changes in white matter levels in the brain are actively occurring during development. People with Down Syndrome have defects in their oligodendrocytes, a type of brain cell that forms white matter. This defect causes people with Down Syndrome to have less white matter than unaffected individuals. White matter insulates nerve fibers and facilitates communication between brain cells; thus, decreased white matter formation slows signal transmission and leads to the learning delays associated with Down Syndrome. This finding could be a significant step in the search for a treatment that promotes brain functioning. Instead of working on a genetic cure for Down Syndrome to stop the extra chromosome from ever having an effect, researchers may now shift their focus to finding therapies that increase oligodendrocyte formation and improve neural communication in people with Down Syndrome.

Proponents claim that a treatment of this kind will increase the quality of life for people with Down Syndrome. On the other hand, many parents of affected children argue that their child is perfectly normal and happy the way they are; they say that their children would not be the same if their disorder were removed (Becker, 2016). This leads to two interesting and as of yet unanswered questions: does treating someone with Down Syndrome remove the essence of who they are by affecting their brain, which “skirts close to intervening with the self”? Or would treatment retain the identity of the affected individual but with better cognitive functions (Becker, 2016)?

Image courtesy of Wikimedia

The uncertainty of the aftereffects of any potential “therapy” makes it difficult for parents to accept scientific breakthroughs with enthusiasm; some even say they would be more likely to support research for treating heart problems found in people with Down Syndrome instead of treating the cognitive neurodevelopmental components of Down Syndrome (Rochman, 2015). Even if treatments were to be given only to babies or fetuses with trisomy 21 before their sense of self and consciousness might have had the chance to develop, there are still important ethical considerations involved. Would treating the child make a difference in who they grow up to be, creating some sort of inauthentic self? Would this alteration have any potential risks, and at what consequence is it still worth attempting to prevent Down Syndrome? Because Down Syndrome is not fatal, any viable treatment options would have to be reliable and safe in order to guarantee that the affected individual would not end up with a potentially worse condition.

If we as a society decide that Down Syndrome is something that must be eliminated as soon as possible, we dismiss any immediate concerns about equality and social acceptance for those with Down Syndrome. When we focus on ways to change or alter these diseases, we are ignoring the contributions people with these conditions are making to society and implying that their presence is not valued. At the same time, the goal of medicine is to develop treatments to improve peoples’ lives and, in this case, to make Down Syndrome a disorder of the past. It seems counter intuitive that researchers are investing time and money into treatments that people may not even want; however, the idea is not to create a treatment for every single person with Down Syndrome regardless of what it may do to their self, but to give people with Down Syndrome and their families more options about how to live with the disorder. Whether they choose to improve cognition or not is up to them, but having that ability represents a significant leap forward in their autonomy. The question of whether Down Syndrome can and should be treated is tied to a larger discussion about how disabilities are viewed on a daily basis, but working towards a cure and working to remove the stigma surrounding people with disabilities do not have to be mutually exclusive.

References

Becker, A. J. 2016. A Pill for Down Syndrome. The Atlantic, March 15. Available at: http://www.theatlantic.com/health/archive/2016/03/down-syndrome-mother/473832/ (accessed June 10, 2016).

Boston University Medical Center. "Discovery of key abnormality affecting brain development in people with Down syndrome." ScienceDaily. www.sciencedaily.com/releases/2016/02/160225135608.htm (accessed June 10, 2016).

Rochman, B. 2015. A Change of Mind. MIT Technology Review, December 16. Available at: https://www.technologyreview.com/s/544531/a-change-of-mind/ (accessed June 10, 2016).

Seibel, B. 2015. Behind the Stigma: How the label of Down Syndrome keeps us from understanding the people who have it. Vantage, April 27. Available at: https://medium.com/vantage/how-the-stigma-of-down-syndrome-separates-us-from-the-people-who-have-it-99e1a36091a6#.qbtd9x6mq (accessed June 10, 2016).

Want to cite this post?



