Should Presidential Candidates Be Required to Undergo Preclinical Alzheimer’s Disease Testing?

By Kaitlyn B. Lee

Kaitlyn “Kai” Lee is a Project Coordinator in the Center for Medical Ethics and Health Policy at Baylor College of Medicine. She helps to investigate the ethical, legal, and social issues of integrating whole genome sequencing into clinical care as part of MedSeq, a project funded by the NIH’s Clinical Sequencing Exploratory Research (CSER) program. Kai earned her BA in Neuroscience from Middlebury College and hopes to continue her education through a joint JD/MPH program.

In her op-ed published in the Houston Chronicle, “Presidential candidates should be tested for Alzheimer’s,” radio and television personality turned author and keynote speaker Dayna Steele advocates testing presidential candidates for Alzheimer’s disease and releasing their results to the voting public. Steele believes voters have a right to know their future president’s Alzheimer’s test results, as she maintains, “I want to know that the candidate I choose not only supports my priorities but is also of sound mind – a mind that will last through four or eight years” (Steele, 2016). Drawing upon her own personal experience with her mother’s Alzheimer’s disease, Steele describes the progression of her mother’s disease from simply forgetting things, to driving while lost, to total mental and physical incapacitation. Steele cites her mother’s rapid 3-year decline to assert that an affected person in a position with as much power as the President would be devastating for the country, arguing that we can avoid such a “catastrophe” by insisting candidates be tested for Alzheimer’s disease and disclose those results to the public.

Presumably, Steele is particularly concerned about testing presidential candidates for Alzheimer’s disease because Alzheimer’s is a progressive neurodegenerative disease that slowly degrades memory, intellectual abilities, and eventually, physical abilities. Alzheimer’s is the most common form of dementia, a catchall term for deterioration of cognitive ability that is severe enough to affect one’s daily life. Because Alzheimer’s is a chronic neurodegenerative disease, symptoms worsen over time. A 2015 report released by the Alzheimer’s Association describes the current understanding of the symptoms and progression of Alzheimer’s disease. In the early stages of the disease, a person can manage independently but may have some trouble planning and organizing and may suffer minor memory lapses, such as forgetting words or misplacing valuable objects. As the disease worsens, individuals exhibit memory loss of significant people or events, confusion with time or place, and personality changes. Finally, as the disease becomes more severe, physical abilities, such as walking, talking and eating deteriorate, and the person will require full-time assistance to perform basic functions until eventual death (“2015 Alzheimer’s disease facts and figures,” 2015). The rate of disease progression differs between individuals, but typically, a person will live 3 to 10 years after clinical symptoms begin (Zanetti et al., 2009).

Neurodegeneration in Alzheimer's Disease,

image courtesy of Wikipedia

Although Steele does not specify in her recommendation what type of testing she believes to be appropriate, someday it may be possible to reliably predict whether an individual will develop Alzheimer’s. During the preclinical stage of Alzheimer’s disease, biomarkers, a general term for biological indicators of disease, begin to present themselves in the body years or even decades before clinical symptoms manifest (Villemagne et al., 2013). Using magnetic resonance imaging (MRI), positron emission tomography (PET), and analysis of specific protein levels (e.g. amyloid beta) in cerebrospinal fluid (CSF), preliminary scientific evidence suggests that biomarkers can be measured to predict an individual’s likelihood of later developing Alzheimer’s, even when he or she may be at present asymptomatic (Cavedo et al., 2014; Langbaum et al., 2013). Although there are no current diagnostic criteria that doctors can use to accurately diagnose Alzheimer’s in a preclinical stage, research is underway to determine standardized biomarker cut-off values and to optimize techniques for CSF assays, PET, and MRI (Sperling et al., 2011). If that possibility is realized, according to Steele’s recommendation, candidates could be required to undergo screenings for Alzheimer’s biomarkers to predict whether they will develop symptoms in the coming years or decades. In this post, I will be discussing testing for Alzheimer’s disease as it relates to predictive preclinical testing for Alzheimer’s biomarkers.

Arguably, Steele’s concerns about testing for Alzheimer’s disease may be more relevant in the upcoming election than ever before, as several candidates in this election have risk factors for Alzheimer’s disease. Age is the biggest risk factor for Alzheimer’s disease, with average risk for a 65-year-old estimated around 10.5% (Sperling et al., 2011). Beyond 65, one’s risk doubles every 5 years, meaning that a 70-year-old has twice the risk of a 65-year-old (Brookmeyer et al., 2011). Three candidates, Donald Trump, Hillary Clinton, and Bernie Sanders, would be over 70 during their term. Bernie Sanders would be the oldest president in U.S. history, ending his term at age 79. In addition, family history is another risk factor for Alzheimer’s. Even if one does not carry the APOE4 gene, an individual has a two- to four- fold risk of getting Alzheimer’s if a first-degree relative has been affected (Fisher Center for Alzheimer’s Research Foundation, 2016). Donald Trump’s father, Fred Trump, suffered from Alzheimer’s for six years before his death in 1999 (Rozhon, 1999). Also, there is some evidence that previous head injury is a risk factor for Alzheimer’s disease, as history of moderate traumatic brain injury (TBI) increases risk by 2.3-fold (Plassman et al., 2000). Hillary Clinton suffered a concussion after falling in December 2012, and although the concussion did not appear to have any lingering effects, it still may put her at higher risk for developing Alzheimer’s later in life (Good, 2014). Given that several candidates in this upcoming election may be at increased risk for developing Alzheimer’s disease, the question of whether or not to test candidates is highly relevant.

