Science in Society Review - Spring 2016 by The Triple Helix at UChicago

Spring 2016 | University of Chicago A Production of The Triple Helix

The Science in Society Review

ISSN 2164-4314

The International Journal of Science, Society, and Law

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The Triple Helix, Inc. is the world’s largest completely student-run organization dedicated to taking an interdisciplinary approach toward evaluating the true impact of historical and modern advances in science. Work with tomorrow’s leaders Our international operations unite talented undergraduates with a drive for excellence at over 25 top universities around the world. Imagine your readership Bring fresh perspectives and your own analysis to our academic journal, The Science in Society Review, which publishes International Features across all of our chapters. Reach our global audience The E-publishing division showcases the latest in scientific breakthroughs and policy developments through editorials and multimedia presentations. Catalyze change and shape the future Our new Science Policy Division will engage students, academic institutions, public leaders, and the community in discussion and debate about the most pressing and complex issues that face our world today. All of the students involved in The Triple Helix understand that the fast pace of scientific innovation only further underscores the importance of examining the ethical, economic, social, and legal implications of new ideas and technologies — only then can we completely understand how they will change our everyday lives, and perhaps even the norms of our society. Come join us!

TRIPLE HELIX CHAPTERS North America Chapters Arizona State University Brown University Cornell University Carnegie Mellon University Georgia Institute of Technology George Washington University Georgetown University The Harker School Harvard University Johns Hopkins University The Ohio State University University of California, Berkeley University of California, Davis University of California, San Diego University of Chicago Yale University Europe Chapter Cambridge University Asia Chapter National University of Singapore Australia Chapter University of Melbourne

TABLE OF CONTENTS Mental Health and the “Happiest Place on Earth”

Conservation’s Panda Problem

Evan Eschliman......................................................................... Kristine Don..............................................................................

The End of the Golden Age of Antibiotics?

Euclid’s Elements: A Guide for the Greats

Aran Shaunak......................................................................... Zeke Gillman..........................................................................

Limited Health Literacy: A Dangerous but Silent Epidemic

Jacqueline Wang....................................................................

The Role of Sociology in Medicine: A Critique of the 2015 MCAT

Senxi Du..................................................................................

Antibodies: The Versatile Drug

Jessica McHugh......................................................................

Euclid’s Elements: A Guide for the Greats

Zeke Gillman..........................................................................

Arsenic in Maine: Building Policy from Geology

Wakanene Kamau..................................................................

A Preview: The Effect of Income Cycling on Hypoglycemia Incidence

The Roosevelt Institute.........................................................

STAFF AT UCHICAGO President Stephen Yu Vice President Salman Arif Editor in Chief, SISR Annie Albright Managing Editors, SISR Jacqueline Wang Erin Fuller Associate Editors, SISR Sumer Vaid Aya Nimer Shyam Vasudevan Writers, SISR Quang Tran Evan Eschliman Isabella Pan Erin Fuller Jacqueline Wang Senxi Du Zeke Gillman Kristine Don Wakanene Kamau Production Directors Helena Zhang Ariel Goldszmidt Events Director Jonathan Chuang Events Coordinators Angela Li Peter Ryffel Franklin Rodriguez E-Publishing Directors Katherine Oosterbaan Aliya Moreira Editors in Chief, Scientia Luizetta Navrazhnykh Jake Russell

Message from Chapter Leadership Dear Reader, It is with great excitement that we bring to you the 2016 Spring Issue of The Science in Society Review. A new year has introduced new directions to consider in some of the most pressing issues of science in society and at The Triple Helix, Inc. we understand the need to investigate these questions in aninterdisciplinary manner. In this vein, our writers, aided by a strong support system of undergraduate editors and faculty mentors, strive to incorporate the perspectives of multiple fields in their articles. For this reason and others, we at The Triple Helix, Inc. pride ourselves on the fact that we bring our writers together with eminent University professors and field professionals for one-on-one collaboration. We are proud to encourage our future leaders in heir rigorous exploration for the key issues in society today. It is our hope that the articles presented herein will stimulate and challenge you to join our dialogue. Stephen Yu President, The Triple Helix uchicago.president@thetriplehelix.org

Managing Editors, Scientia Amanuel Kibrom Michael Cervia Webmaster Tima Karginov

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Editor’s Note: this SISR edition features two articles written and edited by The Triple Helix chapter at the University of Cambridge. They are featured in this issue as a preview of an upcoming international collaboration between the University of Chicago, the University of Cambridge, and several other schools, to produce a portfolio of interdisciplinary articles pertaining to a single internationally relevant question. The portfolio will be published in the Fall 2016 edition of the Science In Society Review.

Mental Health and the “Happiest Place on Earth” Evan Eschliman (University of Chicago) Introduction to Bhutan Bhutan calls itself the “Happiest Place on Earth,” and some statistics suggest that it might indeed be close to claiming that top spot. The small Himalayan kingdom of around 750,000 was ranked as the eighth most subjectively happy country in the world in 2007 [1]. Such a high rank is impressive for such a small nation; however, due to its longstanding prioritization of well-being, it is surprising that Bhutan is not ranked higher. Since 1792, the nation has held the belief that the sole purpose of government is to ensure citizens’ happiness [2]. The “Last Shangri-La” had been largely isolated for many years due to its geographic location and its protectionist policy, but Bhutan ended its feudal society and formally opened itself to the Western world in 1953 [3]. In 1972, facing rapid development and modernization, Bhutan’s Fourth Dragon King Jigme Singye Wangchuck famously held fast to his predecessors’ beliefs and proclaimed that popular measure of Gross Domestic Product would not guide his country’s future [4]. Instead, he proposed and the nation’s novel guiding metric-- Gross National Happiness (GNH)-- putting an official policy behind traditional beliefs. Bhutan’s belief in the purpose of government has not changed since then, but much about the country has: television and Internet were introduced in 1999, © 2016, The Triple Helix, Inc. All rights reserved.

traditional dress-- once ubiquitous-- is becoming increasingly uncommon, and the capital of Thimphu now has one bar for every 250 inhabitants [5]. But there is a looming problem that hangs among the nation’s traditional lanterns and temple rooftops. Paradoxically for a country as focused on happiness as Bhutan, there are severe challenges facing the kingdom’s mental health. GNH: Pros and Cons GNH has many potential advantages as a development principle. Unlike GDP, it puts citizens’ perceived well-being at the forefront of development. Moreover, it encourages participation in cultural traditions, involvement in the community, and even stewardship of the environment [4]. Even though it was originally conceived as a means to align development and modernization with traditional Bhutanese and Buddhist values, the country believes measurement of happiness is of international importance. In 2011, the UN passed Bhutan-proposed measures suggesting that all countries begin to integrate happiness and satisfaction metrics in their national surveys [6]. Although there is global agreement on the importance of monitoring happiness, there is international concern about the true happiness of the Bhutanese people. Using a standardized-- although admittedly Western-designed-- system, THE TRIPLE HELIX Spring 2016

the UN ranked Bhutan as 84th in its 2016 World Happiness Report [7], bringing the moniker of “Happiest Place on Earth” into question.

in Thimphu anyway). Instead, patients seeking treatment often turn to traditional medicine [10]. These traditional medical practices often involve religion- or indigenous plant-based therapies. The methods Current State of Health Care in Bhutan should not entirely be discounted, but do little to help with conditions more than Despite the nation’s determination the very mild. Neuropsychiatric medito ensure individual happiness, little is cine and counseling is free to patients in done for its mentally ill. This shortfall Bhutan, but use remains low [11]. Often, strongly contrasts the nation’s health Dorji reports, patients are brought into care as a whole. Bhutan spends 10% of his office in catatonic states after weeks its GDP on health care, making it free for of seeking traditional treatment, allowing all inhabitants, and its national health the disease to progress [5]. Additionally, care system is considered “exemplary for he sees many patients who come with the region” by the World Health Orga- complaints of physical symptoms [5]. Only nization [8]. However, only 1% of that after sensitive questioning do they reveal health spending is allocated to mental emotional trauma, depressive symptoms, health [3]. Mental health legislation is or the like. These patients are not able to lacking as well. Bhutan passed a mental self-identify the cause of their symptoms health policy 1997, but currently has no due to a pervasive lack of mental health legislation regarding implementation [3]. awareness. This lack of a formal system results in This lack of mental wellness literacy having few mental health care person- has major ramifications in rates of two nel. Bhutan has no psychologists, social linked manifestations of mental illness: workers, or occupational therapists, and suicide and substance abuse. Bhutan had has one practicing psychiatrist [3]. the 20th highest suicide rate in the world in 2002 [12], and it is likely even highProblems and Criticisms of GNH’s Impact er now. The incidence of suicide, Dorji on Mental Health notes, is especially high in rural areas of the country. Karma Tsheetem, secretary Critics of the country’s approach to of the GNH Commission, attributes the mental health— including Dr. Chencho increasing rates to a disconnect between Dorji, Bhutan’s sole practicing psychia- traditional and modern ways of life, saying trist— worry that the obsession with GNH suicide rates will continue to rise until there actually only serves to worsen the nation’s is “a better balance between the spiritual mental wellness and the material” [9]. Even though [13]. Paradoxically for a country education about Along with the importance of as focused on happiness as suicide, rates of happiness occurs substance abuse Bhutan, there are several throughout Bhuin Bhutan are tan, there exists challenges facing the also increasing no program to [14]. Prior to increase mental kingdom’s mental health modernization, health literacy the Bhutanese [10]. This leaves many Bhutanese unaware would drink alcohol almost solely as part of how to seek modern pharmacological of spiritual ceremonies [5]. But now, with or therapeutic treatment (although many the introduction of commercial alcohol in would be unable to access Dr. Dorji’s office 1972, alcoholism is and has been a rapidly 6

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growing problem [14]. A lack of societal stigma regarding consumption inhibits the implementation of laws restricting access to minors and during certain times during the day [5,9]. This absence of stigma and the high prevalence of bars in Thimphu have led to Bhutan’s having the highest per capita alcohol consumption in South Asia [3]. With little government control or shame, Dorji sees that drinking easily leads to alcohol abuse [5]. He believes the “alarming proportion” of substance abuse and alcohol-related problems threatens the nation’s mental health and its GNH [5].

is essential to remember that just as an individual’s mental health is an essential part of his overall health, the mental health of a nation is inextricably linked to its overall development.

Moving Forward

[3] WHO. Bhutan Country Profile. Mental Health Atlas 2011. Department of Mental Health and Substance Abuse.

Despite these challenges, progress is being made towards a more mentally healthy Bhutan [14]. Dorji continues to strongly advocate for international attention for the issue [5]. Universities and other organizations are beginning to invest time and resources into researching and implementing programs to better Bhutan’s mental wellness [14]. The newly elected prime minister, Ushering Tobgay, had placed a spotlight on the obsession with happiness. When he was elected in 2013, he ran on a platform including the idea that “rather than talking about happiness, [Bhutan should] want to work on reducing the obstacles to happiness” [15]. He has since allocated significant government funds to health and mental health infrastructure [15]. As the WHO proclaimed in their Comprehensive Mental Health Action Plan 2013–2020, a person cannot be healthy without being mentally healthy [16,17]. This can be extended to the health of a country and its governance as well. Although the necessary changes are beginning to take place, Bhutan’s situation extends a cautionary tale to the rest of the world. As happiness and general well-being become more and more integrated into development metrics, governments must also increase their support of mental health programs. Going forward, it © 2016, The Triple Helix, Inc. All rights reserved.

References [1] White, A. “A Global Projection of Subjective Well-being: A Challenge To Positive Psychology?” Psychtalk. 56, 17-20. 2007. [2] McDonald, Ross. Rethinking Development. Local Pathways to Global Wellbeing. St. Francis Xavier University, Antigonish, Nova Scotia, Canada. 2005.