Sachdeva, Sarika. (2016). Would a Therapy for Down Syndrome Change Lives For Better or For Worse? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/07/would-therapy-for-down-syndrome-change.html

New Frontiers in Animal Research Neuroethics at the Center for Neuroscience and Society

By Tyler M. John

Tyler John is a postbaccalaureate fellow at the National Institutes of Health Department of Bioethics interested in resource allocation, animal ethics, and moral theory. This fall, he will begin a PhD in Philosophy at Rutgers University. 

The opinions expressed are the authors’ own. They do not reflect any position or policy of any U.S. governmental entity, including the National Institutes of Health or the Department of Health and Human Services. 

On June 9-10, I joined a gathering of philosophers, psychologists, veterinarians, and biomedical researchers for the Animal Research Neuroethics Workshop at the Penn Center for Neuroscience and Society. The workshop, organized by neuroethicists Adam Shriver, James Serpell, and Martha Farah, focused on the ethical issues raised by new advances in neuroscience research with non-human animals. Here, researchers from many disciplines came together to share notes from the field and discuss new neuroethics problems. 

Over two days, we discussed problems like, What is the moral status of so-called “brains in dishes”? Is it morally permissible for scientists to cognitively enhance mice, rats, and chimps, giving them advanced cognitive capacities? Is it even conceptually possible to have a mouse model of human depression given the substantial psychological differences between humans and mice? What, more broadly, should we say about the scientific validity and moral permissibility of current neurological research on non-human animals? 

Despite our vast disciplinary diversity and some disagreement about issues in moral theory, participants were very quickly able to bridge disciplinary divides and create broad areas of consensus. We soon found agreement both on significant matters in practical ethics and on areas where greater analysis is needed from neuroscientists and bioethicists. 

Some of our discussion focused on the institution of animal research as a whole, with neuroscience research serving as a sample of the studies that are currently being performed on non-human animals. From the outset, virtually all participants in the workshop agreed that the institution of animal research is in need of serious reform. Participants differed in their degree of pessimism about the institution of animal research and the possibility of reform, but all raised significant concerns. 

For one, most at the workshop seemed to agree that a minimal requirement of ethical research on non-human animals is that the benefits of research projects outweigh the harms. However, as scientists, bioethicists, and veterinarians discussed this, we quickly realized that there is no existing institution that analyzes the costs and benefits of animal research protocols. On the one hand grant-makers ensure that research has expected benefits, and on the other hand Institutional Animal Care and Use Committees (IACUCs) try to mitigate harms to animals. But no one group takes the costs and benefits into account in a comprehensive way. 

Another problem we discovered is that IACUCs rarely have members with sufficient expertise to critique animal research protocols. This makes it difficult for bad protocols to be rejected. 

Image courtesy of Wikipedia

Several other criticisms of mainstream animal research were discussed by biologist Joseph Garner. Scientists and journals should be publishing negative data, he argued, and scientists should stop treating animals like tools or “reagents” and treat them more like patients. Our failure to treat animals like patients produces research projects with far too little variability. As an analogy, imagine that we conducted human subjects research with the low variability we have in, e.g., research on mice. All of our participants would be 42-year-old white men who live in the same town, have the same exercise regimen, are the same height and weight, and have nearly identical genotypes! Clearly this would be problematic. Moreover, many animals who are in labs suffer from anxiety, depression, and social isolation. In addition to this being bad for these animals, it lowers the quality and validity of research performed on them. 

Later, biologist Helena Hogberg explained that researchers working to create alternative, non-animal models for translational research are fighting their battle uphill. The FDA, she argued, uses the mouse model as their “gold standard”, so that new models have to be validated against mouse models in order to gain approval. But this is a mistake, since mouse models are known to be imperfect models of human disease. At present, it would be possible for an alternative model to be better than mouse models and still not gain approval because its results diverge from mouse models. Regulators should instead use human biomarkers as the gold standard for validating alternative research technologies. 