Donald Trump, Hillary Clinton,

and Bernie Sanders; images

courtesy of  Flickr user

Michael Vadon and

Whizzers's Place

Despite the fact that a number of candidates in this upcoming election may be at increased risk for Alzheimer’s disease, upon closer examination of the respective rights of presidential candidates and the voting public, requiring candidates to undergo testing is problematic. Although Steele believes that the public has a right to know their candidates’ Alzheimer’s test results, the public’s right to know is not enough to outweigh individual candidates’ 4th amendment right to protection against unreasonable government searches and right to medical privacy. The idea of a public’s right to know information about the health of candidates arises from the philosophy that citizens have the right to be governed only with their consent, and that consent is only meaningful when citizens are making informed decisions (Streiffer et al., 2006). Voters consider health to be a key factor in determining a president’s ability to lead, as suggested by results of a 2004 CNN/Gallup poll cited by Brown (2008), in which 96% of those polled felt that the president’s general health was important or very important to being a good president. Especially given that developing Alzheimer’s disease would severely affect a future president’s ability to lead, the case for the public’s right to know candidates’ Alzheimer’s preclinical test results is compelling.

However, voters’ right to know is in conflict with candidates’ 4th amendment right and right to medical privacy. This conflict is a point of divide among voters; although the CNN/Gallup poll found that almost all of those polled believe it is important to have a healthy president, they have mixed responses about how the health of the president should be ensured. The majority of those polled (61%) believed that the president should retain the same rights as citizens to a private medical record, while a substantial minority (38%) advocated for releasing all health information that might affect the president’s ability to lead (Brown, 2008). I believe that candidates’ 4th amendment rights and rights to medical privacy override voters’ right to know, even when the information may affect a future president’s ability to lead, as in the case of preclinical Alzheimer’s testing.

Under the 4th amendment, people are guaranteed that the “right to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures [by the government], shall not be violated, and no warrants shall issue, but upon probable cause” (US Const., amend. IV). Assuming that candidates are entitled to these rights, the question is, would requiring preclinical Alzheimer’s testing be considered an “unreasonable” search for an ostensibly healthy candidate (Brown, 2008)? I would say so. Testing for Alzheimer’s disease is a psychologically distressing process that has potentially harmful and life-changing consequences, especially given that it is a terminal illness with no treatment at this time (Karlawish, 2011). Receiving an Alzheimer’s diagnosis has been shown to result in shock, fear, anxiety, and depression (Husband, 1999; Husband, 2000; Pratt & Wilkinson, 2003). Because candidates are not yet elected, there is a possibility that they will have to resume their normal lives after the election, and they should not have to bear the life-altering consequences that accompany a terminal diagnosis as a result of their run for presidency. Thus, even if a presidential contender has one or more risk factors for Alzheimer’s disease, an increased risk is not enough to justify the potential psychological distress that may accompany the testing process or preclinical diagnosis. Furthermore, because family history is a risk factor for Alzheimer’s disease, candidates’ family members may also get unwanted and unwarranted risk information, which can in turn cause psychological distress. Clearly, preclinical Alzheimer’s disease testing is an “unreasonable search” that can cause harm not only to candidates but also their family members, and thus, government mandated testing would be in violation of the 4th amendment.

US Constitution, image courtesy of Flickr user Lou Gold

Candidates also have a right not to disclose their Alzheimer’s results. If a candidate voluntarily opted to undergo preclinical Alzheimer’s testing, he or she should have a right to keep that information private. Currently, there are no laws that require the president or presidential candidates to reveal anything at all about their health, as they are covered under the Health Insurance Portability and Accountability Act (HIPAA), which allows patients to control privacy over their health information (U.S. Department of Health & Human Services, 2016). Notably, HIPAA makes some allowances for disclosures in situations where 3rd parties are at risk, such as patients with an infectious disease or patients who express a desire to harm themselves or others. Given this reasoning, one could make the argument that because Alzheimer’s disease could affect a future president’s ability to lead, the public is at risk; however, disclosing candidates’ preclinical Alzheimer’s test results would likely do more harm than good, and ultimately, the public is not at risk due to sufficient federal safeguards in place. Even if a candidate does have preclinical biomarkers for Alzheimer’s disease, he or she may still not develop symptoms for years or even decades (Villemagne et al., 2013); getting a positive result may not even affect his or her presidency, if elected. Further, those without a scientific background may mistake a preclinical diagnosis with a current one, and because Alzheimer’s disease is a relatively stigmatizing label, candidates should not have to endure any potential stigma as a result of his or her candidacy.

Given that requiring candidates to undergo Alzheimer’s testing is unethical, could we elect a president who may develop Alzheimer’s disease during his or her term? Possibly, but I would argue that the consequences are not as dire as Steele fears, due to sufficient federal safeguards in place. For example, the President does not make decisions unilaterally, and our system of checks and balances would prevent implementation of any irrational decisions. In the end, if the President were found to be demonstrating diminished capacity, the vice president would succeed him or her under the 25th amendment. Ultimately, given the federal safeguards in place, Alzheimer’s disease is not a significant threat to the presidency, and thus, requiring candidates to be tested is both unethical and unnecessary.

References



Alzheimer’s Association. “2015 Alzheimer’s disease facts and figures.” Alzheimer’s and Dementia 11 (2015): 332-384. PubMed. Web. 20 Mar. 2016.

"Alzheimer’s Disease." Alz.org. Alzheimer's Association, n.d. Web. 14 Feb. 2016.

Arias, J. (2014). Translating Preclinical Test Results into “Real World” Consequences. The Neuroethics Blog. Retrieved on March 23, 2016, from http://www.theneuroethicsblog.com/2014/05/translating-preclinical-test-results.html.

Brown, Teneille R. “Double Helix, Double Standards: Private Matters and Public People.” Journal of Health Care Law and Policy 11.2 (2008): 295-376.

Brookmeyer, R., D.A. Evans, L. Hebert, K.M. Langa, S.G. Heeringa, B.L. Plassman, and W.A. Kukull. “National estimates of the prevalence of Alzheimer’s disease in the United States.” Alzheimer’s and Dementia 7.1 (2011): 61-73.