[4] “Gross National Happiness”. The Centre for Bhutan Studies. Accessed 24 March 2016. [5] Dorji, Chencho. “The Myth Behind Alcohol Happiness.” Accessed April 24, 2016. [6] Ryback, Timothy W. “The U.N. Happiness Project.” The New York Times, March 28, 2016. [7] Helliwell, John; Layard, Richard; Sachs, Jeffrey (April 2, 2012). “World Happiness Report.” Columbia University. [8] “WHO- AIMS Country Report - Bhutan.” Accessed April 24, 2016. [9] Pelzang, Rinchen. Mental health care in Bhutan: policy and issues. WHO South-East Asia Journal of Public Health 2012; 1(3):339-346. [10] “Mental Health Is Non-Entity in Bhutan : Dr Damber Nirola.” Bhutan News Service, September 3, 2014. [11] Saraceno, B., et al., Barriers to improvement of mental health services in low-income and middle-income countries. The Lancet. 370(9593): p. 1164-1174. [12] “Suicide in Bhutan.” World Life Expectancy. Accessed April 24, 2016. [13] “Bhutan: Stigma in Mental Health Issues.” Eye on Asia - China Daily Asia. Accessed April 24, 2016. [14] Tharpa, Rabgye. “Alcohol and Bhutanese Culture.” BBS, February 28, 2012. [15] “Achieving Gross National Happiness Through Community-Based Mental Health Services in Bhutan.”

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Accessed April 24, 2016. [16] “Mental Health in Bhutan in Regards to Gross National Happiness.” Commons Abundance Network. Accessed April 24, 2016.

[17] World Health Organization. Comprehensive mental health action plan 2013–2020. 2013. [18] Prince, M., et al. “No health without mental health.” The Lancet. 370 (9590): p. 859-877.

Conservation’s Panda Problem Kristine Don (University of Chicago)

problem, and that problem is cute, fluffy, and black and white. The Giant Panda is synonymous with conservation and wildlife protection. In fact, the Giant Panda is the face of the World Wide Fund for Nature/World Wildlife Fund (WWF), one of the largest, international, non-governmental, charitable trust organizations. As one of the most iconic and beloved endangered animals in the world, the Giant Panda is often associated with China and its mythical landscape in the popular imagination. Taking care of pandas, however, is expensive. A pair of Giant Pandas in captivity can cost upward of one million USD annually to maintain [1]. The number rises significantly when the costs of breeding Giant Pandas, who are notoriously prudish, are factored in. Should conservationists focus a majority of their resources on protecting just a few charismatic and profitable flagship species, or would those resources be better spent protecting more critically endangered keystone species? Critics argue that the extravagant costs of maintaining the Giant Panda in captivity are siphoning resources from other, more critically endangered species that are crucial for their ecosystems. Focusing the majority of our time and money on just a dozen or so flagship species jeopardizes the approximately 23,000 other species at risk of extinction in the near future [3]. Many of these species are keystone onservation has a

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species; a keystone species is a species that has a disproportionately large effect on its environment relative to its abundance and plays a critical role in maintaining the structure of an ecological community [9, 13]. Examples of endangered keystone species include mangroves, sea otters, and bees. A significant number of these endangered keystone species are concentrated in biodiversity hot spots such as the Amazon rain forest, the coasts, and equatorial coral reefs. These hot spots host at least 60% of the world’s plant, bird, mammal, reptile, and amphibian species and are some of the most productive ecosystem on the planet [4]. These hot spots are also home to the majority of the genetic diversity on the globe and and are important for the world’s agricultural and medical industries. Their collapse would have major impacts not only on the total amount of biodiversity in the world, but also on the global economy. Giant Pandas, however, are not crucial to their ecosystems, and their demise, while unfortunate, would not cause an ecosystem-wide collapse like other, homelier keystone species. Many have argued that the conservation and reproductive programs for the species are fruitless among concerns over inbreeding depression (reduced biological fitness as a result of inbreeding), habitat destruction and fragmentation, and breeding difficulties [5]. Unless China begins seriously protecting and preserving the country’s © 2016, The Triple Helix, Inc. All rights reserved.

bamboo forests, the Giant Panda’s natural habitat, the species is doomed to be on conservation life support for the remainder of its existence. Moreover, researchers estimate that there are approximately 3,000 Giant Pandas remaining in the wild roaming the 40 panda preserves in China [6]. While they are certainly still vulnerable, they are not as critically endangered as many other species, for example, the Javan Rhino, whose extinction appears imminent with only 60 individuals left in the world [7]. At the end of the day, Giant Pandas are not keystone species, are not critically endangered given their relatively large and self-sustaining wild population, and they are difficult and expensive to breed and house in captivity. Would the money spent on saving the Giant Panda be better spent on conservation efforts for keystone species who are not only relatively cheap to conserve, but whose extinction would have massive and potentially catastrophic impacts on highly productive ecosystems? In essence, conservational programs have four options when choosing which species to focus on. Option one is to choose species that need to be saved immediately and face imminent extinction. Option two is to choose species that are vital to the health and productivity of their ecosystems. Option three is to choose species that are cheaper and simpler to save and have a good chance for long term survival. Option four, which the WWF and a host of other conservation organizations have opted for, is to choose species that are charismatic and iconic with high profitability and branding opportunities [13]. Proponents of Giant Pandas assert that organizations like the WWF do more good than harm by raising a significant amount of money and awareness for other protection programs that otherwise would otherwise receive little attention from the general public. Organizations like the WWF pull in huge amounts of money from donations and fundraising events; in just 2015 alone, the WWF raised just over $289 million USD in total rev© 2016, The Triple Helix, Inc. All rights reserved.

enue and support. At $90 million USD, over 34% of that revenue was generated from individual donations. Another 41% of that $289 million USD was sourced from governmental and other grants. The remaining revenue comes from corporate sponsors and WWF network sponsors. While 85% or about $246 million USD of WWF spending is directed toward worldwide conservation, their annual FY15 report does not outline how that spending is allocated among the different conservation and protection projects it supports [2]. The report only outlines that approximately $83 million USD of their annual revenue was spent on public

Would the money spent on saving the Giant Panda be better spent on conservation efforts for keystone species who are not only relatively cheap to conserve, but whose extinction would have massive and potentially catastrophic impacts on highly productive ecosystems? education and the remaining $163 million USD was allocated towards six major conservation and policy programs: forests, oceans, freshwater, climate, food, and wildlife. Within the wildlife program, their annual report explicitly states that the WWF works to “ensure the world’s most iconic species, including tigers, rhinos, and elephants, are secure and recovering in the wild.” Looking through their annual budget report for 2015, however, suggests THE TRIPLE HELIX Spring 2016

that a sizeable portion of their funds goes towards habitat protecting and instigating major conservation policy changes around the world. Furthermore, the WWF primarily works towards assisting and influencing policy-level conservation decisions through information collection, demonstration of conservation approaches, and communications and capacity building [12]. The revenue generated by the WWF does not go directly towards breeding and raising Great Pandas in captivity. Those expenses are the responsibility of zoos and other wildlife parks that aim to use Giant Pandas to raise attendance and generate revenue. Of course, this fact alone should not be used to vilify zoos or wildlife parks, as many of these institutions also play a critical role in funding wildlife research and raising awareness for a variety of important conservation projects. The argument that Giant Pandas siphon resources away from other, more critically endangered keystone species is undermined by the fact that WWF does not actually spend money raising and breeding Giant Pandas but rather to implement policy change and protect a wide variety of ecological habitats. The actions of the WWF help protect entire ecosystems and all the endangered organisms within it. While some may argue that choosing which species to protect based solely on appearance and profitability is ignoble, the reality of the situation is that without money, no endangered species, cute or ugly, stands a reasonable chance of survival in our economically driven world that values profit over the preservation of the beautiful and the wonderful. Isnâ&#x20AC;&#x2122;t it better for less charismatic animals to have some financial resources and protections than none at all? Pragmatically speaking, protecting species like the Javan Rhinos which face imminent extinction because of low population numbers, is rather ineffective because their viability for survival in the wild in the long term is improbable. Factors like the population structure, which 10

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include age, sex, and reproducibility of the last remaining members significantly reduces the effective population size (the number of members within a population that can actually reproduce, in a realistic ecological context) [8]. For example, although there are approximately 60 or so Javan Rhinos left in the wild, a number of those individuals will be too young to reproduce (i.e. their ability to contribute to the success of the species is restricted by time), be past reproductive age (i.e. too old to reproduce), or be otherwise infertile. At a low population size, a population becomes increasingly susceptible to inbreed depression, genetic drift, and stochastic (random) extinction events, which are all detrimental to the long term viability of the species. Therefore, option one, spending resources on species that face imminent extinction, is not a viable goal for long-term conservation as these species are already on life support. Those resources would be better spent protecting habitats and, by extension, all the plants, animals, and organisms in between that live in those habitats. Of the remaining three options left for conservationists, a fusion of protecting both keystone species and highly profitable animals is likely the best choice for the long-term health of our global biosphere. Without charismatic animals like the tiger or the panda to generate money and interest for and in conservation, keystone species like the prairie dog or the sea star would likely receive little resources from the general public no matter how hard scientists and conservationists promoted them. Without financial resources to help protect them, there is almost no hope for vital keystone species whose existence human activity has endangered. Alternatively, focusing all our money and time on species that are aesthetically appealing but are not essential for the sustention of their respective ecosystems jeopardizes the long-term health of our planet and the 23,000 other species that are in peril. Many of these species, such as the stinking ÂŠ 2016, The Triple Helix, Inc. All rights reserved.

cedar and the pygmy hog-sucking louse, play crucial roles in their ecosystems and are both easy and cheap to resuscitate [10]. Furthermore, there are a number of examples of charismatic keystone species out there whose protection and conservation are well justified. Examples include elephants in Tanzania who help maintain the grasslands of the Serengeti plains by uprooting acacia trees, and corals in the oceans which serve as foundation species for entire reef ecosystems [11]. Conservationists need to keep the big picture in mind when choosing conservation projects and allocating resources to each project. A world without the Giant Panda may be unbearable for some, but a world without the common bee is unbearable for all.

References [1] Warren, L. 2006. Panda, Inc. National Geographic Magazine. [2] World Wildlife Fund. 2015. Annual Report. [3] IUCN 2014. The IUCN Red List of Threatened Species. Version 2014.3. [4] Myers, N., Mittermeier, R.A., Mittermeier, C.G., da Fonseca, G.A.B., and J. Kent. 2000. Biodiversity hotspots for conservation priorities. Nature 403: 853-858. [5] Dell’Amore, C. 2013. Is Breeding Pandas in Captivity Worth It? National Geographic Magazine. [6] Zhan, X., Li, M., Zhang, Z., Goossens, B., Chen, Y., Wang, H., Bruford, M., and F. Wei. 2006. Molecular censuring doubles giant panda population estimate in a key nature reserve. Current Biology 16(12): pR451–R452. [7] Save the Rhino. 2016. Rhino Population Figures. [8] Kliman, R., Sheehy, B., and J. Schultz. 2008. Genetic Drift and Effective Population Size. Nature Education 1(3):3. [9] Paine, R.T. 1995. A Conversation on Refining the Concept of Keystone Species. Conservation Biology 9(4): 962–964. [10] MinuteEarth. 2015. Should We Let Pandas Go Extinct? YouTube. [11] 2016. Keystone Species. National Geographic. [12] 2016. Giant Panda. World Wildlife Fund. [13] 2016. Global Species Programe: how WWF classifies species. World Wildlife Fund.