Another reason for this uphill battle is that the FDA does not consider minimizing animal suffering a desideratum for models of human disease. Alternative models must therefore have better predictability than existing models in order to gain widespread adoption, since the fact that they do not harm animals is not relevant from the FDA’s perspective. Some commentators wondered whether the FDA should add animal bioethicists to their staff. Others suggested that the necessity and validity of animal models of each human disease be reviewed every 7-10 years to ensure that research is fruitful. 

The remainder of the workshop focused on new neuroethics questions raised by neurological research on non-human animals. On day one, Kristin Andrews and Martha Farah discussed the idea that research on animals might make some animal non-persons become persons through cognitive enhancement. What if researchers engrafted human neural stem cells into another animal’s developing brain and thereby gave her greater cognition? Would this make her a “person”? Would that matter?

Andrews, a philosopher, argued that this is a fundamentally flawed question, because the notion of a “person” is not well-defined. Instead of carving up the world into persons and non-persons, she argued, we should drop the notion of personhood and focus on what moral and legal implications come with an animal’s having certain capacities like rationality, subjectivity, and relationality. Farah’s talk supported this idea. “Personhood” is not a neurological property, she argued, as no amount of neuroscience can tell us whether someone is a person. And “person” isn’t a particularly useful concept, either. Our ethics should therefore focus on animal behavior, ethology, and structure and function, and not on defining and applying the term “person.”

Program from Animal Research 

Neuroethics workshop

But even if it isn’t useful to talk about persons, questions about the morality of such cognitive enhancement remain. On day two of the workshop, Evan Balaban set the backdrop for this discussion with his research on chimeric chicks. These chicks are crossed with quails so that they have brains that are part-chicken, part-quail, and they sing like quails instead of chickens. Robert Streiffer then commented on the moral significance of creating chimeric animals, focusing on the possibility that cognitively enhancing an animal might change her moral status. 

Streiffer argued that it is morally permissible for an agent to cognitively enhance someone only when and to the extent which her newly-acquired moral status is respected in the future. If, for example, adult dogs and adult humans have different degrees of moral status on account of their different cognitive capacities, we are only permitted to cognitively enhance a dog to develop the cognitive capacities of an adult human if we know that the dog’s higher moral status will be respected after she has developed these greater cognitive capacities. 

Some related questions focused on animal agency. Which non-human animals are moral agents? Are such agents required to follow the same moral norms that you and I are? How should it change our thinking about justice, punishment, and retribution if certain non-human animals are moral agents? When humans experience ego-dystonic motor functioning they find it deeply distressful, disturbing, and shameful. As an example, humans with alien hand syndrome often find their hand performing actions that are opposed to their own agency, which thwart their goals and embarrass them. Would other animals with a lower degree of agency, like mice and fish, face similar kinds of harms from ego-dystonic behavior? If so, how does this bear on the permissibility research that imposes ego-dystonic behavior on these animals? 

At one point, the group discussed new research on “brains in dishes”, or neural networks created in labs used to learn things about the human brain. “How brain-like are these neural networks?” some participants asked, “How brain-like do they have to be before we have to worry about what we do to them?” 

Finally, some discussions throughout the workshop focused on the distinction between affective neuroscience and cognitive neuroscience. For example, participants debated whether translational psychological research is valid only if animals involved in research have the same affective states as humans, and not merely cognitive structures analogous to those which we find in humans. If certain animals do not experience depression just like the depression that is experienced by humans, is it in principle possible to learn about human depression from studying these animals? If so, what are these models able to tell us? 

These discussions at the Animal Neuroethics Workshop make it clear that animal research is a field fraught with unknowns and moral perils. As some participants at the workshop pointed out, it may be legitimate to question the whole enterprise of animal research given our great uncertainty about the permissibility and validity of most invasive animal research projects. We do not, after all, believe that it is permissible to treat other humans in such morally risky ways. But whatever we say about the moral status of animal research in the present day, it is clear that scientists, philosophers, and bioethicists must attend to many questions in animal research neuroethics if we are to bring clarity to this morally opaque project.



*updated on July 21, 2016 at 12:17pm EST.

Want to cite this post?