Cavedo E., S. Lista, Z. Khachaturian, P. Aisen, P. Amouyel, K. Herholz, C.R. Jack, Jr., R. Sperling, J. Cummings, K. Blennow, S. O’Bryant, G.B. Frisoni, A. Khachaturian, M. Kivipelto, W. Klunk, K. Broich, S. Andrieu, M. Thiebaut de Schotten, J.F. Mangin, A.A. Lammertsma, K. Johnson, S. Teipel, A. Drzezga, A. Bokde, O. Colliot, H. Bakardjian, H. Zetterberg, B. Dubois, B. Vellas, L.S. Schneider, and H. Hampel. “The road ahead to cure Alzheimer’s disease: development of biological markers and neuroimaging methods for prevention trials across all stages and target populations.” Journal of Prevention of Alzheimer’s Disease 1.3 (2014): 181-202.

Good, Chris. "Hillary Clinton: 'No Lingering Effects' From 'Serious' Concussion." ABC News. ABC

News Network, 06 June 2014. Web. 14 Mar. 2016.

"HIPAA for Professionals." HHS.gov. N.p., 10 Sept. 2015. Web. 14 Mar. 2016.

Husband, H. J. "Diagnostic Disclosure in Dementia: An Opportunity for Intervention?" Int. J. Geriat. Psychiatry International Journal of Geriatric Psychiatry 15.6 (2000): 544-47. Web. 26 Feb. 2016.

Husband, H. J. "The Psychological Consequences of Learning a Diagnosis of Dementia: Three Case Examples." Aging & Mental Health 3.2 (1999): 179-83. Web. 26 Feb. 2016.

Karlawish, Jason. “Addressing the ethical, policy, and social challenges of preclinical Alzheimer’s disease.” Neurology 77.15 (2011): 1487-1493. PubMed. Web. 23 Mar. 2016.

Langbaum, Jessica B.S., Adam S. Fleisher, Kewei Chen, Napatkamon Ayutyanont, Francisco Lopera, Yakeel T. Quiroz, Richard J. Caselli, Pierre N. Tariot, and Eric M. Reiman. “Ushering in the study and treatment of preclinical Alzheimer’s disease.” Nature Reviews Neurology 9.7(2013): 371-381. PubMed. Web. 23 Mar. 2016.

Plassman, B.L, R.J. Havlik, D.C. Steffens, M.J. Helms, T.N. Newman, D. Drosdick, C. Phillips, B.A. Gau, K.A. Welsh-Bohmer, J.R. Burke, J.M. Guralnik, and J.C. Breitner. “Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias.” Neurology 55.8 (2000): 1158-1166. PubMed. Web. 23 Mar. 2016.

Pratt, Rebekah, and Heather Wilkinson. "A Psychosocial Model of Understanding the Experience of Receiving a Diagnosis of Dementia." Dementia 2.2 (2003): 181-99. Web. 26 Feb. 2016.

Rozhon, Tracie. "Fred C. Trump, Postwar Master Builder of Housing for Middle Class, Dies at 93." The New York Times. The New York Times, 26 June 1999. Web. 10 Mar. 2016.

Sperling, R.A., P.S. Aisen, L.A. Beckett, D.A. Bennett, S. Craft, A.M. Fagan, T. Iwatsubo, C.R. Jack, Jr, J. Kaye, T.J. Montine, D.C. Park, E.M. Reiman, C.C. Rowe, E. Siemers, Y. Stern, K. Yaffe, M.C. Carrillo, B. Thies, M. Morrison-Bogorad, M.V. Wagster, and C.H. Phelps. “Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.” Alzheimer’s and Dementia 7 (2011): 280-292.

Steele, Dayna. "Steele: Presidential Candidates Should Be Tested for Alzheimer's." Houston Chronicle. N.p., 5 Feb. 2016. Web. 14 Feb. 2016.

Streiffer, Robert, Alan Rubel, and Julie Fagan. "Medical Privacy and the Public's Right to Vote: What Presidential Candidates Should Disclose." Journal of Medicine and Philosophy J. of Med. & Philosophy NJMP 31.4 (2006): 417-39. Web. 28 Feb. 2016.

“The Constitution of the United States,” Amendment 4.

"What You Should Know About Testing for Alzheimer’s Disease – New Guidelines." Fisher Center

for Alzheimer's Research Foundation. N.p., n.d. Web. 10 Mar. 2016.

Villemagne, V.L., S. Burnham, P. Bourgeat, B. Brown, K.A. Ellis, O. Salvado, C. Szoeke, S.L. Macaulay, P. Maruff, D. Ames, C.C. Rowe, C.L. Masters, Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group. “Amyloidβdeposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study.” The Lancet Neurology 12.4(2013): 357-367. PubMed. Web. 20 Mar. 2016.

Zanetti, O., S.B. Solerte, and F. Cantoni. “Life expectancy in Alzheimer’s disease (AD).” Archives of Gerontology and Geriatrics 49 (2009): 237-243. PubMed. Web. 20 Mar. 2016.

Want to cite this post?

Lee, K.B. (2016). Should Presidential Candidates Be Required to Undergo Preclinical Alzheimer’s Disease Testing? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/04/should-presidential-candidates-be.html

A Review of Gut Feminism

By Katie Givens Kime

Katie Givens Kime is a doctoral student at Emory University in the Graduate Division of Religion, as well as the Center for Mind, Brain and Culture, and the Psychoanalytic Studies Program. Her dissertation investigates the role of religious conceptions in addiction recovery methods.

As neuroscience has expanded in capacity, resources, and public attention, many in the social sciences and humanities have been loudly critical: “Reductionism! Neurobiological chauvinism!” The essence of such critique is that the objectivity championed by the sciences masks all sorts of hidden biases, unconscious agendas, political motivations and economic purposes. Many historians and philosophers of science have argued that even choosing the object of scientific study and communicating observations inevitably involves language, point-of-view, and value prioritization. This means the nature of scientific knowledge, to an important degree, is unavoidably sociocultural [1].