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The End of the Golden Age of Antibiotics? Aran Shaunak (University of Cambridge)

heralded a revolution in medicine, and mankind believed that it had beaten bacterial infections. But now, looking back, it seems arrogant to have assumed victory. The emergence and spread of antibiotic resistance has rendered current treatments less and less effective over the last 100 years. With a crisis in medicine now looming, we have finally begun to address the issue of antibiotic resistance head-on. Antibiotic resistance occurs when bacteria are no longer killed by a drug that used to kill them. We have known about it since antibiotics were first discovered: Alexander Fleming himself gave a “note of warning” about the development of resistance in his Nobel Prize acceptance speech [1]. He was proven to be right, with resistance to penicillin becoming widespread in the 20 years following its introduction into mainstream medicine [2]. The emergence of antibiotic resistance is simply evolution in action: bacteria that survive a course of antibiotic treatment are more likely to reproduce and so their progeny gradually become less sensitive to future antibiotic treatments. The use of antibiotics has been widespread in modern medicine, but even more so in agriculture, where they are used prophylactically at high levels to prevent disease and promote faster animal growth. This has accelerated bacterial evolution, resulting in resistance spreading across the globe at an alarming rate. As traditional antibiotics are becoming less and less effective, we are relying on our ‘last resort’ antibiotics more and more. True to form, bacteria have begun to develop resistance to them. A class of bacteria called gram-negative he discovery of penicillin

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bacteria (which includes common clinical strains such as Neisseria gonorrhoeae, the causative agent behind gonorrhoea) have become particularly difficult to treat, with carbapenems and colistin being the only two antibiotic classes remaining widely effective against infections caused by these bacteria. However, in 2008, a new gene (termed NDM-1), which confers resistance to carbapenems, was found in India [4] and in January this year a new resistance gene against colistin (termed MCR-1) was discovered in China [5]. We have no other treatment options for bacteria resistant to these last-line antibiotics, and so the discovery that these genes have already spread across the globe [6,7] is a major cause for concern. Resistance to antibiotics is nothing new: there have been clinical cases of infections with bacteria resistant to almost every well-established antibiotic. The difference now is that for once we don’t have an ace up our sleeves. Between 1940 and 1962, 20 new classes of antibiotics were brought to market (in part as a reaction to the emergence of resistance), allowing us to comfortably deal with resistant infections: over the following 50 years only two new classes have been commercialized [8]. This is largely due to the economic pressures of pharmaceutical research: the lifetime profits on the sale of novel antibiotics which have small treatment groups and whose sale is highly restricted to limit the emergence of resistance - are small relative to those on drugs that manage chronic conditions (such as high blood pressure) which are common in western societies and require years of continual treatment. This has led most large pharmaceutical companies to retreat from the increasingly complex field of antibiotic research due © 2016, The Triple Helix, Inc. All rights reserved.

to limited financial incentives [9]. This lack of effective antibiotics is already having a real impact on society. Gonorrhoea has historically been easily treated with a single course of antibiotics, but strains found in Leeds in 2012 were classified as ‘untreatable’, meaning they cannot be cured by any available antibiotic therapies [10]. Meanwhile, the scare of ‘extensively drug resistant TB’ has been overshadowed by the discovery of ‘totally drug resistant TB’ - which is resistant to every licensed tuberculosis treatment - in Italy in 2007 [11], and Iran and India in 2009 [12,13]. Should current trends continue, resistant infections will not only directly cause more deaths, but will have a knock-on effect on the entire

more exotic treatment options beyond antibiotics – for example, creating a genetically engineered version of E.coli that hunts down and kills harmful bacteria [15]. Furthermore, governments are shepherding pharmaceutical companies back into antibiotic research with new schemes and incentives such as rapid FDA approval under the GAIN act [9] and the Innovative Medicines Initiative partnership between biotechnology, pharmaceutical and academic industries - endearingly named ‘New Drugs for Bad Bugs’ - so new discoveries may be on the horizon. Indeed such initiatives have already begun showing results: six new antibiotics were licensed in the second half of 2014 alone. However, developing new drugs

“The development of new antibiotics without having mechanisms to insure their appropriate use is much like supplying your alcoholic patients with a finer brandy” medical field. Almost all medical procedures carry a risk of bacterial infection, including surgery (which breaches the skin) and cancer chemotherapy (which causes suppression of the immune system), which is managed by prophylactic antibiotic treatment. If doctors do not have access to any antibiotic treatments that work, the risks of acquiring a lethal and untreatable infection will outweigh the benefits of many medical procedures, preventing doctors from providing care that is currently taken for granted [3]. A bleak future is a serious risk, but progress is starting to be made towards combating the spread of resistance. New drugs that render resistant bacteria susceptible to certain antibiotics again (called antibiotic resistance breakers) could allow us to reutilize old drugs; for example, the drug co-amoxiclav contains amoxicillin in combination with clavulanic acid, which breaks bacterial resistance to amoxicillin [14]. Scientists have also begun to explore © 2016, The Triple Helix, Inc. All rights reserved.

alone is not enough. If novel antibiotics are used carelessly, bacteria will simply evolve resistance to them. As elegantly put by Dr Dennis Maki, a member of the Infectious Disease Society of America, “The development of new antibiotics without having mechanisms to insure their appropriate use is much like supplying your alcoholic patients with a finer brandy” [16]. Since antibiotics become less effective the more they are used, in the long term the most important measure to prevent disaster is not just the discovery of new drugs, but to use antibiotics more sparingly and more responsibly to reduce the spread of resistance. The emergence of NDM-1 in India was attributed to the widespread use of carbapenems in the Indian healthcare system to treat resistant infections [6], while the emergence of MCR-1 in Japan was associated with high levels of colistin use on pig farms to increase profits [7], indicating that controlling antibiotic use in both medicine and agriculture is essential THE TRIPLE HELIX Spring 2016

for preventing the spread of resistance. Important changes are starting to be implemented: Brazil and Mexico banned the sale of antibiotics without a prescription in 2010, with a number of Latin American countries since following their example [17]. The WHO produced the first ever global report on antimicrobial resistance in 2014, highlighting the importance of changing our patterns of antibiotic use on a global scale [18]. This increasing global awareness of antibiotic resistance provides hope that governments, doctors, farmers and the general public will change their attitude to bacterial infections, since acknowledging the problem is the crucial first step in finding a solution.

otics (OMA) Model. Globalization and Health, 2013.

References

[16] Dennis Maki, IDSA meeting, 1998.

[1] Alexander Fleming, Penacillin, Nobel Lecture December 1945.

[17] Santa-Ana-Tellez, Y et al. Impact of Over-theCounter Restrictions on Antibiotic Consumption in Brazil and Mexico, 2013.

[2] Doern, G. et al, Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999–2000, including a comparison of resistance rates since 1994–1995. Antimicrob Agents Chemother. 2001.

[10] Unemo, M. & Nicholas, R. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 2012. [11] Migliori, GB et al. First Tuberculosis Cases in Italy Resistant to All Tested Drugs. Eurosurveillance, 2007. [12] Velayati, Ali Akbar et al. Emergence of New Forms of Totally Drug-Resistant Tuberculosis Bacilli: Super Extensively Drug-Resistant Tuberculosis or Totally Drug-Resistant Strains in Iran. Chest, 2009. [13] Udwadia, Z. F. et al. Totally Drug-Resistant Tuberculosis in India. Clin. Infect. Dis. 2012 [14] Brown D. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void? Nat Rev Drug Discov. 2015. [15] Hwang, I Y et al. Reprogramming Microbes to Be Pathogen-Seeking Killers. ACS Synth Bio, 2013.

[18] WHO, Antimicrobial resistance: global report on surveillance, 2014.

[3] Laxminarayan, R. et al. Antibiotic resistance—the need for global solutions. Lancet Infect Dis. 2013. [4] Yong, D. et al. Characterization of a new metallo-β-lactamase gene, NDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence Type 14 from India. Antimicrob Agents Chemother. 2009. [5] Liu, Y-Y. et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016. [6] Johnson, AP & Woodford, N. Global spread of antibiotic resistance: the example of New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance. J Med Microbiol. 2013. [7] Hasman, H. et al. Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark. Eurosurveillance, 2015. [8] Coates, A. et al. Novel classes of antibiotics or more of the same? Br J Pharmacol. 2011 [9] Brogan, David M., and Elias Mossialos, Incentives for New Antibiotics: The Options Market for Antibi-

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Euclid’s Elements: A Guide for the Greats Zeke Gillman (University of Chicago)

reat books make great men. Though

this platitude may be overused, it is perhaps the most fitting truism for Euclid’s monumental mathematical treatise known as the Elements. Through the many generations that the Elements have existed, its simple presentation of has progression has influenced the thought of some of the greatest thinkers. Thirteen books together form this introductory mathematical textbook consisting of Euclidean geometry, number theory, arithmetic and other mathematical knowledge prevalent at the time. It has been studied over 24 centuries since its inception around 300 B.C. Euclid, however, most likely did not himself prove most of the theorems in the Elements. Instead he collected and arranged a majority of them in a clear and logical manner so they would proceed from fundamental definitions, axioms, and postulates. The first edition of the textbook was printed in Venice in 1482. Since that times, historian of mathematics Carl Boyer writes, “it has been estimated that…at least a thousand editions have been published. Perhaps no book other than the Bible can boast so many editions, and certainly no mathematical work has had an influence comparable with that of Euclid’s Elements” [1]. As would be expected of any textbook that is of such popularity, the Elements has consistently found itself in the hands of some of the greatest thinkers in human history. Renowned logician Bertrand Russell remarks in his autobiography, “At the age of eleven, I began Euclid, with my brother as my tutor. ... I had not imagined that there was anything so delicious in the world“ [2]. The legendary theoretical physicist Albert Einstein began indulging in the © 2016, The Triple Helix, Inc. All rights reserved.

Elements from an early age too. He wrote, “At the age of 12, I experienced a second wonder of a totally different nature: in a little book dealing with Euclidean plane geometry …Here were assertions, as for example the intersection of the three altitudes of a triangle in one point, which – though by no means evident – could nevertheless be proved with such certainty that any doubt appeared to be out of the question. This lucidity and certainty made an indescribable impression upon me” [3]. Yet, the Elements have not only been read by scientists and mathematicians, but have also been treasured by philosophers, political theorists, and statesmen alike. The writer John Aubrey wrote a short anecdote of his friend Thomas Hobbes, the English political philosopher, and his first foray in rigorous mathematics. He describes Hobbes’ first encounter with the Elements: “He was (vide his life) 40 yeares old before he looked on geometry; which happened accidentally. Being in a gentlemen’s library in …., Euclid’s Elements lay open, and ‘twas the 47 El. Libri I (The proof of the Pythagorean theorem). He read the proposition. ‘By G-,‘ sayd he, ‘this is impossible!’ So he reads the demonstration of it, which referred him back to such a proposition; which proposition he read. That referred him back to another, which he also read. Et sic deinceps, that at last he was demonstratively convinced of that trueth. This made him in love with geometry”[4]. Euclid even took a cherished spot in Abraham Lincoln’s miniscule private library. In a conversation Lincoln had after his speech at the Cooper Institute in 1860, Lincoln spoke of his educational background in legal studies. He said: In the course of my law reading I conTHE TRIPLE HELIX Spring 2016

stantly came upon the word demonstrate. I thought, at first, that I understood its meaning, but soon became satisfied that I did not. I said to myself, What do I do when I demonstrate more than when I reason or prove? How does demonstration differ from any other proof? I consulted Webster’s Dictionary. They told of ’certain proof,’ ’proof beyond the possibility of doubt’; but I could form no idea of what sort of proof that was. I thought a great many things were proved beyond the possibility of doubt, without recourse to any such extraordinary process of reasoning as I understood demonstration to be. I consulted all the dictionaries and books of reference I could find, but with no better results. You might as well have defined blue to a blind man. At last I said,–‘Lincoln, you never can make a lawyer if you do not understand what demonstrate means’; and I left my situation in Springfield, went home to my father’s house, and stayed there till I could give any proposition in the six books of Euclid at sight. I then found out what demonstrate means, and went back to my law studies. [5]

at one point studied and absorbed the Elements, what is, in fact, more intriguing is that all of these thinkers had similar reasons for studying the Elements. Each seemed determine to uncover this method of deduction whose certainty and logical coherence enticed them. To understand the appeal of this method of deduction, let us engage in the very first proposition that is proved in the Elements. In constructing the proof to this proposition, Euclid presents a handful of definitions and postulates, a few of which he will utilize in the construction of the proof for the first proposition. The relevant definitions and postulates include basic notions such as a circle being described by a center and radius and a line as a breadthless length between two points. Using these mathematical facts, Euclid goes about proving the construction of an equilateral triangle on a straight line AB. To begin, Euclid presents the following image:

Yet, while all these thinkers may have

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He then proceeds as follows: Describe the circle BCD with center A and radius AB. Again describe the circle ACE with center B and radius BA. Join the straight lines CA and CB from the point C at which the circles cut one another to the points A and B. Now, since the point A is the center of the circle CDB, therefore AC equals AB. Again, since the point B is the center of the circle CAE, therefore BC equals BA. But AC was proved equal to AB, therefore each of the straight lines AC and BC equals AB. And things which equal the same thing also equal one another, therefore AC also equals BC. Therefore the three straight lines AC, AB, and BC equal one another. Therefore the triangle ABC is equilateral, and it has been constructed on the given finite straight line AB. [6] Euclid demonstrates the existence of the equilateral triangle by means of his construction from basic notions. The idea that the existence of a given object may be shown from the most trivial of statements is perhaps what inspired these great thinkers. In addition, the rules that Euclid utilizes in his proof like “things equal to the same thing are equal to one another” are not only applicable to mathematics. In fact this very notion of equality is one that writer Tony Kushner included in the screenplay for Steven Spieldberg’s Lincoln in which Lincoln uses that first common notion established by Euclid to view the fight for the abolition of slavery and legal equality for African-Americans. “Oh I think it does. I think it really does influence thought” said Dr. Zalman Usiskin, director of the University of Chicago School Mathematics Project, on the effect of Euclid’s Elements on the thinking of such figures. “I think the notion that you can deduce things from other things rigorously is a very powerful notion. It is not your intuition. It’s not your beliefs. It’s logic. It’s pure logic. I think that’s a © 2016, The Triple Helix, Inc. All rights reserved.

powerful thing. The legal system is in some ways based on that.“ Dr. Usiskin even recommended reading works by the philosopher Baruch Spinoza to see the logical structure that Euclid’s work inspired. In Spinoza’s Ethics, every book begins with definitions, axioms, propositions and the like and proceeds from there to prove his conclusion. One may even go so far as to read Lincoln’s Gettysburg Address as in the form of a Euclidean proof. The speech draws on similar mathematical terminology throughout. It is as if Lincoln views the Civil War as the next essential step taken towards the proof of the “proposition that all men are created equal” set forth by the founding fathers. While the connection is evident, to show the direct influence of the Elements on these thinkers is much more difficult. All we may say now is that it has had an influence on their thought. How exactly that influence manifests itself and if the Elements are unique in that role is another issue. “Well one of my favorite phrases is ‘it seems as if.’ It seems as if they were aware. You can’t be sure, however, and some people are not aware even when you think they are,” said Dr. Usiskin. Yet, these stories of great thinkers and their early influences demonstrate the power of analogical thinking and mathematical knowledge. Lincoln, Hobbes, Spinoza and many others not mentioned here were able to apply information from the Elements to their work. The rigors of the Euclidean deductive method did not remain in the confines of the geometrical structures that were Euclid’s objects of study. Rather, they expand into other questions and disciplines. It seems as if this interdisciplinary model is significant in producing creative and influential works of all kind whether that be mathematics, philosophy, or political science.

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References [1] Boyer, Carl B., and Uta C. Merzbach. “Euclid of Alexandria.” A History of Mathematics. New York: Wiley, 1991. 119. Print. [2] Russell, Bertrand. “Childhood.” The Autobiography of Bertrand Russell. London: Routledge, 2000. 30-31. Print. [3] “Albert Einstein” Philosopher-Scientist.” Albert Einstein: Philosopher-Scientist. Ed. Paul Arthur Schilpp. Vol. VII. La Salle: Open Court, 1949. 9-11. Journal of Targeting, Measurement and Analysis for Marketing. Web. 28 Mar. 2016.

[4] Aubrey, John. “Thomas Hobbes.” Aubrey’s Brief Lives. Ed. Oliver Lawson Dick. Boston: Nonpareil, 1949. 150. Print. [5] Ketcham, Henry. “Entering the Law.” The Life of Abraham Lincoln. N.p.: n.p., n.d. N. pag. Authoroma. com. Authoroma. Web. 30 Mar. 2016. [6] Euclid. “Proposition 1.” Elements. N.p.: n.p., n.d. N. pag. Aleph0.clarku.edu. Web. 8 May 2016.

Limited Health Literacy: A Dangerous But Silent Epidemic Jacqueline Wang (University of Chicago)

has been a steadily growing “silent epidemic,” despite having been labeled a dangerous public health problem and a determinant of poorer health outcomes [2]. However, the U.S. government has so far not addressed this undetected crisis as a human rights issue. Despite its commitment to several international covenants, particularly the Universal Declaration of Human Rights (UDHR) and its assertion that all humans have the right to a sufficient standard of health [5]. The U.S. Department of Health and Human Services defines health literacy as “The degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions” [1]. Health literacy is deeply affected by the level of a person’s basic literary skills and influences the degree to which a person can access information and participate in society [1]. Health literacy has multiple dimensions that go beyond literacy, as it requires advanced communication skills, easy access to and understanding of a broad range of scienimited health literacy

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tific and health topics, healthy behaviors, and the healthcare system. In many cases, those with advanced literacy skills can still be overwhelmed with health information and technology. Health literacy is not explicitly addressed in U.S. formal education and healthcare systems, or the culture surrounding healthcare. Many U.S. citizens do not recognize the significance of the wide-reaching consequences of this “silent,” unnoticed public health problem. Approaches to this problem must focus on two primary actors in health literacy—the U.S. government and healthcare providers—who are responsible for empowering and supporting U.S. citizens to develop their skills and understandings of health information. The best way the U.S. government can do this is by enacting specific legislation targeted toward the promotion of health literacy and building meaningful partnerships with the education sector. In turn, healthcare providers can contribute by promoting and participating in such educational programs and renew their focus on effective communication standards and skills within the patient-provider relationship. Thus, the © 2016, The Triple Helix, Inc. All rights reserved.

U.S government and healthcare providers expensive hospital admissions and visits both need to make a more concerted effort [3]. Increasingly complex health-related to directly address the dire consequences information and decisions are reflected and human rights violations of limited in health materials and information that health literacy and bring forth the issues are presented at a reading level that is too of this silent epidemic. high for many readers. NAAL reported The relationship between limited that everyday health promotion and dishealth literacy and poor health outcomes ease prevention activities and materials in the United States is well recorded. required a “proficient” health literacy According to the level, of which only 2003 National As12% of respondents An estimated ninety sessment of Adult possessed through a Literacy (NAAL), million Americans have self-reported survey limited health literacy of 19,000 adults [1]. poor health literacy affects 9 out of 10 EnThose of the “below glish-speaking adults basic” health literacy in the United States and their ability to use level are of particular concern, as they and navigate health information that they cannot sufficiently read a chart or simple encounter on an everyday basis in health- instructions, and are 42% more likely to care facilities, media, and communities [1]. report poor health and 28% more likely An estimated ninety million Americans to lack health insurance than adults with have poor health literacy; people of older “proficient” health literacy levels [1]. age, lower socioeconomic status, education Additionally, the psychological toll that levels, and English proficiency are more affects those with limited health literasusceptible to lower health literacy levels cy is evident in self-reported feelings of [3]. The consequences of poor health lit- shame and “[hiding] their struggle with eracy affect multiple levels of society in reading or vocabulary” [1]. Therefore, making informed decisions about their in many cases, patients’ limited health healthcare, and contribute to increasing literacy goes unnoticed by healthcare gaps in health disparities and poorer health providers, contributing to the ‘silence’ outcomes, resulting in higher mortality of this sweeping epidemic. rates. Low levels of health literacy imply The widespread failure to ensure that healthcare providers and systems are health literacy in the United States is a failing to provide effective services and clear example of significant human rights resources to benefit their patients, despite violations outlined in several internationthe fact that individuals not only with low al treaties and covenants. For example, socioeconomic resources but at all income Article 12 of the International Covenant levels are facing higher costs across the on Economic, Social, and Cultural Rights board for health services . Additionally, (ICESCR) recognizes the “right of everyone one study estimates that low health literacy to the enjoyment of the highest attainannually accumulates between $106 billion able standard of physical and mental to $236 billion in costs for the U.S. govern- health” [4]. Similarly, Article 25 of the ment. Specifically, poor understandings UDHR states, “Everyone has the right of health conditions, systems, and lack to a standard of living adequate for the of effective communication result in low health and well-being of himself and of his rates of treatment and medication com- family, including food, clothing, housing pliance [3]. Another main consequence and medical care and necessary social is lack of knowledge and lowered use of services” [5]. The human right to health preventative services and management of and healthcare is of utmost importance chronic diseases, resulting in unnecessary, in the United States; the US has signed © 2016, The Triple Helix, Inc. All rights reserved.

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the ICESCR and ratified the UDHR. As a clear barrier to good health outcomes, the U.S. government’s negligence to improve limited health literacy is a violation of the human right to adequate health and healthcare. In addition, Article 19 of the International Covenant on Civil and Political Rights (ICCPR) and Article 19 of the UDHR focus on the human right to freedom of opinion and expression, and “to seek, receive, and impart information and ideas through any media and regardless of frontiers” [6]. These covenants define the human right to ready access of information, which is vital for the knowledge and communication that health literacy requires. As a ratified country under both the ICCPR and UDHR, the United States has committed to making multiple levels of information, from the media to its healthcare providers, easily available and to all of its citizens. Thus, it is imperative that all U.S. citizens have easy access to information presented at a comprehensible level. Furthermore, Article 13 of the ICESCR and Article 26 of the UDHR ensure the human right “of everyone to education,” that “education shall be directed to the full development of the human personality and the sense of its dignity, and shall strengthen the respect for human rights and fundamental freedoms,” and that education shall enable and promote “all persons to participate effectively in a free society, promote understanding, tolerance and friendship among all nations and all racial, ethnic or religious groups” [5]. These two covenants clearly promote the empowerment and fostering of knowledge and community that encompass the aims of health literacy. By considering these core international human rights covenants, it is evident that the U.S. has failed to uphold its commitment to human rights covenants in its widespread limited health literacy. There is an urgent need for U.S. governmental implementation of strong legislation and action that specifically address health literacy. The U.S. government 20

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plays a vital role in promoting large-scale improvements in health literacy for its citizens and has the capacity to affect change, regulate, and monitor public health infrastructure and education on a large scale. Amidst a record of minimal to no action, the government has only recently begun to move in the right direction. The first piece of legislation introduced to the government that focused on health literacy was the proposal of the National Health Literacy Act in 2007. This legislation aimed to make health resources more available to researchers, healthcare providers and the public, sponsor projects and research dedicated in developing health literacy tools, and collaborate more with other governmental agencies [7]. However, the bill was not enacted and Congress did not pass it into law, most likely due to lack of a strong leadership and support in the Senate and urgency for this issue. The passing of this bill into law would have been a major step in the right direction; even so, the bill’s effectiveness was limited by its requirement for “at least one public meeting to help raise awareness about the problem of health literacy” for both the national Health Literacy Implementation Center and state resource centers [7]. This bill’s limitations lie in the fact that one or two meetings a year is not sufficient enough to address such a pressing issue, and that a lack of accountability can quickly form without consistent addressing of this issue. It was only in 2010 that the U.S. Department of Health and Human Services first officially identified poor health literacy as a barrier to good health outcomes and included the decrease in gaps in health literacy in their Healthy People 2010 national objectives [8]. This addition of health literacy to the national health agenda demonstrates how this issue was brought into governmental recognition only very recently, which undoubtedly explains how many U.S. citizens have not yet recognized its prevalence and importance. Furthermore, while the 2010 Affordable Care Act (ACA) focuses © 2016, The Triple Helix, Inc. All rights reserved.