John, Tyler. (2016). New Frontiers in Animal Research Neuroethics at the Center for Neuroscience and Society. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/07/new-frontiers-in-animal-research_14.html

The Physical, Social, and Societal Consequences of “Smart” Drugs

By Sunidhi Ramesh

This post was written as part of a class assignment from students who took a neuroethics course with Dr. Rommelfanger in Paris in Summer 2016.

Sunidhi Ramesh, an Atlanta native, is entering her third year at Emory University where she is double majoring in Sociology and Neuroscience and Behavioral Biology.  After experiencing an educational environment in high school that was so competitive that it practically forced students into taking study drugs, cheating, and cutting corners, she founded “The Prism Project,” an initiative that revolves around anonymous stories that highlight the problems that exist within the American education system. She plans to pursue a career in medicine and has served on College Council’s Admissions and Scholarships committee, is presently active on Emory’s Committee of Academic Integrity, and is involved in the Indian Cultural Exchange organization at Emory. 

“I remember the night I first took one. A friend of mine had some extra, so he handed me one the night before a big test. This test was important; I was doing pretty badly in the class, and I knew that my performance on it would decide my final grade. I wasn’t the type to take Adderall to get ahead. But I was desperate. And I thought it was only going to be this one time.

My grades skyrocketed. Like, you don’t understand. I played football and had to take care of my mom after school; the main reason I did so badly before was that I didn’t have the energy to put into school that I wanted to. But these pills… these pills gave me that. The energy I didn’t have.”

This quote is from an anonymous submission to The Prism Project, a page that shares the stories of students who feel as if the education system in the United States does less than it should. The topic of the quote is a subject of heated debates—“smart drugs.”

“Smart drugs,” also known as “nootropics,” are “supplement[s] that [are] ingested primarily for [their] effects on the brain [such as] an increase in cognition, focus, alertness, or well being (1)” in healthy individuals. Although the vast majority of these drugs were initially produced to treat symptoms of attention deficit hyperactivity disorder (ADHD) (2), the global demand for them (primarily for use in schools and work settings) has created a massive, up-and-coming “billion dollar business of being smart (3).”

Image courtesy of Deviant Art

And while most studies and scholars disagree on the actual effects of these drugs (ranging from “none” to “modest” improvements (4)), most researchers have expressed concern regarding their ethical implications and the consequences we may face when similar, more effective compounds are developed in the future (5).

One of the primary concerns involved is “challenging what it means to be normal.” Picture this: one student begins using these drugs to focus more and perform better on exams. He succeeds. The next student, feeling disadvantaged and conflicted, begins doing the same to keep a level playing field. And, suddenly, within weeks, a cycle of frustration and competition forces these little pills to become rampant around an entire school. This is the slippery slope that surrounds cognitive enhancements—the pressure that “normal” individuals begin to feel to become “enhanced.”

And what does this say about the future of our workforce? If our students are primed to only perform well under “enhanced” conditions, will they be able to work efficiently in their future jobs without these “smart” drugs?

Furthermore, the long-term effects of these drugs are largely unknown. A study done in doctors that “deprived [them] of sleep overnight and [gave them] a dose of 200 milligrams of Modafinil or placebo” found that “the doctors taking Modafinil had cognitive improvements, including flexibility of thinking, and reduced impulsivity.” (6) These are the positive (?), known, short-term effects. But what are the consequences of taking such medication often— for months or years at a time? Because these drugs are fairly new, nobody knows. So, should we be concerned? Of course.

Consider, also, the social consequences of a “pressure to perform” and the temptation that workers and students will face “to risk their own health to gain a competitive edge.” Is that a problem of it’s own? Taking into account the trust issues, mild paranoia, and mental stress that would inevitably ensue, I’m willing to bet it is.

What is odd and disturbing about this new trend is how idealistic people seem to be about its infectious spread. “Why would this be bad?” some people seem to claim. “One day, we will all be taking this medication to become smarter and more intelligent than ever before!” The core problem not addressed in this argument is that these medications cost money—money that only a small percentage of the American (or world) population can afford to spend on cognitive enhancement methods such as this one. This then becomes a justice problem. Is it fair to produce and allow products that, realistically, can only enhance a portion of the population?