Feminist theory has leaned more heavily upon this critique than other social sciences, for reasons at the roots of feminist movements. Essentialist claims about the “biology” and “nature” of women’s bodies have historically justified all manner of public policy, cultural conventions, and medical care models that violate and oppress women and other historically vulnerable populations, from the right to vote to equal pay. Thus, when it comes to the engagement of neurobiological data of most any sort, feminist theory is a realm of scholarship where deep suspicion has reigned. Projects revealing the sexism, racism, and classism embedded in the structures of supposedly objective scientific inquiry have been crucial for the success of various waves and stages of feminist liberation movements.

Image courtesy of Duke University Press

Thus, Elizabeth A. Wilson’s recently published monograph, Gut Feminism (2015), is as timely as it is persuasive. Wilson begins by charting how antibiologism is detrimentally “laced into feminist theory” (93).  “In the last thirty years, feminists have produced pioneering theories of the body...how bodies vary across different cultural contexts and historical periods, how structures of gender and sexuality and race constitute bodies in very different ways,” but when it comes to reading biological data, feminist theory lacks “a conceptual toolkit”(3). While gesturing to the understandable anxieties about “biology’s power to determine form and control politics,” (27) Wilson proposes that “...the antibiologism on which feminism cut its teeth has now become politically and intellectually restrictive” (26).   Wilson applauds the recent swell of feminist science studies contributions, but cautions against simply trading battle for betrothal, critique for exuberance, and “rejection of” for “belief in” – because to change from neuro-skeptic to neuro-enthusiast is merely “the coin of antibiologism flipped verso” (5).

Wilson, currently Chair of the Department of Women’s, Gender, and Sexuality Studies at Emory University, is not the first to propose a solution to the supposedly hygienic separation between sociocultural webs and neurobiological architecture, nor does she pretend to be. She cites the excellent overview by Fitzgerald and Callard (2015) of such proposed solutions by critical humanities scholars: that we (social scientists) subject the new brain sciences to a refined sociocritique, or demand their political reform, or welcome them into cultural theory, or use them to upset our taken-for-granted assumptions, or embed them in our accounts of the political, or locate them within a much thicker braid of social and political torsion. The list of such proposals is long and tangled [2].

Wilson situates herself in this sprawling debate via several case studies, such as the role of the gut as an organ of the mind that “ruminates, deliberates, comprehends” (5) beyond merely contributing to minded states. To her intended audience (colleagues investigating neuroscientific-humanities bridges, and scholars in feminist theory and gender studies), she offers compelling possibilities for how biological data might serve and transform the field, and visa versa.

In freshly querying biological data by “tracking the psychic character of the organic interior,” Wilson presents the “belly” as “just the right kind of container for such endeavors” (43).  The stomach is one of the human body’s most malleable organs – it is so easily modified, that it is hard to describe a typically shaped and positioned stomach.

The belly takes shape both from what has been ingested (from the world), from its internal neighbors (liver, diaphragm, intestines, kidney), and from bodily posture. This is an organ uniquely positioned, anatomically, to contain what is worldly, what is idiosyncratic, and what is visceral, and to show how such divisions are always being broken down, remade, metabolized, circulated, intensified, and excreted. (43-44).

Position of the stomach within the

body, courtesy of Wikipedia

Such a proposition might strike those from a natural science perspective as being overly symbolic and interpretive. If this is true, Wilson also engages many recent and robust neuroscientific and psycho-pharmaceutical findings about the gut as an organ of the mind, like the findings of a 2015 study from the Alimentary Pharmabiotic Centre at the University of Cork, which suggests certain kinds of gut bacteria (“psychobacteria”) regulate the neurotransmitter GABA via the vagus nerve (which connects the gut and the brain) (169) and thus regulate our mood. Wilson’s project, arguably distinguishing her from many “neuro-enthusiast” humanities scholars, is not to recruit neuroscientific data to finally “settle” our most outstanding philosophical problems, like what counts as unconscious, or narrative, or what explains economic behavior, or mental distress. (171) Rather, Wilson boldly pulls from an incredibly vast spectrum of concepts, deliberately entangling opposing explanations for problems that reveal the co-implication of psyche and soma.

One of many examples is Wilson’s unfolding of what might be learned from chronic bulimia, which is notoriously difficult to treat. In chronic bulimia, the ability to vomit food without any gag or hack prompt -- seemingly, to “will” the food back up – is a common development, often attributed to a reconditioning of the gag reflex. Wilson fluidly opens a wide array of questions:

Is the gag reflex a simple mechanical action distinct from psychic or deliberative impetus? Does its disconnection from higher cortical centers (and so from conscious cognitive processing) render it a nonpsychological event? What is conditioning, anyway? It seems to me that the gag reflex, this seemingly rudimentary biological action, is a very useful place from which to start thinking about the organic character of disordered eating (60-61).

Wilson suggests that the altering of digestive organs in chronic bulimia, held alongside the striking findings about the “mindedness” of the gut, might offer clues as to why episodes of bingeing and vomiting, now compulsive, fail to seem connected to events in the patient’s internal or external world. “The vicissitudes of ingestion and vomiting are complex thinking enacted organically: bingeing and purging are the substrata themselves attempting to question, solve, control, calculate, protect, and destroy” (63).  No wonder, Wilson notes, with “distress, anger, need, depression, comfort, and attachment” now becoming primarily organic, the capacity for those suffering with chronic bulimia to respond to cognitive behaviorally oriented therapy is so often less successful. And what might we make of how highly effective antidepressants seem to be for such patients, and the failure of agreement in the literature about “how the relationship between mood and bingeing” should be understood?