more heavily on increasing insurance coverage, quality, and improving cost, it is the first legislation to address the importance of health literacy [9]. The ACA directly mentions health literacy four times with regards to the significance of addressing “diverse levels of health literacy” in the distribution of health information, facilitation of collaborative processes between caregivers and patients in informed decision-making, and accessible information on prescription drug labeling and print advertising [9]. However, although the ACA highlights the issue of health literacy, it does not prioritize or address this issue to help improve it. Finally, in 2010, Barack Obama signed the Plain Writing Act of 2010, which requires federal agencies to “use clear communication that the public can understand and use” that can be extended to the communication of health information [11]. However, this legislation does not explicitly address health literacy and, like the ACA, does not prioritize it. Thus, the overall lack of meaningful, specific legislation and action on limited health literacy calls for a critical and renewed focus in approaching this problem. The most feasible, effective approach to health literacy the U.S. government can provide is actual implementation of its most important resource thus far—the 2010 National Plan to Improve Health Literacy. Through this plan, the government aimed to mobilize the public by proposing key approaches to poor health literacy through a multi-sector effort addressing media, government, and healthcare professionals. The plan’s core principle is centered on the human rights issues listed above, and addresses the issue of health literacy. It states; “All people have the right to health information that helps them make informed decisions” [10]. Thus, the U.S. government can approach this problem by reinforcing key strategies of this plan through legislation and facilitating partnerships across different sectors. For example, the plan calls for the government to adopt strategies that © 2016, The Triple Helix, Inc. All rights reserved.

use plain language guidance and involve citizens with limited health literacy in evaluating and developing “accurate, accessible, and actionable” health information [1]. In a study from the University of California–Berkeley School of Public Health, a participatory design to create a guidebook on health insurance enrollment options showed a significant increase in the understandings of healthcare choices of seniors and people with disabilities [1]. The government can increase community involvement and awareness of health literacy by promoting such strategies through a national agenda, and set a precedent for other sectors’ distribution of health information, such as media and healthcare providers. Introducing legislation that sets specific, federal standards for the development and dissemination of health information can increase governmental accountability to improve health literacy levels. In addition, developing citizens’ health literacy skills through educational programs is a crucial step in addressing the gaps in health literacy, calling for effective training and support of educators and education. One example of a successful educational program is how The New York City Office of the Mayor partnered with the Harlem Hospital Center to incorporate health literacy skills into an adult education curriculum that offered tours of healthcare facilities [1]. Through this innovative approach, both literacy educators and students became more familiar with the healthcare system while the government gained insight into the needs of low-literacy populations. Additionally, many adult literacy students acquired health insurance and information on health issues and services in their communities at higher rates. Thus, government promotion and partnership with other sectors like education not only engages the community to improve health literacy but also helps tailor communication to patients with poor health literacy. Another way the government can empower educators is by supporting and training THE TRIPLE HELIX Spring 2016

health educators through programs such as the Integrated Health Network’s 2004 Health Education and Literacy Program, which used 8 “health coaches” to serve over 200,000 uninsured and underinsured residents in St. Louis, Missouri. The program empowered patients to take control of their health and communicate more confidently with healthcare providers [1]. Results of the positive impact of these coaches showed significant increases from 57% to 81% in patients’ acquiring of a primary care provider and 1% to 27% of patients able to discuss their health management plans effectively [1]. Thus, legislation that specifically supports and funds the development of accessible information and educators through government collaboration across multiple sectors would be the first step in addressing the historical lack of health literacy governmental action and accountability in the United States. A major step in improving health literacy is improving and emphasizing communication skills in healthcare providers. The National Plan to Improve Health Literacy states that focusing on the patient-provider relationship provides key intervention methods that

A major step in improving health literacy is improving and emphasizing communication skills in healthcare providers have been proven to be successful in multiple settings. For example, a study done by Schillinger et al. showed that the teach-back method, or “interactive communication loop,” was significantly associated with better glycemic control in patients with diabetes mellitus and low functional health literacy [12]. This method of communication aims to decrease the 22

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gap in patient knowledge by asking the patient to “teach back” the information accurately to the provider in order to confirm their level of understanding. Through this method, providers are able to gauge the patient’s level of understanding as well as assess the effectiveness of their own communication skills. In addition, this method facilitates an environment of open and comfortable communication and rapport between patient and provider. Patients can gain a better understanding of health information and decisions regarding treatments, procedures, and medical devices. In addition, The Agency for Health Care Research and Quality (AHRQ) has written several sets of questions that they recommend patients should pose to their providers that promote the use of plain language and patient self-advocacy [12]. This program, titled Questions Are the Answers, prepares patients and providers for their visits and provides structure for their communication in order to build a better understanding of the circumstances of the patient for both the patient and provider. This resource suggests questions that patients “should know” to ask, questions to ask before, during, and after the appointment, and tools to help patients build their own list of questions through an interactive online quiz [13]. This program thus empowers the patient to take an active role in their healthcare and increases their self-advocacy. It is imperative for healthcare providers to advocate and encourage the use of this resource in both their healthcare facilities and patient consultations. Furthermore, support of educational and training programs for and by healthcare providers would greatly improve the overall quality and awareness of health literacy. These programs should aim to educate healthcare providers in understanding the social aspects of patients’ circumstances that affect their level of health literacy understanding, and would be most effective if incorporated into undergraduate and medical school curricula. Thus, heightened awareness and © 2016, The Triple Helix, Inc. All rights reserved.

earlier training of healthcare providers can result in the provider’s ability to decrease the gap in patient understanding earlier in the patient-provider communication process. Supporting and empowering the patient through healthcare providers’ open and thorough communicative strategies can thus promote higher levels of health literacy among U.S. citizens. The urgency of the human rights violation of limited health literacy in the United States is undeniable. Efforts to stem the rise of this “silent epidemic” have grown slowly over the past two decades in the United States, but have failed to decrease the associated poor health outcomes across America. The best way for the US government and healthcare providers to stem this epidemic is to pass legislation that specifically addresses health literacy and increases governmental accountability and the fostering of partnerships with educational programs, the government can begin to take realistic steps in raising awareness of health literacy as an issue central to the American public. By promoting educational programs for both healthcare providers and patients, healthcare providers can help foster a strong sense of support for this agenda. Focusing on the patient-provider communication by utilizing the teach-back method and national communication standards set by the AHRQ will provide the direct support and empowerment patients with low health literacy require from their healthcare providers. The U.S. government and healthcare providers can prioritize the improvement of health literacy on a large scale, addressing the ninety million citizens that are affected by limited health literacy. Using these strategies, the US will be able to make its first strides in addressing limited health literacy.

References [1] U.S. Department of Health and Human Services. “National Action Plan to Improve Health Literacy.” (2010): n. pag. Web. [2 ] Clark, Brietta. “Using Law to Fight a Silent Epidemic: The Role of Healthy Literacy in Health Care Access, Quality & Cost.” Annals of Health Law 20.2 (2011): n. pag. Web. [3] Center for Health care Strategies, Inc. “What Is Health Literacy?” Center for Health Care Strategies Fact Sheets (2013): n. pag. Web. [4] United Nations Committee on Economic, Social and Cultural Rights. “International Covenant on Economic, Social and Cultural Rights.” United Nations Human Rights Office of the High Commissioner. N.p., n.d. Web. [5] United Nations. “The Universal Declaration of Human Rights.” United Nations. N.p., n.d. Web. [6] United Nations Human Rights Committee. “International Covenant on Civil and Political Rights.” United Nations Human Rights Office of the High Commissioner. N.p., n.d. Web. [7] United States. Cong. Senate. Committee on Health, Education, Labor, and Pensions. National Health Literacy Act of 2007. By Norm Coleman. 110th Cong., 2424 sess. S. Bill. N.p.: n.p., 2007. Print. [8] “Policy Legislation.” Health & Literacy Special Collection: Tools and Resources for Health Literacy Initiatives. World Education, n.d. Web. [9] Somers, Stephen A., and Roopa Mahadevan. “Health Literacy Implications of the Affordable Care Act.” Centers for Health Strategies, Inc. (2010): n. pag. Web. [10] The Office of Disease Prevention and Health Promotion. “National Action Plan to Improve Health Literacy.” Health Literacy and Communication. N.p., n.d. Web. [11] “Plain Language: It’s the Law.” Plain Writing Act of 2010. PlainLanguage.gov: Improving Communication from the Federal Government to the Public, n.d. Web. [12] Nouri, Sarah S., and Rima E. Rudd. “Health Literacy in the “Oral Exchange”: An Important Element of Patient–Provider Communication.” Patient Education and Counseling 98.5 (2015): n. pag. Web. [13] “Questions to Ask Your Doctor.” Agency for Healthcare Research and Quality. U.S. Department of Health & Human Services, n.d. Web.

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The Role of Sociology in Medicine: A Critique of the 2015 MCAT Senxi Du (University of Chicago)

I first learned about the changes to the 2015 Medical College Admissions Test (aka the MCAT: the dreaded hours-long test that looms over pre-med heads all over the country), I was relieved. Sure, the test would now increase from five hours to seven hours, but the awful standardized writing section would be removed (because we all know those essays aren’t real essays – just words organized into a generic pleasing formula that are skimmed at best). More importantly, the Association of American Medical Colleges (AAMC) declared that test questions would be more passage-based, thereby requiring more critical thinking and analysis of new information, instead of its old approach, which focused more on content knowledge and rote memorization. Most importantly, it would include an entirely new section, called the “Psychological, Social, and Biological Foundations of Behavior.” This section would be designed to test “psychology, sociology, and biology concepts that provide a solid foundation for learning in medical school about the behavioral and sociocultural determinants of health.” I imagined that this section would include a wide breadth of questions covering the social determinants of health, defined as the “conditions in the environments in which people are born, live, learn, work, play, worship, and age that affect a wide range of health, functioning, and qualityof-life outcomes and risks.” More importantly, I imagined that this section would encourage students to think critically about these social determinants, their influences on health and medicine, and ways that they might be addressed to improve overall patient health. Over the past few decades, the medhen

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ical field has increasingly acknowledged the importance of these social determinants, which encompass social factors (socioeconomic status, race/ethnicity, social networks, behavior, etc.), cultural factors (including trust of physicians and healthcare), and infrastructural factors (food availability, neighborhood crime rates, the general built environment, etc.).2 The Robert Wood Johnson Foundation, a philanthropic organization dedicated to improving health systems and promoting healthier communities, often funds research and proposals to better understand the social determinants of health. They sponsored a survey to better understand physician perspectives on social needs, and found that 85% of “physicians recognized that unmet social needs are directly leading to worse health” and that 85% said that “patients’ social needs are as important to address as their medical conditions;” however, only 20% of physicians felt “confident or very confident in their ability to address their patients’ unmet social needs.” It can be very frustrating for physicians, after years of medical training, to find themselves without knowledge on providing social resources to their patients. Earlier education on this subject will give future doctors a knowledge base upon which they can gather experiences and resources to address their patients’ social needs. Some medical schools have updated their curricula to include classes on the social determinants of health and health disparities to give their students a different perspective with which they can approach patient care. Our own University of Chicago Pritzker School of Medicine is one of the few schools to offer a full health disparities course, in © 2016, The Triple Helix, Inc. All rights reserved.