Image courtesy of Flickr user eliz.avery

Advocates and opponents of these enhancers disagree significantly as to what exactly constitutes these “smart drugs.” Can caffeine products, such as coffee, be considered brain enhancers as well? Well, coffee and its stimulating effects are natural products of the coffee bean. More importantly, it is readily available to the masses, legal for public consumption, and free from most forms of stigma. On top of the fact that coffee has been consumed since the 10th century, there is ample evidence to ensure that its consumption does not come with any unwanted, long-term side effects. And, from a neuroethics standpoint, coffee does not bring into question concerns of justice, readiness, public involvement/understanding, integrity, and governance/ regulation. Convinced? Good.

With all this in mind, I can’t help but wonder why we (including myself!) have such a large problem with expanding our own potential as human beings. When would “smart drugs” be something desirable? Can we make our doctors more alert during 15 hour surgeries? Or soldiers more active in battle? Our pilots more attentive during international flights? Would we want this any more than we would want enhancements to the general population? I would think so. But why? What does this say about our values and our society?

Frati et al. (2015) may get into answering these questions (7), claiming that “the vast abuse of [these drugs] rises from the mental association between the therapeutic use for ADHD treatment and its misuse in order to improve learning skills in healthy subjects.” Frati’s group further states that “[the medication’s] improper use is based on exceeding the marked borderline between health and disease, which appears in the eyes of abusers increasingly blurred until it disappears (7).” So, as a result, “treatment” starts becoming synonymous with “enhancement” to dissenters around the country.

In terms of getting to the roots of the questions presented here, that’s a start.

We must stay alert when it comes to any large-scale changes that challenge what it means to be “normal” and “human” in modern society. And although larger studies on these drugs still need to be conducted to even begin to tackle the dozens of issues surrounding this topic, the “smart drugs” of today need to be discussed, debated, and monitored to avoid serious, undesirable consequences in the world of tomorrow.

References 



1. Nootropic - Scientific Review on Usage, Dosage, Side Effects. (n.d.). Retrieved June 11, 2016, from https://examine.com/supplements/nootropic/



2. Larimer, M. P. (2005). Attention deficit hyperactivity disorder (ADHD) research developments. Nova Publishers.



3. Chinthapalli, H. U. K. (2015). The billion dollar business of being smart. bmj, 23.



4. Arria, A. M., Wilcox, H. C., Caldeira, K. M., Vincent, K. B., Garnier-Dykstra, L. M., & O'Grady, K. E. (2013). Dispelling the myth of “smart drugs”: Cannabis and alcohol use problems predict nonmedical use of prescription stimulants for studying. Addictive behaviors, 38(3), 1643-1650.



5. Cakic, V. (2009). Smart drugs for cognitive enhancement: ethical and pragmatic considerations in the era of cosmetic neurology. Journal of medical ethics, 35(10), 611-615.



6. Sahakian, B. (n.d.). The Ethics of Smart Drugs. Retrieved June 11, 2016, from http://www.cam.ac.uk/research/discussion/the-ethics-of-smart-drugs



7. Frati, P., Kyriakou, C., Del Rio, A., Marinelli, E., Vergallo, G. M., Zaami, S., & Busardò, F. P. (2015). Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology. Current neuropharmacology, 13(1), 5.





Want to cite this post?



Ramesh, Sunidhi. (2016). The Physical, Social, and Societal Consequences of “Smart” Drugs. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/07/the-physical-social-and-societal.html

Preview the latest issue of AJOB Neuroscience!

Watch this video advertising the soon-to-be published Spring 2016 issue of AJOB Neuroscience.  The video features two AJOBN editors describing the target articles that will appear in issue 7.2.  Keep an eye on http://www.ajobneuroscience.com and The Neuroethics Blog for more information on 7.2's upcoming release. 

Enjoy!