As elsewhere, Wilson suggests we explore etiologies beyond the conventional and flat biological economy, which is usually sequenced as “depression then bingeing; satiety or mood; brain not gut” (64).  As elsewhere, Wilson insists she is not proposing that organs, or psyche and soma, are indistinguishable. “Rather, I am claiming that there is no originary demarcation between these entities; they are always already coevolved and coentangled” (66).

So flows the bold and fluid assertions and explorations of Wilson’s Gut Feminism. Perhaps the pragmatic potential for this work can be illustrated by the case study Wilson cites of a woman suffering from depression, who picks up her prescription for a popular antidepressant. Instead of a bottle of capsules, she finds the pills packaged in flat metallic wrapping, individually separated.

“Each pill is in total solitude,” she said, “like metal shells looking out at each other. They are all in individual prisons”...her next thought was to swallow the pills together. When I asked her why, she said, “so they don’t feel so lonely and claustrophobic” (21).

The gut is a minded organ, image courtesy of YouTube

To bluntly (and surely inadequately) sum up Wilson’s project through the lens of this case: if how we think about things impacts our bodily state, and if the gut is a minded organ, and if the pharmaceutical agent produces particular biochemical results, and if the woman (like every human) is a mind-body co-implicated by both nature and culture, then surely feminist theory and neurobiology have contributions for one another. But more than transactional “conversations,” or pretending a flat and fair “interdisciplinary” field can be created, the sociocultural and the neurobiological come together messily, and Wilson notes, “each is a little undone in the encounter.” One might also add: each is encouraged to expand the imagined value of the other.

[1]: See Papineau, also http://www.scientificamerican.com/article/point-of-view-affects-how-science-is-done/, http://plato.stanford.edu/entries/science-theory-observation/



[2]: See Fitzgerald and Callard for a compelling, fresh proposal of how the conception of empirical experiments might be generatively “entangled.”



References



Fitzgerald, D., & Callard, F. (2015). Social Science and Neuroscience beyond Interdisciplinarity: Experimental Entanglements. Theory, Culture & Society, 32(1), 3–32. http://doi.org/10.1177/0263276414537319



Papineau, D. (2005). Problems with the philosophy of science. In T. Honderich (Ed.), The Oxford companion to philosophy. Oxford: Oxford University Press.



Wilson, E. A. (2015). Gut feminism. Durham ; London: Duke University Press.



Want to cite this post?



Kime, K.G. (2016). "A Review of Gut Feminism." The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/04/a-review-of-gut-feminism.html

Neuroethics and the BRAIN Initiative

By Henry T. Greely

Hank Greely is the Deane F. and Kate Edelman Johnson Professor of Law and Professor, by courtesy, of Genetics at Stanford University. He specializes in ethical, legal, and social issues arising from advances in the biosciences, particularly from genetics, neuroscience, and human stem cell research. He directs the Stanford Center for Law and the Biosciences and the Stanford Program in Neuroscience in Society; chairs the California Advisory Committee on Human Stem Cell Research; and serves on the Neuroscience Forum of the Institute of Medicine, the Advisory Council for the National Institute for General Medical Sciences of NIH, the Committee on Science, Technology, and Law of the National Academy of Sciences, and the NIH Multi-Council Working Group on the BRAIN Initiative. He was elected a fellow of the American Association for the Advancement of Science in 2007. His book, THE END OF SEX AND THE FUTURE OF HUMAN REPRODUCTION, was published in May 2016.

Professor Greely graduated from Stanford in 1974 and from Yale Law School in 1977. He served as a law clerk for Judge John Minor Wisdom on the United States Court of Appeals for the Fifth Circuit and for Justice Potter Stewart of the United States Supreme Court. After working during the Carter Administration in the Departments of Defense and Energy, he entered private practice in Los Angeles in 1981 as a litigator with the law firm of Tuttle & Taylor, Inc. He joined the Stanford faculty in 1985.

On April 2, 2013, President Obama launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative®. (Neuroscience has yet to reveal why an initiative about the brain had to have an acronym that spelled BRAIN; * legal issues explain the trademark notation.) Built on the report, BRAIN 2025: A SCIENTIFIC VISION, of a committee created to advise Francis Collins, the NIH Director, and chaired by neuroscientists Cori Bargmann of Rockefeller University and Bill Newsome of Stanford, the Initiative, in spite of political deadlock and budgetary woes, has survived and, in some respects, even thrived.

At its launch, the BRAIN Initiative was hailed as a project that would bring together at least three U.S. government agencies, charitable foundations, and industry. In reality, the initiative has been more decentralized. It has no overall director and no dedicated staff; it will only get an overall web page this summer. The various federal agencies stay in regular communication, some foundations and some foreign funders have played important roles, three international memoranda of understanding have been completed, and the Initiative has sponsored annual meetings of all BRAIN investigators whatever their funding. Still, it is more a confederation of individual activities, however inter-communicating, than a unitary project [1].

The National Institutes of Health (NIH) has taken the leading role in organizing the Initiative. This is partially because of its large financial stake in it; this fiscal year the NIH budget for the BRAIN Initiative is about $150 million. But other agencies are also spending large amounts on BRAIN – the Defense Advanced Research Projects Administration has a $95 million budget for it this year, the National Science Foundation expects to spend $72 million, and the Intelligence Advanced Research Projects Administration and the Food and Drug Administration both have multi-million dollar BRAIN budgets.

NIH’s role may be more a function of its own complexity than the size of its BRAIN budget. Ten Institutes and Centers at NIH are part of the BRAIN Initiative: the National Institutes of Aging, Alcohol Abuse and Alcoholism, Biomedical Imaging and Bioengineering, Child Health and Human Development, Deafness and Other Communication Disorders, Drug Addiction, Mental Health, Neurological Disorders and Stroke, the National Eye Institute, and the National Center for Complementary and Integrative Health. Many other Institutes and Centers have at least some central nervous system connection (the National Cancer Institute, for example, studies brain tumors). NIH needed to organize its own response to, and its role in, the Initiative.