which students are taught to consider the social context of their patients’ lives. They learn to consider the possibility that uncooperative patients may actually just be struggling to follow simple orders to eat healthier and exercise in low-income, low-resource neighborhoods. This type of social education equips students with the mentality and tools necessary to work with patients of underserved backgrounds.

determined by the sociocultural context in addition to genetics and biology, why are our pre-medical students not getting a proper education in psychology and sociology? The obvious goal of the new MCAT section is to address this very question. However, topics in sociology, particularly those like the social determinants of health take up less than half of one section in

Over the past few decades, the medical field has increasingly acknowledged the importance of these social determinants [of patient health] Many students enter medical school with some degree of knowledge about the social determinants of health, but few have studied it enough to understand their full implications in health disparities and even fewer have sufficient knowledge to begin considering solutions to health inequalities. In a poll of Pritzker medical students before their health disparities course, 56% rated their knowledge on the causes of health disparities in America as “poor/fair” and 31% rated their knowledge as “good,” while only 13% rated their knowledge as “very good/ excellent.” More strikingly, 74% rated their knowledge on potential solutions to health disparities in America as “poor/ fair,” and only a meager 5% rated their knowledge as “very good/excellent.” The goal of these medical school courses is to train their students to think about and implement solutions, whether in their current community or future practices, to ultimately mitigate health disparities. However, this is a difficult task when over half of entering medical students have little to no knowledge on the topic. Pre-medical students endure a rigorous science education, covering biochemistry, genetics, physiology, developmental biology – to just name a few subjects – yet there are no required courses on psychology and, more relevantly, sociology. If health is © 2016, The Triple Helix, Inc. All rights reserved.

the entire exam, maybe about one-tenth of all the questions, if not fewer. I don’t want it to seem as though I think there should be fewer psychology questions. Psychology is an equally important subject for physicians to understand, as it provides scientific theories to understand and predict human behavior. For example, presenting choices to a patient increases their sense of control over their life, which helps explain why the shared-decision making style, in which physicians involve patients in treatment decisions by presenting options and their advantages and disadvantages to ultimately reach a mutually agreed-upon treatment plan, is becoming increasingly popular. There is also a multitude of situations that would require an understanding of both psychological and sociological principles. For example, if a diabetic patient still does not exercise regularly despite doctor’s orders, the doctor may assume the patient is just lazy or uncooperative. On the other hand, the doctor may recognize the fundamental attribution error at play and ask about the patient’s social determinants, only to find that the patient is working two jobs or is being discouraged by family members. These encounters are realistic educational moments that the MCAT might have used to encourage pre-medical students to think critically THE TRIPLE HELIX Spring 2016

about the ways that psychology and sociology will play into their interactions with patients. Unfortunately, this update chose to focus on the rote memorization of theories and theorist names, instead of the practical applications of psychological and sociological theories. The last time the MCAT underwent a major change was in 1992. The introduction of the new section testing topics in psychology and sociology marks a shift in medical education and the entirety of the medical field. The AAMC is very influential in the direction of pre-medical education in undergraduate programs across the nation and bears a large part of the responsibility of ensuring that future physicians obtain a well-rounded education that will help them treat patients of different backgrounds. While the organization is to be commended for recognizing this shift and bringing it to the attention of undergraduate programs, it did not take the extra step of truly highlighting the importance of public health and the social determinants to the future of medicine and medical treatment. Of course, the responsibility of educating pre-medical students in the social determinants of health cannot fall solely on the AAMC, and undergraduate institutions must recognize their part in providing the best education possible for future physicians. As public health continues to rapidly progress and influence the medical field, it will be necessary that the AAMC continue to revise the MCAT to reflect this progress and that undergraduate institutions update their pre-medical curricula. Future physicians will receive a more holistic education and be able to utilize biopsychosocial treatment approaches, ultimately improving patient health outcomes across the board.

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References [1] Psychological, Social, and Biological Foundations of Behavior Section: Overview. (2015). Retrieved May 15, 2016, from https://students-residents.aamc.org/ applying-medical-school/article/mcat-2015-psbboverview/ [2] Social Determinants of Health. (2014). Retrieved May 15, 2016, from https://www.healthypeople. gov/2020/topics-objectives/topic/social-determinants-of-health [3] Health Careâ&#x20AC;&#x2122;s Blind Side: The Overlooked Connection between Social Needs and Good Health. Princeton, NJ: Robert Wood Johnson Foundation; 2011. [4] Vela, M. B., Kim, K. E., Tang, H., & Chin, M. H. (2008). Innovative health care disparities curriculum for incoming medical students. Journal of General Internal Medicine, 23(7): 1028-1032. [5] MCAT Section-by-Section Breakdown. (2016). Retrieved May 15, 2016, from http://www.aucmed.edu/ admissions/mcat-exam/2015-mcat-detailed-look.aspx [6] Lee, E. O., & Emanuel, E. J. (2013). Shared decision making to improve care and reduce costs. NEJM, 368: 6-8.

Antibodies: The Versatile Drug Jessica McHugh (University of Cambridge)

30 years since the first the complement system, a process which monoclonal antibody was licensed results in direct destruction (or lysis) of for therapy, made possible due to a the pathogen [2]. Nobel-prize winning technique described An individual is likely to come into by Georges J.F. Köhler and César Milstein contact with billions of micro-organisms in a landmark paper 11 years before [1]. during their lifetime. A single gram of soil Developed in the Laboratory of Molecu- contains more than one million species of lar Biology in Cambridge, this technique micro-organisms such as bacteria, viruses, allowed for mass production of very yeasts, fungi and parasites [3]. Our body specific antibodies towards a chosen has the potential to produce antibodies target. Today, monoclonal antibodies against any one of these micro-organisms. are one of the most commonly utilised In fact, an individual’s B cell population drug reagents, making pharmaceutical has the capacity to produce 1011 different companies billions of revenue each year. antibodies [2]. Once a B cell encounters But what are antibodies and why was this a pathogen, small mutations in the antitechnique so game-changing? body-coding gene results in subtle changes Antibodies are proteins normally to its structure, either increasing or decreasproduced in your body as a weapon ing its ability to bind. B cells which produce against harmful pathogens. They are se- advantageous antibodies (i.e. those which creted by a type of immune cell called a B efficiently bind to epitopes) are actively cell (or B lymphocyte), and bind pathogens selected for in immune system structures by recognising particular regions called known as germinal centres, resulting in the epitopes. Each B cell produces one kind of production of antibodies with increased antibody which has its own corresponding affinity and sensitivity, thus allowing for epitope. Binding to these helps resolve better clearance of the pathogen [2].This the infection through multiple mechanisms, for example by directly neutralising the pathogen and any released toxins. Antibodies may also work by tagging the pathogen and aiding other immune cells in dealing with the infection to allow immune cells to destroy the target by lysing or engulfing and neutralising the target, using specific mechanisms called Antibody-dependent cell-mediated cytotoxicity (ADCC) and Antibody-dependent cell-mediated phagocytosis (ADCP), Figure 1: Immunofluorescent staining of a rat brain culture. The different colored strains illustrate the antibody specifcity against respectively. Finally, antibodies di erent components of the cells: Microtubule-associated Protein 2, can also initiate activation of MAP2 (green), Neuro lament (red), and DNA (blue). t has been

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sensitivity and specificity are the main reasons why antibodies are so useful in research and in the clinic. Historically, antibodies have been manufactured by exploiting the immune response of various mammals (from rabbits to goats). Inoculation of these animals with an “antigen” (the molecule to be targeted) results in an immune response, and the production of antibodies which recognise this target. The serum of these animals contains multiple different antibodies which can recognise and bind the antigen, known as polyclonal antibodies. However these antibodies only make up a proportion of the total antibodies within the serum, the majority of which do not bind this antigen. The presence of these “non-specific” antibodies, in addition to batch-to-batch variation, can cause problems downstream. In research this can obscure results and cause problems with reproducibility. In the clinic this can cause toxicity problems and dosage uncertainties. Hence, although polyclonal antibodies have been used in the past for treatment of various diseases, it was the development of monoclonal antibody production in 1975 which revolutionised this field. Monoclonal antibody production is a technique involving the fusion of an antibody-producing B cell and an immortal cancer cell line to form a hybridoma. These hybridoma cell lines can be continuously cultured and expanded for the production of a single type of antibody of a desired specificity known as monoclonal antibodies. The first therapeutic monoclonal antibody OKT3 was used for the prevention of kidney transplant rejection. However, these non-human antibodies were picked up by the body as foreign and quickly cleared up by our immune system, becoming subsequently ineffective and even toxic. This technique has since been improved by engineering chimeric antibodies (70% human) and “humanized” antibodies (85-90% human). Although the majority of approved monoclonal antibod28

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ies have been created in this way, more recent technologies such as phage-display techniques, in addition to transgenic ‘humanized mice’, have allowed for the development of fully-human antibodies. For example Humira (adalimumab), the first fully-human therapeutic antibody, was developed using phage-display technology. Developed for the treatment of rheumatoid arthritis, Humira was licensed for therapy in 2003, and has since been used as medication for a variety of different auto-immune diseases, become the world’s best-selling prescription drug. These antibodies have been used in laboratories for decades, and are today used for a huge variety of laboratory techniques. You will probably have already come across fluorescent-microscope images, performed using fluorescently-tagged antibodies which are specific for certain cellular structures. Within the clinic, antibodies are useful for the diagnosis of a huge variety of diseases - many blood tests utilise antibodies for the detection of aberrant cells (such as cancers), infections (such as HIV), auto-antibodies (in autoimmune diseases), or the presence of specific biological indicators/markers (e.g. in pregnancy tests). Most importantly, antibodies can be also be used as drugs for the treatment of diseases. We are now seeing a boom in this industry, with 44 monoclonal antibodies and their derivatives already licensed for use in clinic (as of November 2014) [4], and hundreds more in the pre-clinical stages. In fact 6 out of 10 of the best selling drugs today are monoclonal antibodies, and account for over a third of new drugs being introduced [5]. These antibodies can be used to tag dangerous cells, such as cancerous or auto-immune cells, resulting in their neutralisation or destruction either directly via the immune response. Alternatively, binding of antibodies to specific sites on the receptors of cells can result in either blockage or activation of particular signalling pathways, altering the behaviour of cells. Antibodies can also © 2016, The Triple Helix, Inc. All rights reserved.

are antibodies currently in development for treatment of a huge range of illnesses from migraines [6] to HIV [7], asthma, alzheimers [8] [9] and MRSA [10]. With the advancement of our understanding of diseases at the molecular level, new targets are continuously being identified which can be exploited for the treatment of these diseases. Although our understanding of potential targets is a major limitation in antibody therapy, there are still Figure 2: Functions of conjugated and unconjugated (‘naked’) antibodies. The many improvements specicity and sentisivity of antibodies—coupled with their variety of functions— to be made concernmake them very versatile tools. ing production costs, target soluble molecules such as cytoeffective disease-site kines, inhibiting their action. For example, penetration (such as tumours) and oral anti-TNF antibodies are commonly uti- delivery efficiency. Orally administered lised for treating auto-immune diseases antibodies quickly lose their bioactivity such as rheumatoid arthritis by blocking due to the harsh surrounding environment TNF, a molecule highly responsible for in the gut. Although new developments the patient’s inflammatory symptoms. such as the use of hydrogels looks to imAlternatively the harmful immune cells prove on this (preserving the molecule’s themselves can be targeted, as is the case bioactivity long enough for the agent to with one of the oldest therapeutic anti- reach its target) reaching targets outside bodies still in use today, Alemtuzumab. the gut still remains challenging. Hence Developed in the department of pathology the majority of therapeutic antibodies at Cambridge University in the 1970s by are still administered via intravenous German Waldmann, this antibody has injection. After injection, most of these proved useful in the treatment of a range antibodies remain in the blood with little of different disease from improving bone penetration of other tissues. This is helpful marrow transplants, to leukaemia, to when targeting blood-borne diseases, but autoimmune diseases such as multiple not when targeting sites outside the blood sclerosis. This is due to its ability to target such as cancerous tissues. Using antibody mature immune cells, but not their stem fragments can help increase tissue pencells, hence removing harmful immune etration, but this comes at a price of a cells whilst allowing replenishment of the reduced serum half-life, requiring more immune system. Although many mono- frequent injections [11]. clonal antibodies have been developed for Much research is hence currently the treatment of cancers and auto-immune underway to improve antibody therapy diseases, the scope for antibodies in treat- further, with antibody engineering being ing diseases is virtually unlimited. There one such exciting avenue. Methods are © 2016, The Triple Helix, Inc. All rights reserved.