President Obama speaking on the BRAIN initiative,

image courtesy of Flickr user Open Knowledge.

To do so, in 2014 it created the “Multi-Council Working Group on the NIH BRAIN Initiative,” happily shortened to MCWG. (I have tried to get people to pronounce the acronym as “McWig” but with very limited success.) MCWG has 14 members, one from each of the Advisory Councils for the 10 participating NIH Institutes and Centers and four “at large” members, including me. The directors of the relevant NIH entities normally attend; in addition there are “ex officio” members representing BRAIN activities at DARPA, FDA, IARPA, and NSF.

Since its first meeting in late August 2014, MCWG has met twice a year, summer and winter. Co-chaired by the directors of the National Institute of Neurological Disorders and Stroke, Dr. Walter Koroshetz, and the National Institute for Mental Health, initially Dr. Thomas Insel and now his acting successor, Dr. Bruce Cuthbert, MCWG tries to provide some of the kind of guidance that their Advisory Councils give NIH Institutes and Centers. The group is briefed on current funding areas and grants as well as proposed new funding areas and in turn provides its thoughts to the NIH.

“Thriving,” though doesn’t just mean “has big budgets and a fancy committee.” The BRAIN Initiative is funding exciting and important work. It has no grand substantive goal akin to “sequencing the human genome,” but instead wants to create tools to help us understand the brain (and, after all, the most important product of the Human Genome Project was nearly infinitely cheaper, faster, better sequencing, not the actual sequence).  You can find out more about BRAIN’s progress with things like photoacoustic imaging and miniaturized and highly sensitive electrophysiology and optical imaging instruments at the BRAIN Update blog.

Fine, you say, but what does all of this have to do with neuroethics?

Ethical questions were seen as part of the Initiative from before its beginning. BRAIN 2025 recognized that “Because the brain gives rise to consciousness, our innermost thoughts and our most basic human needs, mechanistic studies of the brain have already resulted in new social and ethical questions.” When President Obama announced the Initiative, he asked the President’s Commission for the Study of Bioethical Issues (PCSBI) to report to him on ethical issues it raised. It did, twice, in GRAY MATTERS, Volumes 1 and 2, which can be found here.

I was asked to serve as an at-large member of MCWG not just (?) for my good looks, but in the hope that I could bring some neuroethics experience to the group. It was immediately clear to me, and quickly became clear to the rest of MCWG, that the BRAIN Initiative needed more neuroethics input. The importance of those issues was also highlighted by a November 2014 neuroethics workshop held by NIH, discussed here.

The NIH has played a large role in the BRAIN initiative,

image courtesy of Wikipedia

For one thing, particular research areas or grants could raise very specific questions that were more granular than the recommendations in GRAY MATTERS. MCWG also recognized that there might be possibilities for the Initiative to lead to some general guidelines for approaching recurring problems in neuroscience research ethics, particularly in work with human subjects but also in research with non-humans. And finally the Working Group realized that the BRAIN Initiative might also be interested in funding some neuroethics research that could, by recommendations or criticism, support its work.

So, at the MCWG co-chairs suggestion, Dr. Christine Grady, Chief of the Department of Bioethics at the NIH Clinical Center and a member of PCSBI, and I were asked to prepare and present a plan for neuroethics activities to MCWG at its summer 2015 meeting. As a result MCWG approved the creation of a MCWG Neuroethics Work Group, co-chaired by Dr. Grady and myself and reporting to MCWG and its co-chairs. (Very happily for us, Dr. Koroshetz threw in from NINDS the very able support of Dr. Khara Ramos from his office as the Work Group’s Executive Secretary and liaison to NIH.) That fall the Work Group was chosen with members from both inside MCWG – Drs. James Eberwine of Penn, Bradley Hyman of Mass. General Hospital, and Rafael Yuste of Columbia – and outside it – Drs. Nita Farahany of Duke, Steve Hyman of the Broad Institute, Karen Rommelfanger of Emory, and Chandra Sripada of Michigan. Some of us met for a working dinner at the International Neuroethics Society annual meeting last fall in November, we’ve had several conference calls, and we held our first in-person meeting on February 9.

So, after just over a thousand words – what does this mean and why should you care?

Well, the MCWG Neuroethics Work Group is working. We are preparing two draft documents laying out ethical issues around data sharing in neuroscience research and about long-term obligations to human research participants who received implanted devices. We are working with other interested parties in cosponsoring workshops on neuroethics issues relevant to the BRAIN initiative. And, although we cannot claim too much credit for it, the NIH recently announced that it would be able to use funds from this fiscal year to support administrative supplements to existing NIH BRAIN Initiative Awards, including those about neuroethics.

Specifically, the PIs on BRAIN Initiative grants have been told that if there are any ethical considerations involved in their research, a supplement to explore those questions, as they fall within the funded specific aims of a given award, would be appropriate. The relevant grants are listed here. Applications for supplements are due May 2, and should follow these instructions. We hope that these will just be a new start for NIH-supported research on neuroethics.

We will have to see where neuroethics goes within the BRAIN Initiative, and, for that matter, what a future Administration holds for the whole initiative. But I think good starts have been made on both points. And I promise you that the MCWG Neuroethics Work Group will continue to look for good ways to apply neuroethics to the BRAIN Initiative – and to apply the BRAIN Initiative, and NIH more broadly, to neuroethics. Feel free to contact me, Dr. Grady, or Dr. Ramos directly with your thoughts or questions at hgreely@stanford.edu, CGrady@cc.nih.gov, or ramoskm@ninds.nih.gov. You can also read a bit about the work group on the NIH BRAIN Initiative website [2].

[1] It may be a case of what Steve Hyman has called a “COA” – a “Crypto-Orwellian Acronym.”



[2] My sincere thanks to Drs. Grady and Ramos for their help with this blog post.

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Greely, H.T. (2016). Neuroethics and the BRAIN Initiative. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/04/neuroethics-and-brain-initiative.html

Erasing Memories

By Walter Glannon, PhD

Walter Glannon, PhD, is Professor of Philosophy at the University of Calgary. He is the author of Bioethics and the Brain (Oxford, 2007) and Brain, Body and Mind: Neuroethics with a Human Face (Oxford, 2011) and editor of Free Will and the Brain: Neuroscientific, Philosophical and Legal Perspectives (Cambridge, 2015).

Neuroscientists can measure changes in the brain associated with different types of memory. Recent experiments on rodents have shown that memories can be manipulated. In one experiment, researchers implanted a false fear memory in a mouse brain, causing it to elicit a fear response to a stimulus to which it was not actually exposed [1]. In a different experiment, researchers electrically stimulated place cells in a mouse hippocampus as well as cells in the reward system during sleep. This induced learned behavior where mice linked a specific location to a reward [2].  This type of manipulation may eventually serve a therapeutic purpose in humans.  Psychiatric disorders including subtypes of major depression, generalized anxiety, phobia, panic and especially post-traumatic stress disorder (PTSD) can be conceptualized as disorders of memory content. In such a model, the neural representation of the emotional component of the memory, or emotional trace, of a traumatic experience persists beyond any adaptive purpose. This causes dysregulation in the fear memory system, resulting in pathology associated with impaired cognitive, affective and volitional functions [3, 4]. I’d also like to propose that unlike disorders of memory capacity, such as anterograde or retrograde amnesia, where one cannot form or retain memories, the problem in disorders of memory content, like PTSD, is the inability to get rid of or “extinguish” them. 

The source of this dysfunction in the fear memory system is neural changes employed during the consolidation and reconsolidation of an emotionally charged memory of fear-inducing stimuli. These changes can be linked to a hyperactive amygdala, the critical region of the brain’s fear system. One model of memory formation in response to fearful or traumatic events is that memory becomes consolidated in the amygdala through the action of released noradrenaline [5, 6]. The memory consolidates further through learned behavior as the subject repeatedly experiences a conditioned stimulus paired with an aversive stimulus. It is thought that memories that have been consolidated need to reconsolidated, or updated, to remain in storage. This occurs when they are retrieved in conscious or unconscious recall of events [7]. One aim of some research directed at treating PTSD is to weaken or prevent the formation of a traumatic emotional memory by disrupting reconsolidation during or immediately after retrieval, because at this time memories are labile and susceptible to alteration [8]. Psychiatrist Roger Pitman explains that “for reconsolidation blockade, or updating, to be successful, two steps are required. First, the problematic memory must be destabilized. Second, its restabilization (reconsolidation) must then be prevented or modified (updated)” [8, p. 2]. An active area of research has been aimed at manipulating changes in genetic machinery such as transcription factors to alter protein production necessary for reconsolidation.

Flowchart of memory consolidation

Several interventions have been used for reconsolidation blockade. It is thought that when a memory is retrieved it becomes labile and susceptible to alteration. The memory must be re-consolidated in order to stay intact. Extinction training, a behavioral intervention, can weaken conditioned fear responses to cues associated with the memory of an experience. The subject learns to dissociate the memory of the experience from the cues [9, 10]. Reconsolidation can also be disrupted pharmacologically. The beta-adrenergic receptor antagonist propranolol can also block the consolidating action (as represented by altered physiological responses associated with a fear response like heart rate and skin conductance) by blockade of beta adrenergic receptors in humans [11]. In essence, one might surmise that by attenuating its emotional salience, the drug takes the sting out of the memory while leaving its cognitive trace intact.

Even so, stress or other environmental factors can trigger a return of a heightened fear response [3, 12] and not all subjects can be trained so that the conditioned stimulus no longer signals danger. If the emotional representation of the memory is weakened but not literally erased, then it is possible that a stimulus reminding the subject of the original traumatic experience could reactivate the memory’s emotionally charged content and reactivate the psychopathology.

Theoretically, a more effective form of reconsolidation blockade would be one that not only weakened but erased the emotional representation of the memory. Because reconsolidation is thought to require protein synthesis [11], a drug that interfered with protein synthesis could block reconsolidation. Infusion of a protein synthesis inhibitor, such as anisomycin perhaps in areas like the basolateral amygdala, during memory retrieval might prevent reconsolidation and effectively erase—not just weaken—any trace of the memory [7, 12]. This would eliminate any possibility of reactivating a fear response because there would be no representation to be reactivated.

People with PTSD may benefit from having memories

erased, image courtesy of Wikimedia Commons

This intervention has been used only in animal models. Because it is still a hypothetical intervention for humans, any claims about memory erasure must be made tentatively. There are a number of challenges in using this intervention as therapy. One problem is that, the longer a memory has been stored in the brain, the more difficult it is to destabilize and alter it (with the exception of memory retrieval in which the memory must be reconsolidated). Retrieval does not always trigger reconsolidation and the labile state necessary for memory disruption. Also, older and stronger memories may be less susceptible to disruption after retrieval due to increased synaptic strength from the effects of protein synthesis and long-term potentiation over extended periods [3, 13].  To be effective, reconsolidation blockade would have to occur not long after the memory had been encoded and consolidated. Another challenge is selectivity. While in theory, implicit memories such as those involved in fear conditioning versus explicit memories employ different neural pathways, the question still remains whether it would be possible to erase a particular memory in the fear system while leaving other memories intact. Not all memories of fearful events are maladaptive or pathological. Many are adaptive and critical for survival by enabling us to recognize and respond appropriately to external threats. Unless it could target a specific memory in a specific node of a specific neural circuit, it is not known whether a protein synthesis inhibitor aimed at erasing it would have unintended and unforeseeable expanding effects that might disable normal adaptive functions in the fear memory system (or even beyond that system with off-target effects). The transgenic “Doogie mice,” who outperformed their normal counterparts on learning and memory tests but were more sensitive to chronic pain, suggest that memory manipulation may involve trade-offs between different neurally mediated cognitive and affective functions [14].