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being tested to improve the serum halflife of antibody fragments through either chemical additions (such as polyethylene glycol (PEG) residues) or multimerization (using multiple fragment combinations). However in addition to improving antibody activity, antibody engineering can now go even further to produce antibodies you wouldn’t normally see in nature, adding new functions to these agents. Under development currently are antibody fragments fused to different molecules. For example, antibodies can be conjugated to molecules such as toxins, radio-isotypes, drugs, or more recently photosensitizers (light-based therapy), delivering them to targeted cells to aid in their destruction. This not only increases the activity of the antibody, but also allows for lower doses to be utilised, potentially reducing side-effects associated with treatments. Conjugation to other molecules such as cytokines or membrane proteins, can give them different advantages. For example, cytokines influence the behaviour of immune cells, and hence by coupling these molecules to antibodies the response of immune cells to the target can be influenced. Dual-specific (bispecific) antibodies are also being developed, potentially connecting immune cells to target cells such as cancer cells. Direct conjugation of antibodies to immune cells, such as T cells, is also being investigated [12]. This would allow these antibodies to directly activate these immune cells, resulting in their action against these targets. Finally research into intracellular antibodies (intrabodies) is also underway which may allow access to new targets not normally found on the surface of cells [11]. The last 40 years has seen leaps and bounds in targeted disease therapy, with antibodies being at the forefront. We are in exciting times, with new disease targets and ways of manipulating them being discovered all the time. Hence antibodies will be an invaluable tool for research and medicine for many years to come and may hold the key to the treatment 30

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of previously-incurable diseases. References [1] Kohler G, C M. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–7. [2] Charles A Janeway J, Travers P, Walport M, Shlomchik MJ. Immunobiology. Garland Science; 2001. [3] Horwath W. Soil Microbial Biomass. Encyclopedia of Environmental Microbiology. 2002. p. 663–70. [4] Ecker DM, Jones SD, Levine HL, Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market The therapeutic monoclonal antibody market. MAbs. 2015;7(1):9–14. [5] Lara Marks. The lock and key of medicine : monoclonal antibodies and the transformation of healthcare. 2015. [6] Sinha G. Migraine mAbs crowd into late-stage trials. Nat Publ Gr. Nature Publishing Group; 2015;33(7):676–7. [7] Hayden EC. Almighty antibodies? A new wave of antibody-based approaches aims to combat HIV. Nat Publ Gr. Nature Publishing Group; 2015;21(7):657–9. [8] Goni F, Peyser DK, Herline K, Sun Y, Wisniewski T. Monoclonal antibody therapy targeting the shared pathological conformer of both beta-amyloid and hyperphosphorylated tau. Alzheimer’s Dement. Elsevier; 2013 Jul;9(4):P839. [9] Catley MC, Coote J, Bari M, Tomlinson KL. Pharmacology & Therapeutics Monoclonal antibodies for the treatment of asthma. Pharmacol Ther. Elsevier Inc.; 2011;132(3):333–51. [10] Sause WE, Buckley PT, Strohl WR, Lynch AS, Torres VJ. Antibody-Based Biologics and Their Promise to Combat Staphylococcus aureus Infections. Trends Pharmacol Sci. Elsevier; 2015 Dec;37(3):231–41. [11] Chames P, Regenmortel M Van, Weiss E, Baty D. Therapeutic antibodies : successes , limitations and hopes for the future. Br J Pharmacol. 2010;(September 2008):220–33. [12] Jackson HJ, Rafiq S, Brentjens RJ. Driving CAR T-cells forward. Nat Rev Clin Oncol. Nature Publishing Group, a division of Macmillan Publishers Limited All Rights Reserved.; 2016 Mar;advance on. Figure 1: “Standard Tissue Culture and Immuno uorescence” by GerryShaw is licensed under CC BY-SA 3.0. All other images were designed by the author.

Arsenic Incidence in Maine: Building Policy Around Geology Wakanene Kamau (University of Chicago)

been acknowledged to have an adverse effect on human health. Found naturally in the Earth’s crust, the World Health Organization estimates that over 200 million people worldwide are exposed to elevated levels of arsenic in drinking water . Since the 1940s the U.S. Federal Government has set regulations on the concentration of permitted arsenic in public water supplies. Today, this responsibility rests in the Environmental Protection Agency, which has refined the baseline Maximum Contaminant Levels (MCL) for arsenic in light of the growing body of scientific literature on arsenic contamination. This refinement process has been a point of active policy debate in Maine, where a unique combination of demographic and geologic factors have made it difficult to determine the effectiveness of the current MCL level of 10 µg/L. In this paper, I will situate the problem of arsenic groundwater contamination in Maine in a system analysis by examining the science behind the arsenic problem, the historical policy efforts to address the problem, and the prevailing contemporary thought on the issue. The US Geological Survey (USGS) considers Maine, along with much of New England to be part of “the Arsenic Belt.” This region rests largely on unconsolidated sedimentary and bedrock aquifers which naturally contain arsenic. A 2010 study conducted by the USGS of 174 towns with 20 or more sampled wells showed that more than 25 percent of the sampled wells in 44 towns exceeded 10 µg/L. In 19 towns, more than 10 percent of the sampled wells had arsenic concentration over 50 µg/L. While prior studies estimated that rsenic has long

nearly 10 percent of domestic wells in Maine contained arsenic, the presence of “hot spot” regions of wells with more than five times the MCL for arsenic in the US had not been well characterized. The results of this study underscore two major problems concerning the nature of arsenic contamination in Maine; first, large geographic variation across Maine in the concentration of arsenic contaminated groundwater; second, a lack of extensive documentation on the incidence of arsenic contamination in individual wells. Before parsing the significance of these two implications, it is important to understand why arsenic contamination is significant. The adverse health effects arsenic occur from both acute short term and chronic exposure. Those affected by intense, acute arsenic exposure (i.e. poisoning event) are subject to nausea, vomiting, abdominal pain, severe diarrhea, and possibly death. Chronic exposure (i.e. drinking water contamination) is linked to multisystem disease including diabetes, cardiovascular disease, and cancers of the bladder, kidney, lungs, and skin . Furthermore, in vivo studies have begun to show that the effects of arsenic exposure may be transgenic, which would mean the effects of arsenic exposure could be passed genetically across generations. This growing body of scientific research prompted the EPA in 2001 to lower the MCL of arsenic in drinking water from 50 µg/L to 10 µg/L for community water systems (e.g. cities, towns, and apartments with their own water supply) and non-transient, non-community water systems (e.g. schools, factories, and churches). When this regulation was made, the EPA estiTHE TRIPLE HELIX Spring 2016

mated that the reduction in MCL would prevent 19-31 cases of bladder cancer and 19-25 cases of lung cancer per year. While this regulation created a national standard that legitimized the threat of arsenic in drinking water on national level, it failed to fully handle the intricacies of drinking water from state to state. Here we reintroduce the two major problems concerning the nature of arsenic contamination in Maine; large geographic water supply variation across the state and lack of extensive documentation on the incidence of arsenic contamination in individual wells. The MCL set by the EPA in 2001 provided a guideline for arsenic contamination for public utility style systems, which did not provide accountability, or have provisions set to handle private water systems. In Maine, where nearly 32

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half of the population of the state relies on private wells for their drinking water supply the public health ramifications of this oversight are frightening. This is the first major obstacle facing water reform in Maine; a large portion of the residents in the state are not connected to major public water utility systems. Large utility systems are easier, logistically and legally, to monitor and regulate. Private wells and other water systems are simply hard to reach --both resource-wise, in personnel or time, and with the legal framework of federal regulatory machinery. As a result, a sizable portion of the state relies on a federally unregulated source to provide their water needs. Without federal oversight on private wells to motivate well testing, we arrive at the second problem concerning the nature of arsenic contamination in Maine; lack of extensive documentation on the incidence of arsenic contamination in individual wells. State legislators in Maine produced two pieces of legislation to promote well water testing; L.D. 1775 (2007) and L.D. 1162 (2015). Both pieces of legislation gained bipartisan support, yet separate governors ultimately vetoed both. L.D. 1775 required well testing as a component of contract of sale of real estate property and suffered stiff opposition from the Maine Association of Realtors who had issues with being placed in a quasi-enforcement position to ensure that water ÂŠ 2016, The Triple Helix, Inc. All rights reserved.

testing occurs. L.D. 1162 was a more modest bill to provide state funding for educational outreach to motivate people to get their wells tested and was vetoed by the Governor for ideological reasons. In brief, the Maine Center for Disease Control in 2013 had received a $300,000, two-year award (2014-16) to build infrastructure reach and distribute well testing kits for rural Mainers from the EPA. In the first year, only 42 of 210 free kits handed out were returned to the state. The Governor took the low return rate to mean that rural Mainers already knew the status of their wells and urged the Maine CDC to not apply for a renewal of the federal grant. If this was truly the case, then Maine would not have still have the second highest age-adjusted incidence rate of bladder cancer and the eighth highest age-adjusted incidence rate of lung cancer. These two cancers are preciously the ones mentioned by the EPA in their decision to reduce the MCL of arsenic in 2001. This dangerous game of fiscal hot potato between state politicians, special interest groups and environmentalists underlies the complicated issues surrounding cost in the arsenic problem. To begin to unpack the economics of the situation we can begin by again turning to the EPA’s reasoning behind lowering the MCL of arsenic. While the scientific data showed that empirical deleterious health effects of arsenic would warrant a MCL of 0 ppb, the costs associated with implementation of 3, 5, 10 and 20 ppb were analyzed in a cost-benefit fashion. In 2001 numbers, EPA estimated that a 5 ppb arsenic rule would cost about $686 million per year nationally, and a 2 ppb standard would cost $2.1 billion nationally. These figures were the projected costs of regulation, upgrade, and maintenance of the arsenic remediation technologies. At 10 ppb, the cost per household was expected to only be between $38 and $327 for small community water systems (<10,000 people) and between $0.86 and $32 for larger community water systems © 2016, The Triple Helix, Inc. All rights reserved.