This might expose the subject to even greater harm than the psychological harm caused by the memory targeted for deletion. As with any other interventions in the brain, these risks have to be weighed against the potential benefit, which could be substantial in some psychiatric disorders. Among their adverse psychological effects, fear memories can impair rational and moral agency by interfering with the deliberative ability to form and execute action plans and recognize and respond to reasons for or against certain actions. The disrupting effects of some traumatic memories on agency and mental states in general justify deleting them from one’s brain.

Is erasing memories worth the risk?

Image courtesy of YouTube.

If we could and should erase the emotionally charged memories associated with psychopathologies, then why stop there? Why not also erase episodic memories that are not pathological but only unpleasant or disturbing? While not as harmful as fear memories associated with mental disorders, persistent unpleasant episodic memories may still cause harm. Erasing these memories may be even more challenging neurophysiologically than erasing a traumatic emotional memory. Traumatic emotional memory and episodic memory are separated into implicit and explicit memory systems involving different mechanisms [15]. Unlike implicit (nondeclarative) fear memories, explicit (declarative) episodic memories are available for conscious recall, which may facilitate retrieval for reconsolidation blockade. Nevertheless, episodic memories often have negative emotional content, and some of this can lead to maladaptive behavior. Suppose that these memories could be erased. Should they be? Constant recall of embarrassing or blameworthy mistakes can haunt a person for years, causing self-doubt and making one indecisive when faced with choices. Yet disturbing memories of actions we should not have performed are necessary for the moral emotions of regret and remorse and provide opportunities for personal and moral growth. They enable us to critically reflect on our behavior, plan more prudently for the future and contribute to our moral sensibility in respecting the rights, needs and interests of others. Erasing a few memories might not undermine these capacities. But a general pattern of erasure might gradually weaken this sensibility and with it the capacity to act in accord with social norms. It could also impair character development by removing reminders of the imperfections reflected in past misdeeds and the need to modify our behavior. Weakening but not erasing the emotional content of an unpleasant episodic memory could have the same effect. It is on the basis of this content that we construct meaning from these memories and use it to imagine and project ourselves into the future. Stripping them of this content would run the risk of converting episodic memories of personal experiences into semantic memories of facts devoid of meaning. This could have deleterious effects on agency and identity by impairing our ability to plan and act and altering our experience of traveling through time.



Research into pharmacological modulation of fear memories is still in its infancy. As in all medical research, there are translational issues in moving from animal to human models of memory. Functional imaging will have a critical role in identifying changes in brain activity at synaptic, circuit and network levels correlating with attenuated or erased memories. A better understanding of genetic and epigenetic factors in reconsolidation, particularly the transcription factors regulating protein synthesis, will also be critical. Although the idea of erasing pathological fear memories is speculative, it may become a promising way of treating or preventing some psychiatric disorders whose development is traceable to these memories [4].

References



1. Noonan D. Meet the two scientists who implanted a false memory into a mouse. Smithsonian Magazine, November 2014.

http://www.smithsonianmag.com/innovation/meet-two-scientists-who-implanted-false-memory-into-a-mouse/Nov. 2014.



2. de Lavilleon, G., Masako Lacroix, M., Rondi-Reig, L and Benchenane, K. (2015). Explicit memory creation during sleep demonstrates a causal role of place cells in navigation. Nature Neuroscience 18: 493-495.



3. Parsons, R. and Ressler, K. (2013). Implications of memory modulation for post-traumatic stress and fear disorders. Nature Neuroscience 16: 146-153.



4. Pitman, R. (2015). Harnessing reconsolidation to treat mental disorders. Biological Psychiatry 78: 819-820.



5. Pitman, R. [1986]. Post-traumatic stress disorder, hormones and memory. Biological Psychiatry 26: 221-223.



6. McGaugh, J. (2015). Consolidating memories. Annual Review of Psychology 66: 1-24.



7. Nader, K., Schafe, G. and LeDoux, J. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406: 722-6.



8. Pitman, R. (2011). Will reconsolidation blockade offer a novel treatment for posttraumatic stress disorder? Frontiers in Behavioral Neuroscience 5: doi: 10.3389/fnbeh.2011.00011.



9. Kindt, M., Soeter, M. and Vervliet, B. (2009). Beyond extinction: erasing human fear responses and preventing the return of fear. Nature Neuroscience 12: 256-8.



10. Soeter, M. and Kindt, M. (2015). An abrupt transformation of phobic behavior after a post-retrieval amnesic agent. Biological Psychiatry 78: 880-6. 4



11. Brunet, A., Orr, S., Tremblay, J., Robertson, K., Nader, K. and Pitman, R. (2008). Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. Journal of Psychiatric Research 42: 503-6.



12. Agren, T., Engman, J., Frick, A., Bjorkstrand, Larsson, E-M, Furmark, T. and Fredrikson, M. (2012). Disruption of reconsolidation erases a fear memory trace in the human amygdala. Science 337: 1550-2.



13. Milekic, M and Alberini, C. (2002). Temporally graded requirement for protein synthesis following memory reactivation. Neuron 36: 521-525.



14. Stull, D. (2001). Better mouse memory comes at a price. The Scientist, April 2. http://www.thescientist.com/?articles.view/articleno/13302/title/Better-Mouse-Memory-Comes-at-a-Price/



15. Squire, L. (2004). Memory systems of the brain: a brief history and current perspectives. Neurobiology of Learning and Memory 82: 171-177.

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Glannon, W. (2016). Erasing Memories. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/04/erasing-memories.html