(>10,000 people). These values were seen to be the most cost-effective “maximizing health risk reduction benefits at a cost that is justified by the benefits.” Additionally, the EPA created a state drinking water revolving fund that would make $3.6 billion available to assist in funding projects that improve water system infrastructure. Combined, these financial and regulatory instruments made major steps in bringing water systems to the new 10 MCL limit. However, these measures again were aimed at community water systems and were not extended to the kind of private well water system found in large regions of Maine. The real cost of private water sanitation rests on well owners. Water use

The future of effective policy to tackle the arsenic problem lies in communitybased mobilization of ‘citizen science’ to promote selfregulation in local communities from a well can either be treated at the point-of-entry into the household or at the point-of-use. Point-of-entry treatment is typically done with anionic exchange systems. This method works by chelating contaminates to a resin bed and requires very little maintenance. Unfortunately these systems also run the very small risk of total failure where all of the captured contamination can be released at once. The most cost-effective method of point-of-use treatment is reverse osmosis, which uses a microscopic membrane to trap contaminants. This method is very effective at removing arsenic, more so than anionic exchange systems . Nevertheless, due to THE TRIPLE HELIX Spring 2016

their small size, they can only produce a few gallons of treated water per day. Prices typically range from $800-$3000 for arsenic specific treatment filters; usually point-of-entry systems are more expensive. Residents of rural areas, where well use is prevalent, typically have lower socioeconomic means than those living in more populous regions. As one might expect, this in turn affects the decision to invest in well remediation even in light of the known health risk. To explore these behavioral hurdles, we can use three social science papers; Flanagan (2013), Mosler (2012), and Fox et al. (2016) to develop a broad understanding of how people’s perception of a health risk can serve as a predictor of health behavior change. Flanagan’s study investigated the results of a survey given to 13 towns in Kennebec County, Maine where 84% of the household are self-supplied by private wells. The 2010 USGS study identified Kennebec county as one of three “large-scale areas of high concentrations of arsenic in groundwater” in Maine3. Flanagan’s study found that even in a publically identified hot spot for arsenic exposure, homeowners in the county had a tendency to underestimate their arsenic-related health risk as compared to their neighbors. The response rate to the survey was 58.3% and while 78% of the households that responded reported that their well had been tested, only 10% had done so in the past year and roughly half had done so more than five years ago. When asked what would prompt them to have their well water tested, the top three most cited responses were “A change in the taste, smell, or appearance of my water” (76%), “Learning that my neighbors have contaminated water” (59%), and“Well testing available for free” (59%). These three responses serve as a meaningful launchpad to investigate how the arsenic problem can be addressed in the future. The response garnering the largest selection,“A change in the taste, smell, 34

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or appearance of my water,” would not prompt households to test their water for arsenic. Unlike other metal contaminants like manganese or iron, arsenic is tasteless, odorless, and colorless. Thus arsenic contamination would not lead to a change in taste, smell, or appearance of water. This lack of a discernable physical trace of arsenic contamination may help account for the optimistic bias of those in Kennebec county about their arsenic-related health risk. The next most cited response was “Learning that my neighbors have contaminated water.” This makes sense, as we would expect that the level of community knowledge of the hyper-local arsenic problem would be a good predictor of well testing behavior. The survey area was chosen because of the extensive efforts to inform citizens of Kennebec county of their increased arsenic-related health risk by the media and government. The final cited response “Well testing available for free” is enlightening because it touches on the reasoning used by some of the current policy efforts to address the arsenic contamination problem in Maine. This kind of policy approaches the arsenic contamination problem as largely an issue of cost. The rationale goes that if funding were provided to subsidize the cost of well testing, then people would get their wells tested. If this approach worked, then we would have seen more than 42 of the 210 free kits distributed by the MCDC returned. A more robust methodology is needed to account for the complexities in the health behavior decision-making process. In this methodological vacuum Mosler introduced his model of Risk, Attitude, Norms, Ability, and Self-Regulation (RANAS)13. In this model. beliefs about the costs in terms of money, time, and effort; and benefits in terms of savings, health, or other advantages of the new behavior are weighed alongside the dos and don’ts expressed by both the community and individual of the household. The RANAS model finally acknowledges the variety of interconnected © 2016, The Triple Helix, Inc. All rights reserved.

factors that motivate decisions and is a necessary tool in informing new policy. The future of effective policy to tackle the arsenic problem lies in a community-based mobilization of ‘citizen science’ to promote self-regulation in local communities. Given the limited current regulatory standards and logistical practicalities of top-down approaches to private well management, bottom-up approaches will become better tools for mitigating arsenic exposure. It is impractical to enact national and state regulations for a hyperlocal problem. In Flanagan’s study, the second most cited reason prompting well testing was “Learning that my neighbors have contaminated water”. If policy can motivate and support citizens to engage with their community on a neighbor-to-neighbor level, it can be a powerful tool in raising awareness. The expert panel narrowed in on the need to promote and strengthen the knowledge base on private wells by developing and deploying datasets on the physical characteristics of wells (location, depth, chemical profile) as well as the demographic information on the well use (water-use, treatment, household profile). Such databases would facilitate the development of the modeling efforts to create dynamic, predictive models of well contamination. Citizen science can play an integral role in creating the infrastructure necessary to collect information on well use at the resolution necessary to create predictive models. New policy aimed at promoting ‘citizen science’ will foster committed local engagement and predictive modeling arsenic contamination needed to effectively tackle the arsenic problem in Maine.

References [1] Naujokas, Marisa F et al. “The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem.” Environmental Health Perspectives (Online) 121.3 (2013): 295. [2] Nielsen, M.G., Lombard, P.J., and Schalk, L.F., 2010, Assessment of arsenic concentrations in domestic well water, by town, in Maine, 2005–09: U.S. Geological Survey Scientific Investigations Report 2010–5199, 68 p. [3] Ratnaike, Ranjit Nihal. “Acute and chronic arsenic toxicity.” Postgraduate medical journal 79.933 (2003): 391-396. [4] Ortiz, Jorge G Muñiz et al. “A transgenic Drosophila model for arsenic methylation suggests a metabolic rationale for differential dose-dependent toxicity endpoints.” Toxicological Sciences 121.2 (2011): 303-311. [5] “Chemical Contaminant Rules | Drinking Water ...” 2015. 22 Feb. 2016 http://www.epa.gov/dwreginfo/ chemical-contaminant-rules [6] Cooper, Mechele. “Arsenic in Maine: Threat from below.” Portland Press Herald. The Portland Press, 03 Sept. 2011. Web. 13 Apr. 2016. [7] “Our View: State Inaction on Arsenic Tests Puts Mainers at Risk.” The Portland Press Herald. Ed. The Editorial Board. The Portland Press, 14 July 2015. Web. 24 Feb. 2016. [8] “State Cancer Profiles - SEER Cancer Statistics.” 2008. 22 Feb. 2016 http://seer.cancer.gov/statistics/scp.html [9] “NRDC: Arsenic and Old Laws: An Analysis of Arsenic ...” 23 Feb. 2016 http://www.nrdc.org/water/ drinking/arsenic/aolinx.asp [10] Laage, Damien, and James T Hynes. “Reorientional dynamics of water molecules in anionic hydration shells.” Proceedings of the National Academy of Sciences 104.27 (2007): 11167-11172. [11] “Estimating Water Treatment Costs Volume 2 Cost Curves ...” 2013. 23 Feb. 2016 http://nepis.epa.gov/ Exe/ZyPURL.cgi?Dockey=3000093F.TXT [12] Flanagan, Sara V, Robert G Marvinney, and Yan Zheng. “Influences on domestic well water testing behavior in a Central Maine area with frequent groundwater arsenic occurrence.” Science of the Total Environment 505 (2015): 1274-1281. [13] Mosler, Hans-Joachim. “A systematic approach to behavior change interventions for the water and sanitation sector in developing countries: a conceptual model, a review, and a guideline.” International journal of environmental health research 22.5 (2012): 431-449. [14] Fox, Mary A et al. “Meeting the public health challenge of protecting private wells: Proceedings and recommendations from an expert panel workshop.” Science of The Total Environment 554 (2016): 113-118.

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A Preview: The Effect of Income Cycling on Hypoglycemia Incidence The Roosevelt Institute

The following is a preview of a policy initiative written by members of the Roosevelt Institute at the University of Chicago. Initiatives usually address a specific problem, outlined below, and posit a progressive policy idea (the “answer”) and analysis. The Roosevelt Institute is a national network of clubs and think tanks at various undergraduate institutions. Roosevelt institute members conceive and writer progressive, non partisan, public policy. For more information, please see p. 34.

Background and Context: A 2014 study from the University of California at San Francisco is titled “Exhaustion of Food Budgets at Month’s End and Hospital Admissions for Hypoglycemia”. The study finds that the frequency of patients presenting in hospitals with hypoglycemia fluctuates throughout the month. Hypoglycemia is a condition where blood glucose drops below normal levels, and it can be precipitated by inadequate nutritional intake and/or poor insulin management. Hospital admissions for hypoglycemia increase steadily from 230 per 100,000 hospital admissions during the first week of the month to 290 per 100,000 during the last week of the month, although importantly, only among low-income patients [1]. High- income patient admissions for hypoglycemia are stable throughout the month [1]. Researchers at UCSF attribute the trend to income and benefit cycles. The “SNAP cycle” is a relatively well-documented phenomenon among families receiving welfare benefits [2]. SNAP, or the Supplemental Nutrition Assistance Program, provides millions of low income families and individuals with the resources to afford a nutritionally adequate diet- it is the largest program in the domestic hunger safety net. The structure of the program varies based upon state implementation; most states, including 36

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California (where the study took place) and Illinois, issue benefits as a once-a-month injection of funds via Electronic Benefit Transfer (EBT) to a debit-like card which may be used at many grocery stores and food outlets. The “SNAP cycle” describes the potential for a cyclic caloric intake to result from one-time disbursals of benefits at the beginning of the month. Like most households, SNAP households use the majority of their funds at the beginning of the month [2]; however, because SNAP households face greater-than-normal difficulties in achieving food security, the resulting decrease in funds at the end of the month may result in poor nutritional consumption. The 2014 study posits that the SNAP cycle, among other income cycles (imagine a scenario where the majority of a family’s income is taken up by rent; in this case, the food budget might be highest in between rent payments, and lowest in the days leading up to or following payment) may be driving low-income patients to hospitals to be treated for hypoglycemia at the end of the month. It is likely that the effect is preferentially affecting diabetic low-income patients, for whom food insecurity is associated with a two- to three-fold increase in risk for hypoglycemia [3]. This is particularly concerning considering the strong positive correlation between poverty and diabetes [4]. © 2016, The Triple Helix, Inc. All rights reserved.

In total, the direct cost of hypoglycemia to the health care system was $1.84 billion in 2009 [5]. The Problem: benefit cycles may drive end-of-month increases in hospital admissions due to severe hypoglycemia, to the detriment of low income diabetic patients. Interested in working with the University of Chicago chapter of the Roosevelt Institute to create a solution to this problem? Join us! The Roosevelt Institute The Roosevelt Institute’s mission is to reimagine the rules of local and global politics by engaging emerging leaders from college students to legislators. Their initiatives range from innovative professional think tanks to the 10 Ideas series (journals which publish the best progressive policy proposals written by Roosevelt students from across the nation). A Roosevelt Institute chapter will be arriving at the University of Chicago in Fall 2016. Student projects include devising answers to the policy question stated above, and more. For more information about the UChicago program, or to stay updated on its progress, please email ryanburgess@uchicago.edu. For more information about the national Institute, please visit http:// rooseveltinstitute.org.

References [1] Seligman, H. K., Bolger, A. F., Guzman, D., Lopez, A., & Bibbins-Domingo, K. (2014). Exhaustion Of Food Budgets At Month’s End And Hospital Admissions For Hypoglycemia. Health Affairs, 33(1), 116-123. doi:10.1377/hlthaff.2013.0096. [2] Wilde, P. E., & Ranney, C. K. (2000). The Monthly Food Stamp Cycle: Shopping Frequency and Food Intake Decisions in an Endogenous Switching Regression Framework. American Journal of Agricultural Economics, 82(1), 200-213. doi:10.1111/0002-9092.00016. [3] Seligman HK, Davis TC, Schillinger D, Wolf MS. Food insecurity is associated with hypoglycemia and poor diabetes self-management in a low-income sample with diabetes. J Health Care Poor Underserved. 2010;21(4):1227–33. [4] Levine, J. A. (2011). Poverty and Obesity in the U.S. Diabetes, 60(11), 2667-2668. doi:10.2337/db11-1118. [5] Norman, C., Mello, M., & Choi, B. (2016). Identifying Frequent Users of an Urban Emergency Medical Service Using Descriptive Statistics and Regression Analyses. Western Journal of Emergency Medicine WestJEM, 17(1), 39-45. doi:10.5811/westjem.2015.10.28508.

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The Triple Helix at the University of Chicago

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THE TRIPLE HELIX Spring 2016